Clinical trial NCT03811912
Conditions: Alopecia Areata
Sponsor: Concert Pharmaceuticals
Start date: 2019-03-21; Completion date: 2019-11-21
Enrollment: 57 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate the efficacy and tolerability of once-daily versus twice-daily dosing of CTP-543, in adult patients with chronic, moderate to severe alopecia areata.

Detailed description:

Arms: arm 1: Participants received 1 x 8 mg CTP-543 tablet and 1 x CTP-543 matching placebo tablet, twice daily (BID) for 24 weeks. arm 2: Participants received 16 mg (2 x 8 mg) CTP-543 tablets, once daily (QD) and after 12 hours, received 2 x CTP-543 matching placebo tablets, QD for 24 weeks.
Interventions: intervention 1: CTP-543 intervention 2: CTP-543 Matching Placebo
Intervention descriptions: intervention 1: CTP-543 administered as 8 mg tablet. intervention 2: Administered as tablets to aid treatment masking.

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Randomized, Parallel-Group Study to Evaluate the Efficacy and 
Tolerability of Two Dosing Regimens of CTP-543 in Adult Patients With 
NCT Number: 
Document Dates: 
Moderate to Severe Alopecia Areata
NCT03811912 
Protocol Amendment 1: 03 January 2019 


CTP-543 
03 January 2019 
Protocol CP543.2002, Amendment 1 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
1 
A RANDOMIZED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY 
AND TOLERABILITY OF TWO DOSING REGIMENS OF CTP-543 IN ADULT 
PATIENTS WITH MODERATE TO SEVERE ALOPECIA AREATA  
INVESTIGATIONAL PRODUCT: 
CTP-543 
PROTOCOL NUMBER: 
CP543.2002; Amendment 1 
AMENDMENT 1 DATE: 
03 January 2019 
ORIGINAL PROTOCOL:  
EudraCT NUMBER: 
17 December 2018 
Not Applicable 
IND NUMBER: 
131,423 
SPONSOR NAME / ADDRESS: 
Concert Pharmaceuticals, Inc. 
65 Hayden Avenue, Suite 3000N 
Lexington, MA 02421 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
2 
 
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION  
 
Contact Information 
Name 
, MD 
Title 
 
Address 
 
 
 
Phone 
 
Facsimile 
 
Email 
 AND 
  
 




CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number:  CP543.2002 
 
 
 
 
 
Signature of Site Principal Investigator 
 
dd mmm yyyy 
 
 
Printed Name of Site Principal Investigator 
Institution Name:   
 
 
 
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Investigational Review Board procedures, instructions from Concert representatives, the 
Declaration of Helsinki, International Conference on Harmonization Good Clinical 
Practices Guidelines, and local regulations governing the conduct of clinical studies. 
 
 
 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
5 
 
 
SUMMARY OF CHANGES 
 
A Randomized Parallel-Group Study to Evaluate the Efficacy and 
Tolerability of Two Dosing Regimens of CTP-543 in Adult Patients 
with Moderate to Severe Alopecia Areata  
 
CP543.2002, Protocol Amendment #1 
03 January 2019 
 
The main purpose of this amendment #1 (to original protocol dated 17 December 2018), is to modify 
the Schedule of Assessments.  It was noted that an ECG at Screening had not been checked in the 
table.  An ‘X’ has been subsequently added to the Schedule of Assessments for the Screening visit.  
The Schedule of Assessments was the only section updated to reflect this change.  
 
 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
6 
 
1. 
SYNOPSIS 
 
Name of Sponsor/Company: 
Concert Pharmaceuticals, Inc.  
Name of Investigational Product: 
CTP-543 
Name of Active Ingredient: 
D8- ruxolitinib; 1H-Pyrazole-1-propanenitrile, β-(cyclopentyl-2,2,3,3,4,4,5,5-d8)-4-(7H-pyrrolo[2,3-
d]pyrimidin-4-yl)-, (βR)-, phosphate 
Title of Study:  
A Randomized Parallel-Group Study to Evaluate the Efficacy and Tolerability of Two Dosing 
Regimens of CTP-543 in Adult Patients with Moderate to Severe Alopecia Areata 
Study center(s): Multicenter study; approximately 10 sites; US 
Studied period (years):  
Estimated date first patient enrolled: February 2019 
Estimated date last patient completed: November 2019 
Phase of development: 2 
 
Objectives:  
The overall objective of the study is to compare the efficacy and tolerability of a 16 mg total daily 
dose of CTP-543 utilizing two different dosing regimens in adult patients with chronic, moderate to 
severe alopecia areata. 
The secondary/exploratory objectives of the study will be for patients to assess their eyebrows and to 
assess the patient reported outcomes of hair coverage and hair coverage quality.   
Methodology:  
This is a randomized, multicenter study to evaluate the efficacy and tolerability of two dosing 
regimens of CTP-543 (8 mg BID vs 16 mg QD), in adult patients with chronic, moderate to severe 
alopecia areata.  Patients will be between 18 and 65 years of age (inclusive), and experiencing an 
episode of alopecia areata lasting at least 6 months and not exceeding 10 years, with at least 50% hair 
loss as measured by the SALT at Screening and Baseline, and are not concurrently being treated for 
alopecia areata with other treatments that might affect hair regrowth or immune response.  Up to 
approximately 75% of alopecia areata patients with alopecia totalis or universalis, and no more than 
10% with only alopecia ophiasis will be enrolled.  
Subjects will be screened up to 28 days prior to initiation of study drug.  The Treatment Period is a 
24-week dosing period where patients will be randomized to receive either CTP-543 8 mg BID or 
CTP-543 16 mg QD and will be analyzed for the primary endpoint of the study.  To minimize bias in 
the evaluation of study endpoints, patients, investigators, and site personnel will be made unaware of 
the active drug dosing regimen by administering one 16 mg tablet and one placebo tablet 12 hours 
apart from each other for the 16 mg QD study group.  


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
7 
 
Figure 1: 
CP543.2002 Study Design 
Study Design 
Patients will provide informed consent prior to completing any screening procedures.  Patients 
meeting screening criteria will continue to the Day 1 Randomization Visit for review of eligibility and 
baseline assessments, including SALT assessment, physical examination, clinical laboratory 
assessments, vital signs, and electrocardiogram.  Patients meeting all eligibility criteria will be 
randomized to 1 of 2 CTP-543 treatment arms.  Randomization will be stratified by classification of 
alopecia areata subtype into one of the following three categories: 1) alopecia areata, 2) alopecia 
totalis or alopecia universalis, or 3) alopecia ophiasis.  
Patients will take the first dose of study drug in the clinic on Day 1.  Patients will be instructed to take 
study drug every 12 hours.  Patients should dose study drug in the clinic on all Study Visit Days after 
clinical laboratory blood draws are completed.   
Patient safety will be monitored throughout the trial.  During the first 8 weeks of the Treatment 
Period, hematology will be conducted every 2 weeks, followed by an assessment every 4 weeks 
thereafter through completion of the study at 24 weeks.  Lipid levels will be assessed every 12 weeks 
throughout the Treatment Period.  Significant cytopenias or other hematologic abnormalities will be 
managed by severity through dose interruption, or discontinuation, and signs and symptoms of 
infection will be closely monitored and treated promptly.  Patients who experience intolerable 
symptoms during treatment may discontinue the study at the discretion of the Investigator.  Patients 
may withdraw consent at any time. 
The Treatment Period will last 24 weeks to assess CTP-543 dosed BID vs CTP-543 dosed QD.  
Assessment of treatment response with SALT for efficacy will occur at 4, 8, 12, 16, 20 and 24 weeks.   
Upon completion of the 24-week Treatment Period, patients will be eligible to either complete 
treatment and exit the study following the safety follow-up visit, or roll-over into a long-term open-
label extension study.  
Number of patients (planned):  
Approximately 60 patients are planned to be enrolled in the study; approximately 30 patients per 
treatment arm. 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
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Diagnosis and main criteria for inclusion:  
Patients eligible for enrollment in the study must meet all of the following inclusion criteria and none 
of the exclusion criteria. 
Inclusion Criteria:  
1. Written informed consent, and authorization for release and use of protected health 
information. 
2. Between 18 and 65 years of age, inclusive, at the time of informed consent. 
3. Definitive diagnosis of alopecia areata. Totalis or universalis and ophiasis subtypes must have 
a current episode lasting at least 6 months and not exceeding 10 years at the time of 
Screening. Total disease duration greater than 10 years is permitted. 
4. At least 50% scalp hair loss, as defined by a SALT score ≥50, at Screening and Baseline.  
5. If of reproductive age, willing and able to use a medically highly effective form of birth 
control during the study and for 30 days following last dose of study medication.  Examples 
of medically highly effective forms of birth control are: 
a. Surgical sterility (via vasectomy, hysterectomy or bilateral ligation) or 
post-menopausal females 
b. Sexual partner is sterile, or of the same sex 
c. Implants of levonorgestrel in females 
d. Oral contraceptive (combined or progesterone only) in females 
e. Double-barrier method (any combination of physical and chemical methods) 
f. Intrauterine device in females, or other method with published data showing that the 
lowest expected failure rate is less than 1% per year 
6. Willing to comply with the study visits and requirements of the study protocol. 
Exclusion Criteria:  
1. History or presence of hair transplants. 
2. Treatment with other medications or agents within 1 month of Screening or during the study 
that may affect hair regrowth or immune response, including but not limited to: 
corticosteroids administered orally, by injection, or applied to areas of skin affected by 
alopecia; platelet-rich plasma injections; topical application to affected areas of anthralin, 
squaric acid, diphenylcyclopropenone, or minoxidil.  
3. Treatment with systemic immunosuppressive medications including but not limited to 
methotrexate, cyclosporine, and azathioprine; chloroquine derivatives; Janus kinase inhibitors 
(ruxolitinib, tofacitinib, etc) or etanercept within 3 months of Screening or during the study; 
or biologics (adalimumab, atlizumab, canakinumab, certolizumab, fontolizumab, golimumab, 
infliximab, mepolizumab, rituximab, secukinumab, tocilizumab, ustekinumab) within 6 
months of Screening or during the study. 
4. Active scalp inflammation, psoriasis, or seborrheic dermatitis requiring topical treatment to 
the scalp, significant trauma to the scalp, or other scalp condition that may interfere with the 
SALT assessment, or untreated actinic keratosis anywhere on the body at Screening and/or 
Baseline. 
5. Known history of moderate to severe androgenic alopecia or female pattern hair loss prior to 
alopecia areata. 
6. Unwilling to maintain a consistent hair style, including shampoo and hair products (including 
hair dye, process, and timing to hair appointments), and to refrain from weaves or extensions 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
9 
 
throughout the course of the study, or shaving of scalp hair for 2 weeks preceding a SALT 
assessment. 
7. Use of adhesive wigs, other than banded perimeter wigs, during the study. 
8. History of a lymphoproliferative disease or malignancy, other than non-melanoma skin 
cancer or cervical carcinoma.  Patients with 3 or more basal or squamous cell carcinomas 
diagnosed in the past 2 years are excluded.  
9. Atypical nevi or cutaneous lesions that are suspicious for malignancy. 
10. History of solid organ or hematological transplantation. 
11. Systemic or invasive infection, as evidenced by fever, inflammation, or systemic signs of 
illness (e.g., malaise, myalgia, specific symptoms like pain, shortness of breath) within 2 
weeks prior to first dose of study drug. 
12. Abnormal levels of thyroid stimulating hormone at Screening, defined as <0.9 x the lower 
limit of normal (LLN) and >1.2 x the upper limit of normal (ULN). 
13. Screening labs outside the normal range for parameters associated with potential risk for 
treatment under investigation.  This will include but is not limited to: 
a. Platelets ≤120  x 109/L or ≥600 x 109/L 
b. Absolute neutrophil count ≤1.5 x 109/L 
c. Hemoglobin levels ≤11 g/dL for females, or hemoglobin levels ≤12. 5 g/dL for males 
14. Screening blood glucose levels of hemoglobin A1c ≥6.5% (48 mmol/mol). 
15. Abnormal liver function at Screening, defined as ≥1.5 × ULN of serum alanine transaminase, 
serum aspartate transaminase, serum alkaline phosphatase, or total bilirubin (unless isolated 
Gilbert’s syndrome). 
16. Abnormal renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 using the 
MDRD equation) at Screening. 
17. At screening, any active or previous Hepatitis B or C infection, or known human 
immunodeficiency virus infection at screening. 
18. Vaccination with herpes zoster vaccine or any live virus vaccine within 6 weeks prior to 
Screening or during the study. 
19. Positive TB test, or history of incompletely treated or untreated tuberculosis. 
NOTE: In cases where performance of a QuantiFERON-TB Gold test is not possible, testing 
with a Tuberculin Skin Test (TST) may be an option after consultation with the Medical 
Monitor.  If the TST is negative, patients can be randomized into the study, assuming they 
meet all other inclusion and none of the exclusion criteria.  If results are equivocal, or there is 
reason to believe the result is a false positive, a QuantiFERON-TB Gold must be performed 
before a subject is eligible for randomization.   
20. History of prolonged QT syndrome or a Screening QTc interval with Fridericia’s correction 
(QTcF) > 450 msec for males or QTcF > 470 msec for females. 
21. History of alcohol, medication, or illicit drug abuse within 1 year before the first dose of 
study drug. 
22. Females who are nursing, pregnant, or planning to become pregnant while in the study, and 
for 30 days after last dose of study medication. 
23. Participation in another investigational study within the greater of 4 weeks or 5 half-lives of 
an investigational medication prior to screening or during the study. 
24. Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (such as, but not limited to 
clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
10 
 
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, 
telithromycin, voriconazole, or fluconazole) dosed for systemic exposure. 
25. Use of strong CYP3A4 inducers (such as, but not limited to barbiturates, carbamazepine, 
efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, 
pioglitazone, rifabutin, rifampin, St. John’s Wort, or troglitazone) dosed for systemic 
exposure. 
26. Donation of blood within a month of first dose of study drug or at any point throughout the 
study and for 30 days after last dose of study medication. 
27. Clinically significant medical condition, psychiatric disease, or social condition, as 
determined by the Investigator, that may unfavorably alter the risk-benefit of study 
participation, adversely affect study compliance, or confound interpretation of study results.  
Investigational product, dosage and mode of administration:  
CTP-543 will be dosed orally as tablets at doses of 8 mg BID, every 12 hours or 16 mg QD in the 
morning with matching placebo in the evening.  
Reference therapy, dosage and mode of administration:  
N/A 
Duration of treatment:  
Patients will receive up to 24 weeks of study drug 
Duration of study participation:  
Patients will participate in the study for up to approximately 32 weeks if exiting the study after the 4 
week Safety Follow-up (4-week Screening, 24-week Treatment, 4 week Safety Follow-up). Upon 
completion of the 24-week Treatment Period, patients will be eligible to either complete treatment 
and exit the study following the 4-week Safety Follow-up visit, or roll-over into a long-term open-
label extension study. 
Criteria for evaluation: 
Efficacy: 
The primary efficacy endpoint will be the relative change in SALT score for each dose regimen from 
baseline at Week 24. 
Secondary efficacy endpoints in each dose regimen include: 
 
Proportion of patients achieving at least a 90%, 75%, and 50% reduction in SALT score from 
baseline at Weeks: 
o  4, 8, 12, 16, 20, and 24 in the Treatment Period 
 
Absolute change in SALT scores from baseline at Weeks: 
o 4, 8, 12, 16, 20, and 24 in the Treatment Period 
 
Relative change in SALT scores from baseline at Weeks: 
o 4, 8, 12, 16, 20 and 24 in the Treatment Period 
 
Change in satisfaction of hair coverage as reported by patient  
Exploratory Endpoints in each dose regimen include:  
 
Change in patient’s eyebrows as measured by the patient’s Visual Analog Scale (VAS)  
 
Change in satisfaction of hair coverage quality as reported by patient  
 
 


CTP-543 
 
03 January 2019 
Protocol CP543.2002, Amendment 1  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
11 
 
Safety: 
Tolerability of CTP-543 will be assessed by evaluating adverse events, vital signs, concomitant 
medications, clinical laboratory and electrocardiogram results, as well as physical examinations. 
Statistical methods: 
Sample Size: 
A sample size of 25 patients (completers) per group provides adequate precision for the estimated 
dosing regimen difference for relative change in SALT score from baseline at Week 24.  Precision of 
the estimated difference is quantified by the width of the 90% confidence interval for the dosing 
regimen difference.   
Efficacy Analyses: 
The Efficacy Population will include all patients who receive study drug and have at least 
1 post-treatment SALT assessment.  For the primary efficacy endpoint and other continuous 
measures, a 90% confidence interval for the dosing regimen difference at Week 24 will be calculated 
using the t-distribution. 
Data will be summarized by dosing regimen (i.e., by treatment group).  Continuous measures will be 
summarized descriptively (mean, standard deviation, median, minimum value, and maximum value) 
and categorical measures will be presented as number and percentage.   
Additional details for statistical methods will be provided in the Statistical Analysis Plan. 
Tolerability Analyses: 
The Safety Population will include all patients who receive study drug.  Adverse events will be coded 
by system organ class and preferred term with the Medical Dictionary for Regulatory Activities.  
Concomitant medications will be summarized by World Health Organization Drug Dictionary 
Anatomical-Therapeutic-Chemical classification and preferred term.  Adverse events, vital sign 
measurements, physical examination findings, electrocardiogram, clinical laboratory information, and 
concomitant medications will be tabulated and summarized by dosing regimen.  By-patient listings 
will be provided for any deaths, serious adverse events, adverse events leading to study 
discontinuation, and adverse events leading to study drug interruption.   


