Clinical trial NCT03468855
Conditions: Vitiligo
Sponsor: Aclaris Therapeutics, Inc.
Start date: 2018-03-19; Completion date: 2019-10-16
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% in subjects with non-segmental facial vitiligo.

Detailed description:
This is a multicenter, open-label study designed to evaluate the safety, tolerability and efficacy of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo. Subjects will be required to have a clinical diagnosis of non-segmental facial vitiligo effecting at least 0.25% of total body surface area (TBSA) (excluding upper and lower eyelids, mucosal lip areas, and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Twenty-four eligible subjects will receive ATI-50002 Topical Solution, 0.46%, BID for 24 weeks.

Arms: arm 1: ATI-50002 topical solution, high dose active, twice-daily, 24 weeks
Interventions: intervention 1: ATI-50002 topical solution
Intervention descriptions: intervention 1: Topical Solution administered twice daily

Protocol documents:
ICF_002.pdf: 
Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 1 of 15
INFORMATION AND CONSENT FORM
Study Title: 
A Study of ATI-50002 Topical Solution for the Treatment of Vitiligo
Study #:
Sponsor:
ATI-50002-VITI-201 
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-50002 Topical 
Solution.  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).
Vitiligo is a disorder in which white patches of skin appear on different parts of the body.  The 
white patches appear because the cells that make the pigment (color) in the skin are destroyed.  
Vitiligo may spread to other areas of the body.  There is no way to tell if vitiligo will spread to 
other areas.  For some people, vitiligo spreads slowly and for others spreading occurs quickly.    
Vitiligo may be 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 vitiligo, the immune system attacks the melanocytes 
(melanin-forming cells).
Current treatment options for vitiligo include medical treatments that you put on your skin or take 
by mouth, treatments that use a topical medicine plus ultraviolet light A (UVA) light (PUVA), 
lasers, removing the color from other areas to match the white patches, surgical options such as 
a skin graft or tattooing small areas of skin, and other treatments such as cosmetics to cover the 
white areas.  


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 2 of 15
Treatments that restore the color to the skin may take 2 to 3 months before small areas of color 
can be seen and 6 to 9 months before more color fills in the areas of white skin.   
The main purpose of this study is to see whether ATI-50002 Topical Solution (0.46%) can help 
the skin color to return in the white patches in people with vitiligo on the face. Researchers also 
want to find out if ATI-50002 Topical Solution applied to the face is safe and tolerable.
It is planned that about 24 people with facial vitiligo will be in this study.
Be aware that this form refers to ATI-50002 Topical Solution (0.46%) as “study drug.”
HOW DOES ATI-50002 TOPICAL SOLUTION WORK?
ATI-50002 Topical Solution is an investigational drug in a Topical Solution that is designed to 
return color to the white areas on the face.  ATI-50002 Topical Solution has not been studied in 
people with facial vitiligo, and whether or not ATI-50002 will work is unknown.  If you receive 
ATI-50002 in this study and the drug is effective, early signs of color in your white facial patches 
(if any occurs) may take up to three months, and more color may appear after 6 months of 
dosing.  There is no guarantee that ATI-50002 will help your facial vitiligo.
IS THERE ANYTHING ELSE I CAN DO FOR MY FACIAL VITILIGO?
You do not have to be in this study to get help for your vitiligo.  Some other things you may be 
able to do are:

Corticosteroids (anti-inflammatory medications), either topically applied or taken by 
mouth,

Calcineurin inhibitors (immunosuppressive medications), applied to the white patches of 
skin

Phototherapy, a treatment that uses ultraviolet light 

Surgery, skin grafts from your own skin with color

Tattooing small areas of skin

Cosmetics to cover the white patches on your skin

Investigational drugs
Although many products are used for this condition, their effectiveness is uncertain.
You should discuss your alternatives to participating in this research with the study doctor or 
study staff.  In addition, you may discuss your options with your regular health care provider.
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.>>


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 3 of 15
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 11 visits to the study center and will last about 28 weeks, up to a 
maximum of 201 days, with a possibility of up to an additional 28 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 or study staff will give you study drug to put on the white patches on your face.  
You should not apply the study drug to your eyelids or the red (mucosal) areas of your lips.  You 
also should not get any study drug in your eyes.  You will apply up to 2 mLs of the study drug 2 
times a day (in the morning and evening approximately 8 to 12 hours apart) for 24 weeks.  If 
your face is clean shaven at the screening visit, you should remain clean shaven throughout the 
study.  
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.
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 vitiligo 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.


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 4 of 15

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.

Blood Testing:  Take some blood through a needle in your arm to do safety and 
laboratory tests.  During the first visit, you will have 7 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 28 weeks 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.

Changes in Health or Medication Questions:  You will be asked about any changes in 
your health and the medications you are taking since the previous study visit.

Skin Examinations:  The study doctor or study staff will examine your face to determine 
the amount of white patches. 

Questionnaires:  You will examine your face to determine and describe the appearance 
and severity of your facial vitiligo (white patches), and assess the impact of the facial 
vitiligo on your life.  At Visit 7 (Day 85), you will be asked to rate your satisfaction with 
the study drug results.

Photography:  The study doctor or study staff will take pictures of your face (your face 
will be included in these photographs) to document the white patches. 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 apply 
the study drug.


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 5 of 15

Apply study drug in the office:  At Visit 2, the study staff will instruct you on how to 
apply the study drug.  You will apply the study drug in the office under the supervision 
and guidance of the study staff.

Subject Instruction Sheet:  You will be given a written instruction sheet.
The following is a schedule of events and tests you will have at each visit:


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 6 of 15
Visit 
1
Visit 
2
Visit 
3
Visit 
4
Visit 
5
Visit 
6
Visit 
7
Visit 
8
Visit 
9 
Visit 
10
Visit 
11
Informed consent

Physical exam


A discussion about 
your age, birth 
date, medical and 
surgical history, 
and history of 
vitiligo

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










Examination of 
your face and 
calculation of the 
percentage of 
white patchy areas


Examination of 
your face, white 
facial patches, and 
colored areas








Examination of the 
percentage of your 
body with white 
patches




Photographs of 
your face








Questions about 
how noticeable is 
your facial vitiligo







Questions about 
how satisfied you 
are with the 
response to study 
drug





Questions about 
the impact of your 
facial vitiligo






Study drug and 
instructions








In office study 
drug application

Changes in Health 
or Medication 
Questions












Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 7 of 15
The results from the tests at Visit 1 will determine whether you are eligible to continue in the 
study.  If you discontinue the study early for any reason, the tests for Visit 11 will be performed.
WILL BEING IN THIS STUDY HELP ME?
The study drug may help your facial vitiligo, but there is no guarantee that being in this study will 
help you.  Your vitiligo might not get better or may even get worse while you are in this study.  
Information from this study might help researchers to better understand vitiligo 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-50002 has been used on people with vitiligo.  
You must be careful to avoid having the study drug run into your eyes because it could cause 
irritation.  
In animal testing, the following temporary side effects occurred on the skin where ATI-50002 
was applied:

Redness

Swelling

Skin peeling
Healthy volunteers took an oral form of ATI-50002, 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-50002 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-50002 Topical Solution 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.


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 8 of 15
It is possible that using ATI-50002 Topical Solution may change how your regular medications, 
vaccines, or supplements work.  It is very important that you tell the study doctor about any 
medications, supplements, or vaccines before you take them during 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

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.
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 facial vitiligo 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

Dizziness

Infection
Risks of study photography
There are no expected physical risks if the study doctor or study staff takes photos of your face 
during the study.  It is possible that people who see the study photos will recognize you. 


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 9 of 15
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.
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 application.  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-50002 Topical Solution, 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 you must use during the study and up to 30 days after the last application 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-50002 Topical Solution that 
nobody knows about yet, which include your facial vitiligo 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.


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 10 of 15
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.
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.
Be aware that your health care payer/insurer might not cover the costs of study-related injuries 
or illnesses.
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.


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 11 of 15
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.
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).


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 12 of 15
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. 
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-50002 Topical Solution.

Others required by law to review the quality and safety of research, including the 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.
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-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 13 of 15
<<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>>


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 14 of 15
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.
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


Information and Consent Form
Aclaris Therapeutics, Inc.
ATI-50002-VITI-201
Initials __________    Date __________
Version 2, dated 07/02/18
Page 15 of 15
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_SAP_000.pdf: 
Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 1 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
     CLINICAL STUDY PROTOCOL 
Protocol Number: ATI-50002-VITI-201 
Amendment 3 
 
An Open-Label Pilot Study of the Safety, Tolerability and Efficacy of ATI-50002 Topical 
Solution Administered Twice-Daily in Adult Subjects with Non-Segmental Facial Vitiligo 
 
Sponsor 
Aclaris Therapeutics, Inc. 
640 Lee Road 
Suite 200 
Wayne, PA 19087 
Telephone: 484-324-7933 
Facsimile: 484-320-2344 
 
Study Contact 
Sue Moran, RN, MSN 
Sr. Director, Clinical Development 
Aclaris Therapeutics, Inc. 
640 Lee Road 
Suite 200 
Wayne PA 19087 
Telephone: 484-329-2129 
Cell:  484-999-7492 
E-mail: smoran@aclaristx.com 
 
Medical Monitor 
Terrence Chew, MD RAC 
Telephone: 858-720-0647 
Serious Adverse Event Facsimile: 484-324-2359 
E-mail: tgchew@icloud.com 
 
 
 
 
 
 
 
 
 
This document is a privileged and confidential communication of Aclaris Therapeutics, Inc. Acceptance of this 
document constitutes an agreement by the recipient that no unpublished information contained herein will be used, 
published or disclosed without prior written approval from Aclaris Therapeutics, Inc. 




Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 3 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
INVESTIGATOR SIGNATURE PAGE 
Protocol Number:  ATI-50002-VITI-201  
 
Protocol Title:  An Open-Label Pilot Study of the Safety, Tolerability and Efficacy of ATI-50002 Topical 
Solution Administered Twice-Daily in Adult Subjects with Non-Segmental Facial Vitiligo 
 
Version 3.0 October 12, 2018 
 
I have reviewed the above-titled protocol and agree that it contains all the information necessary to conduct 
the study as required.  I will conduct the trial in accordance with the principles of ICH Good Clinical 
Practice and the Declaration of Helsinki. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, including 
but not limited to, the protocol, case report forms, investigator’s brochure, material supplied at investigator 
meetings, minutes of teleconferences, etc.  Such materials will only be provided as necessary to site 
personnel involved in the conduct of the trial, involved IRBs or local regulatory authorities. 
I will obtain written informed consent from each prospective trial subject or each prospective trial subject’s 
legal representative prior to conducting any protocol-specified procedures.  The Informed Consent 
Document used will have the approval of the IRB appropriate for my institution. 
 
I will maintain adequate source documents and record all observations, treatments and procedures pertinent 
to trial subjects in their medical records.  I will accurately complete the case report forms supplied by the 
Sponsor in a timely manner.  I will ensure that my facilities and records will be available for inspection by 
representatives of the Sponsor, the IRB, and/or local regulatory authorities.  I will ensure that I and my staff 
are available to meet with Sponsor representatives during regularly scheduled monitoring visits. 
I will notify the Sponsor within 24 hours of any serious adverse events.  Following this notification, a 
written report describing the serious adverse event will be provided to the Sponsor as soon as possible, but 
no later than five days following the initial notification. 
 
Investigator Signature: 
 
 
____________________________________ 
________________________ 
Investigator signature 
 
Date 
 
 
 
____________________________________ 
Investigator printed name 
 
 
 
 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 4 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
AMENDMENT HISTORY 
Protocol Amendment 1 (version 2.0 Dated 19JUN2018) provided the following changes to the original 
protocol (version 1.0, dated 30NOV2017): 
• 
Clarified the area of the face excluded from the TBSA calculation is the area from the eyebrows to 
and including the upper eyelids; the area from the bony rim of the orbit to and including the lower 
eyelids; mucosal lip areas; beard [if applicable] and the forehead and chin areas covered by the 
stereotactic positioning device for photography, 
• 
Updated the number of sites from 3 to 5, 
• 
Changed the age range from ≥ 18 to 65 to ≥ 18, to allow enrollment of subjects who do not have 
evidence of significant poliosis, and based on the medical judgement of the investigator are capable 
of repigmentation, 
• 
Added a contraception requirement for male subjects with a partner who is a WOCBP, 
• 
Clarified that subjects with significant spontaneous repigmentation are excluded to allow the 
inclusion of subjects who have had very minor repigmentation, such as a small macule, 
• 
Revised exclusion criterion for ANC and platelets to below the ACM Laboratory lower limit of 
normal; ANC from < 1,000/mm3 to < 1,800/µL and platelet count from < 50,000/mL to < 
130,000/µL, 
• 
Clarified that a heart rate of ≤ 45 beats/minutes based on the screening ECG should only exclude 
subjects from randomization, if in the opinion of the investigator the low heart rate is clinically 
significant. 
• 
Clarified that subjects with any screening values that meet the study interruption criteria must have 
repeat lab testing performed with results meeting the minimum criteria for resumption, 
• 
Added a specific exclusion criterion for subjects who are positive for HIV, Hepatitis B or C, 
previously covered under Exclusion Criterion 9: Subjects with a current viral infection, 
• 
Added to Permitted Concomitant Medications, Therapies and Over the Counter Products (OTC) 
Section: Male subjects who shave at screening and baseline should maintain the same shaving 
regimen during the study. 
• 
Added to the Prohibited Medications, concomitant use of: 
o Camouflaging agents with a temporary dyeing effect such as dihydroxyacetone, or self-
tanners or, 
o Immune boosting herbal supplements such as astragalus 
• 
Deleted 80% total body VASI from Section 6.4.1 
• 
Revised: Timeframe each bottle of study medication should be used from 14 days to 30 days based 
on updated stability information, 
• 
Added APPENDIX 6, Area of Interest Diagram in order to clarify the areas of the face with vitiligo 
that can be included in the TBSA calculation. 
• 
Replaced Vitiligo Area Severity Index (VASI) Vitiligo Area Scoring Index (VASI) throughout the 
protocol. 
Administrative Letter #1 Dated 29JAN2018 updated Aclaris Therapeutics, Inc. office location. 
Administrative Letter #2 Dated 05OCT2018 changed the number of subjects enrolled from 24 to 33.  The 
changes from both Administrative Letters were incorporated into Protocol Amendment 2, Version 3.0 
Dated 12OCT 2018. 
 
Protocol Amendment 2 (version 3.0 Dated 12OCT2018) extended the treatment period for an additional 24 
weeks of active treatment with a 4-week post-treatment follow-up visit to allow for the timeframe for 
repigmentation which may require 6 to 12 months of treatment.  Protocol Amendment 2 provides the 
following primary changes to Protocol Amendment 1 (version 2.0 Dated 19JUN2018): 
• 
Added Visit 12 (Week 32), Visit 13 (Week 40), Visit 14 (Week 48), and Visit 15 (Week 52). 
• 
Revised the Primary Efficacy Assessment timepoint to Visit 14, Week 48. 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 5 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
• 
Added CPK as an additional safety assessment.  
• 
Added the neck as an acceptable treatment area. 
Clarified that statistical analyses will be performed after all subjects complete Visit 10 and Visit 15 and that 
the primary efficacy assessment will be at Visit 14, Week 48. 
AMENDMENT RATIONALE 
 Protocol Amendment 3.0 dated 08FEB2019 allows for the concomitant use of narrowband-UVB according 
to the Standard of Care protocol for the treatment of vitiligo to see if there is a synergistic effect on 
repigmentation.    
 
ATI-50002 Topical Solution was not a skin sensitizer in a mouse local lymph node assay.  ATI-50002 was 
shown to have the potential to react to light.  In a 3T3 cell assay, ATI 50002 in the absence and presence 
of UVA did not cause toxicity and, therefore, there was no phototoxic potential identified for ATI-50002. 
 
