Conditions: Alopecia Areata
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 66
Healthy volunteers: no

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 12 milligrams (mg) CTP-543 tablet and 1 x CTP-543 matching placebo tablet, twice daily (BID) for 24 weeks. arm 2: Participants received 24 mg (2 x 12 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: Administered as 12 mg tablets. intervention 2: Administered as tablets to aid treatment masking.

Protocol document:
Prot_002.pdf: 
Official Title: 
NCT Number: 
Document Date: 
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 
NCT03941548 
Protocol Amendment 2: 25 July 2019 


CTP-543 
25 July 2019 
Protocol CP543.2003, Amendment 2 
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: 
AMENDMENT 2 DATE: 
AMENDMENT 1 DATE: 
CP543.2003; Amendment 2 
 25 July 2019 
08 April 2019 
ORIGINAL PROTOCOL: 
15 February 2019 
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 
25 July 2019 
Protocol CP543.2003, Amendment 2 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
2 
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information 
Name 
, MD 
Title 
 
Address 
 
 
Phone 
Email 
 
 




CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
4 
 
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number:  CP543.2003 
 
 
 
 
 
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 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
5 
 
Summary of Changes 
 
Section 
Previous Text 
New Text 
Reason for 
Revision 
Synopsis  
(Objectives) 
and  
Section 6 Study 
Objectives 
The secondary/exploratory objectives of the study will be assessing 
the proportion of patients achieving defined threshold reductions in 
SALT score, and for patients to assess their eyebrows, hair coverage 
and hair coverage quality.   
The secondary/exploratory objectives of the study are to assess the 
proportion of patients achieving defined threshold reductions in SALT 
score, and for patients to assess their eyebrows, hair coverage and hair 
coverage quality. 
Modified text 
for clarity 
Synopsis  
(Study Design) 
and 
Section 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 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, Visual Analog Scale 
(VAS) for eyebrows, Clinical Global Impression of Severity (CGI-S), 
Patient Global Impression of Severity (PGI-S), and Patient Satisfaction 
questions. 
Added text to 
clarify 
assessments  
Synopsis  
(Inclusion 
Criteria) 
and 
Section 7.1 
Patient Inclusion 
Criteria 
3. 
Clinical presentation compatible with alopecia areata with a 
history of recurrence and spontaneous remission. 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. 
 
3. 
Clinical presentation compatible with 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. 
 
Deleted text for 
clarity  
Table 1 Schedule 
of Events 
Patient Satisfaction Questions 
 
Day 1 and Week 24 
 
Patient Satisfaction Questions 
 
Screening, Day 1, Week 8, Week 12 and Week 24 
CGI-I 
 
Week 8, 12, and 24 
CGI-S 
 
Screening, Day 1, Week 8, 12, and 24 
PGI-I 
 
Week 8, 12, and 24 
PGI-S 
 
Screening, Day 1, Week 8, 12, and 24 
Revised for 
clarity 
Section 8.1 
Description of 
Treatments 
 
 
CTP-543 12 mg BID (every 12 hours) 
 
 
CTP-543 24 mg QD (2 x 12 mg in the morning and 
placebo tablets in the evenings) 
 
CTP-543 12 mg BID (1 x 12 mg and 1 x placebo tablet every 12 
hours)  
 
CTP-543 24 mg QD (2 x 12 mg in the morning and 2 x placebo tablets 
in the evenings) 
Revised for 
clarity 


CTP-543 
25 July 2019 
Protocol CP543.2003, Amendment 2 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
6 
Section 
Previous Text 
New Text 
Reason for 
Revision 
Section 9.4 
Visual Analog 
Scale (VAS) 
An example of the patient VAS for eyebrows is provided in 
Appendix 0. 
An example of the patient VAS for eyebrows is provided in Appendix 16.3. 
Corrected typo 
Section 9 Study 
Assessments and 
Procedures 
NA 
Added Section 9.5 Global Impression Scales 
Added Section 9.5.1. Clinical Global Impression of Improvement (CGI-I) 
Section 9.5.2. Patient Global Impression of Improvement  
(PGI-I) 
Section 9.5.3. Clinical Global Impression of Severity  
(CGI-S) 
Section 9.5.4. Patient Global Impression of Severity  
(PGI-S) 
Added text to 
clarify 
assessments 
Section 16 
Appendices 
NA 
Section 16.4. Global Impression Scales  
Added Section 16.4.1. Clinical Global Impression Scale of Improvement 
Section 16.4.2. Patient Global Impression Scale of Improvement 
Section 16.4.3. Clinical Global Impression Scale of Severity 
Section 16.4.4. Patient Global Impression Scale of Severity 
Added text of 
actual scales to 
be collected 