CTP-543 
 
03 January 2019 
Protocol CP543.2002 
 
 
  
 
 
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY  
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Table 1: 
Schedule of Events: Treatment Period 
 
 
 
Event 
Screening 
Randomization1 
Treatment Period 
Safety Follow-Up 
Day -28 to Day -1 
(Visit 1) 
Day 12 
(Visit 2) 
Week 2, 6 
(Visit 3, 5) 
Week 4, 8 
(Visit 4, 6) 
Week 12 
(Visit 7) 
Week 16, 20 
(Visit 8, 9) 
Week 243  
(Visit 10) 
Week 284 
(Visit 11) 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility assessment 
X 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
 
X 
X 
Brief physical examination 
 
 
 
X 
X 
X 
 
 
Height  
X 
 
 
 
 
 
 
 
Weight 
X 
X 
 
X 
X 
X 
X 
X 
Pregnancy test5 
X 
X6 
 
X 
X 
X 
X 
 
Tuberculosis test 
X 
 
 
 
 
 
 
 
Clinical laboratory testing7 8 
X9 
X 
X 
X 
X 
X 
X 
X 
Lipid assessment10 
 
X 
 
 
X 
 
X 
X 
HBV and HCV test 
X 
 
 
 
 
 
 
 
12-lead electrocardiogram 
X 
X 
 
 
X 
 
X 
X 
Vital signs 
X 
X 
 
X 
X 
X 
X 
X 
Severity of Alopecia Tool assessment11 
X 
X 
 
X 
X 
X 
X 
 
Photographs12 
X 
X 
 
 
X 
 
X 
 
Visual Analog Scale (VAS) for Eyebrows 
 
X 
 
 
X 
 
X 
 
Patient Satisfaction Questions 
 
X 
 
 
 
 
X 
 
Dispense study drug 
 
X 
 
X 
X 
X 
 
 
Study drug accountability 
 
 
 
X 
X 
X 
X 
 
Adverse events13 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications13 
X 
X 
X 
X 
X 
X 
X 
X 
HBV= hepatitis B virus; HCV = hepatitis C virus 
1 Randomization/Day 1 may occur any time after Screening laboratory results are available and 
reviewed by the Investigator. 
2 All subsequent visits and week increments should be based on the date of Visit 2. All visit 
windows are ±3 days.  
3 Also serves as the Early Termination Visit for patient withdrawal in this period. 
4 The Safety Follow-Up Visit is intended for those patients who do not roll over into an open-
label extension and for patients who have been discontinued from the study and completed the 
Early Termination Visit (Week 24).   
5 Serum pregnancy test for females of childbearing potential only.  
6 Urine pregnancy test should be performed at the randomization visit. 
7 Includes hematology and serum chemistry.  
 8 Collected pre-dose, except on Visit 11. 
9 Will include thyroid stimulating hormone and hemoglobin A1c at Screening only. 
10 Includes total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. 
11 Should be performed by the same rater for the patient for the duration of the study. 
12 Sites will take photographs of patient’s scalps and eyebrow/eyelashes, if involved, to provide visual 
support of baseline SALT as well as potential SALT changes throughout the study. 
13 Collection is ongoing. 


CTP-543 
 
03 January 2019 
Protocol CP543.2002 
 
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CONFIDENTIAL & PROPRIETARY  
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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
1. 
SYNOPSIS ...................................................................................................................6 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................17 
4. 
INTRODUCTION ......................................................................................................18 
4.1. 
Overview of Alopecia Areata .....................................................................................18 
4.2. 
Rationale for the Study ...............................................................................................18 
4.2.1. 
Scientific Rationale .....................................................................................................18 
4.3. 
Preclinical Information for CTP-543 ..........................................................................20 
4.4. 
Clinical Information ....................................................................................................20 
4.4.1. 
Clinical Studies of CTP-543 .......................................................................................20 
5. 
ETHICS ......................................................................................................................23 
5.1. 
Institutional Review Board (IRB) ...............................................................................23 
5.2. 
Written Informed Consent ..........................................................................................23 
6. 
STUDY OBJECTIVES ..............................................................................................24 
6.3 
Study Design ...............................................................................................................24 
6.4 
Method of Treatment Assignment ..............................................................................25 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................26 
7.1. 
Patient Inclusion Criteria ............................................................................................26 
7.2. 
Patient Exclusion Criteria ...........................................................................................26 
7.3. 
Patient Withdrawal Criteria ........................................................................................28 
7.3.1. 
Patient Withdrawal Procedures ...................................................................................29 
7.4. 
Criteria for Study Termination ...................................................................................29 
8. 
DESCRIPTION OF STUDY TREATMENTS ..........................................................30 
8.1. 
Description of Treatments ..........................................................................................30 
8.2. 
Safety Criteria and Management for Stopping Doses ................................................30 
8.3. 
Treatment Compliance ................................................................................................31 
8.4. 
Study Drug Materials and Management .....................................................................31 
8.4.1. 
Physical Description of Study Drug ...........................................................................32 
8.4.2. 
Study Drug Packaging, Labeling, and Storage ...........................................................32 
8.4.3. 
Study Drug Preparation and Administration ..............................................................32 
8.4.4. 
Study Drug Return and Disposal ................................................................................33 


CTP-543 
 
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8.4.5. 
Study Drug Accountability .........................................................................................33 
8.5. 
Concomitant Medications and Procedures .................................................................33 
9. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................34 
9.1. 
Demographic Characteristics and Medical History ....................................................34 
9.2. 
Severity of Alopecia Tool (SALT) .............................................................................34 
9.3. 
Photographs ................................................................................................................35 
9.4. 
Visual Analog Scale (VAS) ........................................................................................35 
9.5. 
Patient Satisfaction Questions ....................................................................................35 
9.6. 
Vital Signs, Weight, and Height .................................................................................35 
9.7. 
Physical Examination .................................................................................................35 
9.8. 
Electrocardiogram .......................................................................................................36 
9.9. 
Clinical Laboratory Assessments ...............................................................................36 
9.10. 
Unscheduled Visit .......................................................................................................38 
10. 
ADVERSE EVENTS..................................................................................................39 
10.1. 
Definition of Adverse Event .......................................................................................39 
10.2. 
Evaluation of Adverse Events ....................................................................................39 
10.2.1. 
Serious Adverse Event ................................................................................................39 
10.2.2. 
Severity/Intensity ........................................................................................................41 
10.2.3. 
Relationship to Study Drug ........................................................................................41 
10.2.4. 
Duration ......................................................................................................................42 
10.2.5. 
Action Taken ..............................................................................................................42 
10.2.6. 
Outcome ......................................................................................................................42 
10.3. 
Follow-Up ...................................................................................................................42 
10.4. 
Pregnancy ...................................................................................................................42 
10.5. 
Recording Adverse Events .........................................................................................43 
10.6. 
Reporting Adverse Events ..........................................................................................43 
10.6.1. 
Reporting Serious Adverse Events .............................................................................43 
10.6.2. 
Reporting Urgent Safety Issues ..................................................................................44 
11. 
STATISTICAL METHODS .......................................................................................45 
11.1. 
Sample Size Rationale ................................................................................................45 
11.2. 
Endpoints ....................................................................................................................45 
11.2.1. 
Efficacy .......................................................................................................................45 
11.2.2. 
Safety ..........................................................................................................................45 
11.3. 
Analysis Populations ..................................................................................................45 


CTP-543 
 
03 January 2019 
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11.4. 
Analyses ......................................................................................................................45 
11.4.1. 
Disposition and Baseline Characteristics ....................................................................46 
11.4.2. 
Efficacy .......................................................................................................................46 
11.4.3. 
Study Drug Exposure ..................................................................................................46 
11.4.4. 
Safety ..........................................................................................................................46 
12. 
REGULATORY CONSIDERATIONS......................................................................49 
12.1. 
Good Clinical Practice ................................................................................................49 
12.2. 
Sponsor’s Responsibilities ..........................................................................................49 
12.3. 
Investigator’s Responsibilities ....................................................................................50 
12.4. 
Protocol Amendments ................................................................................................51 
12.5. 
Audits and Inspections ................................................................................................51 
12.6. 
Quality Control and Quality Assurance ......................................................................51 
13. 
DATA HANDLING AND RECORDKEEPING .......................................................53 
13.1. 
Confidentiality ............................................................................................................53 
13.2. 
Patient Data Protection ...............................................................................................53 
13.3. 
Data Collection ...........................................................................................................53 
13.4. 
Case Report Form Completion ...................................................................................54 
13.5. 
Database Management, Data Clarification, and Quality Assurance ...........................54 
13.6. 
Inspection of Records .................................................................................................54 
13.7. 
Retention of Records ..................................................................................................55 
14. 
PUBLICATION POLICY ..........................................................................................56 
15. 
LIST OF REFERENCES ............................................................................................57 
16. 
APPENDICES ............................................................................................................59 
16.1. 
Severity of Alopecia Tool (SALT) .............................................................................59 
16.2. 
Patient Satisfaction Questions ....................................................................................60 
16.2.1. 
Satisfaction of Hair Coverage Question .....................................................................60 
16.2.2. 
Satisfaction of Hair Coverage Quality Questions .......................................................61 
16.3. 
Patient Visual Analog Scale (VAS) for Eyebrows .....................................................62 
 
 
 


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LIST OF TABLES 
Table 1: 
Schedule of Events: Treatment Period .......................................................................12 
Table 2: 
Potency of CTP-543 in In Vitro Kinase Inhibition Assays .........................................19 
Table 3: 
Selected Hematologic Thresholds for Dose Interruption ...........................................31 
Table 4: 
Investigational Product ...............................................................................................32 
Table 5: 
Clinical Laboratory Assessments ...............................................................................37 
 
LIST OF FIGURES 
Figure 1: 
CP543.2002 Study Design ............................................................................................7 
Figure 2: 
Primary Analysis: Responders at Week 24 ................................................................21 
Figure 3: 
Primary Analysis: Responders by Visit ......................................................................21 
Figure 4: 
Study Design ...............................................................................................................24 
 
  


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
BID 
Twice daily dosing 
CFR 
Code of Federal Regulations 
CTCAE 
Common terminology criteria for adverse events 
CYP3A4 
Cytochrome P450 3A4 
DMC 
Data monitoring committee 
DMP 
Data Management Plan 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
JAK 
Janus kinase 
LLN 
Lower Limit of Normal 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
NDA 
New Drug Application 
PCS 
Potentially clinically significant 
QD 
Once daily dosing 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected for heart rate (Fridericia’s method) 
SALT 
Severity of Alopecia Tool 
STAT 
Signal transducers and activators of transcription 
TEAE 
Treatment-emergent adverse events 
ULN 
Upper Limit of Normal 
VAS 
Visual Analog Scale  


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4. 
INTRODUCTION 
4.1. 
Overview of Alopecia Areata 
Alopecia areata is an autoimmune disorder characterized by patches of non-scarring alopecia 
affecting scalp and body hair.  Alopecia areata is clinically heterogeneous, affects men and 
women, and has a prevalence rate of 0.1% to 0.2% of the United States population [Safavi 1992]. 
There is no preventative therapy or cure.  Alopecia areata often presents as a cyclical disorder 
marked by unpredictable periods of hair loss and spontaneous regrowth, and variation in the 
degree or pattern of hair loss gives rise to different subtypes of alopecia areata, such as patchy, 
ophiasis, totalis, or universalis.  Approximately 7% of patients have severe disease with almost 
complete hair loss and little or no regrowth [Villasante Fricke 2015].  Onset can occur at any age 
and affects both men and women over the course of their lifetime. Approximately 80% of 
alopecia areata patients experience the first episode of hair loss by 40 years of age and 40% by 
20 years of age [Villasante Fricke 2015].  Alopecia areata can have a psychological impact with 
high rates of depression [Sellami 2014] and anxiety reported, particularly in children and 
adolescents [Bilgic 2013], and therefore, psychological counseling is often recommended as part 
of the standard of care [Al-Mutairi 2011]. 
A cause for alopecia areata has not yet been identified, though as in other autoimmune disorders, 
genetic susceptibility and a wide array of environmental triggers are thought to be involved. 
Presently, treatments for alopecia areata include moderately effective intralesional corticosteroid 
injections or topicals, or aesthetic disguises such as makeup and wigs.  Currently, no existing 
therapies for alopecia areata have been approved by the United States Food and Drug 
Administration (FDA), indicating a significant unmet medical need.  
4.2. 
Rationale for the Study 
4.2.1. 
Scientific Rationale 
CTP-543 is a deuterated form of ruxolitinib (Jakafi), a selective JAK inhibitor that modulates 
immune response through reduced intracellular JAK1 and JAK2 signaling.  There is growing 
evidence that hair loss in AA may be mediated by cytotoxic T cell attack of the hair follicle after 
loss of immune privilege, and that this process may be regulated by upstream JAK signaling 
(Xing, 2014).   
The JAKs are intracellular tyrosine kinases that play a central role in the signaling of cytokine 
and growth factor receptors (Ghoreschi, 2009).  Cytokine-induced receptor conformation 
changes activate the JAKs and trigger phosphorylation of the 6-member signal transducers and 
activators of transcription (STAT) protein transcription factor family.  Upon phosphorylation, 
STATs dimerize and translocate to the nucleus to regulate gene transcription.  Therapies that 
inhibit cytokine signaling or downstream JAK signaling have demonstrated efficacy in 
autoimmune disorders such as psoriasis, psoriatic arthritis, and rheumatoid arthritis, and multiple 
JAK inhibitors are in development for autoimmune disorders such as atopic dermatitis, systemic 
lupus erythematosus and others (Levy, 2015). 
In nonclinical pharmacology testing, it was confirmed that CTP-543 inhibited cytokine-
stimulated phosphorylation of signal transducer and activator of transcription (STAT) proteins in 
human cells, suggesting that suppression of JAK/STAT signaling is the primary mechanism of 


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action for CTP-543.  In in vitro kinase inhibition assays, the target potency and selectivity profile 
of CTP-543 for the JAK kinases JAK1, JAK2, JAK3 and Tyk2 was as shown in Table 2.  
Table 2: 
Potency of CTP-543 in In Vitro Kinase Inhibition Assays 
Enzyme 
Inhibition of JAK Kinase 
Activity  
IC50 (nM) 
JAK1 
4.7 
JAK2 
20 
JAK3 
1335 
Tyk2 
37 
Based on the data for CTP-543 summarized above, and published clinical data for other JAK 
inhibitors, including ruxolitinib, baricitinib and tofacitinib (Xing, 2014; Craiglow, 2014; 
Mackay-Wiggan, 2016; Jabbari et al, 2015; Harris 2016; Crispin, 2016; Liu, 2018), JAK 
inhibition may represent a viable therapeutic approach to treating AA, thus supporting Concert’s 
development of CTP-543 as a potential oral treatment for AA. 
Concert Pharmaceuticals is currently conducting a Phase 2 study CP543.2001, “A Double-Blind, 
Randomized, Placebo Controlled Study to Evaluate the Safety and Efficacy of CTP-543 in Adult 
Patients with Moderate to Severe Alopecia Areata”.   
Study CP543.2001 is a double-blind, randomized, placebo-controlled trial of approximately 125 
adults with moderate-to-severe alopecia areata.  Patients were sequentially randomized to receive 
one of three doses of CTP-543 (4, 8, 12 mg twice daily) or placebo for 24 weeks. 
Recently, interim top line analysis was performed for the 4 and 8 mg cohorts.  The primary 
efficacy endpoint in the 8 mg twice-daily cohort was met with 47% of patients achieving a  
≥ 50% reduction in their overall SALT score from baseline compared to placebo (p<0.001).  In 
light of these data, this current study will compare the known effect established for 8 mg BID 
with a once daily equivalent dose, 16 mg QD. 
Dosing Regimen Rationale 
Analyses suggest that across acute and chronic disease states, reducing dosage frequency from 
multiple dosing to QD dosing may improve adherence to therapies among patients, and may 
result in subsequent decreases in health care costs (Srivastava, 2013).  
Based on the established effect for 8 mg BID, a randomized, parallel-group study will be 
conducted to compare tolerability and efficacy of 8 mg BID with a once daily equivalent dose of 
16 mg QD. 
Patients, investigators, and site personnel will be unaware of the active drug dosing regimen to 
minimize bias in the evaluation of study endpoints.  
 




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Figure 2: 
Primary Analysis: Responders at Week 24 
 
For the 4 mg cohort, 21% of patients achieved a ≥ 50% reduction in their overall SALT score 
from baseline, however these differences were not significantly different from placebo. In the 
primary analysis, the response observed in the 8 mg twice-daily dose was significantly different 
than the 4 mg twice daily dose (p < 0.05) (Figure 3). The average baseline SALT score across all 
patients enrolled in the trial was approximately 88.  
Figure 3: 
Primary Analysis: Responders by Visit 
 
CTP-543 was generally well tolerated and there have been no serious adverse events reported.  
The most common adverse events reported across treatment groups (4 mg, 8 mg, and placebo) 


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were headache, upper respiratory tract infection, cough, acne and nausea. For the upper 
respiratory tract infections, there was a higher incidence in the placebo group. In terms of 
hematologic changes, there were only 3 incidents of Grade 3 or 4 changes and these 3 cases were 
distributed equally across the dose groups including placebo. 
The 12 mg dosing cohort is currently ongoing.  


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5. 
ETHICS 
The procedures set out in this study protocol, pertaining to the conduct, evaluation and 
documentation of this study, are designed to ensure that the Sponsor and the Investigator abide 
by Good Clinical Practice (GCP), including but not limited to Title 21 Code of Federal 
Regulations (CFR) Parts 50, 56, and 312, and the International Conference on Harmonisation 
(ICH) guidelines and directives.  Compliance with these regulations also constitutes compliance 
with the ethical principles described in the current revision of the Declaration of Helsinki and 
applicable local regulatory requirements and law.   
The Investigator is responsible for protecting the rights, safety, and welfare of patients under 
his/her care, and for the control of the medications under investigation.  All ethical, regulatory, 
and legal requirements must be met before the first patient is enrolled in the study. 
5.1. 
Institutional Review Board (IRB) 
The Institutional Review Board (IRB) will meet all FDA requirements governing IRBs according 
to CFR, Title 21, Part 56. The Investigator (or designee) must submit this study protocol and any 
amendments, the Sponsor’s approved informed consent form(s) (ICF), patient information 
sheets, patient recruitment materials, and other appropriate documents to the IRB for review and 
approval. Following review of the submitted materials a copy of the written and dated 
approval/favorable opinion will be forwarded to the Sponsor (or designee).  
Any advertisements used to recruit patients for the study will be reviewed by the Sponsor and the 
IRB prior to use. 
5.2. 
Written Informed Consent 
Prior to performing any study-related activities under this protocol, including screening tests and 
assessments, written informed consent with the approved ICF must be obtained from the patient.  
The ICF, as specified by the clinical site’s IRB, must follow the Protection of Human Subjects 
regulations listed in the Code of Federal Regulations, Title 21, Part 50. The background of the 
proposed study, the procedures, the benefits and risks of the study, and that study participation is 
voluntary must be explained to the patient.  The patient must be given sufficient time to consider 
whether to participate in the study.  
A copy of the ICF, signed and dated by the patient, must be given to the patient.  Confirmation of 
a patient’s informed consent must also be documented in the patient’s source documentation 
prior to any testing under this protocol, including screening tests and assessments. The original 
signed consent form will be retained with the study records. 
All ICFs used in this study must be approved by the appropriate IRB and by the Sponsor. The 
ICF must not be altered without the prior agreement of the relevant IRB and the Sponsor. 