Protocol Changes 
Protocol 
Version 
Date 
Section 
Revisions  
4.0 
08FEB2019 
5.6 
5.6.1 
Added:   
NB-UVB treatments may be administered according to the Standard of 
Care protocol for the treatment of vitiligo after the subject has 
completed Visit 9.  NB-UVB treatments should be recorded in the 
source documents and on the Concomitant Therapies Log of the eCRF.   
 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 6 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
SYNOPSIS 
Protocol Number: 
ATI-50002-VITI-201 
 
 
Protocol Title:  
An Open-Label Pilot Study of the Safety, Tolerability and Efficacy 
of ATI-50002 Topical Solution Administered Twice-Daily in Adult 
Subjects with Non-Segmental Facial Vitiligo 
Sponsor: 
Aclaris Therapeutics 
Inc. 
Phase of Development:  Phase 2 
 
Study Medication Description: 
ATI-50002 Topical Solution, 0.46%  
Study Objective: 
The main objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 
Topical Solution, 0.46% in subjects with non-segmental facial vitiligo. 
Study Design: 
This is a multicenter, open-label study designed to evaluate the safety, tolerability and efficacy 
of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo.  Subjects 
will be required to have a clinical diagnosis of non-segmental facial vitiligo effecting at least 
0.25% of total body surface area (TBSA) (excluding: the area from the eyebrows to and 
including the upper eyelids;  the area from the bony rim of the orbit to and including the lower 
eyelids; mucosal lip areas; beard [if applicable], and forehead and chin areas covered by the 
stereotactic positioning device for photography) with at least one area of the face with normal 
pigmentation.  Thirty-three eligible subjects will apply ATI-50002 Topical Solution, 0.46%, 
BID for up to 48 weeks to the vitiliginous areas of the face and neck and a ½” area around 
these areas. 
 
During the screening period, subjects will be assessed for eligibility to receive study 
medication.  Eligible subjects will apply study medication to the vitiliginous areas of the face 
and neck and a ½” margin around these areas (excluding upper and lower eyelids [defined as 
the area from the bony rim of the orbit to and including the eyelids], and mucosal lip area) 
twice-a-day for up to 48 weeks. If applicable, the subject may treat up to the vermillion border 
of the mucosal lip and the skin underneath the beard.  Assessment of response to treatment 
will be performed using Canfield 2-D photographic digital image analysis, Facial VASI, 
Vitiligo Noticeability Scale (VNS), VitiQoL and Subject Vitiligo Satisfaction Scale. These 
will occur as specified in the Schedule of Assessments.  Subjects will be seen at up to 15 study 
visits, including up to 48 weeks of active treatment followed by a 4-week post-treatment 
follow-up visit.  Subjects who consented for the original study treatment period for up to 28 
weeks, and do not consent for the additional visits (Visit 12-15) will complete the study at 
Visit 11 (Week 28.)  Safety and tolerability will be evaluated throughout the study by 
assessment of electro-cardiograms (ECG), clinical laboratory tests, adverse events including 
local site reactions, and vital signs. 
Number of Subjects (planned): 
Approximately 33 subjects will be enrolled. 
Number of Study Sites: 
This study will be conducted at approximately 5 U.S. clinical sites. 
 


Protocol: ATI-50002-VITI-201 
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Page 7 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
Inclusion Criteria: 
In order to be eligible for the study, a subject must fulfill all of the following criteria: 
1. Subject is a male or female ≥ 18 years of age. 
2. Subject has a clinical diagnosis of new onset or actively progressing non-segmental 
facial vitiligo or worsening of existing facial lesions within the past 6 months.  
Actively progressing vitiligo is defined as: subject history of a new vitiliginous lesion 
or objective signs of disease activity (such as: confetti-like depigmentation, trichrome 
lesions, and the Koebner phenomenon) as assessed by the investigator. Subjects may 
have non-facial vitiliginous lesions that are unchanged for more than 6 months 
provided they meet the requirement for active facial lesions. 
3. Subject has non-segmental facial vitiligo effecting at least 0.25% total body surface 
area (TBSA) (excluding: the area from the eyebrows to and including the upper 
eyelids; the area from the bony rim of the orbit to and including the lower eyelids; 
mucosal lip areas; beard [if applicable]; and forehead and chin areas covered by the 
stereotactic positioning device for photography) with at least one area of the face with 
normal pigmentation.  The face is defined as the area from the border of the hairline, 
not including areas with hair such as the eyebrow and if applicable the beard to the 
jawline. 
4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy 
test at the screening visit and a negative urine pregnancy test at the baseline visit and 
must agree to use an approved method of highly effective birth control for the duration 
of the study and for 30 days after last study medication application. 
5. If female, subject who is non-pregnant and non-lactating and not planning a pregnancy 
during the duration of the study. 
6. Subject is in good general health and free of any known disease state or physical 
condition which, in the opinion of the investigator, would interfere with the study 
assessments or put the subject at undue risk by study participation. 
7. Subject is willing and able to follow all study instructions and to attend all study visits. 
8. Subject agrees to refrain from any other treatments for vitiligo from the screening visit 
through the final follow-up visit.  Over the counter (OTC) preparations deemed 
acceptable by the investigator and camouflage makeups are permitted. 
9. Subject is able to comprehend and willing to sign an Informed Consent Form (ICF).  
10. Sexually active male subjects with a partner who is a WOCBP, must agree to use a 
barrier method of contraception from the first application of study medication to at 
least 30 days after the last dose of study medication. 
 
Exclusion Criteria: 
Any subject who meets one or more of the following criteria will not be included in this study:  
1. Subject with evidence of poliosis (white hairs) in > 50% of their facial vitiligo lesions.  
2. Subject with total facial depigmentation. 
3. Subject with significant spontaneous ongoing facial repigmentation (documented based 
on the subject’s reporting in the last 3 months). 
4. Subject who has segmental vitiligo. 


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Page 8 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
5. Subject who has failed phototherapy.  Failed phototherapy is defined as failure to achieve 
satisfactory repigmentation following adequately delivered phototherapy as determined 
by the investigator. 
6. Subject currently has, or has a history of, skin disease (e.g., psoriasis, seborrheic 
dermatitis, etc.) that, in the opinion of the investigator, would interfere with the study 
medication application or study assessments. 
7. Subject has, or has a history of, severe, progressive or uncontrolled autoimmune, 
metabolic, renal, hepatic, gastrointestinal, pulmonary, cardiovascular, genitourinary 
(i.e., renal disease), hematological disease, neurologic or cerebral disorders, infectious 
disease or coagulation disorders that, in the opinion of the investigator, would interfere 
with the study assessments or put the subject at undue risk by study participation.   
8. Subject currently has, a history of, current, or suspected systemic or cutaneous 
malignancy and /or lymphoproliferative disease, other than a history of adequately 
treated, well healed and completely cleared non-melanoma skin cancers (e.g., basal or 
squamous cell carcinoma) treated successfully at least 1 year prior to study entry with 
no evidence of disease. 
9. Subject currently has evidence of active or latent bacterial (including tuberculosis) or 
viral infections at the time of enrollment, or a history of incompletely treated or untreated 
tuberculosis.  Subjects who have initiated therapy for latent tuberculosis for at least 2 
weeks and agree to continue their therapy through completion may participate. 
10. Subject has a history of serious local infection (e.g., cellulitis, abscess) or systemic 
infection, or history of treated infection (e.g., pneumonia, septicemia) within 3 months 
prior to the baseline visit.  Subjects on an antibiotic for a nonserious, acute local infection 
must complete the course prior to enrollment into the study.  
11. Subject has herpes zoster or cytomegalovirus (CMV) that resolved within 8 weeks prior 
to Visit 1. 
12. Subject has a history of frequent outbreaks of oral Herpes Simplex Virus defined as more 
than 4 episodes per year. 
13. Subjects previously treated with depigmenting agents.   
14. 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 
other Screening laboratory values meeting the Study Medication Interruption Criteria 
found in Table 1 must have repeat lab testing performed with results meeting the 
minimum criteria for resumption in order to initiate treatment at Baseline (Visit 2).   
15. Subject who has an absolute neutrophil count <1,800/µL, or platelet count  
< 130,000/µL.   
16. Subject unable to comply with the required washout periods: 
1. Use of any biologic, investigational therapy or procedure for vitiligo within 12 
weeks or 5 half-lives (whichever is longer) of screening (Visit 1). 
2. Use of laser or light-based vitiligo treatments, including tanning beds, within 8 
weeks of screening (Visit 1). 
3. Use of immunomodulating oral or systemic medications (e.g., corticosteroids, 
methotrexate, cyclosporine) or topical treatments that may affect vitiligo (e.g., 
corticosteroids, tacrolimus/ pimecrolimus, retinoids) within 4 weeks of screening 
(Visit 1). 


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Date: 08FEB2019, Version 4.0 
4. Use of any prior concomitant therapy not listed above that may interfere with the 
objective of the study as per the discretion of the investigator, including drugs 
that cause photosensitivity or skin pigmentation (e.g., antibiotics such as 
tetracyclines, sulfa etc.) within 8 weeks of screening (Visit 1).  
5. Subjects who have previously received oral or topical JAK inhibitors. 
17. Subject who has participated in any investigational drug or device trial, regardless of 
indication in which administration of an investigational drug or device occurred within 
30 days or 5 half-lives (whichever is longer) of screening (Visit 1).  Note that 
investigational treatment for vitiligo (in any body area) requires a longer washout – see 
Exclusion criterion #16.1 above. 
18. Subjects with a clinically significant abnormal thyroid-stimulating hormone or free T4 
at screening.  Subjects under treatment with stable thyroid replacement who have a free 
T4 and TSH within the normal range may participate. 
19. Subject has history of sensitivity to any of the ingredients in the study medications. 
20. Subject has a history of, or current alcohol or drug abuse within 2 years of study 
enrollment 
21. Screening ECG findings of: 
1. QTcF >450msec for males or >470msec for females (use of the ECG algorithm 
is acceptable for this purpose) 
2. Clinically significant heart rate ≤ 45 or Heart Rate ≥ 100 beats/minutes 
3. Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular 
rhythm (ectopic atrial rhythm) 
4. Conduction disturbance including PR >240msec, pre-excitation (delta wave and 
PR <120msec), second degree or higher AV block 
5. Acute or chronic signs of ischemia.   
6. Left Bundle Branch Block 
7. Prior myocardial infarction 
22. Positive for HIV, Hepatitis B or C.  Subject with serologic evidence of Hepatitis B 
vaccination (HepB surface Ab without the presence of Hep B sAg) will be allowed to 
participate. 
Duration of Treatment 
The planned study durations are: 
• Enrollment period: 12 weeks (84 days) 
• 
Study participation duration (Visit 1 through Visit 11 is a maximum of 229 days). 
• 
Duration of study participation from Visit 1 thought Visit 15 is a maximum of 372 days. 
 
Criteria for Evaluation: 
Efficacy: 
The percentage of facial depigmentation will be quantified in the Area of Interest (AOI) through 
analysis of digital images (Section 8.1.1 Canfield 2D Digital Facial Image Analysis).   
 
The investigator will evaluate facial repigmentation using the Facial Assessment of the Vitiligo 
AreaScoring Index (F-VASI).   
 


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Page 10 of 67                                                     CONFIDENTIAL 
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Subject will assess facial repigmentation using the Vitiligo Noticeability Scale (VNS).  
Treatment success will be defined as follows:  VNS score of 1 or 2 = treatment not successful, 
VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful.  
Safety: 
The investigator will assess clinical laboratory safety tests, vital signs, ECGs, concomitant 
therapies, urine pregnancy test results, and adverse events (AEs) throughout the study. 
 
Other: 
The investigator will assess the extent of vitiligo using the VASI (total body).  VASI will be 
assessed for descriptive purposes only to track disease progression in untreated areas. 
 
Subjects will assess their satisfaction with the results of the study using the Subject Vitiligo 
Satisfaction scale.  
 
Subjects will assess the impact of vitiligo on their quality of life using the VitiQoL. 
 
Study Medication Administration 
At Visit 2, after confirmation of eligibility, an investigational staff member will instruct the 
subject on the proper study medication application technique and observe the first study 
medication application. The subject will then start the treatment period (up to 48 weeks) and 
will apply a thin film of study medication twice-a-day to the areas of the face and neck with 
vitiligo and at least a ½” margin around the lesions (excluding the area from the bony rim of 
the orbit to the upper and lower eyelids and mucosal lip areas).  If applicable, the subject may 
apply study medication up to the vermillion border of the lip and to the skin underneath the 
beard.  
 
Statistical Methods: 
Summary descriptive statistics (N, mean, median, SD) by visit will be provided for all safety 
and efficacy parameters.  Primary and secondary efficacy parameters are described below: 
The initial analyses will be performed after all subjects complete Visit 10. 
 
Primary Efficacy Parameter  
Mean change from baseline in facial depigmentation in the AOI will be quantified using 
Canfield-2-D photographic image analysis from baseline (Visit 2) compared to (Visit 14). 
 
Secondary Efficacy Parameters: 
Mean change from baseline in facial depigmentation will be calculated as the mean change in 
Facial assessment of the Vitiligo Area and Scoring Index (F-VASI) from baseline (Visit 2) 
compared to Week 24 (Visit 10) and if applicable, Week 48 (Visit 14).  F-VASI is a modification 
of the validated quantitative assessment scale for vitiligo which evaluates the percentage of 
vitiligo involvement of the face only. 
 
Mean change from baseline in facial depigmentation in the AOI based on Canfield 2-D 
Photographic analysis from baseline (Visit 2) compared to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 
and post-treatment Week 52 (Visits 5-11, and 12, 13, 15). 
 


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Page 11 of 67                                                     CONFIDENTIAL 
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Mean change from baseline in the Facial assessment of the Vitiligo Area Scoring Index (F-
VASI) from baseline (Visit 2) compared to Weeks 4, 8, 12, 16, 20 24, 32, 40, and post-treatment 
Week 52 (Visits 5-9, 11, 12-13, 15). 
 
Mean change from baseline in the VitiQoL from baseline (Visit 2) compared to Week 12, 16, 
20, 24, and 48 (Visits 7-10, 14).  
 
Treatment success based on the subject’s assessment of vitiligo on the Vitiligo Noticeability 
Scale at Week 4, 8, 12, 16, 20, 24, 32, 40, 48 and post-treatment Week 52 (Visits 5-15). 
 
Mean change from baseline in total VASI from baseline (Visit 2) to Week 4, 8, 12, 16, 20 24 
and 48 (Visits 5-15) will be assessed for descriptive purposes only to track disease progression 
in untreated areas. 
 
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 relevant abnormal laboratory 
results will also be tabulated and presented.  Change from baseline (Visit 2) in the Local 
Tolerability Assessments (LTA) to end of treatment (Visit 10) will be summarized. 
 
Data from all enrolled and treated subjects will be presented and summarized. Safety 
summaries will include listings by study medication of adverse events incidences within each 
MedDRA System Organ Class, and changes from pre-application values in vital signs. 
Adverse event summaries will be presented showing the proportion of subjects experiencing 
adverse events, both overall and by MedDRA System Organ Class.    
 