CTP-543 
25 July 2019 
Protocol CP543.2003, Amendment 2 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
7 
1.
SYNOPSIS
Name of Sponsor/Company: 
Concert Pharmaceuticals, Inc.  
Name of Investigational Product: 
CTP-543 
Name of Active Ingredient: 
D8- ruxolitinib 
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; Canada and United States 
Studied period (years):  
Estimated date first patient enrolled: Q2 2019 
Estimated date last patient completed: Q1 2020 
Phase of development: 2 
Objectives: 
The overall objective of the study is to compare the efficacy and tolerability of a 24 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 are to assess the proportion of patients achieving 
defined threshold reductions in SALT score, and for patients to assess their eyebrows, 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 (12 mg BID vs 24 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 12 mg BID or 
CTP-543 24 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 2 x 12 mg tablets and 2 x placebo tablets 12 hours 
apart from each other for the 24 mg QD study group. 


CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
8 
 
Figure 1: 
CP543.2003 Study Design 
 
Study Design 
Patients will provide informed consent prior to initiating 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, Visual Analog Scale (VAS) for eyebrows, Clinical 
Global Impression of Severity (CGI-S), Patient Global Impression of Severity (PGI-S), and Patient 
Satisfaction questions. 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 and 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.  Periodic skin 
examinations are recommended to detect non-melanoma skin cancers including basal cell, squamous 
cell and Merkel cell carcinoma. 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 an open-label 
extension study.  
 
 


CTP-543 
25 July 2019 
Protocol CP543.2003, Amendment 2 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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Number of patients (planned): 
Approximately 60 patients are planned to be enrolled in the study; approximately 30 patients per 
treatment arm. 
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.
Patient is willing to participate and is capable of giving informed consent. Note: Consent must be
obtained prior to any study-related procedures.
2.
Male or Female patient between 18 and 65 years of age, inclusive, at the time of informed
consent.
3.
Clinical presentation compatible with 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.
Note: Other causes of hair loss such as cicatricial alopecia (pseudopelade), trichotillomania or 
syphilis should be ruled out if the clinical presentation is atypical or the history of recurrence 
and spontaneous remission is unclear.  
4.
Patient has moderate to severe alopecia areata at Screening and Baseline visits as determined by a
minimum of 50% scalp hair loss, as defined by a SALT score ≥50.
5.
Patients involved in any sexual intercourse that could lead to pregnancy:
a.
Females subjects of childbearing potential must agree to use a highly effective
contraceptive method from at least 4 weeks prior to Baseline until at least 4 weeks after
the last study product administration.
i.
Highly effective contraceptive methods include hormonal contraceptives
(combined oral contraceptive, patch, vaginal ring, injectable, or implant),
intrauterine devices or intrauterine systems, vasectomized partner(s), tubal
ligation or bias barrier methods of contraception (e.g. male condom with cervical
cap, male condom with diaphragm, and male condom with contraceptive sponge)
in conjunction with spermicide.
Note: Patients must have been on a stable dose of hormonal contraceptives 
for at least 4 weeks before Baseline.  
Note: The above list of contraceptive methods does not apply to patients who 
are abstinent for at least 4 weeks before Baseline and will continue to be 
abstinent from penile-vaginal intercourse throughout the study.  The 
reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the 
patient. 
ii.
Female patient of childbearing potential has had a negative serum pregnancy test
at Screening and negative urine pregnancy test at Baseline.
Note: A female subject of nonchildbearing potential is defined as follows: 
- Female subject who has had surgical sterilization (hysterectomy, bilateral
oophorectomy, or bilateral salpingectomy)
- Female subject who has had a cessation of menses for at least 12 months
prior to the screening visit without an alternative medical cause
b.
Male subjects must agree to use one of the highly effective contraceptive methods listed
in Inclusion Criterion 5.a.i., from Baseline until at least 4 weeks after the last study


CTP-543 
25 July 2019 
Protocol CP543.2003, Amendment 2 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
10 
product administration.  If the female partner of a male patient uses any of the hormonal 
contraceptives methods listed above, this contraceptive method must be used by the 
female partner from at least 4 weeks before Baseline until at least 4 weeks after the last 
study product administration. 
c.
Male subjects should not donate sperm during this study and for at least 30 days after the
end of study.
6.
Patients must be 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 (intranasal and inhaled corticosteroids are allowed, eye and ear drops containing
corticosteroids are also allowed); topical or oral retinoids; oral cyclines (minocin,
tetracycline); platelet-rich plasma injections; topical application to affected areas of anthralin,
squaric acid, diphenylcyclopropenone, or minoxidil; antimalarials.
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 and hair style regimen, including shampoo and
hair products (including hair dye, process, and timing to hair appointments), and to refrain
from weaves or extensions 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 5 years are excluded.
9.
Atypical nevi or cutaneous lesions that are suspicious for malignancy.
10. History of solid organ or hematological transplantation.
11. Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection
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


CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
11 
 
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. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B 
core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening.   
18. Vaccination with herpes zoster vaccine or plans to receive a live attenuated vaccine during 
the study and up to 6 weeks or 5 half-lives (of the study product), whichever is longer, after 
the last study product administration.  
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.  
NOTE: Subjects with documented completed treated with latent TB are not excluded.   
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, 
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 > 499 mL of blood or plasma within 56 days of Screening (during a 
clinical trial or at a blood bank donation) and for 30 days after last dose of study medication. 
27. Patient has a known or suspected allergy to CTP-543 or any component of the investigational 
product. 
28. Subject has had major surgery within 8 weeks prior to Baseline or has a major surgery 
planned during the study. 
29. Subject has received any UV-B phototherapy (including tanning beds), has had psoralen-UV-
A (PUVA) treatment, or excimer laser within 4 weeks prior to Baseline. 
30. Clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality, 
psychiatric disease, or social condition, as determined by the Investigator, that may 


CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
12 
 
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 12 mg BID, every 12 hours or 24 mg QD (2 x 
12 mg) 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 an 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  
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 confidence intervals for the dosing regimen 
difference.   
  
 


CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2  
 
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CONFIDENTIAL & PROPRIETARY 
13 
 
Efficacy Analyses: 
All treatment group comparisons for efficacy are for estimation purposes and no formal inferential 
testing will be performed. 
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, confidence intervals for the dosing regimen difference at Week 24 will be calculated. 
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 
 
25 July 2019 
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CONFIDENTIAL & PROPRIETARY 
 
14 
 
 
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/ET  
(Visit 10) 
Week 284 
(Visit 11) 
Informed consent 
X 
 
 
 
 
 
 
 
Eligibility assessment 
X 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical and surgical 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 
X 
X 
Tuberculosis test6 
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 (SALT) assessment11 
X 
X 
 
X 
X 
X 
X 
 
Photographs12 
X 
X 
 
 
X 
 
X 
 
Clinical Global Impression of Improvement 
 
 
 
X13 
X 
 
X 
 
Clinical Global Impression of Severity 
X 
X 
 
X13 
X 
 
X 
 
Visual Analog Scale (VAS) for Eyebrows 
 
X 
 
 
X 
 
X 
 
Patient Global Impression of Improvement 
 
 
 
X13 
X 
 
X 
 
Patient Global Impression of Severity 
X 
X 
 
X13 
X 
 
X 
 
Patient Satisfaction Questions 
X 
X 
 
X13 
X 
 
X 
 
Study Product Administration at study site 
 
X 
X 
X 
X 
X 
 
 
Dispense study drug 
 
X 
 
X 
X 
X 
 
 
Study drug accountability 
 
 
 
X 
X 
X 
X 
 
Adverse events14 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications14 
X 
X 
X 
X 
X 
X 
X 
X 


CTP-543 
 
25 July 2019 
Protocol CP543.2003, Amendment 2 
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
 
15 
 
ET=Early termination; 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 for subsequent visits.  
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 For females of childbearing potential, a serum pregnancy test will be performed at all visits 
aside from the randomization visit where a urine pregnancy test will be performed. 
6 If PPD (skin test) is performed, subject will need to return to the clinic 24-48 hours after placement for 
PPD reading.  
7 Includes hematology and serum chemistry.  
 8 When possible, collect 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, when possible, for the patient for the duration of the study. 
12 For participants who authorize photographs to be taken of their scalp involvement and/or eye and nail 
involvement.  
13 Will be conducted at Visit 6 (Week 8) only.  
14 Error! Reference source not found.Collection is ongoing. 
 