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6. 
STUDY OBJECTIVES 
The overall objective of the study is to compare the efficacy and tolerability of a 16 mg total 
daily dose of CTP-543 utilizing two different dosing regimens in adult patients with chronic, 
moderate to severe alopecia areata. 
The secondary/exploratory objectives of the study will be to assess the patient reported outcomes 
of hair coverage and hair coverage quality. 
6.3 
Study Design 
This is a randomized, parallel group multicenter study to evaluate the efficacy and tolerability of 
two dosing regimens of CTP-543 (8 mg BID vs 16 mg QD), in adult patients with chronic, 
moderate to severe alopecia areata.  Patients will be between 18 and 65 years of age and 
experiencing an episode of alopecia areata lasting at least 6 months and not exceeding 10 years, 
with at least 50% hair loss as measured by the SALT at Screening and Baseline, and are not 
concurrently being treated for alopecia areata with other treatments that might affect hair 
regrowth or immune response.  Up to approximately 75% of alopecia areata patients with 
alopecia totalis or universalis, and no more than 10% with only alopecia ophiasis will be 
enrolled.  
Patients may be screened up to 28-days prior to initiation of study drug.  The Treatment Period is 
a 24-week dosing period where patients will be randomized to receive either CTP-543 8 mg BID, 
or CTP-543 16 mg QD and will be analyzed for the primary endpoints of the study.  To 
minimize bias in the evaluation of study endpoints, patients, investigators, and site personnel will 
be unaware of the active drug dosing regimen by administering one 16 mg tablet and one placebo 
tablet 12 hours apart from each other for the 16 mg QD study group.    
 
Figure 4: 
Study Design 
 
Patients will provide informed consent prior to completing any screening procedures.   


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Patients will take the first dose of study drug in the clinic on Day 1. Patients will be instructed to 
take study drug every 12 hours.  Patients should dose study drug in the clinic on all Study Visit 
Days after clinical laboratory blood draws are completed. 
Patient safety will be monitored throughout the trial.  The subject will be tested to ensure they do 
not have the Hepatitis B or C virus, thyroid function abnormalities or latent or active 
Tuberculosis, during the screening period.  During the first 8 weeks of the Treatment Period, 
hematology and serum chemistry will be conducted every 2 weeks, followed by an assessment 
every 4 weeks thereafter through completion of the study at 24 weeks. Lipid levels will be 
assessed every 12 weeks throughout the Treatment Period.  Significant cytopenias or other 
hematologic abnormalities will be managed by severity through dose interruption, or 
discontinuation, and signs and symptoms of infection will be closely monitored and treated 
promptly.  Patients who experience intolerable symptoms during treatment may discontinue the 
study at the discretion of the Investigator.  Patients may withdraw consent at any time. 
The Treatment Period will last 24 weeks to assess BID and QD doses, in parallel.  Assessment of 
treatment response with SALT for efficacy will occur at 4, 8, 12, 16, 20 and 24 weeks.   
Upon completion of the 24-week Treatment Period patients will be eligible to either complete 
treatment and exit the study following the safety follow-up visit, or roll-over into a long-term 
open-label extension study. 
Approximately 60 patients are planned to be enrolled in the study; approximately 30 patients per 
treatment arm.   
6.4 
Method of Treatment Assignment 
Patients meeting screening criteria will continue to the Day 1 Randomization Visit for review of 
eligibility and baseline assessments, including SALT assessment, physical examination, clinical 
laboratory assessments, vital signs, and electrocardiogram.  Patients meeting all eligibility 
criteria will be randomized to 1 of 2 CTP-543 treatment arms (8 mg BID or 16 mg QD). 
Randomization will also be stratified by classification of alopecia areata subtype into one of the 
following three categories: 1) alopecia areata, 2) alopecia totalis or alopecia universalis, or 3) 
alopecia ophiasis.  


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7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
Patients eligible for enrollment in the study must meet all of the following inclusion criteria and 
none of the exclusion criteria. 
7.1. 
Patient Inclusion Criteria 
1. Written informed consent, and authorization for release and use of protected health 
information. 
2. Between 18 and 65 years of age, inclusive, at the time of informed consent. 
3. Definitive diagnosis of alopecia areata. Totalis or universalis and ophiasis subtypes must 
have a current episode lasting at least 6 months and not exceeding 10 years at the time of 
Screening. Total disease duration greater than 10 years is permitted. 
4. At least 50% scalp hair loss, as defined by a SALT score ≥50, at Screening and Baseline.  
5. If of reproductive age, willing and able to use a medically highly effective form of birth 
control during the study and for 30 days following last dose of study medication.  
Examples of medically highly effective forms of birth control are: 
a. Surgical sterility (via vasectomy, hysterectomy or bilateral ligation) or 
post-menopausal females 
b. Sexual partner is sterile, or of the same sex 
c. Implants of levonorgestrel in females 
d. Oral contraceptive (combined or progesterone only) in females 
e. Double-barrier method (any combination of physical and chemical methods) 
f. Intrauterine device in females or other method with published data showing that the 
lowest expected failure rate is less than 1% per year (not all intrauterine devices meet 
this criterion). 
6. Willing to comply with the study visits and requirements of the study protocol. 
7.2. 
Patient Exclusion Criteria 
1. History or presence of hair transplants. 
2. Treatment with other medications within 1 month of Screening or during the study that 
may affect hair regrowth or immunosuppression, such as: corticosteroids administered 
orally, by injection, or applied to areas of skin affected by alopecia; topical application of 
anthralin, squaric acid, diphenylcyclopropenone, or minoxidil.  
3. Treatment with systemic immunosuppressive medications including but not limited to 
methotrexate, cyclosporine, and azathioprine; chloroquine derivatives; JAK inhibitors 
within 3 months of Screening (ruxolitinib, tofacitinib, etc), etanercept; or biologics 
(adalimumab, atlizumab, canakinumab, certolizumab, fontolizumab, golimumab, 
infliximab, mepolizumab, rituximab, secukinumab, tocilizumab, ustekinumab) within 
6 months of Screening. 
4. Active scalp inflammation, psoriasis, or seborrheic dermatitis requiring topical treatment 
to the scalp, significant trauma to the scalp, or untreated actinic keratosis on the scalp at 
Screening and/or Baseline. 


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5. Known history of moderate to severe androgenic alopecia or pattern hair loss prior to 
alopecia areata. 
6. Unwilling to maintain a consistent hair style, including shampoo and hair products 
(including hair dye, process, and timing to visits), and to refrain from weaves or 
extensions throughout the course of the study, or shaving of scalp hair for at least 2 
weeks prior to a SALT assessment. 
7. Use of adhesive wigs, other than banded perimeter wigs, during the study. 
8. History of a lymphoproliferative disease or malignancy with recurrence within the 
5 years prior to the first study drug administration, other than non-melanoma skin cancer 
or cervical carcinoma.  Patients with 3 or more basal or squamous cell carcinomas 
diagnosed in the past 2 years are excluded.  
9. Atypical nevi or cutaneous lesions that are undiagnosed but suspicious for malignancy. 
10. History of solid organ or hematological transplantation. 
11. Systemic or invasive infection, as evidenced by fever, inflammation, or systemic signs of 
illness (e.g., malaise, myalgia, specific symptoms like pain, shortness of breath) within 2 
weeks prior to first dose of study drug. 
12. Abnormal levels of thyroid stimulating hormone at Screening, defined as <0.9 x the 
lower limit of normal (LLN) and >1.2 x the upper limit of normal (ULN). 
13. Screening labs outside the normal range for parameters associated with potential risk for 
treatment under investigation. This will include but is not limited to: 
a. Platelets ≤120  x 109/L or ≥600 x 109/L 
b. Absolute neutrophil count ≤1.5 x 109/L 
c. Hemoglobin levels ≤11 g/dL for females, or hemoglobin levels ≤12. 5 g/dL for 
males  
14. Screening blood glucose levels of hemoglobin A1c ≥6.5% (48 mmol/mol). 
15. Abnormal liver function at Screening, defined as ≥2 × ULN of any 3 or more of the 
following: serum alanine transaminase, serum aspartate transaminase, serum alkaline 
phosphatase, total bilirubin. 
16. Abnormal renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 using 
the MDRD equation). 
17. At screening, any active or previous Hepatitis B or C infection, or known human 
immunodeficiency virus infection. 
18. Vaccination with herpes zoster vaccine or any live virus vaccine within 6 weeks prior to 
Screening or during the study. 
19. Positive TB test, or history of incompletely treated or untreated tuberculosis. 
NOTE: In cases where performance of a QuantiFERON-TB Gold test is not possible, 
testing with a Tuberculin Skin Test (TST) may be an option after consultation with the 
Medical Monitor.  If the TST is negative, patients can be randomized into the study, 
assuming they meet all other inclusion and none of the exclusion criteria.  If results are 


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equivocal, or there is reason to believe the result is a false positive, a QuantiFERON-TB 
Gold must be performed before a subject is eligible for randomization.   
20. Prolonged QT or heart-rate corrected QT (QTc) interval with Fridericia’s correction 
(QTcF) > 450 msec for males or QTcF > 470 msec for females. 
21. History of alcohol, medication, or illicit drug abuse within 1 year before the first dose of 
study drug. 
22. Females who are nursing, pregnant, or planning to become pregnant while in the study, 
and for 30 days after last dose of study medication. 
23. Participation in another investigational study within the greater of 4 weeks or 5 half-lives 
of an investigational medication prior to screening or during the study. 
24. Use of strong CYP3A4 inhibitors (such as, but not limited to clarithromycin, conivaptan, 
grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, 
nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, 
or fluconazole). 
25. Use of strong CYP3A4 inducers (such as, but not limited to barbiturates, carbamazepine, 
efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, 
phenytoin, pioglitazone, rifabutin, rifampin, St. John’s Wort, or troglitazone).  
26. Donation of blood within a month of first dose of study drug or at any point throughout 
the study and for 30 days after last dose of study medication. 
27. Clinically significant medical condition, psychiatric disease, or social conditions that, as 
determined by the Investigator, may unfavorably alter the risk-benefit of study 
participation, adversely affect study compliance, or confound interpretation of study 
results.  
7.3. 
Patient Withdrawal Criteria 
All patients are free to withdraw from participation in the study at any time, for any reason, and 
without prejudice.  The Investigator must withdraw any patient from the study if the patient 
requests to stop participating in the study.  The Investigator, Sponsor, or its designee may 
remove a patient from the study at any time and for any reason.  In addition, patients should be 
withdrawn if they: 
 Experience an intolerable adverse event 
 Require a medication that is prohibited by the protocol 
 Do not follow guidelines specified in the protocol (ie, is noncompliant with protocol 
procedures or study treatment administration) 
 Any medically appropriate reason or significant protocol violation, in the opinion of 
the Investigator 
 Are lost to follow up 
Patients who withdraw or are withdrawn from the study will not be replaced. 


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7.3.1. 
Patient Withdrawal Procedures 
A patient who prematurely discontinues study treatment/study participation should have all 
Week 24 assessments performed as an Early Termination Visit, and return for the Safety Follow-
up Visit (See Table 3). The Safety Follow-Up Visit may be waived by the Sponsor in instances 
where patients have discontinued dosing prior to the Early Termination Visit on a case-by-case 
basis. 
If a patient terminates early from the study, the Investigator will record the reason(s) for early 
termination on the relevant electronic case report form (eCRF).  The specific reason for the 
withdrawal should be carefully documented on the eCRF.   
Patients who require a dose interruption lasting more than 21 consecutive days for management 
of adverse events should be discontinued from the study. Adverse events resulting in patient 
early termination will be followed to the satisfactory resolution and determination of outcome, as 
ascertained by the Investigator (and/or Sponsor, or its designee); See Section 10 Adverse Events.  
The data will be recorded on the appropriate eCRF. 
7.4. 
Criteria for Study Termination 
There are no prospective stopping criteria for this study. The Sponsor reserves the right to 
discontinue the study at any time for clinical or administrative reasons.   
Any termination required by the Sponsor must be implemented by the Investigator, if instructed 
to do so, in a time frame that is compatible with the patient’s well-being. 
 


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8. 
DESCRIPTION OF STUDY TREATMENTS 
8.1. 
Description of Treatments 
In the Treatment Period, patients will be stratified by alopecia areata subtype and randomized to 
1 of 2 CTP-543 treatment arms in a 1:1 ratio.  Treatments arms will include:  
 CTP-543 8 mg BID (every 12 hours)  
 CTP-543 16 mg QD (16 mg in the morning and placebo tablet in the evenings) 
8.2. 
Safety Criteria and Management for Stopping Doses 
Patients who experience hematologic adverse events as described in Table 3 or adverse events 
that may reflect an unfavorable risk-benefit profile may have their dose interrupted or be 
discontinued from the study at the discretion of the Investigator. The Medical Monitor should be 
consulted whenever possible prior to decisions for dose interruption or patient discontinuation 
from the study.  
Patients who require a dose interruption lasting more than 21 consecutive days will be 
discontinued from the study.  
Patients who are discontinued from the study should undergo an Early Termination Visit and 
subsequent Safety Follow-up Visit as appropriate per Section 7.3.1 Patient Withdrawal 
Procedures, and associated adverse events followed as described in See Section 10 Adverse 
Events. 
Hematology and serum chemistry parameters will be assessed every 2 weeks for the first 8 
weeks of the Treatment, and every 4 weeks thereafter for the remainder of the study.  Prior to 
dose interruption, hematology parameters should be confirmed with repeat testing at an interval 
deemed appropriate by the Investigator (e.g., at the next protocol-defined visit or an Unscheduled 
Visit), except in severe cases where immediate interruption of dosing is necessary for the safety 
of the patient. Blood draws confirming dose interruption criteria should occur prior to the 
first daily dose on the day of draw.  
Dose interruption requirements for hematologic abnormalities are provided below.  However, 
less significant changes may warrant clinical intervention and the Investigator should use his/her 
best clinical judgment when considering a dose interruption whether for singular or aggregate 
hematology results above the limits provided in Table 3, or for other clinical signs, symptoms, or 
considerations that suggest dose interruption is in the best interest of the patient.  
 
 




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8.4.1. 
Physical Description of Study Drug 
Study drug will be CTP-543, a deuterated analog of ruxolitinib or an identical placebo tablet.  
Details regarding formulation and dosage are presented in Table 4.  
 
Table 4: 
Investigational Product 
 
Investigational Product 
(CTP-543 or Placebo) 
Product Name: 
CTP-543  
Dosage Form: 
Tablet 
Dosage Strength of CTP-543 
8 mg,16 mg or placebo 
Route of Administration 
Oral 
Physical Description 
White, capsule-shaped tablets 
8.4.2. 
Study Drug Packaging, Labeling, and Storage 
CTP-543 active and placebo tablets will be packaged and labeled by an appropriately qualified 
vendor. Each patient will receive a dosing card at each 4 week study visit.  Details of the 
packaging, labeling and dispensing instructions can be found in the Pharmacy Manual. 
The label(s) for the investigational product will include sponsor name, address and telephone 
number, the protocol number, investigational product name, dosage form, amount of 
investigational product per container, lot number, unique dosing card number, storage 
conditions, and required caution statements and/or regulatory statements, as applicable.  
Additional information may be included on the label as applicable per local regulations. 
Adequate supplies of study drug will be provided to each site. Study drug should be stored in the 
original package between 15°C to 25°C (59°F to 77°F), as stated on the product label, in a 
secure, temperature-monitored, locked area, under the responsibility of the Investigator or other 
authorized individual until dispensed to the patients. 
Study drug dispensed to patients should be stored in the original package at room temperature as 
stated on the package label.  No special handling procedures are required. 
8.4.3. 
Study Drug Preparation and Administration 
No study drug preparation is required.  Patients will take the first dose of study drug in the clinic 
on Day 1 and will be instructed to take study drug every 12 hours.  Patients should dose study 
drug in the clinic on all Study Visit Days after clinical laboratory blood draws are completed.  
Study drug should be taken at approximately the same times each day, with water, and 
consistently with or without meals.  Patients should be instructed to take study drug as prescribed 
according to the Week, Day, and Time of day designations in the dosing card.  If a dose is 
missed, the patient should skip the missed dose and resume dosing at the next scheduled dose. 
The patient should not take two doses at the same time.  Deviations from prescribed dosing 
should be discussed at each visit for assessment of compliance and retraining when necessary. 


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8.4.4. 
Study Drug Return and Disposal 
The Sponsor (or designee) will review with the Investigator and relevant site personnel the 
process for study treatment return, disposal, and/or destruction, including responsibilities for the 
site versus the Sponsor (or designee).  Specific requirements for destruction or return are defined 
in the Pharmacy Manual. 
8.4.5. 
Study Drug Accountability 
To satisfy regulatory requirements regarding drug accountability, all study drug will be 
reconciled in full.  The Investigator or designee must maintain accurate records of the receipt of 
study drug, including date received, lot number, amount received, condition of the package, and 
the disposition of study drug. 
Current dispensing records will also be maintained, including the date and amount of medication 
dispensed to each individual patient.  Returned study drug records will be maintained and final 
study drug reconciliation will also be recorded for each patient. 
8.5. 
Concomitant Medications and Procedures 
All medications, including over-the-counter therapies (e.g., vitamins, herbal, and nutritional 
supplements), taken at the time of the Screening Visit through the Follow-Up Visit will be 
recorded in the patient’s source documentation and documented in the eCRF. 
Any concomitant medication deemed necessary for the wellbeing of the subject may be given at 
the discretion of the Investigator.  Use of medications that are prohibited per protocol will 
require patient withdrawal from the study. 
The following treatments are not permitted during the study: 
 Medications that may affect hair regrowth or immunosuppression (such as: 
corticosteroids administered orally, by injection, or applied to areas of skin affected 
by alopecia; topical application of anthralin, squaric acid, diphenylcyclopropenone, or 
minoxidil; 
 Treatment with systemic immunosuppressive medications including but not limited to 
methotrexate, cyclosporine, and azathioprine; chloroquine derivatives; Janus kinase 
inhibitors (ruxolitinib, tofacitinib, etc), etanercept; or biologics (adalimumab, 
atlizumab, canakinumab, certolizumab, fontolizumab, golimumab, infliximab, 
mepolizumab, rituximab, secukinumab, tocilizumab, ustekinumab); 
 Use of strong CYP3A4 inhibitors (such as, but not limited to clarithromycin, 
conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, 
mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, 
telithromycin, voriconazole, or fluconazole); 
 Use of strong CYP3A4 inducers (such as, but not limited to barbiturates, 
carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, 
phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John’s Wort, or 
troglitazone).  