 
 
 


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TABLE OF CONTENTS 
 
SYNOPSIS ............................................................................................................................. 6 
 
INTRODUCTION ................................................................................................................ 18 
 
Summary ...................................................................................................................................... 18 
 
STUDY RATIONALE .......................................................................................................... 20 
 
Study Rationale ........................................................................................................................... 20 
 
STUDY OBJECTIVES ......................................................................................................... 20 
 
Primary Objective ...................................................................................................................... 20 
 
Secondary Objectives ................................................................................................................ 20 
 
SELECTION AND DISPOSITION OF STUDY POPULATION ......................................... 20 
 
Number of Subjects and Study Sites ....................................................................................... 20 
 
Study Population Characteristics ............................................................................................ 20 
 
Inclusion Criteria........................................................................................................................ 21 
 
Exclusion Criteria ....................................................................................................................... 21 
 
Previous and Concomitant Medications and Therapies ..................................................... 23 
 
Permitted Concomitant Medications, Therapies and Over the Counter 
Products (OTC) ........................................................................................................................... 23 
5.6.1. 
Prohibited and/ or Restricted Medications ....................................................................... 24 
 
Subject Identifier (SI) ................................................................................................................ 24 
 
Replacement Subjects ............................................................................................................... 25 
 
Subject Withdrawal Criteria .................................................................................................... 25 
 Study Termination ..................................................................................................................... 25 
 
INVESTIGATIONAL PLAN ................................................................................................ 26 
 
Overall Study Design .................................................................................................................. 26 
 
STUDY PROCEDURES ................................................................................................................. 26 
 
Schedule of Assessments .......................................................................................................... 27 
 
Study Visits Description and Procedures .............................................................................. 30 
6.4.1. 
Visit 1/ Screening (Day -28 to 0) .......................................................................................... 30 
6.4.2. 
Visit 2 (Day 1) / Baseline ........................................................................................................ 30 
6.4.3. 
Visit 3-9 (Weeks 1, 2, 4, 8, 12, 16 and 20) These visits must occur on the 
following weeks after Visit 2: ................................................................................................ 32 
6.4.4. 
Visit 10 (Week 24) ................................................................................................................... 32 
6.4.5. 
Visit 11 (Week 28) ................................................................................................................... 33 
6.4.6. 
Visit 12 (Week 32) ................................................................................................................... 34 


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6.4.7. 
Visit 13 (Week 40) ................................................................................................................... 34 
6.4.8. 
Visit 14 (Week 48) ................................................................................................................... 35 
6.4.9. 
Visit 15 (Week 52) ................................................................................................................... 35 
 
STUDY TREATMENT ........................................................................................................ 36 
 
Investigational Study Medication ........................................................................................... 36 
 
Subject Study Medication Assignment ................................................................................... 36 
 
Application of Study Medication ............................................................................................. 37 
 
Study Medication Weights ........................................................................................................ 37 
 
Treatment Compliance .............................................................................................................. 37 
 
Dose Modification ...................................................................................................................... 38 
 
Study Medication Accountability ............................................................................................ 38 
 
Other Study Supplies ................................................................................................................. 38 
 
Blinding ........................................................................................................................................ 38 
 Study Medication Packaging, Labeling, Storage and Security ........................................... 38 
 
STUDY ASSESSMENTS ..................................................................................................... 39 
 
Assessments of Efficacy ............................................................................................................. 39 
8.1.1. 
Canfield 2D Digital Facial Image Analysis ........................................................................... 39 
8.1.2. 
Facial Vitiligo Area Scoring Index (F-VASI) and Facial Total Body Surface 
Area (TBSA) .............................................................................................................................. 40 
8.1.3. 
Vitiligo Noticeability Scale (VNS) .......................................................................................... 41 
8.1.4. 
Vitiligo Area Scoring Index (VASI)........................................................................................ 41 
8.1.5. 
Subject Vitiligo Satisfaction Scale (SVSS) ............................................................................ 42 
8.1.6. 
Vitiligo-Specific Quality of Life Instrument (VitiQoL) ...................................................... 43 
 
Assessment of Safety .................................................................................................................. 43 
8.2.1. 
ECGs ............................................................................................................................................ 43 
8.2.2. 
Physical Examination .............................................................................................................. 43 
8.2.3. 
Vital signs .................................................................................................................................. 44 
8.2.4. 
Clinical Laboratory Assessments .......................................................................................... 44 
8.2.5. 
Local Tolerability Assessment (LTA) ................................................................................... 45 
8.2.6. 
Pregnancy tests ........................................................................................................................ 47 
 
Other Assessments ..................................................................................................................... 47 
8.3.1. 
Demographics, Medical History and Vitiligo History ....................................................... 47 
 
ADVERSE EVENTS ............................................................................................................ 48 
 
Definitions ................................................................................................................................... 48 


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9.1.1. 
Adverse events (AE) ................................................................................................................ 48 
9.1.2. 
Serious adverse event (SAE) .................................................................................................. 48 
9.1.3. 
Unexpected adverse event ..................................................................................................... 49 
9.1.4. 
Adverse event reporting period ........................................................................................... 49 
9.1.5. 
Severity ...................................................................................................................................... 49 
9.1.6. 
Relationship to study medication ........................................................................................ 49 
 
Reporting Procedures ............................................................................................................... 50 
9.2.1. 
Procedures for reporting adverse events ........................................................................... 50 
9.2.2. 
Procedure for reporting a serious adverse event ............................................................. 50 
9.2.3. 
Safety Monitoring Discontinuation Criteria ....................................................................... 50 
9.2.4. 
Study Medication Interruption and Discontinuation Criteria ........................................ 51 
9.2.4.1 
Study Medication Interruption ........................................................................................... 51 
9.2.4.2 
Study Medication Discontinuation .................................................................................... 52 
 PREGNANCY ...................................................................................................................... 53 
 Definition of Women of Child Bearing Potential (WOCBP) ................................................ 53 
 Highly Effective Methods of Birth Control ............................................................................. 53 
 STATISTICAL ANALYSES ................................................................................................. 54 
 Sample Size and Power Calculations ...................................................................................... 54 
 Statistical Methods ..................................................................................................................... 54 
 TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE ....................................................................................................................... 56 
 Training ........................................................................................................................................ 56 
 Monitoring ................................................................................................................................... 56 
 Data Management ...................................................................................................................... 56 
 Quality Assurance ...................................................................................................................... 56 
 ETHICS AND GENERAL STUDY CONDUCT CONSIDERATIONS .................................. 57 
 Institutional Review Board (IRB)/Ethics Committee (EC) ................................................. 57 
 Ethical Conduct of the Study ..................................................................................................... 57 
 Subject Information and Consent ............................................................................................ 57 
 Study Conduct and Protocol Amendments ............................................................................ 57 
 Regulatory Documents .............................................................................................................. 58 
 Contractual Requirements ....................................................................................................... 58 
 Data Collection and Archiving ................................................................................................. 58 
13.7.1. Data collection .......................................................................................................................... 58 


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13.7.2. Source documentation ............................................................................................................ 58 
13.7.3. Archiving ................................................................................................................................... 58 
 REFERENCES ..................................................................................................................... 60 
:  Subject Instructions for Study Medication Application to the 
Face and Neck (If Applicable) ........................................................................................ 61 
:  Vitiligo History ................................................................................................. 63 
:  Fitzpatrick’s Skin Type Chart ........................................................................ 64 
:  VitiQoL ............................................................................................................... 65 
:  Subject Vitiligo Satisfaction Scale ................................................................. 66 
:  Area of Interest ................................................................................................ 67 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AE  
Adverse Event 
ALT 
Alanine aminotransferase 
ANOVA 
Analysis of Variance 
AOI 
Area of Interest 
AST 
Aspartate Aminotransferase 
BID, b.i.d. 
Twice-daily 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
°C 
Degrees Centigrade 
CD 
Cluster of Differentiation 
CMV 
Cytomegalovirus 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
e.g.  
for example (Latin; exempla gratia) 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
°F 
Degrees Fahrenheit 
F-VASI 
Facial VASI 
FDA 
Food and Drug Administration 
G 
Gram 
GCP 
Good Clinical Practice 
HCl 
Hydrochloride 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human Immunodeficiency Virus 
IC50, IC90 
Inhibitory concentration 
ICF 
Informed Consent Form 
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  
LDH 
Lactate dehydrogenase 
LTA 
Local Tolerability Assessment 


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Abbreviation 
Term 
MedDRA 
Medical Dictionary for Regulatory Activities 
µM 
Micromolar 
mL 
Milliliter 
Mm 
Millimeter 
NIAMS 
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
NCS 
Not Clinically Significant 
nM 
Nanomolar 
NMSC 
Nonmelanoma Skin Cancer 
NSV 
Non-segmental Vitiligo 
OTC 
Over-The-Counter 
PP 
Per-protocol 
PRO 
Patient-Reported Outcome 
PUVA 
Psoralen and Ultraviolet A 
SAE 
Serious Adverse Event 
SI 
Subject identifier 
SN 
Subject Number 
SOP 
Standard Operation Procedure 
SVSS 
Subject Vitiligo Satisfaction Scale 
STAT 
Signal Transducer and Activator of Transcription 
TEAE 
Treatment Emergent Adverse Event 
US 
United States 
UVA 
Ultraviolet A  
UVB 
Ultraviolet B 
VASI 
Vitiligo Area Scoring Index 
VitiQoL 
Vitiligo-Specific Quality-of-Life Instrument 
VNS 
Vitiligo Noticeability Scale 
WOCBP 
Women of childbearing potential  


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INTRODUCTION 
Aclaris Therapeutics, Inc. is developing ATI-50002 Topical Solution for the treatment of non-
segmental vitiligo of the face.  ATI-50002 is a potent highly selective inhibitor of Janus kinase 1 
(JAK1) and Janus kinase 3 (JAK3). 
 
 
Summary 
Overview of Vitiligo 
 
Vitiligo is an autoimmune dermatologic condition characterized by patchy depigmentation of the 
skin due to loss of cutaneous melanocytes.  The affected skin lacks epidermal melanocytes, 
whereas hair follicles within the lesional skin are often spared, likely due to the immune privilege 
of the hair follicle.  Vitiligo affects 1-2% of the world’s population, occurring in all races and both 
genders (Fitzpatrick T, Mosher D, 2017) (NIAMS 2017).  People with vitiligo may be at increased 
risk of social or psychological distress, sunburn, eye problems, such as inflammation of the iris 
(iritis), and hearing loss.  There is a genetic predisposition to vitiligo. The average age of vitiligo 
onset is about 20 years, with onset most commonly observed between the ages of 10 and 30 
(Fitzpatrick T, Mosher D, 2017).   
 
There are several clinical classifications of vitiligo.  Segmental vitiligo presents as one or more 
macules in a unilateral distribution. All other types of vitiligo are classified as non-segmental 
vitiligo (NSV), which is most common.  
 
NSV occurs most often on the face, followed by the trunk.  Depigmented patches typically evolve 
over time, vary in size from a few to several centimeters in diameter, are flat areas of normal-
feeling skin, and may have a hyperpigmented edge (Ezzedine K, et al. 2012). The edges typically 
are well-defined but irregular.   Body hair typically remains pigmented although hair 
depigmentation may occur with disease progression.  Scalp involvement and other hair bearing 
areas may appear with patches of white or gray hairs. 
 
Focal vitiligo is characterized by depigmentation in one area, or macule. Other forms of non-
segmental vitiligo often produce symmetric patches, sometimes covering large areas. Mucosal 
vitiligo affects only mucosal membranes. Generalized vitiligo may be acrofacial, in which 
depigmentation occurs on the distal fingers and periorificial areas, or vulgaris, which is 
characterized by widely distributed, scattered patches. Universal vitiligo manifests as complete or 
nearly complete depigmentation, and frequently is associated with multiple endocrinopathy 
syndrome.  
 
Recent observations have pointed to a role for cellular immunity in the pathogenesis of vitiligo 
(Wang et al. 2011). Pathogenesis incorporates both intrinsic defects within melanocytes that 
activates the cellular stress response as well as autoimmune mechanisms that target these cells 
(Rashighi M, Harris JE, 2017).  Despite some advances in explaining the origins of the disorder, 
current therapies, such as topical corticosteroids, topical immunomodulators and psoralen 
phototherapy may have serious side effects and limited therapeutic utility. Vitiligo is a disfiguring 
disease for which current therapies have proven unsatisfactory.   
 


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Immunopathology and Pathophysiology of Vitiligo 
 
Over the past two decades, basic and translational research studies have identified several 
pathogenic pathways that promote vitiligo (Rashighi M, Harris JE, 2017) (Frisoli ML, Harris JE, 
2017).  These immune pathways prominently involve interferon-γ (IFN-γ) dependent chemokines 
and CD8+ T-cells.  Signaling by Janus kinases (JAKs) is pivotal to these pathogenic pathways 
(Villarino et al, 2015).  As such, inhibition of IFN-γ using JAK inhibitors is a leading candidate 
for a clinical treatment strategy.  Of the JAK sub-types, JAK1 and JAK3 are associated with 
vitiliginous pathology.   
 
ATI-50002 is a JAK1/3 inhibitor with enzyme IC50 activities of 2nM and 36nM against JAK1 and 
JAK3, respectively (Data on file).  At a cellular/physiologic level, ATI-50002 inhibits interferon-
γ-induced pSTAT1 activation with an IC50 of 38nM (Data on file).   The anticipated IC90 
concentration is approximately 0.4µM.  To expect ATI-50002 to inhibit JAK1/3-mediated 
signaling, a significant excess of the inhibitor must be present in the target tissue.  Based upon 
tissue penetration studies (Franz chamber with human skin) using the 0.46% ATI-50002 
formulation, extrapolated ATI-50002 concentrations were found to be in the range of 10-20µM 
(Data on file).  A 10µM concentration should deliver drug to epidermis and dermis at levels 
anticipated to achieve inhibition of JAK1/3 signaling and inhibit T-cell-mediated melanocyte 
depletion.   
 
Vitiligo Treatments 
 
Existing treatments include topical and systemic immunosuppressants, phototherapy, and surgical 
techniques, which together may serve to arrest disease progressions, stabilize depigmented lesions 
and encourage repigmentation.  Depigmentation creams are used in cases where repigmentation 
therapies are ineffective or greater than 50% BSA is involved.  Current treatments for vitiligo are 
only moderately effective and are both financially and practically burdensome (Frisoli ML, Harris 
JE, 2017).  Topical immunosuppressants, which suppress immune responses in the superficial skin 
where the immune infiltrate is located are most useful in treating disease that is localized, 
comprising less than 5% of the body surface area (BSA) (Frisoli ML, Harris JE, 2017).  
Phototherapy is effective for more widespread disease, or disease that is active and expanding with 
the appearance of new lesions.  Excimer laser is also effective when treating localized disease that 
is unresponsive to topical therapies, or when a more rapid response is desired.  Highly active, 
vitiligo can be stabilized through oral pulse steroid therapy, which is continued until another 
therapy (is therapeutic (Frisoli ML, Harris JE, 2017).   
 
Vitiligo responds slowly to treatment, with early signs of repigmentation visible within 2-3 months 
of initiating treatment, and significant improvement taking up to 6 months to observe (Frisoli ML, 
Harris JE, 2017). Biomarkers may serve as excellent early indicators of treatment responses.  These 
include both serum biomarkers as well as biomarkers that can be directly measured within lesional 
skin. 


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STUDY RATIONALE  
 
Study Rationale 
Preclinical and preliminary clinical information suggests that blockade of the IFN-γ pathway may 
treat vitiligo. Inhibitors of the JAK/STAT pathway, particularly JAK1 and JAK3, are known to 
downregulate the effects of IFN-γ (through the inhibition at JAK1).  Two case reports have 
demonstrated the potential for compounds that are JAK inhibitors (ruxolitinib and tofacitinib) to 
repigment areas of vitiligo in patients (Craiglow BG, King BA, 2015) (Harris JE, Rashighi M, 
Nguyen N, et al, 2016).  In a recent study in a small cohort of patients, treatment with topical 
ruxolitinib for 20 weeks produced significant improvement in facial vitiligo (Rothstein BA et al., 
2017). As ATI-50002 is a potent inhibitor at JAK1 and JAK3, it is strongly suggested that ATI-
50002 may be effective in the treatment of vitiligo.   
 
This study will evaluate the safety, tolerability and efficacy of ATI-50002 Topical Solution, 0.46% 
applied twice-daily for up to 48 weeks in subjects with non-segmental facial vitiligo.   
 
 
STUDY OBJECTIVES 
 
Primary Objective 
The primary objective of this study is to assess the safety, tolerability and efficacy of ATI-50002 
Topical Solution, 0.46% in subjects with non-segmental facial vitiligo. 
 
Secondary Objectives 
Secondary objectives include: 
• Assessment of the subject’s satisfaction with repigmentation following treatment using the 
Subject Vitiligo Satisfaction scale (SVSS). 
• Assessment of the impact of vitiligo of the subject’s quality of life using the Vitiligo-
Specific Quality-of-Life Instrument (VitiQoL).   
 
 
SELECTION AND DISPOSITION OF STUDY POPULATION 
 
Number of Subjects and Study Sites 
A total of 33 subjects will be enrolled at approximately 5 US sites.  
 
Study Population Characteristics 
Male and female subjects, ≥ 18 years old, with a clinical diagnosis of new onset or actively 
progressing non-segmental facial vitiligo or worsening of existing facial vitiligo within the past 6 
months.  
 