 
 


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2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF
FIGURES
1.
SYNOPSIS ...................................................................................................................7 
2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............16 
3.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................21 
4.
INTRODUCTION ......................................................................................................23 
4.1. 
Overview of Alopecia Areata .....................................................................................23 
4.2. 
Rationale for the Study ...............................................................................................23 
4.2.1. 
Scientific Rationale .....................................................................................................23 
4.3. 
Preclinical Information for CTP-543 ..........................................................................25 
4.4. 
Clinical Information ....................................................................................................25 
4.4.1. 
Clinical Studies of CTP-543 .......................................................................................25 
5.
ETHICS ......................................................................................................................28 
5.1. 
Institutional Review Board (IRB) ...............................................................................28 
5.2. 
Written Informed Consent ..........................................................................................28 
6.
STUDY OBJECTIVES ..............................................................................................29 
6.3 
Study Design ...............................................................................................................29 
6.4 
Method of Treatment Assignment ..............................................................................30 
7.
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................31 
7.1. 
Patient Inclusion Criteria ............................................................................................31 
7.2. 
Patient Exclusion Criteria: ..........................................................................................32 
7.3. 
Patient Withdrawal Criteria ........................................................................................34 
7.3.1. 
Patient Withdrawal Procedures ...................................................................................34 
7.4. 
Criteria for Study Termination ...................................................................................35 
8.
DESCRIPTION OF STUDY TREATMENTS ..........................................................36 
8.1. 
Description of Treatments ..........................................................................................36 
8.2. 
Safety Criteria and Management for Stopping Doses ................................................36 
8.3. 
Treatment Compliance ................................................................................................37 
8.4. 
Study Drug Materials and Management .....................................................................37 
8.4.1. 
Physical Description of Study Drug ...........................................................................38 
8.4.2. 
Study Drug Packaging, Labeling, and Storage ...........................................................38 
8.4.3. 
Study Drug Preparation and Administration ..............................................................38 
8.4.4. 
Study Drug Return and Disposal ................................................................................39 


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8.4.5. 
Study Drug Accountability .........................................................................................39 
8.5. 
Concomitant Medications and Procedures .................................................................39 
9.
STUDY ASSESSMENTS AND PROCEDURES ......................................................41 
9.1. 
Demographic Characteristics and Medical and Surgical History ...............................41 
9.2. 
Severity of Alopecia Tool (SALT) .............................................................................41 
9.3. 
Photographs ................................................................................................................42 
9.4. 
Visual Analog Scale (VAS) ........................................................................................42 
9.5. 
Global Impression Scales ...........................................................................................42 
9.5.1 
Clinical Global Impression of Improvement (CGI-I) .................................................42 
9.5.2 
Patient Global Impression of Improvement (PGI-I) ...................................................43 
9.5.3 
Clinical Global Impression of Severity (CGI-S) ........................................................43 
9.5.4 
Patient Global Impression of Severity (PGI-S) ..........................................................43 
9.6. 
Patient Satisfaction Questions ....................................................................................43 
9.7. 
Vital Signs, Weight, and Height .................................................................................43 
9.8. 
Physical Examination .................................................................................................43 
9.9. 
Electrocardiogram .......................................................................................................44 
9.10. 
Clinical Laboratory Assessments ...............................................................................44 
9.11. 
Unscheduled Visit .......................................................................................................45 
10.
ADVERSE EVENTS..................................................................................................46 
10.1. 
Definition of Adverse Event .......................................................................................46 
10.2. 
Evaluation of Adverse Events ....................................................................................46 
10.2.1. 
Serious Adverse Event ................................................................................................46 
10.2.2. 
Severity/Intensity ........................................................................................................47 
10.2.3. 
Relationship to Study Drug ........................................................................................48 
10.2.4. 
Duration ......................................................................................................................48 
10.2.5. 
Action Taken ..............................................................................................................49 
10.2.6. 
Outcome ......................................................................................................................49 
10.3. 
Follow-Up ...................................................................................................................49 
10.4. 
Pregnancy ...................................................................................................................49 
10.5. 
Recording Adverse Events .........................................................................................49 
10.6. 
Reporting Adverse Events ..........................................................................................50 
10.6.1. 
Reporting Serious Adverse Events .............................................................................50 
10.6.2. 
Reporting Urgent Safety Issues ..................................................................................50 
11.
STATISTICAL METHODS .......................................................................................51 