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9. 
STUDY ASSESSMENTS AND PROCEDURES 
The schedule of assessments and procedures is presented in  
Table 1 should be referenced for details regarding the collection of each assessment at each visit. 
9.1. 
Demographic Characteristics and Medical History 
Demographic characteristics (i.e., sex, ethnic origin, date of birth, and calculated body mass 
index) will be collected at the Screening Visit, between Day -28 and -1, and detailed on the 
eCRF.  
The patient’s alopecia areata will be classified by the Investigator into one of three categories 
defined for this study: 
1) Alopecia areata: patchy type hair loss, 
2) Alopecia totalis or universalis: complete hair loss on the scalp with or without body hair 
loss, 
3) Alopecia ophiasis: band-like hair loss limited to the periphery of the scalp along the back 
of the hair line in the occipital region and possibly extending over each ear in temporal 
regions. 
Key criteria that distinguish alopecia areata from other forms of hair loss may include abrupt 
onset of disease, a history of recurrence and spontaneous remission, response to topical or 
intralesional steroid treatment, and distribution of hair loss pattern. Care must be taken during the 
evaluation to assess for other causes of hair loss such as trichotillomania, or scarring alopecia 
and other forms of non-scarring alopecia. Evidence of thinning hair should be distinguished from 
pattern hair loss or telogen effluvium and evidence of inflammation should be investigated to 
rule out infection, as appropriate. 
Thorough medical history, including current medications, nail and facial hair involvement, co-
morbidities, serious infection history and exposure risk, including HIV, as well as history or 
vaccination against herpes zoster will be collected at the Screening Visit, and at the 
Randomization Visit on Day 1. 
Medical history should be thoroughly probed for potential exposure to serious infections such as 
HIV, history or vaccination against herpes zoster, as well as cancer risk due to the potential 
immunosuppressive properties of CTP-543 and known adverse events associated with JAK 
inhibitors. 
9.2. 
Severity of Alopecia Tool (SALT) 
The SALT score was introduced as part of investigative guidelines published by the National 
Alopecia Areata Foundation [Olsen 2004].  The SALT is a measure of hair absence that 
quantifies the amount of scalp surface without hair in a pre-specified quadrant of the scalp (right 
side, top, left side, back), that is further summed after applying a quadrant-specific multiplier 
indicative of scalp surface area contribution, to provide an overall score of total hair loss.  The 
SALT assessment will occur via live examination of the patient during clinic visits.   
SALT will be used to determine efficacy for the study.  To reduce variability, one rater should 
perform the SALT assessment for the patient for the duration of the study.  All investigators 
using the SALT should be trained prior to use.  Please consult the associated Site Operations 


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Manual for additional details regarding SALT scoring and training requirements for this study. 
An example of the SALT assessment tool is provided in Appendix 16.1.  
9.3. 
Photographs 
Sites will take photographs of their patient’s scalps to provide visual support of Baseline 
assessment of SALT as well as potential changes in SALT scores throughout the study. No 
analyses of photographs will occur.  The photographs will correspond to the 4 defined quadrants 
of the SALT assessment and will be taken when SALT assessments are performed.  
For those patients with eye and nail involvement in their alopecia areata phenotype, a photograph 
of the eyes and hands for eyelash/eyebrow and nail involvement, respectively, will be taken to 
document potential changes throughout the study compared to Baseline. No formal analyses of 
photographs will occur.  
9.4. 
Visual Analog Scale (VAS) 
The visual analog scale is a scale of continuous measure initially developed for pain that has 
been used in a variety of clinical settings where the endpoint of interest is based on a subjective 
perception.  The visual analog scale is a distinct 100 millimeter line anchored on the left end at 
full degree of impairment and on the right end at no degree of impairment, where indication of 
the degree of impairment perceived at the time of assessment is captured by marking the 
appropriate position on the line between the anchor points. The measured distance of the mark 
from the left anchor will be recorded in millimeters.  
As specified in the Schedule of Events, patients will rate his/her eyebrows on the patient VAS. 
The left and right anchor points for the patient’s eyebrow VAS are “None” and “Full”, 
respectively.  The patient VAS will measure the patient’s eyebrows at the time of completion.  
An example of the patient VAS is provided in Appendix 16.3. 
9.5. 
Patient Satisfaction Questions  
Questions regarding the patient’s assessment of satisfaction with hair coverage will be performed 
as indicated in the schedule of assessments (see Section 16.2).  
9.6. 
Vital Signs, Weight, and Height 
Vital signs will be measured after the patient has been in a supine or semi-supine position for at 
least 5 minutes and will include blood pressure, pulse rate, respiratory rate, and oral temperature.   
Weight will be measured per institution standard of care. Patients should wear light clothing and 
remove his/her shoes before weight is measured.  Height will be measured per institution 
standard of care, after the patient has removed his/her shoes. Height will only be measured at the 
Screening Visit. Weight and vital signs will be measured at each study visit according to the 
Schedule of Events. Weight and height will be used to calculate the patient’s body mass index at 
Screening. Weight and height will be converted as needed to kilograms and centimeters, 
respectively, prior to statistical analyses. 
9.7. 
Physical Examination 
A complete physical examination will include an examination of all major organ systems, with 
an emphasis on assessing for active signs and symptoms of infection, and will be performed as 


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indicated in the Schedule of Events. Brief physical examinations including abdominal palpation, 
and head, eyes, ears, nose and throat assessment will be performed at all other intermediate visits 
as specified in Table 1.  
9.8. 
Electrocardiogram 
Twelve-lead electrocardiograms will be performed after the patient has rested in a supine or 
semi-supine position for at least 5 minutes.  Individual parameters including heart rate, PR, QT, 
QTcF, QRS, and RR intervals will be collected. Repeat electrocardiograms (if deemed 
necessary) should be performed at least 5 minutes apart. The Investigator should indicate review 
of the electrocardiogram reports throughout the study by signing and dating each report.   
9.9. 
Clinical Laboratory Assessments 
Clinical laboratory assessments are presented in Table 5 Clinical laboratory samples should be 
collected at the beginning of each clinic visit and prior to the first daily dose on all Study Visit 
Days.  
The results of clinical laboratory tests conducted at the Screening Visit must be assessed by the 
Investigator to determine each patient’s eligibility for participation in the study.  The Investigator 
should indicate review of the laboratory reports throughout the study by signing and dating each 
report.  
All clinical laboratory results that fall outside the reference range will be interpreted by the 
Investigator as Abnormal, not clinically significant, or Abnormal, clinically significant. 
Laboratory results deemed Abnormal, clinically significant will be recorded as an adverse event 
in the eCRF and should be fully investigated and repeated for verification.  Clinically significant 
laboratory abnormalities indicative of hematologic or other effects requiring intervention should 
be discussed with the Medical Monitor. Additional tests and evaluations required to establish the 
significance or etiology of a clinically significant abnormal result or to monitor the course of an 
adverse event should be obtained when clinically indicated.  Whenever possible, the etiology of 
the clinically significant abnormal findings will be documented on the eCRF.   
Any significant laboratory abnormalities that are either serious or unexpected will be promptly 
reported to the Sponsor.  Any additional relevant laboratory results obtained by the Investigator 
during the course of this study will be reported to the Sponsor or designee. 


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Table 5: 
Clinical Laboratory Assessments 
Hematology 
Chemistry 
Serum Pregnancy 
Complete blood count  
Absolute neutrophil count 
Absolute eosinophil count 
Platelet count 
White blood cell count with 
differential 
Absolute reticulocyte count  
Hemoglobin A1c 
Alanine aminotransaminase  
Albumin  
Alkaline phosphatase  
Amylase  
Aspartate aminotransaminase  
Total bilirubin 
Direct bilirubin 
Indirect bilirubin 
Blood urea nitrogen  
Calcium 
Carbon dioxide  
Chloride  
Creatinine 
Creatine kinase  
Glucose 
Lipase 
Total protein 
Phosphorus 
Potassium 
Sodium 
Uric Acid 
Human chorionic gonadotropin 
(females of childbearing potential 
only) 
 
 
 


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Table 5: 
Clinical Laboratory Assessments (Continued) 
Serology 
Lipids 
Other 
Hepatitis B virus  
Hepatitis C virus  
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
triglycerides 
Tuberculosis Test  
- QuantiFERON-TB Gold (QFT) 
-Tuberculin skin test (TST), also 
called purified protein derivative 
or PPD (with MM consultation) 
Thyroid stimulating hormone 
9.10. 
Unscheduled Visit 
In addition to regularly scheduled protocol visits, an Unscheduled Visit may be conducted to 
ensure appropriate safety monitoring or follow-up of the patient, at the discretion of the 
Investigator. For example, an Unscheduled Visit may be scheduled to monitor potential or actual 
clinically meaningful safety laboratory results, for confirming hematology results to support dose 
interruption or resumption of dosing thereafter, or for other clinical signs, symptoms, or 
considerations that warrant additional safety follow-up. Only those criteria requiring additional 
monitoring should be performed at an Unscheduled Visit. An Unscheduled Visit will not replace 
regularly scheduled protocol visits.  


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10. 
ADVERSE EVENTS 
10.1. 
Definition of Adverse Event 
An adverse event is any untoward medical occurrence that may appear or worsen in a patient 
during the course of a study.  It may be a new intercurrent illness, a worsening concomitant 
illness, an injury, or any concomitant impairment of the patient’s health, including laboratory test 
values, regardless of etiology.  Any worsening (ie, any clinically significant adverse change in 
the frequency or intensity of a pre-existing condition) should be considered an adverse event.  A 
diagnosis or syndrome should be recorded on the adverse event page of the eCRF rather than the 
individual signs or symptoms of the diagnosis or syndrome. A worsening of the condition under 
study, alopecia areata, will not be reported as an adverse event.  
All patients will be monitored for adverse events during the study.  Assessments may include 
monitoring of the following parameters:  the patient’s clinical symptoms, laboratory, physical 
examination findings, or findings from other tests and/or procedures. 
An adverse event reported after informed consent, but before the first dose of study drug (i.e., 
Day 1), will be considered a pretreatment adverse event and will be captured on the eCRF.  
Adverse events will be considered treatment-emergent if the onset is after the first dose of study 
drug or if an ongoing Adverse Event worsens after dosing is initiated.   
An abnormal laboratory value is considered to be an adverse event if the abnormality: 
 results in discontinuation from the study; 
 is judged by the Investigator to be of significant clinical importance requiring 
treatment, modification/interruption of investigational product dose, or any other 
therapeutic intervention 
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event.   
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the adverse event eCRF.  If the abnormality was not a part of 
a diagnosis or syndrome, then the laboratory abnormality should be recorded as the adverse 
event.  If possible, the laboratory abnormality should be recorded as a medical term and not 
simply as an abnormal laboratory result (e.g., record thrombocytopenia rather than decreased 
platelets). 
10.2. 
Evaluation of Adverse Events 
A qualified Investigator will evaluate all adverse events as to seriousness, severity/intensity, 
relationship to study drug, duration, action taken, and outcome.   
10.2.1. 
Serious Adverse Event  
A serious adverse event is an adverse event, as per Title 21 CFR 312.32 and ICH E2A.II.B that 
fulfills the following criteria: 
 Is fatal (results in death); 


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 Is life-threatening (Note: the term "life-threatening" refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event that 
could hypothetically have caused death had it been more severe); 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay); 
 Results in persistent or significant disability/incapacity (a substantial disruption of the 
patient's ability to conduct normal life functions); 
 Is a congenital anomaly/birth defect; or 
 Constitutes an important medical event that may jeopardize the patient or may require 
medical or surgical intervention to prevent one of the other outcomes listed above. 
Important medical events are defined as those occurrences that may not be immediately 
life-threatening or result in death, hospitalization, or disability, but may jeopardize the patient or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  
Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization.   
Events not considered to be serious adverse events are hospitalizations for: 
 A procedure for protocol/disease-related investigations (e.g., sampling for laboratory, 
pharmacokinetic, and pharmacodynamic tests).  However, hospitalization or 
prolonged hospitalization for a complication of such procedures remains a reportable 
serious adverse event. 
 Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an adverse event. 
 A procedure that is planned (i.e., planned prior to the starting of treatment on study); 
must be documented in the source document and the eCRF.  Hospitalization or 
prolonged hospitalization for a complication remains a reportable serious adverse 
event. 
 An elective treatment of or an elective procedure for a pre-existing medical condition 
that does not worsen.  
 Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above. 
If an adverse event is considered serious, the adverse event eCRF must be completed. 
For each serious adverse event, the Investigator will provide information on severity, start and 
stop dates, relationship to investigational product, action taken regarding investigational product, 
and outcome. 
Queries pertaining to serious adverse events will be handled through the electronic data capture 
system or other appropriate means.  Urgent queries (e.g., missing causality assessment) may be 
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10.2.2. 
Severity/Intensity 
For both adverse events and serious adverse events, the Investigator must assess the 
severity/intensity of the event.  
The National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.0 should be used to grade the severity/intensity of all events.  These criteria will be 
provided in the Site Operations Manual.  If a CTCAE criterion does not exist, the Investigator 
should grade the severity according to the following criteria:  
 Grade 1 (mild): does not interfere with the patient’s usual function 
 Grade 2 (moderate): interferes to some extent with patient's usual function 
 Grade 3 (severe): interferes significantly with patient's usual function 
 Grade 4 (life-threatening): results in a threat to life or in an incapacitating disability 
 Grade 5 (death): results in death 
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is 
based on patient/event outcome or action criteria associated with events that pose a threat to a 
patient’s life or functioning.   
Seriousness, not severity, serves as a guide for defining regulatory obligations. 
10.2.3. 
Relationship to Study Drug 
Relationship should be assessed and provided for every adverse event/serious adverse event 
based on currently available information.  Relationship is to be reassessed and provided as 
additional information becomes available.  Adverse events will be classified by the Investigator 
as follows: 
Definitely Related: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out.  The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to drug administration and cannot be explained by 
concurrent disease or other drugs or chemicals.  The event resolves or improves upon withdrawal 
of drug (de-challenge).  The event would be considered as definitely related to the study drug 
upon results of a positive re-challenge procedure. 
Probably Related: There is evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication).  However, the influence of 
other factors that may have contributed to the event (e.g., the patient’s clinical condition, other 
concurrent disease, concomitant medications or events) is unlikely, and the event follows a 
clinically reasonable response upon withdrawal of drug (de-challenge).   
Possibly Related: There is evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the study drug). However, the influence of other 
factors may have contributed to the event (e.g., the patient’s clinical condition, other concurrent 
disease, concomitant medications or events).  
Unlikely Related: A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to drug administration makes a causal relationship improbable (e.g., the event did 


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not occur within a reasonable time after administration of the trial medication) and in which 
other drugs or concurrent or underlying disease provide plausible explanations (e.g., the patient’s 
clinical condition, other concomitant treatments). 
Not related: The adverse event is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology.  There must be an 
alternative, definitive etiology documented by the clinician. 
10.2.4. 
Duration 
For all adverse events whether or not considered serious, the Investigator will provide a record of 
the start and stop dates of the event. Every effort should be made to resolve all adverse events 
with continued follow-up with the patient until appropriate resolution can be achieved. If an 
event is unresolved at the end of the study it will be recorded as ongoing.  
10.2.5. 
Action Taken 
The Investigator will record the action taken with investigational product as a result of an 
adverse event or serious adverse event on the eCRF, as applicable (e.g., discontinuation, or 
interruption of investigational product, as appropriate) and record if concomitant and/or 
additional treatments were given for the event. 
10.2.6. 
Outcome 
The Investigator will record the outcome of adverse events on the eCRF, as applicable (e.g., 
recovered, recovered with sequelae, not recovered, or death (due to the adverse event).   
10.3. 
Follow-Up 
Adverse events assessed as not related to study drug, including clinically significant laboratory 
tests, electrocardiograms, or physical examination findings, must be followed until the event 
resolves, the condition stabilizes, the event is otherwise explained, or the final study visit occurs, 
whichever comes first.     
Adverse events assessed as related to study drug and serious adverse events will be followed for 
as long as necessary to adequately evaluate the patient’s safety, or until the event stabilizes, is 
otherwise explained, death occurs, or the patient is lost to follow up.  If resolved, a resolution 
date should be provided.  The Investigator is responsible for ensuring that follow-up includes any 
supplemental investigations indicated to elucidate the nature and/or causality of the adverse 
event.  This may include additional clinical laboratory testing or investigations, examinations, or 
consultation with other health care professionals as is practical.  
10.4. 
Pregnancy 
The Sponsor must be informed within 24 hours upon learning that a patient, or male patient’s 
partner, has become pregnant any time after the first dose of study drug until 30 days after the 
last dose of study drug. The Pregnancy Notification eCRF should be used to report the pregnancy 
to the Sponsor or its designee.  Patient pregnancies (or pregnancy of a male patient’s partner) 
must be followed until termination of pregnancy or the birth of the child.  The Pregnancy 
Outcome eCRF should be used to report information regarding the status of the infant. 


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If a female partner of a male patient taking investigational product becomes pregnant, the male 
patient taking the investigational product should notify the Investigator, and the pregnant female 
partner should be advised to call her healthcare provider immediately. 
10.5. 
Recording Adverse Events 
All adverse events (regardless of seriousness or relationship to study drug) including those from 
the time informed consent is obtained through to the final study visit are to be recorded in the 
eCRF.  Each individual adverse event is to be listed as a separate entry.  The Investigator will 
provide information about dates of onset and resolution, seriousness, severity, action(s) taken, 
outcome, and relationship to the study drug. All adverse events should be documented in the 
patient’s source documents.  
10.6. 
Reporting Adverse Events 
The Investigator must report to Sponsor or its designee all adverse events that occur during the 
study from the time written informed consent is given until the final study visit or early 
termination, regardless of their relationship to the study drug. Serious adverse events and 
pregnancies will be reported from the time written informed consent is given through 30 days 
beyond the last dose of study drug. 
10.6.1. 
Reporting Serious Adverse Events 
The Investigator is required to notify the Sponsor, and the Sponsor’s designated Drug Safety 
Unit within 24 hours after becoming aware of the occurrence of a serious adverse event.  All 
serious adverse events will be reported through completion of the adverse event eCRF.  The 
Investigator will be responsible for reporting serious adverse events to the IRB. 
Medical Monitor and Emergency Contact Information: 
 
 
, MD 
Telephone:  
 
Facsimile:  
 
Email:  
 AND 
  
 
Serious Adverse Event Reporting Contact Information: 
 
 Safety Group Email: 
 
 
Serious Adverse Event Help Line: 
 
Serious Adverse Event Fax Line: 
 
If an Investigator becomes aware of a serious adverse event within 30 days after the last dose of 
study drug and it is considered by him/her to be caused by the study drug with a reasonable 
possibility, the event must be documented and reported through completion of the adverse event 
eCRF. 