 


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Inclusion Criteria 
In order to be eligible for the study, a subject must fulfill all of the following criteria: 
1. Subject is a male or female ≥ 18 years of age. 
2. Subject has a clinical diagnosis of new onset or actively progressing non-segmental facial 
vitiligo or worsening of existing facial lesions within the past 6 months.  Actively 
progressing vitiligo is defined as: subject history of a new vitiliginous lesion or objective 
signs of disease activity (such as: confetti-like depigmentation, trichrome lesions, and the 
Koebner phenomenon) as assessed by the investigator. Subjects may have non-facial 
vitiliginous lesions that are unchanged for more than 6 months provided they meet the 
requirement for active facial lesions. 
3. Subject has non-segmental facial vitiligo effecting at least 0.25% total body surface area 
(TBSA) (excluding: the area from the eyebrows to and including the upper eyelids, the area 
from the bony rim of the orbit to and including the lower eyelids; mucosal lip areas; beard 
[if applicable]; and forehead and chin areas covered by the stereotactic positioning device 
for photography) with at least one area of the face with normal pigmentation.  The face is 
defined as the area from the border of the hairline, not including hair bearing skin 
(eyebrows and beard, if applicable) to the jawline. 
4. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at 
the screening visit and a negative urine pregnancy test at the baseline visit and must agree 
to use an approved method of highly effective birth control for the duration of the study 
and for 30 days after last study medication application. 
5. If female, subject who is non-pregnant and non-lactating and not planning a pregnancy 
during the duration of the study. 
6. Subject is in good general health and free of any known disease state or physical condition 
which, in the opinion of the investigator, would interfere with the study assessments or put 
the subject at undue risk by study participation. 
7. Subject is willing and able to follow all study instructions and to attend all study visits. 
8. Subject agrees to refrain from any other treatments for vitiligo from the screening visit 
through the final follow-up visit.  Over the counter (OTC) preparations deemed acceptable 
by the investigator and camouflage makeups are permitted. 
9. Subject is able to comprehend and willing to sign an Informed Consent Form (ICF).  
10. Sexually active male subjects with a partner who is a WOCBP, must agree to use a 
barrier method of contraception from the first application of study medication to at least 
30 days after the last dose of study medication. 
 
 
Exclusion Criteria 
Any subject who meets one or more of the following criteria will not be included in this study:  
1. Subject with evidence of poliosis (white hairs) in > 50% of their facial vitiligo lesions.  
2. Subject with total facial depigmentation. 
3. Subject with significant spontaneous ongoing repigmentation (documented based on the 
subject’s reporting in the last 3 months). 
4. Subject who has segmental vitiligo. 
5. Subject who has failed phototherapy.  Failed phototherapy is defined as failure to achieve 
satisfactory repigmentation following adequately delivered phototherapy as determined 
by the investigator. 


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6. Subject currently has, or has a history of, skin disease (e.g., psoriasis, seborrheic 
dermatitis, etc.) that, in the opinion of the investigator, would interfere with the study 
medication application or study assessments. 
7. Subject has, or has a history of, severe, progressive or uncontrolled autoimmune, 
metabolic, renal, hepatic, gastrointestinal, pulmonary, cardiovascular, genitourinary (i.e., 
renal disease), hematological disease, neurologic or cerebral disorders, infectious disease 
or coagulation disorders that, in the opinion of the investigator, would interfere with the 
study assessments or put the subject at undue risk by study participation. 
8. Subject currently has a history of, current, or suspected systemic or cutaneous 
malignancy and /or lymphoproliferative disease, other than a history of adequately 
treated, well healed and completely cleared non-melanoma skin cancers (e.g., basal or 
squamous cell carcinoma) treated successfully at least 1 year prior to study entry with no 
evidence of disease. 
9. Subject currently has evidence of active or latent bacterial (including tuberculosis) or 
viral infections at the time of enrollment, or a history of incompletely treated or untreated 
tuberculosis.  Subjects who have initiated therapy for latent tuberculosis for at least 2 
weeks and agree to continue their therapy through completion may participate. 
10. Subject has a history of serious local infection (e.g., cellulitis, abscess) or systemic 
infection, or history of treated infection (e.g., pneumonia, septicemia) within 3 months 
prior to the baseline visit.  Subjects on an antibiotic for a nonserious, acute local infection 
must complete the course prior to enrollment into the study.  
11. Subject has herpes zoster or cytomegalovirus (CMV) that resolved within 8 weeks prior 
to Visit 1. 
12. Subject has a history of frequent outbreaks of oral Herpes Simplex Virus defined as more 
than 4 episodes per year. 
13. Subjects previously treated with depigmenting agents.   
14. 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 
other Screening laboratory values meeting the Study Medication Interruption Criteria 
found in Table 1 must have repeat lab testing performed with results meeting the 
minimum criteria for resumption in order to initiate treatment at Baseline (Visit 2). 
15. Subject who has an absolute neutrophil count <1,800/µL, or platelet count  
< 130,000/µL.  
16. Subject unable to comply with the required washout periods: 
1. 
Use of any biologic, investigational therapy or procedure for vitiligo within 12 
weeks or 5 half-lives (whichever is longer) of screening (Visit 1). 
2. 
Use of laser or light-based vitiligo treatments, including tanning beds, within 8 
weeks of screening (Visit 1). 
3. 
Use of immunomodulating oral or systemic medications (e.g., corticosteroids, 
methotrexate, cyclosporine) or topical treatments that may affect vitiligo (e.g., 
corticosteroids, tacrolimus/ pimecrolimus, retinoids) within 4 weeks of screening 
(Visit 1). 
4. 
Use of any prior concomitant therapy not listed above that may interfere with the 
objective of the study as per the discretion of the investigator, including drugs that 
cause photosensitivity or skin pigmentation (e.g., antibiotics such as tetracyclines, 
sulfa, tranexamic acid, etc.) within 8 weeks of screening (Visit 1).  


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5. 
Subjects who have previously received oral or topical JAK inhibitors. 
17. Subject who has participated in any investigational drug or device trial, regardless of 
indication in which administration of an investigational drug or device occurred within 30 
days or 5 half-lives (whichever is longer) of screening (Visit 1).  Note that investigational 
treatment for vitiligo (in any body area) requires a longer washout – see Exclusion 
criterion #16.1 above. 
18. Subjects with a clinically significant abnormal thyroid-stimulating hormone or free T4 at 
screening.  Subjects under treatment with stable thyroid replacement who have a free T4 
and TSH within the normal range may participate. 
19. Subject has history of sensitivity to any of the ingredients in the study medications. 
20. Subject has a history of, or current alcohol or drug abuse within 2 years of study 
enrollment 
21. Screening ECG findings of: 
1. QTcF >450msec for males or >470msec for females (use of the ECG algorithm 
is acceptable for this purpose) 
2. Clinically significant heart rate ≤ 45 or Heart Rate ≥ 100 beats/minutes 
3. Rhythm disturbance other than sinus arrhythmia or ectopic supraventricular 
rhythm (ectopic atrial rhythm) 
4. Conduction disturbance including PR >240msec, pre-excitation (delta wave and 
PR <120msec), second degree or higher AV block 
5. Acute or chronic signs of ischemia.   
6. Left Bundle Branch Block 
7. Prior myocardial infarction 
22. Positive for HIV, Hepatitis B or C.  Subject with serologic evidence of Hepatitis B 
vaccination (HepB surface Ab without the presence of Hep B sAg) will be allowed to 
participate. 
 
Previous and Concomitant Medications and Therapies 
At Screening (Visit 1), the Investigator or designee will question the subject to ensure they have 
not used any excluded therapies (Section 5.6.1).  Concomitant therapies are any new or existing 
therapies received from Screening (Visit 1) until Week 52 (Visit 15).  Concomitant therapies 
include drug (e.g., prescription and over the counter [OTC]), and non-drug (e.g., chiropractic, 
physical therapy, energy-based) treatments. 
 
 
Permitted Concomitant Medications, Therapies and Over the Counter Products 
(OTC) 
All topical products used on the face and neck should be reviewed by the investigator or designee 
and are permitted, if in the opinion of the investigator or designee will not affect the safety or 
efficacy of the subject during the study.  Subjects will be allowed to take medications not restricted 
by the protocol as long as they have been on a stable dose prior to study entry.  Vitamins, minerals, 
and dietary supplements are permitted during the 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 therapies such as topical corticosteroids are permitted as long as they are not applied on 
or near the face and treated areas of the neck. Inhaled or intranasal corticosteroids are allowed in 


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the study.  Male subjects who shave at screening and baseline should maintain the same shaving 
regimen during the study. 
 
NB-UVB treatments may be administered according to the Standard of Care protocol for the 
treatment of vitiligo after the subject has completed Visit 9.  NB-UVB treatments should be 
recorded in the source documents and on the Concomitant Therapies Log of the eCRF.   
 
Prior permitted concomitant medications taken within 30 days of beginning treatment with ATI-
50002 Topical Solution will be documented in the subject’s source document and eCRF.  In 
addition, any new permitted medications administered during protocol treatment and through 
Week 28 (Visit 11) will be documented in the subject’s source document and eCRF.   
 
5.6.1. 
Prohibited and/ or Restricted Medications 
Use of any medication, herbal supplements or other over-the-counter product known to: have 
an immunomodulatory effect (e.g. astragalus); or known to affect pigmentation including 
topical products on the face that could potentially lighten the skin (e.g., hydroquinones, 
azaleic acid, Kojic acid, mequinol, retinoids, niacinamide, arbutin) or known to temporarily 
dye the skin on the face and treated areas of the neck (such as dihydroxyacetone or hennas) 
are prohibited throughout the study.  Subjects treated with depigmenting agents such as 
monobenzyl ether or hydroquinone are excluded from the study. 
  
The following medications and therapies require a specific washout period prior to study entry and 
are not permitted during the study:   
1. Use of any biologic, investigational therapy or procedure for vitiligo within 12 
weeks or 5 half-lives (whichever is longer) of screening (Visit 1). 
2. Use of laser or light-based vitiligo treatments, including tanning beds, within 8 
weeks of screening (Visit 1).  Subjects with regular outdoor light exposure not for 
the intent of tanning may participate.  NB-UVB treatments may be administered 
according to the Standard of Care protocol for the treatment of vitiligo after the 
subject has completed Visit 9.  NB-UVB treatments should be recorded in the 
source documents and on the Concomitant Therapies Log of the eCRF. 
3. Use of immunomodulating oral or systemic medications (e.g., corticosteroids, 
methotrexate, cyclosporine) or topical treatments that may affect vitiligo (e.g., 
corticosteroids, tacrolimus/ pimecrolimus, retinoids) within 4 weeks of screening 
(Visit 1). 
4. Use of any prior concomitant therapy not listed above that may interfere with the 
objective of the study as per the discretion of the investigator, including drugs that 
cause photosensitivity or skin pigmentation (e.g., antibiotics such as tetracyclines, 
sulfas, tranexamic acid) within 8 weeks of screening (Visit 1).  
5. Subjects who have previously received oral or topical JAK inhibitors. 
 
Subject Identifier (SI) 
The Investigator will assign a unique five-digit subject identifier (SI) to each subject at Screening 
(Visit 1).  
 
The SI format will be NN-NNN, using leading zeros as appropriate, where: 


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• The first 2 digits are the investigational center site number assigned by Aclaris. 
• The final 3 digits are the subject number (SN), assigned in ascending numerical order by 
the Investigator or designee, without omitting or repeating any number, starting with 001.  
For example, the SI for the twenty-third subject that signs an informed consent form at site number 
01 would be 01-023. The subject will be identified using the SI in all study documentation for the 
duration of the study. 
 
 
Replacement Subjects 
Subjects who are receive study medication at Visit 2 and do not complete the study will not be 
replaced. 
 
 
Subject Withdrawal Criteria 
Subjects will be informed that they are free to withdraw from the study at any time and for any 
reason. The investigator may remove a subject from the study if, in the investigator's opinion, it is 
not in the best interest of the subject to continue the study. Examples of other reasons subjects may 
be discontinued from the study are: a change in compliance with an inclusion or exclusion 
criterion, occurrence of AEs, occurrence of pregnancy, use of a prohibited therapy or subject is 
unwilling or refuses to continue with the protocol defined study visits and/or subject withdraws 
consent (Refer to Section 9.2.4 for study medication discontinuation criteria).  
 
In case of premature discontinuation of study participation, all efforts will be made to perform all 
Visit 10 (Week 24) assessments or if continuing for the additional 24 weeks, Visit 15 (Week 52). 
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. 
 
 
Study Termination 
This study may be terminated prematurely in whole or in part due to a change in the benefit/risk 
profile for ATI-50002 Topical Solution such that continuation of the study would not be justified 
on medical or ethical grounds.  This determination may be made by the Study Investigators in 
conjunction with the Sponsor, or by IRB or the U.S. Food and Drug Administration (FDA).  The 
Sponsor may also elect to terminate the study if enrollment is sufficiently slow to prevent the 
completion of the study in an acceptable timeframe, or if ATI-50002 development is discontinued. 
If the study is terminated prematurely, the Sponsor will notify the Study Investigators and the 
FDA. The Investigator must promptly notify all enrolled subjects and the IRB of study termination. 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 26 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
INVESTIGATIONAL PLAN 
 
Overall Study Design 
This Phase 2, multicenter, open label study is designed to evaluate the safety, tolerability and 
efficacy of ATI-50002 Topical Solution in subjects with facial non-segmental vitiligo.  Subjects 
will be required to have a clinical diagnosis of new onset or actively progressing non-segmental 
facial vitiligo involving at least 0.25% TBSA (excluding upper and lower eyelids, mucosal lip 
areas, beard [if applicable]; and forehead and chin areas covered by the stereotactic positioning 
device for photography) with at least one area of the face with normal pigmentation.  The face is 
defined as the area from the border of the hairline, not including hair bearing skin to the jawline.  
Thirty-three subjects will receive ATI-50002 Topical Solution, 0.46%, BID for up to 48 weeks. 
 
During the screening period, subjects will be assessed for eligibility to receive study medication.  
Eligible subjects will apply study medication to the vitiliginous areas of the face and neck 
including ½” margin around these areas (excluding the upper and lower eyelids and mucosal 
areas of the lips) twice-a-day for up to 48 weeks. Assessment of response to treatment will be 
performed using the Canfield 2-D Photographic image analysis, Facial VASI, Vitiligo 
Noticeability Scale, VitiQoL, and Subject Vitiligo Satisfaction Scale.  These assessments will 
occur as specified in the Schedule of Assessments.  Subjects will be seen at up to 15 study visits, 
including up to 48 weeks of active treatment followed by 4 weeks of post treatment follow-up. 
 
Safety and tolerability will be evaluated throughout the study by assessment of electro-
cardiograms (ECG), clinical laboratory tests, adverse events including local site reactions and 
vital signs. 
 