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11.1. 
Sample Size Rationale ................................................................................................51 
11.2. 
Endpoints ....................................................................................................................51 
11.2.1. 
Efficacy .......................................................................................................................51 
11.2.2. 
Safety ..........................................................................................................................51 
11.3. 
Analysis Populations ..................................................................................................51 
11.4. 
Analyses ......................................................................................................................52 
11.4.1. 
Disposition and Baseline Characteristics ....................................................................52 
11.4.2. 
Efficacy .......................................................................................................................52 
11.4.3. 
Study Drug Exposure ..................................................................................................52 
11.4.4. 
Safety ..........................................................................................................................52 
12. 
REGULATORY CONSIDERATIONS......................................................................55 
12.1. 
Good Clinical Practice ................................................................................................55 
12.2. 
Sponsor’s Responsibilities ..........................................................................................55 
12.3. 
Investigator’s Responsibilities ....................................................................................56 
12.4. 
Protocol Amendments ................................................................................................57 
12.5. 
Audits and Inspections ................................................................................................57 
12.6. 
Quality Control and Quality Assurance ......................................................................57 
13. 
DATA HANDLING AND RECORDKEEPING .......................................................58 
13.1. 
Confidentiality ............................................................................................................58 
13.2. 
Patient Data Protection ...............................................................................................58 
13.3. 
Data Collection ...........................................................................................................58 
13.4. 
Case Report Form Completion ...................................................................................59 
13.5. 
Database Management, Data Clarification, and Quality Assurance ...........................59 
13.6. 
Inspection of Records .................................................................................................59 
13.7. 
Retention of Records ..................................................................................................60 
14. 
PUBLICATION POLICY ..........................................................................................61 
15. 
LIST OF REFERENCES ............................................................................................62 
16. 
APPENDICES ............................................................................................................64 
16.1. 
Severity of Alopecia Tool (SALT) .............................................................................64 
16.2. 
Patient Satisfaction Questions ....................................................................................65 
16.2.1. 
Satisfaction of Hair Coverage Question .....................................................................65 
16.2.2. 
Satisfaction of Hair Coverage Quality Questions .......................................................66 
16.3. 
Patient Visual Analog Scale (VAS) for Eyebrows .....................................................67 
16.4. 
Global Impression Scales ...........................................................................................68 


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16.4.1. 
Clinical Global Impression of Improvement (CGI-I) .................................................68 
16.4.2. 
Patient Global Impression of Improvement (PGI-I) ...................................................69 
16.4.3. 
Clinical Global Impression of Severity (CGI-S) ........................................................70 
16.4.4. 
Patient Global Impression of Severity (PGI-S) ..........................................................71 


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LIST OF TABLES 
Table 1: 
Schedule of Events: Treatment Period .......................................................................14 
Table 2: 
Potency of CTP-543 in In Vitro Kinase Inhibition Assays .........................................24 
Table 3: 
Selected Hematologic Thresholds for Dose Interruption ...........................................37 
Table 4: 
Investigational Product ...............................................................................................38 
Table 5: 
Clinical Laboratory Assessments ...............................................................................45 
 
LIST OF FIGURES 
Figure 1: 
CP543.2003 Study Design ............................................................................................8 
Figure 2: 
Primary Analysis: Responders at Week 24 ................................................................26 
Figure 3: 
Primary Analysis: Responders by Visit ......................................................................27 
Figure 4: 
Study Design ...............................................................................................................29 
 
  


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AA 
Alopecia Areata 
BID 
Twice daily dosing 
CFR 
Code of Federal Regulations 
CGI-I 
Clinical Global Impression of Improvement 
CGI-S 
Clinical Global Impression of Severity 
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 
PGI-I 
Patient Global Impression of Improvement 
PGI-S 
Patient Global Impression of Severity 
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 


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Abbreviation or Specialist Term 
Explanation 
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 
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.  


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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. 
Dosing Regimen and Dose Selection 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).  Therefore, Concert will 
explore further the tolerability and efficacy of BID versus QD dosing with CTP-543.   
The selection of the 12 mg BID and 24 mg QD dose of CTP-543 for this study is supported by 
the safety data of CTP-543 observed in the multiple ascending dose (MAD) study in healthy 
volunteers as well as safety and efficacy data from an ongoing Phase 2 study in patients with 
moderate to severe AA.  
In the MAD study, doses of CTP-543 up to 16 mg BID and 32 mg QD were administered for 7 
consecutive days and appeared to be generally well-tolerated.  The MAD study, along with the 
preclinical safety package for the compound, supported the advancement of CTP-543 into an 
initial Phase 2 clinical trial in patients with AA (CP543.2001).   
CP543.2001 was designed as a sequential, double blind, placebo-controlled, Phase 2 study to 
assess CTP-543 at 4 mg BID and 8 mg BID compared to placebo over 24-weeks of dosing.  Each 
dosage strength was assessed sequentially and interim efficacy and safety results have been 
reported for the 4 mg BID and 8 mg BID 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 the 4 mg twice-daily cohort there was a 21% response; however, this was not 
significantly different from placebo.   