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10.6.2. 
Reporting Urgent Safety Issues 
If the study site staff becomes aware of an actual or potential urgent safety issue, then the 
Sponsor and Sponsor’s designee (Medical Monitor) must be immediately contacted so that 
appropriate urgent safety measures can be agreed upon.  An urgent safety issue is defined as:  
 An immediate hazard to the health or safety of patients participating in a clinical 
study 
 A serious risk to human health or potentially a serious risk to human health 
An urgent safety issue may include:  (1) issues with an investigational drug or comparators; 
(2) study procedures; (3) inter-current illness (including pandemic infections); (4) concomitant 
medications; (5) concurrent medical conditions; or (6) any other issues related to the safe 
conduct of the study or that pose a risk to study patients. 
In exceptional circumstances of imminent hazard and in order to safeguard the health or safety of 
individuals, the Investigators may take urgent safety measures before informing the Sponsor, but 
the Sponsor must be informed immediately after the hazard has resolved.   


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11. 
STATISTICAL METHODS 
Additional details for statistical methods will be provided in the Statistical Analysis Plan. 
11.1. 
Sample Size Rationale 
A sample size of 25 patients (completers) per group provides adequate precision for the 
estimated dosing regimen difference for relative change in SALT score from baseline at 
Week 24.  Precision of the estimated difference is quantified by the width of the 90% confidence 
interval for the dosing regimen difference.   
11.2. 
Endpoints 
11.2.1. 
Efficacy 
The primary efficacy endpoint will be relative change in SALT score for each dose regimen from 
baseline at Week 24. 
Secondary efficacy endpoints in each dose regimen include: 
 Proportion of patients achieving at least a 90%, 75%, and 50% reduction in SALT score 
from baseline at Weeks: 
 4, 8, 12, 16, 20, and 24 in the Treatment Period 
 
Absolute Change in SALT scores from baseline at Weeks: 
o 4, 8, 12, 16, 20, and 24 in the Treatment Period 
 
Relative Change in SALT scores from baseline at Weeks: 
o 4, 8, 12, 16, 20 and 24 in the Treatment Period 
 Change in satisfaction of hair coverage as reported by the patient 
Exploratory endpoints in each dose regimen include: 
o Change in patient’s eyebrows as measured by the patient’s Visual Analog Scale (VAS) 
 Change in satisfaction of hair coverage quality as reported by patient 
11.2.2. 
Safety 
Safety and tolerability of CTP-543 will be assessed by evaluating adverse event, vital signs, 
concomitant medications, clinical laboratories, and electrocardiogram results, as well as physical 
examinations.  
11.3. 
Analysis Populations 
The Efficacy Population will include all patients who receive study drug and have at least 1 post-
treatment SALT assessment.  The Safety Population will include all patients who receive study 
drug. Patients will be summarized according to study drug regimen received (i.e., as treated) 
should it differ from the randomized arm. 
11.4. 
Analyses 
For the Treatment Period, data will be summarized by dosing regimen (BID versus QD).  All 
data for analysis will be listed by patient. 


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Continuous measures will be summarized descriptively (mean, standard deviation, median, 
minimum value, and maximum value) and categorical measures will be presented as number and 
percentage.   
11.4.1. 
Disposition and Baseline Characteristics 
Disposition will be summarized by randomized dosing regimen. The number and percentage of 
patients, who are randomized, treated, prematurely discontinued, and completers will be 
summarized.  
Baseline characteristics will be summarized by dosing regimen for patients participating in the 
Treatment Period. 
Medical history will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. Concomitant medications will be summarized by World Health Organization Drug 
Dictionary Anatomical-Therapeutic-Chemical classification and preferred term.   
Concomitant medications will be summarized by World Health Organization Drug Dictionary 
for Anatomical-Therapeutic-Chemical classification and preferred term.  
11.4.2. 
Efficacy 
For the primary efficacy endpoint and other continuous measures, a 90% confidence interval for 
the dosing regimen difference at Week 24 will be calculated using the t-distribution.  For 
categorical measures (e.g. proportion of responders), a 90% confidence interval for the dosing 
regimen difference at Week 24 will be calculated based on normal approximation for the 
binomial distribution, using the Wald continuity correction [(1/n1 + 1/n2/2].  
11.4.3. 
Study Drug Exposure 
For each patient, the number of days of exposure to CTP-543 will be summed across the 
Treatment Period. The total number of days on study drug will exclude dose interruptions. The 
total number of days of exposure to CTP-543 will be summarized with the mean, standard 
deviation, median, minimum, and maximum number of days on the dose. Drug compliance will 
also be summarized. 
11.4.4. 
Safety 
All safety summaries will be descriptive with no statistical hypothesis testing and based on the 
Safety Population. All safety endpoints will be listed in by-patient data listings. 
Adverse events will be coded using MedDRA and summarized by system organ class and 
preferred term.  Clinically significant deteriorations in physical examination findings will be 
reported and summarized as adverse events. 
Laboratory values will be converted to the project-defined unit of measurement, as applicable, 
before analysis. Abnormal, clinically significant laboratory values will be reported and 
summarized as adverse events. 
Adverse Events 
An adverse event reported after informed consent, but before the first dose of study drug (i.e., 
Day 1), will be considered a pre-treatment adverse event.  Treatment-emergent adverse events 
(TEAEs) will be defined as any adverse event that occurs after administration of the first dose of 


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study drug until Week 24 or the Early Termination Visit.  The number and percentage of patients 
who report TEAEs will be summarized by system organ class and preferred term.  
Treatment emergent adverse events will also be summarized by intensity as well as relationship 
to study drug.   
Patients who report the same preferred term on multiple occasions will be counted once for the 
preferred term: under the highest severity when summarized by severity and under the closest 
relationship to study drug when summarized by relationship.  If a patient reports multiple 
preferred terms for a system organ class, the patient will be counted only once for that system 
organ class. 
The number and percentage of patients who experience TEAEs will be summarized by dosing 
regimen for the following: 
 By system organ class and preferred term 
 By severity/intensity, system organ class, and preferred term 
 By relationship to study drug, system organ class, and preferred term 
 Serious adverse events by system organ class and preferred term 
 Serious adverse events by relationship to study drug, system organ class, and 
preferred term 
 Adverse events resulting in discontinuation of study drug by system organ class and 
preferred term 
 Adverse events that result in study drug dose interruption by system organ class and 
preferred term 
By-patient listings will be provided for any deaths, serious adverse events, and adverse events 
leading to discontinuation of treatment.   
Clinical Laboratory 
Clinical laboratory variables will be presented in 3 ways.  First, change from Baseline to each 
scheduled assessment will be summarized descriptively.  Baseline will be defined as the 
laboratory value obtained before the first dose of study drug on Day 1; if Day 1 values are 
unavailable, then values obtained at the Screening Visit will be used. 
Second, treatment-emergent potentially clinically significant (PCS) laboratory values will be 
identified.  Potentially clinically significant values are defined as those that meet Grade 3 or 
Grade 4 toxicity criteria from the CTCAE criteria.  Treatment-emergent PCS laboratory values 
are those in which the baseline value is not PCS and the post-baseline value is PCS. 
Third, treatment-emergent adverse events that result in dose interruption will also be identified.  
The mean change from Baseline to each scheduled assessment will be summarized descriptively 
by dosing regimen for each clinical laboratory variable specified in this protocol. 
The number and percentage of patients with Abnormal, clinically significant laboratory values 
(per Investigator judgment) and the number and percentage of patients with treatment-emergent 
PCS laboratory values will be summarized by dosing regimen for each clinical laboratory 
variable. 


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Vital Signs 
The mean change from baseline to each scheduled assessment will be summarized descriptively 
by dosing regimen for each vital sign variable specified in this protocol. 
Baseline will be defined as the last vital sign value obtained before the first dose of study drug on 
Day 1; if Day 1 values are unavailable, then values obtained at the Screening Visit will be used.  
Electrocardiogram 
The change from baseline in electrocardiogram intervals (PR, QT, QTcF, QRS, and RR) to each 
scheduled assessment will be summarized descriptively by dosing regimen. 
Exploratory Endpoints 
VAS scale for eyebrows will be tabulated and analyzed by dosing regimen, as appropriate.   
Patient reported outcomes of satisfaction of hair coverage and satisfaction of hair coverage 
quality will be tabulated and analyzed by dosing regimen, as appropriate.   
Additional detail will be outlined in the Statistical Analysis Plan.  
 


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12. 
REGULATORY CONSIDERATIONS 
It is the responsibility of the clinical site and staff to notify the Sponsor and Sponsor’s designee 
immediately upon becoming aware of a serious breach of GCP or of the study protocol.  It is the 
responsibility of the Sponsor or its designee to notify appropriate regulatory authorities of any 
serious breach which is likely to effect, to a significant degree, the safety or mental integrity of 
the patients of the study or the scientific value of the study.  
12.1. 
Good Clinical Practice 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that the Sponsor, its authorized 
representative, and Investigator abide by GCP, as described in ICH Guideline E6 and in 
accordance with the general ethical principles outlined in the Declaration of Helsinki.  The study 
will receive approval from the IRB prior to commencement.  The Investigator will conduct all 
aspects of this study in accordance with applicable national, state, and local laws of the pertinent 
regulatory authorities. 
12.2. 
Sponsor’s Responsibilities 
The Sponsor or its designee is responsible for the following: 
 Selecting qualified Investigators 
 Providing Investigators with the information they need to properly conduct an 
investigation 
 Ensuring proper monitoring of the investigation 
 Ensuring that the applicable regulatory authorities, and all participating Investigators 
are properly informed of significant new information regarding adverse events or 
risks associated with the medication being studied 
Before an investigational site can enter a patient into the study, a representative of the Sponsor 
will visit the investigational study site to: 
 Determine the adequacy of the facilities 
 Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of the Sponsor or its representatives.  This 
will be documented in a Clinical Study Agreement between the Sponsor and the 
Investigator. 
During the study, a monitor from Concert Pharmaceuticals or its representative will have regular 
contacts with the investigational site, for the following: 
 Provide information and support to the Investigator(s) 
 Confirm that facilities remain acceptable 
 Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 


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 Perform source data verification.  This includes a comparison of the data in the case 
report forms with the patient’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records for 
each patient (e.g., clinic charts). 
 Record and report any protocol deviations. 
 Confirm adverse events and serious adverse events have been properly documented on 
eCRFs and confirm any serious adverse events have been forwarded to the Sponsor and 
those serious adverse events that met criteria for reporting have been forwarded to the 
IRB. 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
As the Sponsor, Concert Pharmaceuticals has delegated some responsibilities to a designee, or 
Contract Research Organization. 
12.3. 
Investigator’s Responsibilities 
Investigator responsibilities are set out in the ICH Guideline for GCP and in the local 
regulations.  Each Investigator participating in this study is required to maintain complete and 
accurate study documentation in compliance with current GCP standards and all applicable local 
regulations related to the conduct of a clinical study. 
The Principal Investigator will ensure that all persons assisting with the study are adequately 
informed about the protocol, any amendments to the protocol, the study drug, and their 
study-related duties and functions.  The Principal Investigator will maintain a list of sub-
Investigators and other appropriately qualified persons to whom he or she has delegated 
significant study-related duties.  Individuals ineligible from conducting or working on clinical 
studies, including those ineligible as a result of debarment under the Generic Drug Enforcement 
Act of 1992, will not be allowed to conduct or work on studies sponsored by Concert 
Pharmaceuticals.  The Investigator is required to immediately disclose to the Sponsor in writing, 
if any person involved in the conduct of the study is debarred pursuant to a hearing by the FDA 
under this anti-fraud law, or if any proceeding for debarment is pending, or is (to the best of the 
Investigator’s knowledge) threatened.  
The Investigator is responsible for keeping a record of all patients who sign an informed consent 
document and are screened for entry into the study.  Patients who fail screening must have the 
reason(s) recorded in the patient’s source documents. 
The Investigator should inform the IRB of any event likely to affect the safety of patients or the 
continued conduct of the study, in particular any change in safety.  Additionally, all updates to 
the Investigator’s Brochure will be sent to the IRB.  A progress report will be sent to the IRB and 
the protocol will be reviewed annually (e.g., re-approved) or more frequently, as required by the 
IRB or local regulations.  
The Investigator will maintain a copy of all correspondence with the IRB, including copies of 
approved documents.  The Investigator will also maintain a copy of the IRB membership list 
with occupation and qualification (or a statement confirming compliance with GCP requirements 
for committee composition).   


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The Investigator will notify the IRB of the conclusion of the clinical study within 1 month of 
completion or termination of the study.  The final report sent to the IRB will also be sent to the 
Sponsor along with the completed electronic case report forms (eCRFs) and all necessary 
regulatory documents, thereby fulfilling the Investigator’s regulatory responsibility. 
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to patient records (e.g., 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of eCRFs and queries. 
12.4. 
Protocol Amendments 
Any permanent change to the protocol, whether it is an overall change or a change for specific 
study center(s), must be handled as a protocol amendment.  All amendments to the protocol will 
be written by the Sponsor.  The Investigator will not make any changes to this protocol without 
prior written consent from the Sponsor and subsequent approval by the IRB.  Except for 
administrative amendments, Investigators must await IRB approval of protocol amendments 
before implementing the change(s).  The Sponsor will ensure submission of any protocol 
amendments to the appropriate regulatory agencies. 
Administrative amendments are defined as having no effect on the safety of the research 
subjects, scope of the investigation, or quality of the study.  However, a protocol change 
intended to eliminate an apparent immediate hazard to patients should be implemented 
immediately, and the IRB notified within 5 days.   
When, in the judgment of the chairman of the local IRB, the Investigators, and/or the Sponsor, 
the amendment to the protocol substantially alters the study design and/or increases the potential 
risk to the patient, the currently approved written ICF will require similar modification.  In such 
cases, repeat informed consent will be obtained from patients enrolled in the study before 
continued participation under the new amendment. 
12.5. 
Audits and Inspections 
The Sponsor’s Quality Assurance Unit (or representative) may conduct audits at the study site(s).  
Audits will include, but are not limited to:  drug supply, presence of required documents, the 
informed consent process, laboratory specimen processing, and comparison of eCRFs with 
source documents.  The Investigator agrees to cooperate with audits conducted at a reasonable 
time and in a reasonable manner. 
Regulatory authorities worldwide may also audit the Investigator during or after the study.  The 
Investigator should contact the Sponsor immediately if this occurs, and must fully cooperate with 
the audits conducted at a reasonable time in a reasonable manner. 
The Investigator is required to make all study documentation promptly available for inspection, 
review or audit at the study site upon request by Sponsor, its representatives, or any appropriate 
regulatory agencies. 
12.6. 
Quality Control and Quality Assurance 
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative for compliance with applicable government regulations with respect to current 
GCP and standard operating procedures.   


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A quality control and quality assurance plan addressing aspects of the study that may impact data 
integrity or the protection of human subjects may be instituted for this study.  All audit findings 
will be summarized and placed on file with appropriate documentation of response/resolution. 


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13. 
DATA HANDLING AND RECORDKEEPING 
13.1. 
Confidentiality 
All information disclosed or provided by the Sponsor (or designee), or generated or produced 
during the study including, but not limited to, the protocol, the eCRFs, the Investigator’s 
Brochure, and the results obtained during the course of the study, are confidential.  The 
Investigator or any person under his/her authority agrees to keep confidential and not to disclose 
the information to any third party without the prior written approval of the Sponsor. 
Submission of this protocol and any other necessary documentation to the IRB is expressly 
permitted, IRB members having the same obligation of confidentiality.  Authorized regulatory 
officials and sponsor personnel (or designee) will be allowed full access to inspect and copy the 
records.  The copied and inspected records will remain at the site and will not be transmitted or 
removed from the site.  Study drug, patient bodily fluids, and/or other materials collected shall be 
used solely in accordance with this protocol, unless otherwise agreed to in writing by the 
Sponsor and responsible ethics committee(s) or regulatory authorities. 
Patients’ names may, however, be made known to a regulatory agency or other authorized 
officials in the event of inspections.  Documents containing the full name or other personally 
identifiable information of the patient are to remain at the site.  This information will not be 
transferred to the Sponsor nor be contained in regulatory filings.   
13.2. 
Patient Data Protection 
Prior to any testing under this protocol, including screening tests and assessments, candidates 
must also provide all authorizations required by local law (e.g., protected health information 
authorization).  
Patients will be identified only by unique patient numbers in eCRFs and other datasets generated 
for this study.  The patient will not be identified by name in the eCRF, in any study samples or 
study reports.  All data generated in this study is for research purposes only.  The Sponsor, its 
partner(s) and designee(s), and various government health agencies may inspect the records of 
this study.  Every effort will be made to keep the patient’s personal medical data confidential.  
The Sponsor will protect individual patient information to the fullest extent possible during this 
study.  At no time will a patient become identified in any publication or presentation.  However, 
the patient may have to become identified in the event of a regulatory authority audit or 
inspection in order to verify the accuracy of the data.  Access to patient information is at the 
discretion of the Sponsor and cannot occur prior to database lock or other specified events as 
determined solely by the discretion of the Sponsor. 
13.3. 
Data Collection 
All data obtained for analysis in the clinical study described in this protocol will use an 
electronic data capture system.  Data reported in the eCRFs should be consistent with and 
substantiated by the patient’s medical record and original source documents.  Any discrepancies 
must be explained.   
Prior to the start of the study, the Principal Investigator will complete a Delegation of Authority 
form (Site Signature and Delegation Log), showing the signatures and handwritten initials of all 


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individuals and the delegation of responsibilities, such as identifying those individuals who are 
authorized to make or change entries on eCRFs. 
13.4. 
Case Report Form Completion 
Data within the eCRF will be monitored by a Clinical Research Associate according to the 
Monitoring Plan.  Queries will be generated based on discrepancies found while monitoring.  
Site personnel will review and respond to these queries appropriately.  Additionally, the 
Sponsor’s designee and the Sponsor may periodically perform aggregate data reviews, which 
could result in queries being generated for site personnel resolution.  The completed eCRF for 
each patient must be signed and dated by the Principal Investigator to signify that the Principal 
Investigator has reviewed the eCRF and certifies it to be complete and accurate. 
13.5. 
Database Management, Data Clarification, and Quality Assurance 
The Sponsor’s designee (i.e., a designated Contract Research Organization) will be responsible 
for data management.  Data Management will develop a Data Management Plan (DMP) 
document, and provide it to the Sponsor for approval.  The DMP document will define all 
activities in the data collection and cleaning process.  The detailed DMP will be based on the 
protocol, work scope, contract, analysis plans, data-flows, eCRFs, data cleaning procedures, 
other supporting documents, and data management standards and practices. 
The programmed data validations will be run to check for database completeness and 
consistency, and queries will be generated upon data entry or via review by a Clinical Data 
Manager after entry.  The sites will respond to the data queries in a timely manner. 
Quality control procedures will be conducted prior to database lock according to the designated 
Contract Research Organization standard operating procedures. 
When the database has been declared to be complete and accurate, it will be locked.  Any 
changes to the database after that time will only be made by joint written agreement between the 
Sponsor, Statistician, Data Manager, and Quality Assurance Auditor according to designated 
standard operating procedures of the Contract Research Organization. 
13.6. 
Inspection of Records 
According to the ICH guidelines for GCP, the Sponsor or designee must verify data entered in 
the eCRF entries against the source documents. The objective of source document verification is 
to comply with GCP and international regulatory requirements and to reduce the risks of fraud.  
Source document verification means ensuring that source documents are an accurate and 
confirmable reflection of the patient’s evaluations during participation in the study and that all 
relevant information recorded in the source document is accurately entered into the eCRF. All 
source documents should be correctly labeled and filed and associated with a single, verifiable 
patient. 
All data required for this study should be captured in source notes.  No data obtained by the 
Investigator or other study personnel should be captured directly in the eCRF.  All source 
documents pertaining to this study will be maintained by the Investigator and made available for 
inspection by authorized persons.  If electronic progress notes and other electronic source 
documents are not compliant with applicable regulatory guidance, they are not considered a valid 
source for this study.  All patient progress notes must be dated and signed at the time of the visit.  