 
STUDY PROCEDURES 
The investigator, a designated and appropriately trained staff member, independent evaluator(s), 
or the subject, will perform the study assessments according to the schedule of assessments 
(Section 6.3). The same staff member should perform the assessments for a given subject 
throughout the study. If this becomes impossible, an appropriate designee with overlapping 
experience with the subject and study should perform the assessments. The same lighting 
conditions and subject positioning should be used for all evaluations for a given subject. 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 27 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
Schedule of Assessments 
 
Screening 
Baseline 
Treatment 
 
Post-
Treatment 
Visit 1 
Visit 2 
 
Visit 
3 
Visit 
4 
 
Visit 
5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
 
Visit 
9  
Visit 
10 
Visit  
11 
Week 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-28 to 0 
1 
8 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment 
Window(days) 
N/A 
N/A 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 14 
Informed consent1 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria  
X 
X 
 
 
 
 
 
 
 
 
 
Physical exam2 
X 
 
 
 
 
 
 
 
 
 
X 
Demographics & 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
Vitiligo History  
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical CBC, 
Chemistry, Virology, 
Serum Pregnancy, 
Urinalysis4 
X4 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test5 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
ECG  
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Facial BSA 
X 
X 
 
 
 
 
 
 
 
 
 
Facial Vitiligo 
AreaScoring Index (F-
VASI)6 
 
X 
Pre-dose 
 
 
X 
X 
X 
X 
X 
X 
X 
Total body VASI 
X 
X 
Pre-dose 
 
 
 
 
X 
 
 
X 
 
Canfield 2D 
Photography7 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Vitiligo Noticeability 
Scale (VNS) 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Subject Vitiligo 
Satisfaction Scale8 
(SVSS) 
 
 
 
 
 
 
X 
X 
X 
X 
X 
VitiQoL 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
Local Tolerability 
Assessment (LTA) 
Investigator 
 
X 
Pre and 
post dose 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Local Tolerability 
Assessment (LTA) 
Subject 
 
X 
Pre and 
post dose 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Subject Eligibility 
Confirmation 
 
X 
 
 
 
 
 
 
 
 
 
Subject instructions9  
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Dispense study 
medication 10  
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Collect, medication, 
assess compliance 10 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
In office study 
medication 
application11 
 
X 
 
 
 
 
 
 
 
 
 
Concomitant therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 28 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
Screening 
Baseline 
Treatment 
 
Post-
Treatment 
Visit 1 
Visit 2 
 
Visit 
3 
Visit 
4 
 
Visit 
5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
 
Visit 
9  
Visit 
10 
Visit  
11 
Week 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
Treatment Day 
-28 to 0 
1 
8 
15 
29 
57 
85 
113 
141 
169 
197 
Treatment 
Window(days) 
N/A 
N/A 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 4 
± 14 
For Subjects Continuing to Visit 12-15: 
Revised ICF for 
Visits 12-15 
 
 
 
 
 
 
 
 
 
X12 
X12, 14 
Subject 
instructions9 
 
 
 
 
 
 
 
 
 
X 
X14 
Dispense study 
medication10 
 
 
 
 
 
 
 
 
 
X13 
X13,14 
 1A 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, clinical laboratory sampling or urine pregnancy tests). 
2 A physical exam includes: general appearance, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, 
abdominal, neurological, musculoskeletal, lymphatic and skin assessment. 
3Vitals signs include: oral or ear temperature, blood pressure, heart rate, respiration rate (height and weight at screening only). 
4 Clinical laboratory sampling include: CBC, Chemistry with lipids, and Urinalysis.  Quantiferon Gold, HIV, Hepatitis B and C, 
TSH, T3, Free T4 and Serum Pregnancy should be done at screening visit only.  Subjects with any Screening laboratory values 
meeting the Study Medication Interruption Criteria found in Table 1 must have repeat lab testing performed with results meeting 
the minimum criteria for resumption in order to initiate treatment at Baseline (Visit 2). 
5 UPT must be performed in WOCBP prior application of study medication at Baseline (Visit 2) and must be negative for the 
subject to continue in the study.  UPTs in WOCBP must also be obtained at Visit 5, 6, 7, 8, 9, 10, and 11.  WOCBP must have a 
negative serum pregnancy test at Screening (Visit 1) and a negative UPT at baseline (Visit 2) prior to application of study 
medication. 
6 F-VASI must be determined at Baseline (Visit 2) and Visits 5-11.  During the baseline visit, F-VASI should be determined prior 
to application of study medication. 
7 Canfield photography will be performed at Prior to dosing at Baseline (Visit 2) and at Visits 5, 6, 7, 8, 9, 10 and 11. 
8 Subjects will complete the Subject Vitiligo Satisfaction Scale at Visits, 7, 8, 9, and 10 and at post-treatment Visit 11.   
9 The study staff must instruct the subject to apply study medication according to the instructions in APPENDIX 1. 
10 The study staff must weigh the study medication bottle(s) with cap prior to dispensing to the subject and after the study 
medication bottles are returned to the investigational site.  Staff should review the usage based on the weight of the bottle and 
counsel the subject as necessary. 
11 At Baseline (Visit 2), the first application of study medication should be performed by the subject under the supervision of the 
study staff and the subject should be observed for 20 minutes after the initial application. 
 12A written, signed ICF with the additional visits (Visits 12 -15) must be obtained from each subject prior to performing any Visit 
12 study related procedure. 
13 For subjects who consent to continue for additional study visits, Visit 12-15, study medication should be dispensed. 
14 If a subject completes Visit 10 prior to implementation of Amendment 3, they may return for Visit 11 to sign consent, receive 
additional study medication and have the other tests performed as detailed in the Schedule of Assessments. 
 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 29 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
Procedures 
Open-Label Treatment 
Post-
Treatment 
 
Visit 12 
Visit 13 
Visit 14 
 
Visit 15 
 
Week 
32 
40 
48 
52 
Treatment Day 
225 
281 
337 
365 
Treatment Window(days) 
± 7 
± 7 
± 7 
± 7 
Physical exam2 
 
 
 
X 
Vital signs3  
X 
X 
X 
X 
Clinical CBC, Chemistry, Urinalysis4 
X 
X 
X 
X 
Urine pregnancy test5 
X 
X 
X 
X 
ECG  
 
 
 
X 
Facial Vitiligo Area Scoring Index (F-VASI)6 
X 
X 
X 
X 
Total body VASI 
 
 
X 
 
Canfield 2D Photography7 
X 
X 
X 
X 
Vitiligo Noticeability Scale (VNS) 
X 
X 
X 
X 
Subject Vitiligo Satisfaction Scale8 (SVSS) 
X 
X 
X 
 
VitiQoL 
 
 
X 
 
Subject instructions9  
X 
X 
X 
 
Dispense study medication 10  
X 
X 
 
 
Collect, medication, assess compliance 10 
X 
X 
X 
 
Concomitant therapies 
X 
X 
X 
X 
Adverse events  
X 
X 
X 
X 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 30 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
 
Study Visits Description and Procedures 
A written, signed informed consent form (ICF) must be obtained from each subject prior to 
performing any study related procedure (i.e., physical examination, clinical laboratory sampling, 
urine pregnancy test, ECG, or photography). 
 
6.4.1. 
Visit 1/ Screening (Day -28 to 0)  
At this visit, the investigator or designee will: 
1. Review and explain the nature of the study to the subject, obtain the subject’s signature on 
the appropriate approved ICF and provide a signed and dated copy to the subject. 
2. Assign a SI to the subject. 
3. Confirm the subject meets all inclusion criteria and no exclusion criteria. 
4. Collect demographic and medical history information (including vitiligo history). 
5. Collect concomitant therapies information. 
6. Perform a physical examination. 
7. Measure vital signs. 
8. Conduct an ECG. 
9. Collect blood samples for clinical laboratory tests including serum pregnancy test. 
10. Quantify the facial vitiligo BSA involvement.  The subject must have non-segmental facial 
vitiligo involving at least 0.25% TBSA (excluding the upper and lower eyelids, mucosal 
lip areas, and forehead and chin areas covered by the stereotactic positioning device) with 
at least one facial area with normal pigmentation.   
11. Perform the Vitiligo Area & Scoring Index (VASI). 
12. Review the study instructions with the subject. 
13. Schedule Visit 2 as appropriate. 
 
6.4.2. 
Visit 2 (Day 1) / Baseline 
This visit must occur within 28 days after Visit 1.  
 
Subsequent study visit dates must be scheduled based on the date of Visit 2. 
 
This visit may not occur before the investigator reviews the Visit 1 clinical laboratory test results 
for all the measured analytes. For the subject to continue in the study all clinical laboratory test 
results must be within the range of normal for the laboratory or, if there are any abnormal results, 
they must be defined as not clinically significant (NCS) by the investigator.  Subjects with any 
Screening laboratory values meeting the Study Medication Interruption Criteria found in Table 1 
must have repeat lab testing performed with results meeting the minimum criteria for resumption 
in order to initiate treatment at Baseline (Visit 2).  For WOCBP, the serum pregnancy test from 
Visit 1 must be negative for a subject to continue in the study. 
 
The investigator must review the evaluator’s interpretation of each subject’s Visit 1 ECG prior to 
Baseline/Visit 2 and comment on the clinical significance of any result that is defined by the 
evaluator as abnormal. The subject must not continue in the study and apply study medication, if 
the Visit 1 ECG meets any of the Criteria in Exclusion Criterion 21. 


Protocol: ATI-50002-VITI-201 
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Page 31 of 67                                                     CONFIDENTIAL 
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At this visit, the investigator or designee will perform the following procedures PRIOR TO 
APPLICATION OF STUDY MEDICATION: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report changes on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study requirements, is eligible to continue 
in the study and has followed all study instructions. 
4. Confirm the subject meets all inclusion criteria and no exclusion criteria. 
5. Confirm Facial vitiligo TBSA is at least 0.25% with at least one area of normal 
pigmentation on the face. 
6. Measure vital signs. 
7. Perform a urine pregnancy test for WOCBP; results must be negative for the subject to 
apply the first dose of study medication. 
8. Quantify the facial vitiligo BSA involvement.  The subject must have non-segmental facial 
vitiligo involving at least 0.25% TBSA (excluding: the area from the eyebrows to and 
including the upper eyelids, the area from the bony rim of the orbit to and including the 
lower eyelids; mucosal lip areas; and forehead and chin areas covered by the stereotactic 
positioning device) with at least one facial area with normal pigmentation.   
9. Perform the Facial Vitiligo Area Scoring Index (F-VASI). 
10. Perform the total body VASI. 
11. Confirm subject is eligible to apply the first dose of study medication. 
12. Have the subject perform a pre-application Local Tolerability Assessment (LTA). 
13. The Investigator or designee will perform a pre-application LTA. 
14. Collect blood samples for clinical laboratory tests. 
15. Take standardized photographs. 
16. Conduct an ECG. 
17. Have the subject complete the VitiQoL. 
18. Discharge from the study subjects who are not eligible to apply the first dose of study 
medication. 
 
For subjects who are eligible to apply the first dose of study medication the investigator or designee 
will perform the following procedures:  
1. Dispense study medication to the subject. 
2. An investigational staff member will instruct the subject on the proper study medication 
application technique and will observe the subject’s first study medication application. 
3. A staff member will monitor the subject for at least 20 minutes after the first study 
medication application completion time to detect any adverse events. 
4. Have the subject perform a post-application LTA 10 (±4) minutes after the application 
completion time. 
5. The investigator or designee will perform a post-application LTA 20 (±4) minutes after the 
application completion time. 
6. Review the study instructions with the subject. 
7. Schedule Visit 3 as appropriate. 
 
 
 


Protocol: ATI-50002-VITI-201 
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Page 32 of 67                                                     CONFIDENTIAL 
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6.4.3. 
Visit 3-9 (Weeks 1, 2, 4, 8, 12, 16 and 20) These visits must occur on the 
following weeks after Visit 2: 
• Visit 3, 1 week (±4 days) 
• Visit 4, 2 weeks (±4 days) 
• Visit 5, 4 weeks (±4 days) 
• Visit 6, 8 weeks (±4 days) 
• Visit 7, 12 weeks (±4 days) 
• Visit 8, 16 weeks (±4 days) 
• Visit 9, 20 weeks (±4 days). 
 
At these visits, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions, is eligible to continue 
in the study and has followed all study instructions. 
4. Measure vital signs. 
5. AT VISIT 3, 5-9, ONLY collect blood samples for clinical laboratory tests. 
6. AT VISIT 3, 5-9, ONLY conduct an ECG. 
7. AT VISIT 3-9, Have the subject perform an LTA. 
8. AT VISIT 3-9, The investigator or designee will perform an LTA. 
9. AT VISITS 5-9 ONLY, perform the F-VASI 
10. AT VISIT 7 ONLY, perform the total body VASI. 
11. AT VISIT 5-9 ONLY, have the subject complete the Vitiligo Noticeability Scale (VNS). 
12. AT VISIT 7-9 ONLY, have the subject complete the VitiQoL. 
13. AT VISITS 5-9, ONLY perform a urine pregnancy test for WOCBP; results must be 
negative for the subject to continue in the study. 
14. AT VISIT 7-9 ONLY, have the subject complete the Subject Vitiligo Satisfaction Scale 
(SVSS). 
15. AT VISITS 5-9 ONLY, take standardized photographs. 
16. Dispense and/or collect study medication as appropriate. 
17. Review the study instructions with the subject. 
18. Schedule the next visit as appropriate. 
 
6.4.4. 
Visit 10 (Week 24) 
This visit must occur 24 weeks (±4 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 


Protocol: ATI-50002-VITI-201 
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Page 33 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
4. Measure vital signs. 
5. Conduct an ECG. 
6. Collect blood samples for clinical laboratory tests. 
7. Perform a urine pregnancy test for WOCBP. 
8. Have the subject perform an LTA. 
9. The investigator will perform an LTA. 
10. Perform the F-VASI. 
11. Perform the total body VASI. 
12. Have the subject complete the VNS. 
13. Have the subject complete the SVSS.  
14. Have the subject complete the VitiQoL. 
15. Collect all study medication. 
16. Take standardized photographs. 
17. Review the study instructions with the subject. 
18. For subjects who agree to continue to participate in additional study visits (Visits 12-15): 
a. Obtain consent for additional study visits, Visit 12-15: 
b. Dispense study medication. 
c. Review study instructions with the subject. 
19. Schedule Visit 12.  For subjects who do not consent to continue with additional study 
visits (Visit 12-15), schedule the next visit, Visit 11. 
 
6.4.5. 
Visit 11 (Week 28) 
For subjects who agree to continue with additional visits (Visit 12-15) at Visit 10, Visit 11 should 
be marked as not done, unless Visit 11 is when the subject consents to the additional Visits 12-15. 
 
This visit must occur 28 weeks (±14 days) after Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form 
3. Confirm the subject continues to comply with all study requirements and has followed all 
study instructions 
4. Conduct a physical examination 
5. Measure vital signs 
6. Conduct an ECG 
7. Collect blood samples for clinical laboratory tests 
8. Perform a urine pregnancy test for WOCBP 
9. Have the subject perform an LTA 
10. The investigator or designee will perform an LTA 
11. The investigator or designee will perform the F-VASI 
12. Have the subject complete the VNS 
13. Have the subject complete the SVSS 
14. Have the subject complete the VitiQoL 
15. Take standardized photographs 


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16. Discharge the subject from the study, unless the subject agrees to continue with additional 
study visits (Visit12-15). 
17. For subjects who agree to continue with additional study visits (Visits 12-15). 
a. Obtain consent for additional study visits, Visit 12-15. 
b. Dispense study medication. 
c. Review study instructions with the subject. 
18. Schedule Visit 12, 32 weeks from Visit 2. 
 
6.4.6. 
Visit 12 (Week 32) 
This visit must occur 32 weeks (± 7 days) of Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 
4. Measure vital signs. 
5. Collect blood samples for clinical laboratory tests. 
6. Perform a urine pregnancy test for WOCBP. 
7. Perform the F-VASI. 
8. Have the subject complete the VNS. 
9. Have the subject complete the SVSS.  
10. Dispense and collect study medication. 
11. Take standardized photographs. 
12. Review the study instructions with the subject. 
13. Schedule the Visit 13 40 weeks ± 7 days from Visit 2. 
 
6.4.7. 
Visit 13 (Week 40) 
This visit must occur 40 weeks (± 7 days) of Visit 2. 
At this visit, the investigator or designee will perform the following procedures: 
 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 
4. Measure vital signs. 
5. Collect blood samples for clinical laboratory tests. 
6. Perform a urine pregnancy test for WOCBP. 
7. Perform the F-VASI. 
8. Have the subject complete the VNS. 
9. Have the subject complete the SVSS.  


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Page 35 of 67                                                     CONFIDENTIAL 
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10. Dispense and collect study medication. 
11. Take standardized photographs. 
12. Review the study instructions with the subject. 
13. Schedule the Visit 14 48 weeks ± 7 days from Visit 2. 
 
6.4.8. 
Visit 14 (Week 48) 
This visit must occur 48 weeks (± 7 days) of Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 
4. Measure vital signs. 
5. Collect blood samples for clinical laboratory tests. 
6. Perform a urine pregnancy test for WOCBP. 
7. Perform the F-VASI. 
8. Have the subject complete the VNS. 
9. Have the subject complete the SVSS.  
10. Collect study medication. 
11. Have the subject complete the VitiQoL. 
12. Take standardized photographs. 
13. Review the study instructions with the subject. 
14. Schedule the Visit 15 52 weeks ± 7 days from Visit 14. 
 
6.4.9. 
Visit 15 (Week 52) 
This visit must occur 52 weeks (± 7 days) of Visit 2. 
 
At this visit, the investigator or designee will perform the following procedures: 
 
1. Query the subject in a non-directive manner about any changes in her/his health since the 
previous visit and report all AEs on the appropriate form. 
2. Query the subject about any changes in her/his concomitant therapies since the previous 
visit and report changes on the appropriate form. 
3. Confirm the subject continues to comply with all study restrictions and has followed all 
study instructions. 
4. Measure vital signs. 
5. Conduct an ECG. 
6. Perform a physical examination. 
7. Collect blood samples for clinical laboratory tests. 
8. Perform a urine pregnancy test for WOCBP. 
9. Perform the F-VASI. 