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An independent Data Monitoring Committee (DMC) was chartered for this study to routinely 
assess accumulated safety data.  The DMC met at predetermined intervals, to review existing 
unblinded safety data and to make recommendations whether to continue the existing protocol as 
planned and proceed to the next cohort or to modify the protocol based on the accumulated 
safety data.  Following a review of accumulated safety data for the 4 mg BID and 8 mg BID, the 
DMC were requested to review the available safety data to-date to determine if the safety data 
support the addition of an additional cohort of subjects to evaluate the safety and efficacy of a 
12 mg BID dose of CTP-543.   Based on a review of the accumulated safety data to-date, the 
DMC made the recommendation that escalation from the 8 mg BID cohort to the 12 mg BID 
cohort was warranted.  Subsequently, the CP543.2001 clinical protocol was submitted to the 
Food and Drug Administration (FDA).  Consequently, agreement to include an additional Cohort 
of subjects for the evaluation of a 12 mg BID was received from the FDA and the placebo 
controlled 12 mg BID cohort was initiated in October 2018.   
The 12 mg BID cohort is fully enrolled and the first subject enrolled has reached 16 weeks of 
dosing when the DMC convened its first meeting of the 12 mg BID cohort to review 
accumulated safety data to-date and agreed that the study should proceed as planned with no 
modifications to the protocol.  To-date, the 12 mg BID dose appears to be generally well 
tolerated with no dose interruptions due to hematologic abnormalities.  
The purpose of this current proposed study is to compare efficacy and safety of a 12 mg BID vs 
24 mg CTP-543 administered once daily. There is evidence with ruxolitinib (the non-deuterated 
form of CTP-543) in healthy volunteers that even with greater overall drug exposure, QD dosing 
may be better tolerated than BID dosing as evidenced by a higher maximum tolerated dose (Shi, 
et al, 2011). Therefore, given the approval of the DMC to study the 12 mg BID dose in the 
ongoing Phase 2 study and no safety data to date suggesting dose intolerability, there is 
reasonable justification to study 12 mg BID and the daily equivalent dose of 24 mg QD in this 
study. 
4.3. 
Preclinical Information for CTP-543 
The 
CTP-543 Investigator’s Brochure should be consulted for more detailed technical information, 
current discussion of nonclinical evaluations, and relevant information regarding the known 
safety profile of CTP-543 to date, and potential safety concerns based on known effects of 
ruxolitinib.  
4.4. 
Clinical Information 
4.4.1. 
Clinical Studies of CTP-543 
To date, 3 clinical studies have evaluated CTP-543. 
Two clinical studies with CTP-543 in healthy volunteers have been completed. Study 
CP543.1001 was a pharmacokinetic/pharmacodynamic study consisting of a first-in-human 
single ascending dose study and a sequential multiple ascending dose study.  The objective of the 
study was to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of CTP-543 in 
healthy volunteers.  A total of 82 subjects were planned for the study; 32 subjects in 4 cohorts 
randomized at a ratio of 3:1 CTP-543 to placebo for the single ascending dose part (Part A), and 
thereafter, 50 subjects in 5 cohorts randomized at a ratio of 4:1 CTP-543 to placebo for the 


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multiple ascending dose part (Part B). The doses studied in the single ascending dose study were 
8 mg, 16 mg, 32 mg, and 48 mg. The doses studied in the multiple ascending dose study were 8 
mg once daily, 8 mg twice daily, 24 mg once daily, 32 mg once daily, and 16 mg twice daily, 
dosed for 7 consecutive days. 
The second clinical study CP543.1002, also performed in healthy volunteers was a single dose 
cross-over study to assess safety and tolerability and to compare the metabolite and 
pharmacokinetic profiles of CTP-543 versus ruxolitinib. A total of 12 subjects were enrolled in 
the study; 2 groups of 6 subjects each were dosed with either 15 mg of ruxolitinib (1 x 15 mg 
tablet) or 16 mg of CTP-543 (2 x 8 mg tablets) in period 1 who then crossed over to the alternate 
treatment for period 2.  
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, is ongoing. 
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. 
Interim top line analysis for the 4 and 8 mg cohorts showed that 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) (Figure 2).   
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.  


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Figure 3: 
Primary Analysis: Responders by Visit 
 
CTP-543 was generally well tolerated and there were no serious adverse events reported.  The 
most common adverse events reported across treatment groups (4 mg, 8 mg, and placebo) 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 BID 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, and applicable local regulations.  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, and applicable local regulations. 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 24 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 are to assess the proportion of patients 
achieving defined threshold reductions in SALT score, and for patients to assess their eyebrows, 
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 (12 mg BID vs 24 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 12 mg 
BID, or CTP-543 24 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 2 x 12 mg tablets and  
2 x placebo tablets 12 hours apart from each other for the 24 mg QD study group.     
Figure 4: 
Study Design 
 
 
 
 