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The Sponsor reserves the right to terminate the study for refusal of the Investigator to supply 
original source documentation for this clinical study. 
The Investigator will note in a source independent from the eCRF the following information: 
 Information to confirm that the patient exists (e.g., initials, date of birth, and sex); 
 Confirmation that the patient satisfies the inclusion/exclusion criteria; 
 Confirmation that the patient is taking part in the clinical study; 
 Confirmation of the informed consent process; 
 Visit dates and documentation of protocol assessments and procedures; 
 Information concerning all adverse events; 
 Details of concomitant and investigational medications. 
Source document verification is not a substitute for clinical study monitoring, the purpose of 
which is to ensure that the protocol has been followed correctly, the eCRF has been fully and 
accurately completed, source document verification has been carried out, and the study timelines 
and enrollment goals and requirements have been met. 
13.7. 
Retention of Records 
For investigational drug studies, clinical Investigators must retain study records for a period of 
2 years following the date a marketing application is approved for the drug for the indication for 
which it is being investigated; or, if no application is to be filed or if the application is not 
approved for such indication, until two years after the investigation is discontinued and FDA is 
notified. 
The Investigator must maintain all study documentation as confidential, and take measures to 
prevent accidental or premature destruction of these documents. 
The Investigator must notify the Sponsor prior to destroying any study essential documents. 
If the Investigator can no longer ensure archiving, he/she shall inform the Sponsor.  The relevant 
records shall be transferred to a mutually agreed upon designee. 


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14. 
PUBLICATION POLICY 
The results of this study may be published in a medical publication, journal, or may be presented 
at a medical conference or used for teaching purposes.  Additionally, this study and its results 
may be submitted for inclusion in all appropriate health authority study registries, as well as 
publication on health authority study registry websites, as required by local health authority 
regulations.  Selection of first authorship will be based on several considerations, including, but 
not limited to study participation, contribution to the protocol development, and analysis and 
input into the manuscript, related abstracts, and presentations in a study. 


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15. 
LIST OF REFERENCES 
First Author (Year) 
Citation 
Al-Mutairi (2011) 
Al-Mutairi N, Eldin ON. Clinical profile and impact on quality of life: 
seven years experience with patients of alopecia areata. Indian J 
Dermatol Venereol Leprol. 2011 Jul-Aug;77(4):489-93. 
Bilgic (2013) 
Bilgiç Ö, Bilgiç A, Bahalı K, Bahali AG, Gürkan A, Yılmaz S. 
Psychiatric symptomatology and health-related quality of life in 
children and adolescents with alopecia areata. J Eur Acad Dermatol 
Venereol. 2014 Nov;28(11):1463-8. 
Craiglow (2014) 
Craiglow BG, King BA. Killing two birds with one stone: oral 
tofacitinib reverses alopecia universalis in a patient with plaque 
psoriasis. J Invest Dermatol. 2014:134(12): 2988-2990. 
Crispin (2016) 
Crispin MK, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK 
inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 
2016 Sep:1(15):e89766. 
CTP-543 Investigator’s 
Brochure 
Investigator’s Brochure, CTP-543 (D8-ruxolitinib), Concert 
Pharmaceuticals, Inc. 2017 
Ghoreschi (2009) 
Ghoreschi K., Laurence A., O’Shea JJ. Janus kinases in immune cell 
signaling. Immunol Rev. 2009;228(1):273-87. 
Harris (2016) 
Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R, 
Christiano AM, Mackay-Wiggan J. J Am Acad Dermatol. 
2016:74(2):370-371. 
Jabbari (2015) 
Jabbari A, Dai Z, Xing L, et al.  Reversal of Alopecia Areata Following 
Treatment with the JAK1/2 Inhibitor Baricitinib. EBioMedicine. 
2015(2): 351–355. 
Jakafi (2016) 
Jakafi prescribing information. Incyte Corporation. Wilmington, DE. 
2016. 
Mackay-Wiggan (2016) 
Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces 
hair regrowth in patients with moderate-to-severe alopecia areata. JCI 
Insight. 2016 Sep:1(15):e89790. 
Olsen (2004) 
Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata 
investigational assessment guidelines--Part II. National Alopecia Areata 
Foundation. J Am Acad Dermatol. 2004 Sep;51(3):440-7. 
Safavi (1992) 
Safavi K. Prevalence of alopecia areata in the First National Health and 
Nutrition Examination Survey. Arch Dermatol. 1992;128(5):702. 
Sellami (2014) 
Sellami R, Masmoudi J, Ouali U, et al. The relationship between 
alopecia areata and alexithymia, anxiety and depression: a case-control 
study. Indian J Dermatol. 2014 Jul;59(4):421. 
Shi (2011) 
Shi JG, Chen X, McGee RF, et al. The pharmacokinetics, 
pharmacodynamics, and safety of orally dosed INCB018424 phosphate 
in healthy volunteers. J Clin Pharmacol. 2011;51:1644-54. 
Srivastava (2013) 
Kunal Srivastava, Anamika Arora, Aditi Kataria, et al. Impact of 
reducing dosing frequency on adherence to oral therapies: a literature 
review and meta-analysis. Patient Prefer Adherence. 2013; 7: 419–434. 


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Villasante Fricke (2015) 
Villasante Fricke AC, Miteva, M.  Epidemiology and burden of alopecia 
areata: a systematic review. Clin Cosmet Investig Dermatol. 
2015 Jul 24;8:397-403. 
Xing (2014) 
Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic 
T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 
Sep;20(9):1043-9. 









SAP_001.pdf: 
Official Title: 
A Randomized, Parallel-Group Study to Evaluate the Efficacy and 
Tolerability of Two Dosing Regimens of CTP-543 in Adult Patients With 
Moderate to Severe Alopecia Areata
NCT Number: 
NCT03811912 
Document Date: 
SAP Version 1: 11 September 2019 




Concert Pharmaceuticals Inc.
CONFIDENTIAL
Statistical Analysis Plan
Protocol No. CP543.2002
11 September 2019
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DOCUMENT VERSION CONTROL
Version Number
Date
Comments/Changes
0.1
14 August 2019
DRAFT 1
0.2
26 August 2019
DRAFT 2
0.3
04 September 2019
DRAFT 3
1.0
11 September 2019
FINAL




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Statistical Analysis Plan
Protocol No. CP543.2002
11 September 2019
Version:  1.0
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS ............................................................................................. 6 
LIST OF IN-TEXT TABLES.............................................................................................. 7 
1. 
PURPOSE OF THE STATISTICAL ANALYSIS PLAN............................................. 8 
2. 
PROTOCOL SUMMARY........................................................................................... 9 
2.1 
Study Objectives ............................................................................................ 9 
2.2 
Study Design.................................................................................................. 9 
2.3 
Study Population.......................................................................................... 10 
2.4 
Treatment Regimens.................................................................................... 10 
2.5 
Treatment Group Assignments or Randomization ....................................... 10 
2.6 
Sample Size Determination.......................................................................... 10 
3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS.................................. 11 
4. 
ANALYSIS POPULATIONS.................................................................................... 13 
4.1 
Efficacy Population....................................................................................... 13 
4.2 
Safety Population......................................................................................... 13 
5. 
STUDY PATIENTS.................................................................................................. 14 
5.1 
Disposition of Patients.................................................................................. 14 
5.2 
Protocol Deviations ...................................................................................... 14 
6. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS......................... 15 
6.1 
Prior and Concomitant Medications ............................................................. 16 
7. 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................ 17 
8. 
EFFICACY EVALUATION....................................................................................... 18 
8.1 
Primary Efficacy Endpoint............................................................................ 18 
8.1.1 
Severity of Alopecia Tool.................................................................... 18 
8.2 
Secondary Efficacy Endpoints ..................................................................... 18 
8.2.1 
Satisfaction of Hair Coverage............................................................. 18 
8.3 
Exploratory Efficacy Endpoints .................................................................... 19 
8.3.1 
Visual Analog Scale............................................................................ 19 
8.3.2 
Satisfaction of Hair Coverage Quality................................................. 19 
8.4 
Overview of Efficacy Analysis Issues........................................................... 19 
8.4.1 
Handling of Dropouts or Missing Data................................................ 19 
8.4.2 
Multicenter Studies ............................................................................. 20 
8.4.3 
Assessment Visit Windows................................................................. 20 
8.5 
Analysis Methods......................................................................................... 20 
8.5.1 
Primary Efficacy Analysis ................................................................... 21 
8.5.2 
Secondary Efficacy Analyses ............................................................. 22 
8.5.3 
Exploratory Efficacy Analyses ............................................................ 22 
8.6 
Examination of Subgroups........................................................................... 22 
9. 
SAFETY EVALUATION .......................................................................................... 23 
9.1 
Overview of Safety Analysis Methods.......................................................... 23 
9.2 
Adverse Events............................................................................................ 23 
9.3 
Clinical Laboratory Evaluation...................................................................... 25 
9.4 
Vital Signs, Physical Findings, and Other Observations Related to Safety . 25 
9.4.1 
Vital Signs........................................................................................... 25 


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9.4.2 
ECG.................................................................................................... 25 
9.4.3 
Physical Examinations........................................................................ 26 
10. PHARMACOKINETIC EVALUATION..................................................................... 27 
11. INTERIM ANALYSES AND DATA MONITORING ................................................. 28 
12. CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL........................ 29 
13. REFERENCES ........................................................................................................ 30 
14. LIST OF PLANNED TABLES ................................................................................. 31 
15. LIST OF PLANNED FIGURES................................................................................ 34 
16. LIST OF PLANNED DATA LISTINGS .................................................................... 35 
17. APPENDICES.......................................................................................................... 37 
17.1 
Study Flow Chart.......................................................................................... 37 
17.2 
Schedule of Events ...................................................................................... 38 
18. ATTACHMENTS...................................................................................................... 39 


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LIST OF ABBREVIATIONS
Abbreviation or 
Specialist Term
Explanation
AE
Adverse event
ATC
Anatomical-Therapeutic-Chemical
BID
Twice daily dosing
CI
Confidence interval
CSR
Clinical study report
CTCAE
Common terminology criteria for adverse events
ECG
Electrocardiogram
eCRF
Electronic case report form
HDL
High-density lipoprotein
ICH
International Conference on Harmonisation
LOCF
Last Observation Carried Forward
MedDRA
Medical Dictionary for Regulatory Activities
QD
Once daily dosing
QT
QT interval 
QTcF
QT interval corrected for heart rate (Fridericia’s method)
SAE
Serious Adverse Event
SALT
Severity of Alopecia Tool
SAP
Statistical Analysis Plan
SD
Standard deviation
SI
International System of Units
SOC
System organ class
TEAE
Treatment-emergent adverse events
VAS
Visual Analog Scale 
WHO
World Health Organization


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LIST OF IN-TEXT TABLES
Table 8-1 
Efficacy Variables and Analysis Methods ......................................21 


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1. PURPOSE OF THE STATISTICAL ANALYSIS PLAN
This statistical analysis plan (SAP) contains detailed information to aid in the implementation of 
the statistical analyses and reporting of the study data for use in the clinical study report (CSR)
for study CP543.2002.  This SAP is being written with due consideration of the 
recommendations outlined in the most recent International Conference on Harmonisation (ICH) 
E9 Guideline, entitled Guidance for Industry: Statistical Principles for Clinical Trials, and the 
most recent ICH E3 Guideline, entitled Guidance for Industry: Structure and Content of Clinical 
Study Reports.
This SAP describes the data sets that will be used for analysis, as well as patient characteristics, 
efficacy, safety, and clinician-reported and patient-reported perception of disease severity and 
improvement parameters.  The details of the specific statistical methods stated in the protocol 
will be provided and any changes from the protocol-specified analyses will be documented in the 
SAP prior to database lock.  If additional analyses are required to supplement the planned 
analyses described in this SAP after the database lock, they may be completed and will be 
described in the CSR.  Table, figure, and listing specifications are provided as an attachment in a
separate document. This SAP is based on the latest version of the protocol (Amendment 1), dated 
03 January 2019.


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2. PROTOCOL SUMMARY
2.1
Study Objectives
The overall objective of the study is to compare the efficacy and tolerability of a 16 mg total
daily dose of CTP-543 utilizing two different dosing regimens in adult patients with chronic,
moderate to severe alopecia areata. 
The secondary/exploratory objectives of the study will be to assess the patient reported outcomes 
of hair coverage and hair coverage quality.
2.2
Study Design
This is a randomized, parallel group multicenter study to evaluate the efficacy and tolerability of
two dosing regimens of CTP-543 (8 mg twice daily dosing (BID) vs 16 mg once daily dosing
(QD)), in adult patients with chronic, moderate to severe alopecia areata. Patients will be 
between 18 and 65 years of age and experiencing an episode of alopecia areata lasting at least 6 
months and not exceeding 10 years, with at least 50% hair loss as measured by the Severity of 
Alopecia Tool (SALT) at Screening and Baseline, and are not concurrently being treated for 
alopecia areata with other treatments that might affect hair regrowth or immune response. Up to 
approximately 75% of alopecia areata patients with alopecia totalis or universalis, and no more 
than 10% with only alopecia ophiasis will be enrolled. 
Patients may be screened up to 28-days prior to initiation of study drug. The Treatment Period is 
a 24-week dosing period where patients will be randomized to receive either CTP-543 8 mg BID, 
or CTP-543 16 mg QD and will be analyzed for the primary endpoints of the study. To minimize 
bias in the evaluation of study endpoints, patients, investigators, and site personnel will be 
unaware of the active drug dosing regimen by administering one 16 mg tablet and one placebo 
tablet 12 hours apart from each other for the 16 mg QD study group.
Patients will take the first dose of study drug in the clinic on Day 1. Patients will be instructed to
take study drug every 12 hours. Patients should dose study drug in the clinic on all Study Visit
Days after clinical laboratory blood draws are completed.
Patient safety will be monitored throughout the trial. The patient will be tested to ensure they do
not have the Hepatitis B or C virus, thyroid function abnormalities or latent or active
Tuberculosis, during the screening period. During the first 8 weeks of the Treatment Period,
hematology and serum chemistry will be conducted every 2 weeks, followed by an assessment
every 4 weeks thereafter through completion of the study at 24 weeks. Lipid levels will be
assessed every 12 weeks throughout the Treatment Period. Significant cytopenias or other
hematologic abnormalities will be managed by severity through dose interruption, or
discontinuation, and signs and symptoms of infection will be closely monitored and treated
promptly. Patients who experience intolerable symptoms during treatment may discontinue the
study at the discretion of the Investigator. Patients may withdraw consent at any time. The 
Treatment Period will last 24 weeks to assess BID and QD doses, in parallel. Assessment of
treatment response with SALT for efficacy will occur at 4, 8, 12, 16, 20 and 24 weeks. Upon 
completion of the 24-week Treatment Period patients will be eligible to either complete


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treatment and exit the study following the safety follow-up visit, or roll-over into a long-term 
open-label extension study.
Approximately 60 patients are planned to be enrolled in the study; approximately 30 patients per
dosing regimen.
2.3
Study Population
The study population will consist of male and female patients of any ethnicity between 18 and 65 
years of age, inclusive, with diagnosis of alopecia areata with a current episode lasting at least 6 
months and not exceeding 10 years at the time of Screening. Total disease duration greater than 
10 years is permitted.  Patients must also exhibit at least 50% scalp hair loss, as defined by a 
SALT   DW 6FUHHQLQJ DQG %DVHOLQH
A full list of the inclusion and exclusion criteria can be found in Sections 7.1 and 7.2 in the 
CP543.2002 Protocol. 
2.4
Treatment Regimens
CTP-543 will be dosed orally as tablets.  Doses and frequency will be allocated as follows:
x
CTP-543 8 mg BID (every 12 hours)
x
CTP-543 16 mg QD (16 mg in the morning and placebo tablet in the evenings)
2.5
Treatment Group Assignments or Randomization
Patients meeting all inclusion criteria and none of the exclusion criteria will be randomized to 
CTP-543 8 mg BID or CTP-543 16 mg QD in a 1:1 ratio.  Randomization will be stratified by 
classification of alopecia areata subtype into one of the following three categories: 1) alopecia 
areata, 2) alopecia totalis or alopecia universalis, or 3) alopecia ophiasis.
2.6
Sample Size Determination
A sample size of 25 patients (completers) per group provides adequate precision for the 
estimated dosing regimen difference for relative change in SALT score from baseline at Week 
24. Precision of the estimated difference is quantified by the width of the 90% confidence 
interval (CI) for the dosing regimen difference.