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Page 36 of 67                                                     CONFIDENTIAL 
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10. Perform the total body VASI. 
11. Have the subject complete the VNS. 
12. Take standardized photographs. 
13. Discharge the subject from the study. 
 
STUDY TREATMENT 
 
Investigational Study Medication 
The study medication for this study is ATI-50002 Topical Solution, 0.46%. The study medication 
is a thin clear solution.  The inactive ingredients include: water, Transcutol P, propylene glycol, 
PEG400, dimethyl sulfoxide (DMSO), Kolliphor CS 20, benzyl alcohol, poloxamer 188, and 
povidone K30. 
 
STUDY MEDICATION INFORMATION 
Study medication name 
ATI-50002 
Dosage Strength 
0.46% 
Manufacturer 
PMRS, Inc., Horsham, PA 
Pharmaceutical Form 
Topical Solution 
Container 
Amber Glass Bottle, 30 mL with screw cap (20mL fill) 
 
Amber Glass Bottle, 120 mL with screw cap (100mL fill) 
Storage Conditions 
59°F to 77°F (15°C to 25°C)  
Dose regimen 
Route 
Topical 
Frequency 
Twice-daily 
Duration of administration 
Up to 48 weeks 
Other supplies 
Disposable, single-use applicators will be provided. 
 
 
Subject Study Medication Assignment 
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 investigational staff member will enter the subject identifier, subject initials, and date 
dispensed on the Subject Kit label, and record the Subject Kit number in the subject’s eCRF. 
 
The site will dispense study medication bottles provided in the individual Subject Kits first and 
then dispense the individual 120 ml (100 ml fill) bottles to the subject, as needed. 
 


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Application of Study Medication 
Subjects will be instructed to apply a thin film of ATI-50002 Topical Solution, up to 2-mL, twice-
daily; once in the morning and approximately 8-12 hours later to the vitiliginous areas of the face 
and neck including a ½” inch margin around these areas (excluding: the area from the bony rim of 
the orbit to and including the upper and lower eyelids; and mucosal lip areas) following the 
instructions in APPENDIX 1.   The subject must wash her/his hands thoroughly before and after 
each study drug application. At each study visit, subjects should bring the study medication 
including unused bottles.  The disposable applicators should be disposed of at the subject’s home 
out of the reach of children. 
 
Following review of study medication instructions, subjects will apply the first dose of study 
medication in the office under the instruction and supervision of the study staff.   
During the Baseline visit (Visit 2), the study staff member will: 
• Dispense the appropriate study medication bottle. 
• Weigh the bottle with the cap prior to the first study medication application. 
• Instruct the subject on the appropriate application technique following instructions in 
APPENDIX 1. 
• Observe the subject’s first study medication application to ensure proper coverage and 
monitor the subject for at least 20 minutes.   
• After the first application, the study staff should weigh the study bottle with the cap. 
• Dispense the study medication to the subject.     
• Provide feedback on the application procedure, if needed.  
 If the subject develops a new patch of vitiligo on the face or neck during the study, the investigator 
or designee will instruct the subject to treat the new area of facial vitiligo.  The investigator must 
incorporate the new area of facial vitiligo, once it is clinically evident, into the F-VASI assessment.  
New areas of vitiligo on the face or other body areas that develop during the study are not 
considered adverse events. 
 
 
Study Medication Weights 
A study staff member will weigh the study medication bottles with the cap prior to dispensing to 
the subject and after collection of the study medication bottles during study treatment visits.  The 
weights should be recorded in the source documents. Bottles that are not dispensed to the subject 
do not need to be weighed. 
 
 
Treatment Compliance 
The investigator or designee will be responsible for monitoring subject compliance through 
questioning the subject, documenting missed doses, if any, weighing the bottle before dispensing 
and after return and visual inspection of the quantity in the study medication bottles (used and 
unused).  Study staff will counsel the subjects, as required to make sure subjects are compliant 
with study medication applications.  The subject will be given a calendar to complete to confirm 
administration of twice-daily doses. 
 


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Dose Modification  
If the subject experiences application site AE(s), study medication may be stopped for up to a total 
of 3 days or the frequency of study medication application may be reduced from twice-daily to 
once-daily for up to a total of 6 days.  Dose interruptions must be documented in the source 
document and eCRF.  Dose modifications greater than these must be reviewed and approved by 
the Medical Monitor.  Refer to Section 9.2.4 for Study Medication Interruption or Discontinuation 
due to related SAEs or specific abnormal laboratory values.   
 
 
Study Medication Accountability 
The Principal Investigator or designee is responsible for ensuring accountability for the 
investigational agent, including reconciliation of medications and maintenance of medication 
records.  Upon receipt of study medication, the clinical site will check for accurate delivery and 
acknowledge receipt by signing (or initialing) and dating the shipment documentation provided.  
One copy of this document will be returned to Aclaris Therapeutics, Inc. (or designee) and one 
copy will be maintained in the study file. In addition, an accurate study medication disposition 
record will be kept, specifying the amount dispensed for each subject and the date of dispensing. 
This inventory record will be available for inspection at any time. At the completion of the study, 
the original inventory record will be available for review by Aclaris Therapeutics, Inc. upon 
request.  Final medication accountability will be performed by the study monitor at the completion 
of the study and all used and unused study medication bottles will be returned to Aclaris 
Therapeutics, Inc. or designee for disposal.  
 
Other Study Supplies 
Aclaris Therapeutics, Inc. or a third party will provide: 
• Supplies and instructions for collecting, labeling, shipping and result reporting for the 
clinical laboratory tests and urine pregnancy tests 
• A scale to weigh the study medication bottles. 
• Equipment, supplies, and training for taking standardized photographs 
• Equipment, supplies, and training for performing standardized ECGs 
• Study medication applicators 
• An insulated lunch box to transport study medication 
 
 
Blinding 
The study is an open-label study. 
 
 
Study Medication Packaging, Labeling, Storage and Security 
The study medication must be used by the study subjects only.  Investigational site staff will 
explain the application of the study medication to subjects.   
 


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Study medication will be provided by Aclaris Therapeutics, Inc. and labeled according to 
regulations.  Study medications must be stored in a secure area with limited access under 
appropriately controlled and monitored storage conditions.  Study medication should be stored at 
controlled room temperature 59°F - 77°F (15°C – 25°C).  Subjects will be instructed to store the 
study medication in the original glass bottle (in the carton provided) at room temperature, away 
from heat, moisture, direct light, and to keep it from freezing and out of the reach of children. 
 
The study medication will be supplied in amber glass 30-mL bottles with a 20-mL fill.  Disposable 
applicators will be provided.   
 
One Subject Kit box will contain 24 bottles, in individual boxes and disposable applicators.  Each 
kit will be labeled with a single-panel label.  Each box and bottle will be labeled with a single 
panel label.   
 
Additional supplies will be packaged in amber glass 120 ml (100 mL fill) bottles in individual 
cartons.  Each carton and bottle will be numbered with a unique number and labeled with a single-
panel label. 
 
 
STUDY ASSESSMENTS 
The investigator, a designated and appropriately trained staff member (e.g., subinvestigator) or the 
subject will perform the study assessments according to the schedules noted below.  
 
The same individual should perform the assessments for a given subject throughout the study. If 
this becomes impossible, an appropriate designee with overlapping experience with the subject 
and the study should perform the assessments.  
 
Similar lighting conditions and subject positioning should be used for all evaluations for a given 
subject.  A Wood’s lamp should be used to assess the subject’s vitiliginous lesions. 
 
 
Assessments of Efficacy 
8.1.1. 
Canfield 2D Digital Facial Image Analysis 
A qualified investigational staff member will take 18 photographs (5 lighting modalities x 3 
views [left, front, right]) of the face at baseline and then monthly during the study.  Each imaging 
session includes a sequence of images including the following lighting/capture modalities: 
• Standard 1 (default settings) – General purpose white light photograph, the typical 
“clinical” photo. Provides balanced cross lighting for good subjective evaluation of most 
skin features. 
• Standard 2 (default settings) – ‘Diffuse light’. Provides even, white light across the entire 
image with a minimum of highlight and shadow.  Ideal for many quantitative image 
analysis applications. 
• Cross Polarized (default settings) – Polarized light sources with a Perpendicular polarizer 
over the camera lens.  Filters out surface reflections for superior visualization of sub-
surface detail (vascular features, erythema, pigment, etc.)  


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• UV Fluorescence - NF (default settings) – UV filters (365nm band pass) over powerful 
strobes captured through an un-attenuated lens. The Fluorescence photo is geared toward 
enhancing the visibility of pigment features that absorb UV light. Fluorescing Porphyrin 
details are also visible.   
• Parallel Polarized (default settings) – Polarized light sources with a Parallel polarizer 
over the camera lens.  Passes only surface reflections for superior visualization of 
topographical data (wrinkles, fine lines, pores, etc.) 
 
Equipment, supplies, training and detailed instructions for obtaining and managing photographs 
will be provided to the investigational center prior to the initiation of subject enrollment. 
 
Canfield Scientific will conduct image analysis. The obtained cross-polarized image will be 
transformed using Canfield’s RBX technique to separate melanin (Brown image) from 
hemoglobin (Red image). A segmentation algorithm detects hyperpigmentation (pigmented areas 
with concentration higher than normal skin concentration) and depigmentation (pigmented areas 
with concentration lower than normal skin concentration) within the areas of interest (AOI) from 
the RBX Brown images. Area of detected pigmentation and intensity measurements can be 
reported by the algorithm after segmentation.   The measurement will be the ratio of the detected 
area of pigmentation and the AOI.  The primary endpoint will be based on the quantification of 
depigmentation in the AOI over time.   
 
Area of Interest 
The AOI includes approximately 90% of the total facial surface area and is defined as the area 
from the border of the hairline to the jawline.  Hair bearing areas such as the eyebrows and the 
areas of the forehead and chin covered by the stereotactic positioning device for photographs are 
not included in the AOI. Refer to APPENDIX 6 for a diagram of the AOI. 
8.1.2. 
Facial Vitiligo Area Scoring Index (F-VASI) and Facial Total Body Surface 
Area (TBSA) 
The F-VASI is an assessment of the subject’s facial vitiligo modified from the VASI for the face 
only. The investigator or designee will assess the face using a Wood’s lamp to assist in the 
identification of the vitiliginous lesions and then calculate the F-VASI score based on the 
descriptor that best matches the presentation of the subject at each individual visit:  Baseline (Visit 
2) and Visits 5, 6, 7, 8, 9, 10,11 (if applicable) and if continuing for 24 additional weeks of 
treatment, Visit 12-15.  The investigator should not refer to any other visits assessments when 
performing the F-VASI. 
 
The percentage of vitiligo involvement for the face is calculated using the palmar method.  The 
palmar method uses the palmar surface area of the investigator’s hand as an estimation guide and 
defines the surface of the hand including fingers to be 1.0% of the total body surface area.  
 
At screening and baseline, the Facial TBSA will be calculated and must be at least 0.25% 
(excluding: the area from the eyebrows to and including the upper eyelids; the area from the 
bony rim of the orbit to and including the lower eyelids; mucosal lip areas, and the area of the 
chin and forehead covered by stereotactic photographic device) and include at least one area of 
normal pigmentation.  The face is then clinically evaluated by visual assessment for the pattern 


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of skin depigmentation using a visual scale.  The publication by Hamzavi I, Jain H, McLean D, 
Shapiro J, Zeng H, and Lui H. 2004 will be provided to the investigators to depict the pattern of 
depigmentation as illustrated in descriptive patient photographs. 
 
Facial VASI = % BSA x residual depigmentation 
 
• 
BSA - used as a guide to estimate % of vitiligo involvement of the face 
• 
Extent of residual depigmentation is expressed by the following percentages: 
• 
0 
• 
10% - only specks of depigmentation are present 
• 
25% - the pigmented area exceeds the depigmented area 
• 
50% - the depigmented and pigmented areas are equal 
• 
75% - the depigmented area exceeds the pigmented area 
• 
90% - specks of pigment are present 
• 
100% - no pigment is present 
8.1.3. 
Vitiligo Noticeability Scale (VNS) 
The VNS is the subject’s assessment of the noticeability of facial vitiligo determined at Visits 5, 
6, 7, 8, 9, 10, 11 (if applicable) and if continuing for an additional 24 weeks of treatment, Visit 12-
15.  The subject will complete the following question: 
 
Compared to before treatment, how noticeable is the vitiligo now? 
• 
More noticeable (1) 
• 
As noticeable (2) 
• 
Slightly less noticeable (3) 
• 
A lot less noticeable (4) 
• 
No longer noticeable (5) 
 
Treatment success will be defined as follows:  VNS score of 1 or 2 = treatment not successful, 
VNS score of 3 = treatment partially successful, or VNS score of 4 or 5 = treatment successful.   
8.1.4. 
Vitiligo Area Scoring Index (VASI) 
The VASI will be assessed by the investigator or designee to track the total body vitiligo status 
throughout the study at screening (Visit 1), baseline (Visit 2), Week 12 (Visit 7), Week 24 (Visit 
10), and Week 48 (Visit 14).  The body is divided into the following 6 separate and mutually 
exclusive sites:  head/neck, hands, upper extremities (excluding hands), trunk, lower extremities 
(excluding feet), and feet.  The investigator or designee will assess each of the 6 body sites using 
a Wood’s lamp to assist in the identification of the vitiliginous lesions. 
 
The percentage of vitiligo involvement for each body region is calculated using the palmar 
method.  The palmar method uses the palmar surface area of the investigator or designee’s hand 
as an estimation guide and defines the surface of the evaluator’s hand including fingers to be 
1.0% of the total body surface area. Each of the 6 body sites is then clinically evaluated by visual 
assessment for the pattern of skin depigmentation using a visual scale.  The publication by 
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, and Lui H. 2004 will be provided to the 
investigators to depict the pattern of depigmentation as illustrated in descriptive patient 
photographs. 


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Total body VASI = Sum of all the values from the body sites (in Hand units) x (Residual 
depigmentation) 
• 
Hand unit - One hand unit is approximately 1% BSA – used as a guide to estimate % of 
vitiligo involvement in each body area. (Body is divided into 6 areas) 
• 
Extent of residual depigmentation is expressed by the following percentages: 
• 
0 
• 
10% - only specks of depigmentation are present 
• 
25% - the pigmented area exceeds the depigmented area 
• 
50% - the depigmented and pigmented areas are equal 
• 
75% - the depigmented area exceeds the pigmented area 
• 
90% - specks of pigment are present 
• 
100% - no pigment is present 
 
8.1.5. 
Subject Vitiligo Satisfaction Scale (SVSS) 
The SVSS is the subject’s assessment of her/his satisfaction with the status of the overall 
repigmentation of the treated areas of the face with vitiligo, at a particular point in time (See 
APPENDIX 5). The subject should NOT refer to any other assessments to assist with these 
assessments.  
 
 
At Visits 7-10, and if applicable, Visit 11 and Visits 12-14, the subject will assess the treatment areas 
of the face with vitiligo using the scale below and report the one integer that best describes her/his 
satisfaction with the status of the repigmentation of the treated areas of his or her face. 
 
Please report the number that best describes how satisfied you are with the results of the study 
medication applications on the treated areas of the face. 
 
How satisfied or dissatisfied are you with the appearance of your facial vitiligo as a result of the 
study medication applications? 
Subject’s Vitiligo Satisfaction Scale 
Grade Descriptor 
1 
Extremely satisfied 
2 
Moderately satisfied 
3 
A little satisfied 
4 
Neither satisfied or dissatisfied 
5 
A little dissatisfied 
6 
Moderately dissatisfied 
7 
Extremely dissatisfied 
 
An investigational staff member will educate the subject on the SVSS scale before each evaluation 
and direct the subject to assess the treated areas of the face. The staff member should not influence 
the subject’s assessment. 
 


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The study staff member will report the SVSS grade the subject indicates in the source document. 
Both the subject and the study staff member must sign/initial the source document to indicate the 
subject performed the SVSS as instructed. 
 
8.1.6. 
Vitiligo-Specific Quality of Life Instrument (VitiQoL)  
The subject will complete the VitiQoL questionnaire at baseline (Visit 2), Visits 7, 8, 9, 10, Visit 
11 (if applicable) and Visit 14 (Week 48) (see Appendix 4).  The study staff should instruct the 
subject to answer the questions based on the impact of vitiligo over the past month.  The response 
to each question will be scored on a 0 (not at all) to 6 (all of the time) continuous bipolar scale.   
 