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Patients will provide informed consent prior to completing any screening procedures.   
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.  Periodic skin examinations are recommended to detect non-melanoma skin cancers 
including basal cell, squamous cell and Merkel cell carcinoma. 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 an 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, Visual Analog Scale (VAS) for 
eyebrows, Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Severity 
(PGI-S), and Patient Satisfaction questions. Patients meeting all eligibility criteria will be 
randomized to 1 of 2 CTP-543 treatment arms (12 mg BID or 24 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. Patient is willing to participate and is capable of giving informed consent. Note: Consent 
must be obtained prior to any study-related procedures. 
2. Male or Female patient between 18 and 65 years of age, inclusive, at the time of informed 
consent. 
3. Clinical presentation compatible with 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. 
Note: Other causes of hair loss such as cicatricial alopecia (pseudopelade), 
trichotillomania or syphilis should be ruled out if the clinical presentation is atypical or 
the history of recurrence and spontaneous remission is unclear.  
4. Patient has moderate to severe alopecia areata at Screening and Baseline visits as 
determined by a minimum of 50% scalp hair loss, as defined by a SALT score ≥50. 
5. Patients involved in any sexual intercourse that could lead to pregnancy:  
a. Females subjects of childbearing potential must agree to use a highly effective 
contraceptive method from at least 4 weeks prior to Baseline until at least 4 weeks 
after the last study product administration.  
i. Highly effective contraceptive methods include hormonal contraceptives 
(combined oral contraceptive, patch, vaginal ring, injectable, or implant), 
intrauterine devices or intrauterine systems, vasectomized partner(s), tubal 
ligation or bias barrier methods of contraception (e.g. male condom with 
cervical cap, male condom with diaphragm, and male condom with 
contraceptive sponge) in conjunction with spermicide.  
Note: Patients must have been on a stable dose of hormonal contraceptives 
for at least 4 weeks before Baseline.  
Note: The above list of contraceptive methods does not apply to patients 
who are abstinent for at least 4 weeks before Baseline and will continue to 
be abstinent from penile-vaginal intercourse throughout the study.  The 
reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the 
patient. 
ii. Female patient of childbearing potential has had a negative serum 
pregnancy test at Screening and negative urine pregnancy test at Baseline. 
Note: A female subject of nonchildbearing potential is defined as follows:  
– 
Female subject who has had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or bilateral salpingectomy) 
– 
Female subject who has had a cessation of menses for at least 12 months 
prior to the screening visit without an alternative medical cause 
 


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b. Male subjects must agree to use one of the highly effective contraceptive methods
listed in Inclusion Criterion 5.a.i., from Baseline until at least 4 weeks after the
last study product administration.  If the female partner of a male patient uses any
of the hormonal contraceptives methods listed above, this contraceptive method
must be used by the female partner from at least 4 weeks before Baseline until at
least 4 weeks after the last study product administration.
c.
Male subjects should not donate sperm during this study and for at least 30 days
after the end of study.
6. Patients must be 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 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 (intranasal and inhaled corticosteroids are allowed, eye and ear drops containing
corticosteroids are also allowed); topical or oral retinoids; oral cyclines (minocin,
tetracycline); platelet-rich plasma injections; topical application to affected areas of
anthralin, squaric acid, diphenylcyclopropenone, or minoxidil; antimalarials.
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 and hair style regimen, including shampoo
and hair products (including hair dye, process, and timing to hair appointments), and to
refrain from weaves or extensions 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 5 years are excluded.
9. Atypical nevi or cutaneous lesions that are suspicious for malignancy.
10. History of solid organ or hematological transplantation.


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11. Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive 
infection 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. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to 
hepatitis B core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening.  
18. Vaccination with herpes zoster vaccine or plans to receive a live attenuated vaccine 
during the study and up to 6 weeks or 5 half-lives (of the study product), whichever is 
longer, after the last study product administration.  
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.  
NOTE: Subjects with documented completed treated with latent TB are not excluded.   
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, 
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, 
telaprevir, telithromycin, voriconazole, or fluconazole) dosed for systemic exposure. 


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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 > 499 mL of blood or plasma within 56 days of Screening (during a 
clinical trial or at a blood bank donation) and for 30 days after last dose of study 
medication. 
27. Patient has a known or suspected allergy to CTP-543 or any component of the 
investigational product. 
28. Subject has had major surgery within 8 weeks prior to Baseline or has a major surgery 
planned during the study. 
29. Subject has received any UV-B phototherapy (including tanning beds), has had psoralen-
UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Baseline. 
30. Clinically significant medical condition or physical/laboratory/ECG/vital signs 
abnormality, 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.  
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 if they believe the safety of the 
patient or the integrity of the data are at risk.  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 (i.e., e.g. patient may be withdrawn 
if 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 
 Female patient becomes pregnant 
Patients who withdraw or are withdrawn from the study will not be replaced. 
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 1). 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. 