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3. GENERAL ANALYSIS AND REPORTING CONVENTIONS
The following is a list of general analysis and reporting conventions to be applied to this study,
unless otherwise specified.
All data displays (tables, listings, and figures) will have a header showing the sponsor company 
name, protocol number, page number, and display status (i.e. “DRAFT” or “FINAL”), as well as 
a footer indicating file name and run date/time.  Summary tables and data listings will be 
summarized by dosing regimen and overall, as appropriate. All data collected per-protocol and 
all derived variables will be listed.
Categorical variables will be summarized using counts (n) and percentages (%) and will be 
presented in the form “n (xx.x).” If a count is 0, 0% will be shown for the percentage. If a 
percentage is 100%, 100% will be shown with no decimal place. To ensure completeness, 
summaries for categorical variables will include all categories, even if no patients had a response 
in a particular category. Unless otherwise specified, the denominator for each percentage will be 
based on the number of patients in the population being summarized (header n).   If missing 
values are present, counts will be shown but will not be included in percentage calculations.
Continuous variables will be summarized using mean, standard deviation (SD), minimum, 
maximum, median, and number of patients. The mean and median will be reported to an 
additional level of precision than the original observations, and the SD will be reported to two 
additional levels of precision than the original observations. The minimum and maximum will be 
the same precision as the original data. In general, any calculated values, such as those due to 
unit conversion, will be rounded to the same number of decimal places as the original data.
Confidence intervals will be 90%. No formal hypothesis tests will be performed. Testing will be 
performed only for the Treatment Period.  Estimates and confidence intervals may be reported to 
1 more decimal than the original data.  
Summary tables and data listings: 
x
No preliminary rounding will be performed; rounding will only occur after analysis. 
x
Data from patients excluded from an analysis population will be presented in the data 
listings but will not be included in the calculation of summary statistics, where 
applicable.
x
Data from each patient will be separated by a blank line. Within a data listing, if a 
descriptive item appears line after line (e.g., repetition of a patient number, date, visit, 
etc.), only the first occurrence will be displayed (e.g., in Listing of Vital Signs, patient
number, date and visit will only be displayed on first row when presenting all parameters 
collected at same visit). Repetition of actual results or outcomes (e.g., Adverse Events 
(AEs), lab results, vital sign values, etc.) will not be collapsed. 
x
Data listings will be sorted by dosing regimen, patient, and week and/or time of 
assessment, as applicable.


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x
When change from baseline or change to baseline is calculated, baseline is the last 
observation obtained prior to dosing of the study drug.
Mock tables and data listings will be provided as attachments to this analysis plan. Minor 
changes to the mocks after formal SAP approval will not necessitate re-approval unless changes 
to the text of the SAP are required.
All statistical deliverables will be produced, validated, and reviewed for accuracy/consistency in 
accordance with 
 standard operating procedures and the processes described in the 
statistical validation plan.
SAS® (SAS Institute, Cary, North Carolina) statistical software, version 9.4 or later, will be used 
for all analyses. Adverse Events and Medical History will be coded in Medical Dictionary for 
Regulatory Activities (MedDRA) Version 19.1. Concomitant medications will be coded in 
World Health Organization (WHO) Drug Version E (2016.01) and Anatomical-Therapeutic-
Chemical (ATC) classification and preferred term.


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4. ANALYSIS POPULATIONS
Analysis populations will be summarized and listed for each patient, by dosing regimen.
4.1
Efficacy Population
The Efficacy Population will include all patients who receive study drug and have at least 1 post-
treatment SALT assessment during the Treatment Period. Patients in the Efficacy Population 
will be analyzed according to their randomized dosing regimen.
4.2
Safety Population
The Safety Population will include all patients who receive study drug during the Treatment 
Period. Patients in the Safety Population will be analyzed according to the actual dosing regimen
received during the study. 


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5. STUDY PATIENTS
5.1
Disposition of Patients
Disposition will be summarized by randomized dosing regimen for all patients screened in the 
study. The following disposition information will be summarized (percentages based on the 
number randomized, with the exception of the reasons for discontinuation):
x
The number of patients screened.
x
The number of patients randomized.
x
The number and percentage of patients treated within the Efficacy and Safety
Populations.
x
The number and percentage of patients who completed the study (defined as completing 
all study visits through Visit 11), completed Visit 10 and rolled into the open-label 
extension, and who completed 24 weeks of treatment but did not roll into the open-label 
extension and did not complete the safety follow up visit.
x
The number and percentage of patients who prematurely discontinued, and the frequency 
and percentage of each discontinuation reason. The denominator for the percentage of 
each discontinuation reason will be the number of patients who discontinued.
Disposition and patient visits will also be presented for each patient in patient data listings.
Patient data listings will list date of informed consent, date of first/last treatment, date of end of 
study/early termination, and reasons for discontinuation. A Kaplan Meier curve of time to study 
completion or early termination will also be presented. Patients who have completed the study 
will be censored.
5.2
Protocol Deviations
Protocol deviations will be collected at both the site and patient level on the electronic Case
Report Form (eCRF). A data review will be conducted before database lock by the sponsor to 
classify protocol deviations as minor or major.  Deviations that may alter or confound 
interpretation of the study results will be classified as major deviations. Protocol deviations will 
be summarized by deviation classification and category for all randomized patients and listed by 
patient in a data listing.


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6. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS
Demographic characteristics (ie, sex, ethnic origin, race, date of birth, and calculated body mass 
index) will be collected at the Screening Visit, between Day -28 and -1, and detailed on the 
eCRF. Demographic characteristics will be summarized using descriptive statistics for all 
randomized patients. 
Baseline characteristics will be summarized using descriptive statistics for all randomized 
patients and will include the following: 
x
baseline total SALT score.
x
alopecia areata type (current episode; defined below).
x
alopecia areata type (at disease onset; defined below).
x
duration of current episode in months (calculated as: [date of randomization – date of 
current episode onset + 1] / 30.4375).
x
duration of disease at onset in months (calculated as: [date of randomization – date of 
disease onset + 1] / 30.4375).
x
current nail involvement.
x
current eyelash/eyebrow involvement.
x
current other facial hair involvement.
x
prior Herpes Zoster vaccination.
x
time since Herpes Zoster vaccination in months.
Other co-morbidities may be identified and included as baseline characteristics. 
The patient’s alopecia areata will be classified by the Investigator into one of three categories 
defined for this study:
1)
Alopecia areata: patchy type hair loss,
2)
Alopecia totalis or universalis: complete hair loss on the scalp with or without body 
hair loss,
3)
Alopecia ophiasis: band-like hair loss limited to the periphery of the scalp along the 
back of the hair line in the occipital region and possibly extending over each ear in 
temporal regions.
The alopecia totalis and alopecia universalis category will be separated into each individual 
subtype for summaries. Alopecia areata category at baseline, defined as the current episode, and 


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alopecia areata category at disease onset will be summarized with the number and percent of 
patients in each category.
All demographics and baseline characteristics will also be listed within a by-patient data listing
for all randomized patients.
Medical history will be summarized by frequencies of System Organ Class (SOC) and preferred 
term and will be coded using MedDRA Version 19.1. All medical history for each patient in the 
Safety Population will be included in a data listing.
6.1
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by WHO Drug ATC classification
level 2 and preferred term and listed within a by-patient data listing.
Medications are classified as prior if the medication started and stopped prior to the first dose 
date of study drug or as concomitant if used on or after the first dose date of study drug.
Concomitant medications will be recorded from Screening through the Follow-Up Visit at 
Week 28.
Partial and completely missing dates will be imputed for the purposes of classifying concomitant 
medications as follows:
x
Partial dates will be imputed following the same algorithm as in Section 9.2 for 
Treatment-emergent adverse events (TEAEs).
x
For an entirely missing start date (i.e. day, month, and year are missing), the start date 
will be set to the date of administration of study drug unless the stop date is prior to the 
date of administration of study drug, in which case the start date will be set to the stop 
date.
For an entirely missing stop date (i.e. day, month, and year are missing), the medication will be 
treated as ongoing.


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7. MEASUREMENTS OF TREATMENT COMPLIANCE
Patients will strive for 100% compliance with the daily dosing schedule. Treatment compliance 
will be summarized as time on treatment as well as percent of planned dose received for each 
dosing regimen. Time on treatment will be defined as date of last dose in the treatment period 
minus the date of first dose in the treatment period + 1. Percent of planned dose received will be 
calculated for the entire treatment period as follows:
100 כ ܾ݈ܶܽ݁ݐݏ ܦ݅ݏ݌݁݊ݏ݁݀െܾ݈ܶܽ݁ݐݏ ܴ݁ݐݑݎ݊݁݀
ܾ݈ܶܽ݁ݐݏ ܧݔ݌݁ܿݐ݁݀
Tablets Expected is defined as the time on treatment multiplied by the expected number of active 
dose pills taken daily (x2 for the 8 mg BID group; x2 for the 16 mg QD group). Dose 
interruptions will be ignored in this calculation. Derived patient compliance, compliance per the 
eCRF (80% or higher versus less than 80%), and dosing exceptions will be listed in by-patient 
data listings.


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8. EFFICACY EVALUATION
8.1
Primary Efficacy Endpoint
The primary efficacy endpoint will be the relative change in SALT score for each dose regimen 
from baseline at Week 24.
8.1.1 Severity of Alopecia Tool
The SALT is a measure of hair absence that quantifies the amount of scalp surface without hair 
in a pre-specified quadrant of the scalp (right side, top, left side, back), that is further summed 
after applying a quadrant-specific multiplier indicative of scalp surface area contribution, to 
provide an overall score of total hair loss. Total SALT score is computed as [(left quadrant raw 
score x 0.18) + (right quadrant raw score x 0.18) + (top quadrant raw score x 0.40) + (back 
quadrant raw score x 0.24)]. The SALT assessment will occur via live examination of the patient 
during clinic visits.
As the SALT score is by nature a measurement of total surface without hair, it is important to 
note that in the context of this SAP, endpoints will follow these definitions:
x
Absolute change = difference in SALT measurements (baseline SALT score minus 
follow-up SALT score)
x
Relative change = percent change of the follow-up SALT score, where baseline SALT
score is the denominator (i.e. absolute change divided by the baseline score, multiplied by
100)
8.2
Secondary Efficacy Endpoints 
Secondary efficacy endpoints include:
x
Proportion of patients achieving at least a 90%, 75%, and 50% relative reduction in 
SALT score from baseline at Weeks 4, 8, 12, 16, 20, and 24;
x
Absolute change in SALT scores from baseline at Weeks 4, 8, 12, 16, 20, and 24 in the 
Treatment Period;
x
Relative change in SALT scores from baseline at Weeks 4, 8, 12, 16, 20, and 24 in the 
Treatment Period;
x
Change in satisfaction of hair coverage as reported by patient
8.2.1 Satisfaction of Hair Coverage 
Results of the patient satisfaction questions will be collected on Day 1 and at Week 24. Patients
will answer the question “How satisfied are you with the hair coverage on your scalp today?”.


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Responses range from 1-5 as follows: 1 (very dissatisfied), 2 (dissatisfied), 3 (somewhat 
satisfied), 4 (mostly satisfied), 5 (very satisfied). 
8.3
Exploratory Efficacy Endpoints
Exploratory efficacy endpoints include:
x
Change in patient’s eyebrows as measured by the patient’s Visual Analog Scale (VAS);
x
Change in satisfaction of hair coverage quality as reported by patient;
x
3URSRUWLRQ RI SDWLHQWV DFKLHYLQJ DQ DEVROXWH 6$/7 VFRUH RI   DQG  DW :HHNV
4, 8, 12, 16, 20 and 24;
8.3.1 Visual Analog Scale
The VAS is a scale of continuous measure initially developed for pain that has been used in a 
variety of clinical settings where the endpoint of interest is based on a subjective perception. The 
VAS is a distinct 100 millimeter line anchored on the left end at full degree of impairment and 
on the right end at no degree of impairment, where indication of the degree of impairment 
perceived at the time of assessment is captured by marking the appropriate position on the line 
between the anchor points. The measured distance of the mark from the left anchor will be 
recorded in millimeters.
As specified in the Schedule of Events, patients will rate his/her eyebrows on the patient VAS.
The left and right anchor points for the patient’s eyebrow VAS are “None” and “Full”,
respectively. The patient VAS will measure the patient’s eyebrows at the time of completion.
Since the VAS was measured right to left in terms on increasing impairment, the VAS analysis 
value will be calculated by taking 100 minus the collected value
8.3.2 Satisfaction of Hair Coverage Quality 
Results of the patient satisfaction of quality questions will be collected on Day 1 and at Week 24. 
Patients will answer 7 questions with responses ranging from 1-5 as follows: 1 (very 
dissatisfied), 2 (dissatisfied), 3 (somewhat satisfied), 4 (mostly satisfied), 5 (very satisfied).  The 
list of questions is provided in the protocol, Appendix 16.2.2. 
8.4
Overview of Efficacy Analysis Issues
8.4.1 Handling of Dropouts or Missing Data
The Last Observation Carried Forward (LOCF) approach will be implemented for missing SALT 
score data, e.g., if the SALT score in the Week 16 visit window is missing, the next and closest 
available on-treatment SALT score measurement before the Week 16 visit window will be used
for all remaining SALT assessments: Week 16, Week 20 and Week 24. Missing baseline values 
will not be carried forward. If a SALT assessment is missing between two non-missing SALT 


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assessments visits, the SALT score at that visit will be interpolated using the mean of the closest 
pre- and post-assessments.
If the number of discontinuations due to adverse events is substantial, other methods will be 
explored.
8.4.2 Multicenter Studies
Patients will be enrolled at approximately 10 sites.  To reduce variability, one rater should 
perform each clinician dependent assessments (SALT) for the patient for the duration of the 
study. All investigators using the SALT will be trained prior to use. Data from all sites will be 
pooled.
8.4.3 Assessment Visit Windows
The visit schedule for all study assessments is provided in Appendix 17.2. Patients will be 
considered completed for efficacy analyses after Week 24 (Visit 10). Patients will either
complete treatment at Week 24 and have a Safety Follow-up visit at Week 28 prior to exiting the 
study, or if eligible, may enroll into an open-label extension study of CTP-543 at their Week 24
visit.
For scheduled visits, there will be no reassignment of the analysis visit based on date, and all 
data will appear in summary tables based on the nominal timepoint.
Both unscheduled visits and repeat visits will be reassigned to the closest prior visit. If an 
assessment was already documented at that visit, the scheduled data will be used in summaries. 
If the scheduled data was missing, then the re-assigned unscheduled visit/repeat visit will be used 
in summaries. All visits will be included in by-patient data listings.
8.5
Analysis Methods
No formal hypothesis tests will be conducted. All confidence intervals will be 90%.  Testing will 
be based on the Efficacy Population and performed only for the Treatment Period.
Table 8-1 gives an overview of the analysis methods that will be used for each of the efficacy 
variables.


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Table 8-1
Efficacy Variables and Analysis Methods
Efficacy Variables
Collection Times
Method 
Primary
SALT (relative change)
Baseline, Week 24
Mean and 90% confidence 
interval (t-distribution)
Secondary
Responder Analysis
SALT (90%, 75%, 50% relative 
reduction)
Baseline, Week 4, 8, 
12, 16, 20, 24
Proportion and 90% 
confidence interval 
(binomial approximation)
SALT (absolute change)
Baseline, Week 4, 8, 
12, 16, 20, 24
Mean and 90% confidence 
interval (t-distribution)
SALT (relative change)
Baseline, Week 4, 8, 
12, 16, 20, 24
Mean and 90% confidence 
interval (t-distribution)
Satisfaction of hair coverage
Baseline, Week 24
Proportion and 90% 
confidence interval 
(binomial approximation);
Shift table
Exploratory
VAS for Eyebrows (percent 
change)
Baseline, Week 24
Mean and 90% confidence 
interval (t-distribution)
Satisfaction of hair coverage 
quality
Baseline, Week 24
Proportion and 90% 
confidence interval 
(binomial approximation);
Shift table
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score)
Baseline, Week 4, 8, 
12, 16, 20, 24
Proportion and 90% 
confidence interval 
(binomial approximation)
8.5.1 Primary Efficacy Analysis
The aim of this study is to compare 16 mg doses of CTP-543 taken in 2 different dosing 
regimens (8 mg BID or 16 mg QD). Comparisons between dosing regimens will be assessed 
using the mean relative change from baseline at Week 24 with 90% confidence intervals.


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8.5.2 Secondary Efficacy Analyses
Descriptive statistics and 90% confidence intervals will be reported for the SALT score 
(observed values, relative change, and absolute change) at each time point for each dosing 
regimen and by subtype. By-patient data listing will also be presented for patient SALT scores.  
The mean of observed value, absolute change, and relative change SALT scores along with 90% 
confidence intervals for each dosing regimen will be presented using line graphs.
Responders at 90%, 75%, and 50% by visit will be summarized with proportions and 90% 
confidence intervals (using the binomial approximation with a Wald continuity correction). 
Responders are defined as patients with at least 90%, 75%, or 50% reduction in SALT score by 
visit. Percent reduction is calculated as the baseline SALT score minus the current value, divided 
by the baseline value, multiplied by 100. Responders will be presented graphically by dosing 
regimen as a bar graph at 24 Weeks and as a line graph across time.
Responses to the patient satisfaction question will be summarized with proportions and 90% 
confidence intervals (using the binomial approximation with a Wald continuity correction).
Responses will be also categorized as “Satisfied” (including responses of “Very satisfied,” 
“Mostly satisfied,” and “Somewhat satisfied”) and “Dissatisfied” (including responses of “Very 
dissatisfied” and “Dissatisfied”) and presented as a 2 x 2 shift table from baseline to Week 24.
Response will also be listed in the by-patient data listings.
8.5.3 Exploratory Efficacy Analyses
VAS for Eyebrows scores will be summarized using percent change from baseline at Week 24. 
Descriptive statistics will be presented with 90% confidence intervals around the mean (t-
distribution). Results will also be listed in the by-patient data listings.
The satisfaction of hair quality questions will be summarized with descriptive statistics at 
baseline and Week 24, and will be listed in the by-patient data listings. Responses to the patient 
satisfaction question will be summarized as proportions with 90% confidence intervals. 
Responses will be also categorized as “Satisfied” (including responses of “Very satisfied,” 
“Mostly satisfied,” and “Somewhat satisfied”) and “Dissatisfied” (including responses of “Very 
dissatisfied” and “Dissatisfied”) and presented as a 2 x 2 shift table from baseline to Week 24.
Additional analyses by dosing regimens will be performed at Weeks 4, 8, 12, 16, 20, and 24 for 
patients who achieve DQ DEVROXWH 6$/7 VFRUH RI   RU . Responders by visit will be 
summarized with proportions and 90% confidence intervals (using the binomial approximation
with a Wald continuity correction). 
8.6
Examination of Subgroups
Descriptive statistics will be provided by alopecia subtype.