 
Assessment of Safety 
Safety will be assessed throughout the study by the investigator or a designated and appropriately 
trained staff member. 
 
8.2.1. 
ECGs 
Standard 12-lead ECGs will be performed by a qualified staff member at Screening (Visit 1), 
Baseline (Visit 2), Day 8 (Visit 3), Visits 5-10, Visit 11 (if applicable) and if continuing for the 
additional visits, Visit 15.  The ECGs must be obtained using a standard 12-lead ECG with a 
10mm/mV amplitude, at 25mm/sec and a 5-10-second duration. To ensure a steady heart rate the 
subject must rest quietly in the supine position for at least 5 minutes prior to performing the ECG.  
 
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 either directly on the tracing or in a separate report.   The evaluator 
will interpret the results of every ECG and define the ECG as “normal” or “abnormal”.  Variations 
such as minor ST changes (i.e., <0.5mm depression) and early re-polarization are considered 
normal.  
 
The investigator must review the evaluator’s interpretation of each subject’s screening ECG prior 
to Baseline (Visit 2). The investigator will review, sign and date the evaluator’s interpretation of 
all ECG reports in a timely manner and comment on the clinical significance of any result that is 
defined by the evaluator as abnormal.  
 
Any abnormalities that are, in the opinion of the investigator, clinically significant, must be 
reported as history if found prior to the start of the first study medication application or as an AE 
if found after the start of the first study medication application (see Section 9.1.1). 
8.2.2. 
Physical Examination 
The investigator or designee will perform a physical examination for all body systems (general 
appearance, examination of head, eyes, ears, nose and throat, respiratory, cardiovascular, 
abdominal, neurological, musculoskeletal, lymphatic and skin assessment) at Screening (Visit 1) 
and end of study Week 28 (Visit 11) or if continuing for the additional visits, Week 52 (Visit 15). 
 


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Any measure that is, in the opinion of the investigator, abnormal AND clinically significant (CS) 
must be recorded as history if found prior to the first study medication application or as an AE if 
found after the first study medication application begins.  
 
8.2.3. 
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 history if found prior to the first study medication application, or as an AE if 
found after the first study medication application begins.  
 
A systolic blood pressure >140mm Hg or a diastolic blood pressure >90 mmHg is considered 
abnormal and therefore must be defined as CS or not clinically significant (NCS) in the eCRF.   A 
weight >300 lbs. is considered abnormal and therefore must be defined as CS or NCS in the eCRF. 
8.2.4. 
Clinical Laboratory Assessments 
At the visits detailed in the Schedule of Assessments, a qualified staff member will collect non-
fasting samples for clinical laboratory analysis. Approximately 18.5 ml of blood will be collected 
at Visit 1 and approximately 10.5 ml for each sample detailed in the Schedule of Assessments a 
total of approximately 113 ml per subject for Visit 1-11, approximately 42 ml for Visits 12-15, 
and up to approximately 155 ml for the entire study. 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 
Phosphorus 
    Monocytes 
Potassium 
    Neutrophils 
Sodium 
 
Total bilirubin 
Urinalysis 


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Total protein 
 
Uric acid 
Total cholesterol, LDL, HDL, 
Triglycerides 
CPK 
Screening Only 
Virology (HepB, HCV, HIV) 
Quantiferon Gold 
T3/T4, TSH 
Serum pregnancy 
 
 
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 for each subject prior to Baseline (Visit 2). The investigator must 
report all laboratory results that are BOTH outside the normal range for the laboratory AND, in 
the opinion of the investigator, CS as medical history if found prior to the first study medication 
treatment or as an AE if found after the first study medication treatment begins. The investigator 
must review all laboratory reports in a timely manner. 
8.2.5. 
Local Tolerability Assessment (LTA)  
The LTA is the investigator’s assessment of the average overall severity of signs and the subject’s 
assessment of the average overall severity of symptoms associated with an application site reaction 
on the treated areas of the face. The investigator and subject must NOT refer to any other evaluation 
to assist with these assessments. This is not a comparison with the assessment at any other time point. 
 
At Visits 2-11, the investigator and the subject will evaluate the LTA signs and the LTA symptoms 
respectively.  
 
LTA Signs (Investigator or designee assessment): 
• 
Erythema 
• 
Edema 
• 
Scaling/dryness 
 
LTA symptoms (Subject assessment): 
• 
Stinging 
• 
Burning 
The investigator will assess the LTA signs as follows: 
• At Visit 2: 
o Prior to the first study medication application 
o 20 (±4) minutes after the application completion time. 
• At Visits 3-11. 
 


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


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2 
Moderate: Definite itching, slightly bothersome 
3 
Severe: Intense itching, bothersome and/or uncomfortable 
 
Local Tolerability Assessment – Burning/ Stinging 
Grade 
Descriptor 
0 
Clear: No burning or stinging 
1 
Mild: Slight warmth or tingling, not bothersome 
2 
Moderate: Definite warmth or tingling, slightly bothersome 
3 
Severe: Intense feeling of heat or tingling, bothersome and/or uncomfortable 
 
Follow these steps to complete the LTA for each symptom by a subject: 
• An investigational center staff member, other than the evaluating investigator, will show 
the appropriate LTA symptom grading scale to the subject and instruct the subject on the 
time interval to be considered 
• The staff member should not give any opinion on the meaning of the LTA descriptors 
• The subject should verbally indicate the appropriate grade for each symptom and the staff 
member will report the grade in the source document 
• Both the subject and the staff member must sign/initial the source document to indicate the 
subject performed the LTA for symptoms as instructed 
• The staff member must not influence the subject’s assessment. 
8.2.6. 
Pregnancy tests 
Subjects who are WOCBP must have a negative serum pregnancy test result at Screening (Visit 1) 
to continue in the study, and a negative UPT at Baseline (Visit 2) prior to application of study 
medication.  In addition, the investigator or designee will perform a urine pregnancy test for 
subjects who are WOCBP at monthly visits during the study. 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-treatment urine pregnancy test is positive, the subject will be withdrawn from the study and 
the subject’s pregnancy documented and followed. 
 
Other Assessments 
8.3.1. 
Demographics, Medical History and Vitiligo 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 extensive vitiligo 
history at screening 
 


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ADVERSE EVENTS 
Adverse events will be monitored throughout the study and reported on the appropriate Aclaris 
Therapeutics, Inc. AE eCRF.   
 
 
Definitions 
9.1.1. 
Adverse events (AE) 
An AE is any untoward medical occurrence in a subject administered a study medication(s) and 
which does not necessarily have a causal relationship with the study medication.  An AE can 
therefore be any unfavorable and unintended sign or symptom associated with the use of a study 
medication (including an abnormal laboratory finding), whether or not related to the study 
medication.  
 
Thus, any new, clinically significant worsening of an existing sign, symptom or disease, should be 
considered an AE.  
 
Every new episode or clinically significant worsening of a chronic condition (e.g., headaches, 
seasonal allergies, depression, or hypertension) should be reported as a separate AE, even if the 
condition is reported in the subject’s medical history. 
 
The investigator should, when certain, report a diagnosis rather than the signs, symptoms or 
clinically significant abnormal laboratory values associated with the AE. Otherwise, signs, 
symptoms or abnormal laboratory values may be used to describe the AE. 
Any CS abnormality discovered prior to the first study medication treatment should be reported as 
medical history, not as an AE. 
 
9.1.2. 
Serious adverse event (SAE) 
A Serious Adverse Event is any untoward medical occurrence that at any dose: 
• Results in death 
• Is life threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect 
• Is an important medical event. 
The term “life threatening” refers to an event in which the subject was at risk of death at the time 
of event; it does not refer to an event that hypothetically might have caused death if it were more 
severe. 
 
Inpatient hospitalization is considered to have occurred if the subject is admitted to the hospital on 
an in-patient basis, even if released the same day. Prolongation of hospitalization is defined as an 
additional night stay in the hospital. Hospitalization for a diagnostic test (even if related to an AE) 
or elective hospitalization that was planned before study enrollment (signing the ICF) are not 
themselves reasons for an event to be defined as a SAE. 
 


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


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Reporting Procedures 
9.2.1. 
Procedures for reporting adverse events 
At each post-enrollment visit, the investigator will question the subject to elicit AEs using a non-
directive question such as “Has there been any change in your health since the previous study 
visit?”  If appropriate, based on the subject’s response to non-directed questioning to elicit AEs, 
the investigator will follow-up with directed questions and appropriate evaluations.  
Any AE noted during the reporting period must be reported in the source documents and on the 
appropriate AE eCRF. AEs that are defined as “Not Related” to the study medications will be 
followed until they are resolved or until the subject’s last study visit. AEs that are defined as 
“Related” to the study medications will be followed until they are resolved or, if not resolved after 
the subject’s last study visit, until in the opinion of the investigator, the AE reaches a clinically 
stable outcome with or without sequelae. 
 
9.2.2. 
Procedure for reporting a serious adverse event 
Upon becoming aware of a SAE occurring during the AE reporting period, whether or not related 
to the study medications, the investigator must: 
 
1. 
Take the appropriate medical action to ensure the subject’s safety. 
Immediately (within 24 hours) inform the Medical Monitor of the SAE by telephone: 
Terrence Chew, M.D. 
Office Telephone: 858-720-0647 
SAE facsimile 484-324-2359 
E-mail: tgchew@icloud.com 
2. 
Within 24-hours complete, as fully as possible, an AE eCRF and an SAE form; fax or e-mail 
the forms and any other relevant information (e.g., concomitant medication eCRF, medical 
history eCRF, laboratory test results) to the Aclaris Therapeutics, Inc. Medical Monitor. 
3. 
Monitor and document the progress of the SAE until it resolves or, if not resolved after the 
subject’s last study visit, until in the opinion of the investigator the AE reaches a clinically 
stable outcome with or without sequelae AND the investigator and Aclaris Therapeutics, Inc.  
Medical Monitor agree that the SAE is satisfactorily resolved. 
4. 
Inform the Aclaris Therapeutics, Inc. Medical Monitor of SAE updates by telephone 
followed by an SAE form update sent by e-mail. 
5. 
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). 
 
9.2.3. 
Safety Monitoring Discontinuation Criteria 
Any subject who develops any of the following ECG findings during the active treatment phase 
will be instructed to stop study medication and will be withdrawn from the study: 
• A post-study medication ECG result where the evaluator’s interpretation shows any of the 
following: 


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o Clinically significant rhythm disturbance other than sinus rhythm or ectopic 
supraventricular rhythm (ectopic atrial rhythm) 
o Clinically significant conduction disturbance including PR >240msec, pre-
excitation (delta wave and PR <120msec), second degree or higher AV block  
o New finding of QRS>120ms (if not present at screen.  For example, subjects with 
Right Bundle Branch Block at screening would not need to be withdrawn from the 
study if their subsequent ECGs remained unchanged). 
o Evidence of QT-interval prolongation, defined as an increase in the QTcF 
interval>60ms from Visit 1 
o Acute signs of ischemia or infarction 
o Any ECG abnormality which may, in the opinion of the investigator, represent a 
new medical issue of concern 
Site staff must perform protocol-required procedures for trial discontinuation and follow-up.  
 
9.2.4. 
Study Medication Interruption and Discontinuation Criteria 
9.2.4.1 
Study Medication Interruption 
Treatment with ATI-50002 Topical Solution should be temporarily interrupted in the event of 
severe adverse events considered related to ATI-50002, or in the event of one or more of the 
abnormal laboratory values in Table 1. 
 
 


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


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• Serum creatinine: > 2 x ULN persisting for >2 weeks of treatment discontinuation or 
second occurrence of > 2 x ULN 
The continued treatment of subjects who experience other serious or severe adverse events 
considered related to study treatment should be discussed with the Sponsor’s medical monitor. 
 
PREGNANCY 
 
Definition of Women of Child Bearing Potential (WOCBP) 
WOCBP includes any female who has experienced menarche and who has not undergone 
successful surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy) or is not postmenopausal. Postmenopausal is defined as ≥12 months with no 
menses without an alternative medical cause.  WOCBP must have a negative serum pregnancy test 
at screening and a negative UPT at baseline prior to application of study medication. 
 
 
Highly Effective Methods of Birth Control 
The Investigator or subinvestigator will discuss the potential risk factors associated with pregnancy 
and the importance of maintaining a highly effective method of contraception throughout the study 
with all WOCBP (for example, those which result in a low failure rate - i.e., less than 1% per year- 
when used consistently and correctly).  All WOCBP must use a highly effective method of birth 
control during the study and for 30 days after the final application of study medication in a manner 
such that risk of failure is minimized.   
 
Highly effective methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
• intrauterine device (IUD) 
• obstruction of fallopian tubes via medical device (Essure TM ) 
• 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. 
 


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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 may have been or 
was pregnant at the time of study medication exposure (including at least 2 days after study 
medication administration) the investigator must immediately notify the Aclaris Therapeutics, Inc. 
Medical Monitor and record the event on a pregnancy surveillance form. While not an AE or SAE, 
the investigator must report every pregnancy using a pregnancy surveillance form and follow the 
reporting procedures described for SAE reporting. 
 
Protocol-required procedures for trial discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (e.g., x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated. In addition, the investigator must report 
to Aclaris Therapeutics, Inc.’s Medical Monitor on the pregnancy surveillance form, follow-up 
information regarding the course of the pregnancy, including perinatal and neonatal outcome. 
Infants should be followed for a minimum of six weeks. 
  
 
STATISTICAL ANALYSES   
 
Sample Size and Power Calculations 
Thirty-three subjects will be enrolled.  This is a pilot study and the first study with ATI-50002 
Topical Solution for the treatment of facial vitiligo.  A formal power calculation was not 
performed.  The initial analyses will be performed after all subjects complete Visit 10 (Week 24). 
 
 
Statistical Methods 
Summary descriptive statistics (N, mean, median, SD) by visit will be provided for all safety and 
efficacy parameters.  Primary and secondary efficacy parameters are described below: 
 


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Primary Efficacy Parameter  
Mean change from baseline in facial depigmentation in the AOI will be quantified using Canfield-
2-D photographic image analysis from baseline (Visit 2) compared to Week 48 (Visit 14).  
 
Secondary Efficacy Parameters: 
Mean change from baseline in facial depigmentation will be calculated as the mean change in 
Facial assessment of the Vitiligo Area Scoring Index (F-VASI) from Visit 2 compared to Week 
24 (Visit 10) and if applicable, Week 48 (Visit 14).  F-VASI is a modification of the validated 
quantitative assessment scale for vitiligo which evaluates the percentage of vitiligo involvement 
of the face only. 
 
Mean change from baseline in facial depigmentation in the AOI based on Canfield 2-D 
Photographic analysis from Visit 2 compared to Weeks 4, 8, 12, 16, 20, 24, 32, 40, and post-
treatment Week 52 (Visits 5-11, and 12, 13, and 15). 
 
Mean change from baseline in the Facial assessment of the Vitiligo Area Scoring Index (F-VASI) 
from Visit 2 compared to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and post-treatment Week 52 (Visits 
5-11, and Visits 12, 13, 14 and 15). 
 
Mean change from baseline in the VitiQoL from Visit 2 compared to Week 12, 16, 20, 24, and 48 
(Visits 7-10, 14).  
 
Treatment success based on the subject’s assessment of vitiligo on the Vitiligo Noticeability Scale 
(VNS) at Week 4, 8, 12, 16, 20, 24, 32, 40, and 48. 
 
Mean change from baseline in total VASI from Visit 2 to Visits 7 and Visit 14 (Week 48) will be 
assessed for descriptive purposes only to track disease progression in untreated areas. 
 
Safety analyses will include descriptive statistics calculated on the safety parameters using the 
safety population. The proportion of subjects with treatment-emergent adverse events will be 
tabulated and presented by Medical Dictionary for Regulatory Activities (MedDRA) System 
Organ Class. Vital signs and clinically relevant abnormal laboratory results will also be tabulated 
and presented.  Change from baseline in the Local Tolerability Assessments (LTA) to end of 
treatment (Visit 10) will be summarized. 
 