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9. SAFETY EVALUATION
9.1
Overview of Safety Analysis Methods
Safety and tolerability of CTP-543 will be assessed by evaluating the following for the Safety 
Population:
x
Adverse events
x
Clinical laboratory results
x
Vital signs
x
Electrocardiogram (ECG) results
x
Concomitant medications
x
Physical examinations
All safety summaries will be descriptive with no statistical hypothesis testing and based on the 
Safety Population. Patients will be summarized according to the study drug received (i.e., as 
treated), should it differ from the randomized dosing regimen. All safety endpoints will be listed 
in by-patient data listings.
9.2
Adverse Events
Adverse events will be coded using MedDRA and summarized by system organ class and 
preferred term.  Clinically significant deteriorations in physical examination findings will be 
reported and summarized as adverse events.
An adverse event reported after informed consent, but before the first dose of study drug (i.e., 
Day 1), will be considered a pre-treatment adverse event.  Treatment-emergent adverse events 
will be defined as any adverse event that occurs after administration of the first dose of study 
drug.  The number and percentage of patients who report TEAEs will be summarized by system 
organ class and preferred term. 
Treatment emergent adverse events will also be summarized by intensity as well as relationship 
to study drug.  
Partial dates will be imputed for the purposes of defining TEAEs as follows:
x
For a missing start day where the month and year are present, the start day will be set to 
the first day of the month, unless 1) the first day of the month is before the date of 
administration of study drug and the month and year are the same as the month and year 
of the date of administration of study drug, and 2) the end date is on or after the date of 


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administration of study drug or the end date is completely missing, in which case the start 
day will be set to the first day of administration of study drug.
x
For a missing start day and month where the year is present, the start day and month will
be set to January 1st, unless 1) January 1st is before the date of administration of study 
drug, and 2) the end date is on or after the date of administration of study drug or the end 
date is completely missing, in which case the start day and month will be set to that of the 
first date of administration of study drug.
x
For a missing end day where the month and year are present, the end day will be set to 
the last day of the month, unless the month and year are the same as the month and year 
of the last contact date for the patient, in which case the end day will be set to that of the 
patient's last contact date.
x
For a missing end day and month where the year is present, the end day and month will 
be set to the patient's last contact date, unless the year of the patient's last contact date is 
greater than the end year, in which case the end day and month will be set to December 
31st.
For an entirely missing stop date (i.e. day, month, and year are missing), the TEAE will be 
treated as ongoing.
Patients who report the same preferred term on multiple occasions will be counted once for the 
preferred term: under the highest severity when summarized by severity and under the closest 
relationship to study drug when summarized by relationship.  Missing severity or relationship 
will not be imputed. If a patient reports multiple preferred terms for a SOC, the patient will be 
counted only once for that SOC.
The number and percentage of patients who experience TEAEs will be summarized by dosing 
regimen for the following:
x
By SOC and preferred term.
x
By severity/intensity, SOC, and preferred term.
x
By relationship to study drug, SOC, and preferred term.
x
Serious adverse events (SAEs) by SOC and preferred term.
x
SAEs by relationship to study drug, SOC and preferred term.
x
AEs resulting in discontinuation of study drug by SOC and preferred term.
x
AEs that result in study drug dose interruption by SOC and preferred term.
x
AEs that meet Grade 3-4 Common terminology criteria for adverse events (CTCAE)
hematology results by system organ class and preferred term.


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x
AEs that meet Grade 3-4 CTCAE serum chemistry results by system organ class and 
preferred term.
By-patient listings will be provided for all AEs, SAEs, and AEs related to the study drug, as well 
as AEs leading to study drug withdrawal or death. A by-patient listing will also be created for 
any pregnancies that occur.  TEAEs that result in dose interruption will also be identified. 
9.3
Clinical Laboratory Evaluation
Observed measurements along with change from baseline for each assessment will be 
summarized descriptively by dosing regimen and visit for each clinical laboratory parameter.
Hematology parameters for patients that meet Grade 3 or Grade 4 toxicity criteria from the 
CTCAE v4.0 will be summarized for each scheduled visit and overall for all post-baseline visits.
In addition, hematology parameters of interest will be plotted as mean values over time. Serum 
chemistry parameters for patients that meet Grade 3 or Grade 4 toxicity criteria from the CTCAE 
v4.0 will be summarized for each scheduled visit and overall for all post-baseline visits.
Laboratory values will be converted to International System of Units (SI) before analysis. If 
laboratory values are recorded as above or below a threshold (i.e. “<2”, “>30”, etc.), they will be 
counted as missing for continuous summaries. Abnormal, clinically significant laboratory values 
(per Investigator judgment) will be reported and summarized as AEs.
All laboratory parameter results will be included in by-patient data listings.  Reference ranges for 
each clinical laboratory parameter will also be summarized in a data listing.
9.4
Vital Signs, Physical Findings, and Other Observations Related to Safety
9.4.1 Vital Signs
Baseline will be defined as the last vital sign value obtained before the first dose of study drug on 
Day 1; if Day 1 values are unavailable, then values obtained at the Screening Visit will be used.
Observed vital sign measurements along with change from baseline for each assessment will be 
summarized descriptively by dosing regimen and visit for each vital sign variable specified in the 
protocol (Systolic Blood Pressure, Diastolic Blood Pressure, Pulse Rate, Respiratory Rate, and 
Oral Temperature).  Vital signs will also be presented for each patient in a data listing.
9.4.2 ECG
Observed Overall ECG Interpretations will be summarized as Normal, Abnormal and Not 
Clinically Significant, or Abnormal and Clinically Significant for each scheduled visit by dosing 
regimen.  In addition, observed and change from baseline measurements of ECG intervals (PR, 
QT, QTcF, QRS, and RR) for each scheduled assessment will be summarized descriptively by 
dosing regimen and visit as well as listed within a by-patient data listing. Patients receiving study 
drug will be identified and summarized by dosing regimen and visit, as well as overall for the 
following clinically notable categories:


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x
QTcF > baseline and > 450 msec
x
QTcF > baseline and > 480 msec
x
QTcF > baseline and > 500 msec
x
QTcF increase from baseline > 30 msec
x
QTcF increase from baseline > 60 msec
9.4.3 Physical Examinations
A listing of physical examinations will be provided. Deteriorations from baseline on physical 
examination will be coded as adverse events and summarized as such. 


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10.PHARMACOKINETIC EVALUATION
Pharmacokinetic endpoints will not be collected for this study.


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11.INTERIM ANALYSES AND DATA MONITORING
No interim analyses or data monitoring committee are planned for this study.


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12.CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL
The following alterations were made to the original analyses planned in the protocol:
x
Additional analyses of patients who achieve absolute SALT scores of   RU  at 
Weeks 4, 8, 12, 16, 20, and 24 were added.


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13.REFERENCES
Mendoza TR, Osei JS, Shi Q, Duvic M. Development of the alopecia areata symptom impact scale. J 
Investig Dermatol Symp Proc. 2013 Dec;16(1):S51-2.
Olsen EA, Hordinsky MK, Price VH, et al. Alopecia areata investigational assessment guidelines--Part II. 
National Alopecia Areata Foundation. J Am Acad Dermatol. 2004 Sep;51(3):440-7.


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14.LIST OF PLANNED TABLES
 Table ID
Table No.
Title
Population
Unique?
DS_TAA
14.1.1
Summary of Patient 
Disposition
All Screened Patients
Y
DS_TAB
14.1.2
Summary of Protocol 
Deviations
All Randomized 
Patients
Y
DM_TAA
14.1.3
Summary of Demographics
All Randomized 
Patients
Y
DM_TAB
14.1.4
Summary of Baseline 
Characteristics
All Randomized 
Patients
Y
MH_TAA
14.1.5
Summary of Medical History 
by System Organ Class and 
Preferred Term
Safety Population
Y
EX_TAA
14.1.6
Summary of Study Drug 
Administration and 
Compliance by Dosing 
Regimen
Safety Population
Y
CM_TAA
14.1.7.1
Summary of Prior Medications
Safety Population
Y
CM_TAB
14.1.7.2
Summary of Concomitant 
Medications
Safety Population
N
EF_TAA
14.2.1
Summary of Relative Change 
from Baseline in Total SALT 
Score at Week 24
Efficacy Population
Y
EF_TAC
14.2.2.1
Summary of Total SALT 
Scores by Dosing Regimen and 
Visit
Efficacy Population
Y
EF_TAE
14.2.2.2
Summary of 90%, 75%, and 
50% Responders (SALT 
Relative Change) by Visit
Efficacy Population
Y
EF_TAG
14.2.2.3
Summary of Satisfaction of 
Hair Coverage Question
Efficacy Population
Y
EF_TAH
14.2.2.4
Shift from Baseline to Week 
24 Satisfaction of Hair 
Coverage Question
Efficacy Population
Y
EF_TAI
14.2.3.1
Summary of Visual Analog 
Scale for Eyebrows (mm)
Efficacy Population
Y
EF_TAJ
14.2.3.2
Summary of Satisfaction of 
Hair Coverage Quality 
Questions
Efficacy Population
N
EF_TAK
14.2.3.3
Shift from Baseline to Week 
24 Satisfaction of Hair 
Coverage Quality Questions
Efficacy Population
N


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EF_TAL
14.2.3.4
Analysis of Patients Achieving 
  RU  $EVROXWH
SALT Scores by Visit
Efficacy Population
Y
AE_TAA
14.3.1.1
Summary of Treatment-
Emergent Adverse Events
Safety Population
Y
AE_TAB
14.3.1.2
Summary of Treatment-
Emergent Adverse Events by 
System Organ Class and 
Preferred Term
Safety Population
Y
AE_TAC
14.3.1.3
Summary of  Treatment-
Emergent Serious Adverse 
Events by System Organ Class 
and Preferred Term
Safety Population
N
AE_TAD
14.3.1.4
Summary of All Treatment-
Emergent Adverse Events 
Leading to Discontinuation of 
Study Drug System Organ 
Class and Preferred Term
Safety Population
N
AE_TAE
14.3.1.5
Summary of Treatment-
Emergent Adverse Events 
Resulting in Study Dose 
Interruption by System Organ 
Class and Preferred Term
Safety Population
N
AE_TAF
14.3.1.6
Summary of CTCAE Grade 3-
4 Hematology Treatment-
Emergent Adverse Events by 
System Organ Class and 
Preferred Term
Safety Population
N
AE_TAG
14.3.1.7
Summary of CTCAE Grade 3-
4 Serum Chemistry Treatment-
Emergent Adverse Events by 
System Organ Class and 
Preferred Term
Safety Population
N
AE_TAH
14.3.1.8
Summary of Treatment-
Emergent Adverse Events by 
Severity/Intensity, System 
Organ Class, and Preferred
Term
Safety Population
Y
AE_TAI
14.3.1.9
Summary of Treatment-
Emergent Adverse Events by 
Relationship to Study Drug, 
System Organ Class, and 
Preferred Term
Safety Population
N
AE_TAJ
14.3.1.10
Summary of Treatment-
Emergent Serious Adverse 
Events by Relationship to 
Safety Population
N


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Study Drug, System Organ 
Class, and Preferred Term
LB_TAA
14.3.4.1.1
Summary of All Clinical 
Laboratory Values: 
Hematology
Safety Population
Y
LB_TAB
14.3.4.1.2
Summary of All Clinical 
Laboratory Values: Serum 
Chemistry
Safety Population
N
LB_TAC
14.3.4.2.1
Summary of CTCAE Grade 3-
4 Key Clinical Laboratory 
Values: Hematology
Safety Population
Y
LB_TAD
14.3.4.2.2
Summary of CTCAE Grade 3-
4 Key Clinical Laboratory 
Values: Serum Chemistry
Safety Population
N
VS_TAA
14.3.5.1
Vital Signs Summary
Safety Population
Y
EG_TAA
14.3.5.2
12-Lead Electrocardiogram 
Summary
Safety Population
N
EG_TAB
14.3.5.3
Summary of Abnormal, 
Clinically Significant 12-Lead 
Electrocardiogram Values by 
Dosing Regimen and Visit
Safety Population
Y
EG_TAC
14.3.5.4
Summary of Clinically Notable 
12-Lead Electrocardiogram 
Values by Dosing Regimen 
and Visit
Safety Population
Y


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15.LIST OF PLANNED FIGURES
 Figure 
ID
Figure No.
Title
Population
Unique?
DS_FAA
14.1.1
Kaplan-Meier Plot for Time to 
Study Completion or Early 
Termination
Safety Population
Y
EF_FAA
14.2.1.1
Relative Change in SALT Scores by 
Dosing Regimen across Time 
Efficacy Population
Y
EF_FAB
14.2.1.2
Responders by Dosing Regimen at 
Week 24
Efficacy Population
Y
EF_FAC
14.2.1.3
Responders by Dosing Regimen
across Time
Efficacy Population
Y
EF_FAD
14.2.1.4
Mean SALT Scores by Dosing 
Regimen across Time
Efficacy Population 
Y
EF_FAE
14.2.1.5
Mean Absolute Change in SALT 
Scores by Dosing Regimen across 
Time
Efficacy Population
N
LB_FAA
14.3.4.1.1
Key Clinical Laboratory Values: 
Hematology Parameters
Safety Population
Y


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16.LIST OF PLANNED DATA LISTINGS
 Listing 
ID
Listing 
No.
Title
Population
Unique?
RN_LAA
16.1.1
Randomization Codes
All Randomized 
Patients
Y
LB_LAA
16.1.10.1
Clinical Laboratory Reference 
Range
N/A
Y
DS_LAA
16.2.1.1
Patient Disposition
All Randomized 
Patients
Y
DS_LAB
16.2.1.2
Screen Failures
N/A
Y
DS_LAC
16.2.1.3
Patient Visits
All Randomized 
Patients
Y
DS_LAD
16.2.2
Protocol Deviations
All Randomized 
Patients
Y
DS_LAE
16.2.3
Analysis Sets
All Randomized 
Patients
Y
DM_LAA
16.2.4.1
Patient Demographic and Baseline 
Characteristics
All Randomized 
Patients
Y
DM_LAB
16.2.4.2
Alopecia Areata History
All Randomized 
Patients
Y
MH_LAA
16.2.4.3
Medical History
Safety Population
Y
CM_LAA
16.2.4.4
Prior and Concomitant 
Medications
Safety Population
Y
EX_LAA
16.2.5.1
Treatment Compliance
Safety Population
Y
EX_LAB
16.2.5.2
Dosing Exceptions
Safety Population
Y
EF_LAA
16.2.6.1
SALT Score
Efficacy Population
Y
EF_LAB
16.2.6.2
Visual Analog Scale (VAS) for 
Eyebrows
Efficacy Population
Y
EF_LAC
16.2.6.3
Satisfaction of Hair Coverage 
Question
Efficacy Population
N
EF_LAD
16.2.6.4
Satisfaction of Hair Coverage 
Quality Questions
Efficacy Population
N
AE_LAA
16.2.7.1
All Adverse Events
Safety Population
Y
AE_LAB
16.2.7.2
Serious Adverse Events
Safety Population
N
AE_LAC
16.2.7.3
Adverse Events Related to Study 
Drug
Safety Population
N
AE_LAD
16.2.7.4
Adverse Events Leading to Study 
Drug Discontinuation
Safety Population
N
AE_LAE
16.2.7.5
Adverse Events Leading to Study 
Drug Interruption 
Safety Population
N
AE_LAF
16.2.7.6
Adverse Events Leading to Death
Safety Population
N


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AE_LAG
16.2.7.7
Pregnancy
Safety Population
N
PE_LAA
16.2.8
Physical Examinations
Safety Population
Y
LB_LAB
16.2.9.1
Clinical Laboratory Data: 
Hematology
Safety Population
Y
LB_LAC
16.2.9.2
Clinical Laboratory Data: Serum 
Chemistry 
Safety Population
N
VS_LAA
16.2.10.1
Vital Signs
Safety Population
Y
EG_LAA
16.2.10.2
12-Lead Electrocardiogram
Safety Population
Y


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17.APPENDICES
17.1 Study Flow Chart


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17.2 Schedule of Events
Screening
Randomization1
Treatment Period
Safety    
Follow-Up
Day -28 to Day -112
Day 12
Week 2, 6
(Visit 3, 5)
Week 4, 8
(Visit 4, 6)
Week 12
(Visit 7)
Week 16, 20
(Visit 8, 9)
Week 243
(Visit 10)
Week 284    
(Visit 11)
Event
(Visit 1)
(Visit 2)
Informed consent
X
Eligibility assessment
X
X
Demographics
X
Medical history
X
X
Randomization
X
Physical examination
X
X
X
X
Brief physical examination
X
X
X
Height 
X
Weight
X
X
X
X
X
X
X
Pregnancy test5
X
X
X
X
X
X
Tuberculosis test
X
Clinical laboratory testing7,8
X4
X
X
X
X
X
X
X
Lipid assessment10
X
X
X
X
HBV and HCV test
X
12-lead electrocardiogram
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
Severity of Alopecia Tool assessment11
X
X
X
X
X
X
Photographs12
X
X
X
X
X
X
Visual Analog Scale (VAS) for Eyebrows
Patient Satisfaction Questions
Dispense study drug
X
X
X
X
Study drug accountability
X
X
X
X
Adverse events13
X
X
X
X
X
X
X
X
Concomitant medications13
X
X
X
X
X
X
X
X
HBV= hepatitis B virus; HCV = hepatitis C virus
1 Randomization/Day 1 may occur any time after Screening laboratory results are available and
reviewed by the investigator.
2 All subsequent visits and week increments should be based on the date of Visit 2. All 
visit windows are ±3 days.
3 Also serves as the Early Termination Visit for patient withdrawal in this period.
4 The Safety Follow-Up Visit is intended for those patients who do not roll over into an open-label 
extension and for patients who have been discontinued from the study and completed the Early 
Termination Visit (Week 24).
5 Serum pregnancy test for females of childbearing potential only.
6 Urine pregnancy test should be performed at the randomization visit.
7 Includes hematology and serum chemistry.
8 Collected pre-dose, except on Visit 11.
9 Will include thyroid stimulating hormone and hemoglobin A1c at Screening only.
10 Includes total cholesterol, low-density lipoprotein, high-density lipoprotein, and 
triglycerides.
11 Should be performed by the same rater for the patient for the duration of the study.
12 Sites will take photographs of patient’s scalps and eyebrow/eyelashes, if involved, to 
provide visual support of baseline SALT as well as potential SALT changes throughout the 
study.
13 Collection is ongoing.


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18. ATTACHMENTS
Attachment A: “CP543.2002 – TLF Shells” – Shells for Planned Tables, Figures, and Listings