Data from all enrolled and treated subjects will be presented and summarized. Safety summaries 
by study will include listings of adverse events incidences within each MedDRA System Organ 
Class, and changes from pre-application values in vital signs. Adverse event summaries will be 
presented showing the proportion of subjects experiencing adverse events, both overall and by 
MedDRA System Organ Class. 
    


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TRAINING, MONITORING, DATA MANAGEMENT AND QUALITY 
ASSURANCE 
 
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. 
 
 
Monitoring 
The conduct of the study will be closely monitored by representatives of Aclaris Therapeutics, Inc. 
to verify adherence to ICH Good Clinical Practice (GCP) guidelines, and applicable SOPs.  
Reports of these verifications will be archived with the study report.  The investigator will allow 
the Aclaris Therapeutics, Inc. representative’s designee and/or any regulatory agency to have 
direct access to all study records, eCRFs, corresponding subject medical records, study 
medication-dispensing records and study medication storage area, and any other documents 
considered source documentation.  The investigator also agrees to assist the representative, if 
required. 
 
 
Data Management 
Data-management activities of this study will be subcontracted.  Edit checks and review processes 
will be performed by the sub-contractor until all data clarifications are resolved. The data will be 
exported to be stored in SAS datasets (or equivalent) by the sub-contractor. After all data 
clarifications are resolved and subject’s evaluability is determined, the database will be locked. 
 
 
Quality Assurance 
The study is conducted under the sponsorship of Aclaris Therapeutics, Inc. in compliance with the 
applicable regulatory requirements as well as applicable ICH guidelines, Declaration of Helsinki, 
and in respect of the Aclaris Therapeutics, Inc. and/or sub-contractor SOPs for study conduct and 
monitoring. 
 
Audits may be carried out by Aclaris Therapeutics, Inc. or Aclaris Therapeutics, Inc.’s 
representatives, and inspections may be performed by regulatory authorities or IRB/ECs before, 
during or after the study.  The investigator will provide the auditing/inspecting group direct access 


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


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A protocol violation is defined as any divergence from the protocol-specific study procedures or 
schedules that may result in an increased risk to a study subject or that affect the scientific integrity 
of the study.  All protocol violations must be reviewed by the Medical Monitor and reported to the 
IRB by the Investigator, as directed by the IRB-specific procedures. 
 
 
Regulatory Documents 
The investigator must maintain a study file containing current and complete regulatory 
documentation in compliance with the current ICH E6 GCP guideline. This file will be reviewed 
as part of the routine monitoring for this study. 
 
 
Contractual Requirements 
A contractual agreement will be signed between Aclaris Therapeutics, Inc. and each investigator.  
This document will contain supplemental information, including financial terms, confidentiality, 
study schedule, third party responsibility, and publication rights. 
 
 
Data Collection and Archiving 
13.7.1. 
Data collection  
 
The Investigator must maintain required records for all study subjects.  Data for this study will be 
recorded in the subject's source document and on the eCRFs.  All data on these eCRFs should be 
recorded completely and promptly.  A copy of the completed eCRFs for each subject will be 
retained by the investigational center. 
 
Records of the subject’s participation in this study will be held confidential except as disclosure is 
required by law. The study doctor, the sponsor, persons working on behalf of the sponsor, and 
under certain circumstances, the United States Food and Drug Administration and the Institutional 
Review Board will be able to inspect and copy confidential study-related records that identify 
subjects by name. Therefore, absolute subject confidentiality cannot be guaranteed. If the results 
of this study are published or presented at meetings, the subject’s identity will not be revealed. 
 
13.7.2. 
Source documentation 
Investigators must keep accurate separate records (other than the eCRFs) of all subjects' visits that 
include all pertinent study related information.  A statement should be made indicating that the 
subjects have been enrolled in this clinical study and have provided written informed consent.  Any 
AEs must be completely documented. Source documentation includes results of any diagnostic 
tests conducted during the study.   
 
13.7.3. 
Archiving 
All pertinent data, samples, photographs, correspondence, original or amended protocol, reports 
and all other material relating to the study will be maintained securely in Aclaris Therapeutics, Inc. 
/contract research organization/investigator archives for the legally required duration for archiving. 
 


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The investigator should maintain the essential study documents as specified in ICH GCP, and in 
compliance with all regulatory requirements. The investigator should ensure these documents are 
protected from accidental destruction or disposal. 
 
If the Investigator needs to re-assign responsibility for maintaining these documents (e.g., due to 
retirement) it must be transferred to a person willing to accept this responsibility.  The investigator 
must notify Aclaris Therapeutics, Inc., in writing, of the name and address of the new individual. 
 
 
 
 


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REFERENCES 
 
Craiglow BG, King BA.  Tofacitinib citrate for the treatment of vitiligo:  a pathogenesis-directed 
therapy.  JAMA Dermatol. 2015;151(10):1110-1112. 
Data on File, Aclaris 2017. 
Ezzedine K, Lim HW, Suzuki T et al.  Revised classification/ nomenclature of vitiligo and related 
issues:  the Vitiligo Global Issues Consensus Conference.  2013.  Pigment Cell Melanoma Res. 
2012;25(3): E1-13. 
Fitzpatrick, TB, Mosher DB, Pathak M.  Vitiligo Facts.  American Vitiligo Research Foundation.  
http://www.avrf.org/facts/frequently-asked-questions/print.html. Accessed November 2017.   
Frisoli ML, Harris JE.  Vitiligo:  Mechanistic insights lead to novel treatments.  J Allergy Clin 
Immunol (2017). 
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. Parametric modeling of  
narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the 
Vitiligo Area Scoring Index. Arch Dermatol. 2004 Jun;140(6):677-83. 
Harris JE, Rashighi M, Nguyen N, et al.  Rapid skin repigmentation on oral ruxolitinib in a patient 
with coexistent vitiligo and alopecia areata (AA).  J Am Acad Dermatol. 2016;74(2);370-371. 
Lilly E, Lu P, Borovicka J et al.  Development and validation of a vitiligo-specific quality-of-life 
instrument (VitiQoL) J AM Acad Dermatol 2013;69:e11-8. 
Rashighi M, Harris JE.  Vitiligo Pathogenesis and Emerging Treatments.  Dermatologic Clinics. 
2017:35, 257-265.  
Rothstein BA, Joshipura D, Saraiya A, et al.  Treatment of vitiligo with the topical Janus kinase 
inhibitor ruxolitinib.  J Am Acad Dermatol; 2017: 76(6): 1054-1060. 
Villarino AV, Kanno Y, Ferdinand JR, O’Shea JJ.  Mechanisms of JAK/STAT signaling in 
immunity and disease. J Immunol. 2015:194(1)21-27. 
Wang CQ, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N, 
Sullivan-Whalen M, Gilleaudeau P, Cohen JA, Krueger JG. Th17 cells and activated  
dendritic cells are increased in vitiligo lesions. PLoS One. 2011 Apr 
25;6(4):e18907.  
 
 


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:  Subject Instructions for Study Medication Application to the Face and 
Neck (If Applicable) 
General Instructions:  
1. Before application of study medication, your face and neck (if applicable) should be 
clean (free of any makeup, moisturizers, sunscreen, etc.), and dry. This will allow the 
study medication to penetrate down into the skin to ensure you are getting the best 
application.  
2. You will be asked to apply a thin layer of study medication to the white areas of your 
face and if applicable, your neck including ½ inch around the white areas (excluding your 
eyelids and red (mucosal) lip areas) with an applicator as instructed by the study doctor or 
the study staff. Keep applying study medication to the same facial and neck areas 
throughout the study, even if the color is returning in these areas.  
3. You will want the tip of your applicator to be saturated but not too much as to cause 
dripping. An applicator should only be dipped in the bottle once and then discarded.  You 
may use more than one applicator per session as needed to ensure all areas of your face 
and if applicable, your neck designated by the study staff for treatment have medication 
applied. 
4. Keep the study medication out of your eyes. If the study medication gets in your eyes, 
rinse the area well with water for up to 15 minutes. Contact the study doctor for further 
advice on managing the eye exposure.  
5. You will apply study medication twice a day, approximately 8 to 12 hours apart. Once 
you apply study medication, do not wash your face of neck (If applicable) for at least 6 
hours.  
6. Remember to bring your study medication bottles, both used and unused, to each study 
visit.  
7. Avoid exposing your face and neck (if applicable) to excessive natural or artificial 
ultraviolet radiation (e.g., sunlight, tanning beds) and use sunscreen on the face and neck 
(if applicable), if excessive sun exposure cannot be avoided.  
8. Remove any products applied to the face and neck (if applicable) at least 1 hour before 
study visits. Do not apply study medication less than 6 hours before a study visit. If your 
visit is in the morning you should wait until after the visit to apply your study medication.  
9. Open one bottle of study medication at a time.  Each bottle of study medication should be 
used for 60 days only, even if there is remaining study medication.  
 
Preparation for Study Medication Application  
1. Gather a washcloth or towel, the study medication bottle, disposable applicators and a 
mirror.  
2. Wash your hands with soap and water before and after using this study medication.  
3. Gently wash your face and if applicable, your neck, ensuring all facial and neck areas are 
clean. Use your normal cleansing regime as approved by your study doctor. Do not use 
abrasive cleansers or materials on your face and if applicable, your neck.  
4. Pat your face and if applicable your neck dry with a clean towel and then let it air dry 
until it is completely dry to the touch.  


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 62 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
Study Medication Application:  
1. Unscrew the cap from the bottle. Place the open bottle on a stable, level surface.  
2. Dip a disposable applicator into the bottle of study medication for about 2 seconds. Tap 
the tip of the applicator twice inside the edge of the bottle to remove any excess study 
medication. The applicator should be saturated, but not dripping.  
3. Swipe the applicator across your facial and if applicable, your neck areas, applying a thin 
layer of study medication over all facial and neck areas and about ½ inch around these 
areas affected by vitiligo. Your face and if applicable your neck should be wet, but not 
dripping wet. Dispose of the applicator. Do not dip the same applicator in the study 
medication bottle more than once.  
4. If you need additional study medication to cover your entire affected facial and neck 
areas, use a new applicator and repeat the application process as described in #2 and #3.  
 
After Study Medication Application  
1. Securely close the study medication bottle and dispose of any used applicators.  
2. Wash your hands after using this product.  
3. Allow the study medication to completely dry.  
4. Do not apply any products (moisturizers, sunscreens, cosmetics, etc.) to your face and if 
applicable, your neck until the study medication has completely dried, at least 30 minutes 
after applying study medication.  
5. Do not wash your face and if applicable, your neck for at least 6 hours after applying the 
study medication.  
 
Missed Doses  
If you miss a dose of this study medication, apply it as soon as possible. However, if it is almost 
time for your next dose, skip the missed dose, and go back to your regular dosing schedule. Tell 
the study staff about any missed doses at your next study visit.  
 
Storage  
Store the study medication in the original glass bottle and box at room temperature, away from 
heat, moisture, and direct light. Do not refrigerate or freeze. Keep out of reach of children. 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 63 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
: Vitiligo History   
The following Vitiligo history will be obtained: 
 
Onset of initial diagnosis vitiligo (Month/Year): _______________________________ 
 
Initial presentation: ______________________________________________________ 
(segmental, non-segmental, mixed) 
 
Location: ______________________________________________________________ 
 
Current clinical type: _____________________________________________________ 
(segmental, non-segmental, mixed) 
 
Location: ______________________________________________________________ 
 
Onset of current episode of vitiligo (Month/Year):______________________ 
 
 
History of Treatments for Vitiligo: 
Treatment (Drug, Device, Other) 
Start Date   
(DD/MMM/YYYY) 
Stop Date 
(DD/MMM/YYYY) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 64 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
:  Fitzpatrick’s Skin Type Chart 
Fitzpatrick Skin Type 
Description (Sunburn & Tanning History According to Skin Type) 
Skin Type 
Always Burns; never tans (pale white skin) 
I 
Burns easily; tans minimally (white skin) 
II 
Burns moderately; tans uniformly (light brown skin) 
III 
Burns minimally; always tans (moderate brown skin) 
IV 
Rarely burns; tans profusely (dark brown skin)  
V 
Never burns; deeply pigmented (dark black Skin) 
VI 
 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 65 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
:  VitiQoL 
The aim of these questions is to measure how much your skin has affected you over the 
past month. 
 
During the past month,  
Not                          All of 
at all                      the time 
 ↓                   ∙                     ↓ 
1. Have you been bothered by the appearance of your skin 
condition? 
□  □  □  □  □  □  □ 
2. Have you felt frustrated about your skin condition? 
□  □  □  □  □  □  □ 
3. Has your skin condition made it hard to show affection? 
□  □  □  □  □  □  □ 
4. Has your skin condition affected your daily activities? 
□  □  □  □  □  □  □ 
5. When you were talking to someone, have you worried about 
what they may be thinking about you? 
□  □  □  □  □  □  □ 
6. Have you been afraid that people would find fault with you? 
□  □  □  □  □  □  □ 
7. Have you felt embarrassed or self-conscious because of your 
skin? 
□  □  □  □  □  □  □ 
8. Has your skin condition influenced the clothes you wear? 
□  □  □  □  □  □  □ 
9. Has your skin condition affected your social or leisure 
activities? 
□  □  □  □  □  □  □ 
10. Has your skin condition affected your emotional well-being? 
□  □  □  □  □  □  □ 
11. Has your skin condition affected your overall physical health? □  □  □  □  □  □  □ 
12. Has your skin condition affected your grooming practices (i.e. 
hairstyle, use of cosmetics)? 
□  □  □  □  □  □  □ 
13. Has your skin condition affected your sun protection efforts 
during recreation (i.e. limiting exposure time during peak sun 
hours, seeking shade, wearing hat, long sleeves or pants)? 
 
□  □  □  □  □  □  □ 
14. Has your skin condition affected the possibility of making new 
friends? 
□  □  □  □  □  □  □ 
15. Have you worried about progression or spread of disease to 
other new areas of the body? 
□  □  □  □  □  □  □ 
 
Please check how severe you currently feel your  
skin condition is:   
No skin                             Most 
Involvement               severe case 
 ↓                      ∙                       ↓        
16. Severity of skin condition. 
 
□  □  □  □  □  □  □ 
Have you answered every item?  Yes  □  No  □         Initial ________Date ________ 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 66 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
:  Subject Vitiligo Satisfaction Scale 
 
Please circle the grade below that best describes how satisfied or dissatisfied you are with the results 
of the study medication applications on the treated areas of the face. 
 
How satisfied or dissatisfied are you with the appearance of your facial vitiligo because of the study 
medication applications? 
 
Subject’s Vitiligo Satisfaction Scale 
Grade Descriptor 
1 
Extremely satisfied 
2 
Moderately satisfied 
3 
A little satisfied 
4 
Neither satisfied or dissatisfied 
5 
A little dissatisfied 
6 
Moderately dissatisfied 
7 
Extremely dissatisfied 
 
 
Initial ________Date ________ 
 
 


Protocol: ATI-50002-VITI-201 
Aclaris Therapeutics, Inc. 
 
 
Page 67 of 67                                                     CONFIDENTIAL 
Date: 08FEB2019, Version 4.0 
:  Area of Interest 
The area of Interest (AOI) mask template will be applied to all images obtained in the study. The 
following guidelines will be used to delineate boundaries for the AOI. For the Left and Right 
Oblique image template, horizontal and vertical guidelines will be placed at the outer canthus as 
well as a vertical guideline at the commissure and the center of the lip. For boundary points not 
defined by these guidelines, Canfield may adjust the template points along the brow line, 
hairline, jawline, lip line, beard, nose tip and/or bridge, and top of the cheek bone.   
 
For the Frontal template, vertical guidelines will be placed at the outer canthi and a horizontal 
guideline will be placed at the right inner canthus to delineate the edges of the AOI. For the 
boundaries not defined by these guidelines, Canfield may adjust the template points along the 
brow line and headrest (see Figure 1). 
 
Figure 1: Area of Interest Diagram 
 
2a. Right Oblique AOI                                 2b. Frontal AOI                      2c. Left Oblique AOI 
 
 
The Facial VASI should be calculated based on the depigmented areas within the mask template 
above excluding the facial areas covered by a beard, if applicable.  Study staff may instruct the 
subject to treat the areas of depigmentation which are blocked by the stereotactic device (forehead 
and chin) and the eyebrow area down to the level of the bony rim of the orbit and the beard, if 
applicable.