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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 12 mg BID (1 x 12 mg and 1 x placebo tablet every 12 hours)  
 CTP-543 24 mg QD (2 x 12 mg in the morning and 2 x placebo tablets 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 
12 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.  Study drug will be dispensed at study visits as specified in the schedule of events 
(Table 1).  To maintain the blind for investigators, subjects, and site personnel, subjects will take 
IP in the am and pm no matter which regimen they are assigned to:  

12 mg BID (1 x 12 mg in AM + placebo; 1 x 12 mg in PM + placebo)

24 mg QD (2 x 12 mg QD in AM; 2 x placebo in PM)
Additional details on the packaging, labeling and dispensing instructions can be found in the 
Study 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 approximately 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 not take two doses at the same time.  The missed dose should be 


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skipped and the patient should resume regular dosing at the next scheduled time.  Deviations 
from prescribed dosing should be discussed at each visit for assessment of compliance and 
retraining when necessary. 
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 Study 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 one month prior to Screening and 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 may 
require patient withdrawal from the study. 
The following treatments and procedures 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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 PUVA treatment, UV-B phototherapy (including tanning beds) or excimer laser, 
excessive sun exposure or use of tanning booths. 
 Obtain hair transplants. 
 
 
 


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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 and Surgical History 
Demographic characteristics (i.e., sex, ethnic origin, date of birth) 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 by the investigator during clinic 
visits.   
SALT will be used to determine efficacy for the study.  To reduce variability, one rater, 
whenever possible, 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 Study Manual for additional details regarding SALT scoring and training 


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requirements for this study. An example of the SALT assessment tool is provided in 
Appendix 16.1.  
9.3. 
Photographs 
Sites may 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, may 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) for Eyebrows 
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 for eyebrows will measure the patient’s eyebrows at the time of 
completion.  An example of the patient VAS for eyebrows is provided in Appendix 16.3. 
9.5.  
Global Impression Scales 
The Global Impression Scales are measures commonly used in clinical trials to allow integration 
of several sources of information into a single rating of the patient’s condition. The Global 
Impression Scales employ a Likert scale measuring either disease state severity or improvement 
after treatment. 
In this study, the Global Impression Scales of Improvement and Severity will be performed by 
both the clinician and the patient at selected times during the study as indicated in Table 1. The 
Global Impression of Severity should consider the condition of the patient at the time of the 
assessment. The Global Impression Scale of Improvement will consider the condition of the 
patient at the time of the assessment compared to Baseline. 
9.5.1  
Clinical Global Impression of Improvement (CGI-I) 
The Clinical Global Impression Scale of Improvement will be assessed by the Investigator and 
will consider the Investigator’s perceived change of the patient’s alopecia areata at the time of 
the assessment compared to Baseline.  The Investigator may select one of seven numeric choices 
representing “Very Much Worse” to “Very Much Improved”. To reduce variability, one rater 
should perform the CGI-I assessment for the patient for the duration of the study. An example of 
the CGI-I is provided in Appendix 16.4.1. 


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9.5.2  
Patient Global Impression of Improvement (PGI-I) 
The Patient Global Impression Scale of Improvement will be assessed by the patient and will 
consider his/her perceived change in alopecia areata at the time of the assessment compared to 
Baseline. The patient may select one of seven numeric choices representing “Very Much Worse” 
to “Very Much Improved”. An example of the PGI-I is provided in Appendix 16.4.2. 
9.5.3 
Clinical Global Impression of Severity (CGI-S) 
The Clinical Global Impression Scale of Severity will be assessed by the Investigator and will 
consider the severity of the patient’s alopecia areata at the time of assessment.  The Investigator 
may select one of five numeric choices representing “Extremely severe” to “Not at all severe”. 
To reduce variability, one rater should perform the CGI-S assessment for the patient.  An 
example of the CGI-S is provided in Appendix 16.4.3. 
9.5.4  
Patient Global Impression of Severity (PGI-S) 
The Patient Global Impression Scale of Severity will be assessed by the patient and will consider 
the severity of his/hers alopecia areata at the time of assessment. The Patient may select one of 
five numeric choices representing “Extremely severe” to “Not at all severe”. An example of the 
PGI-S is provided in Appendix 16.4.4. 
9.6. 
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 Appendix 16.2).  
9.7. 
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. 
9.8. 
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 periodic skin 
examinations are recommended to detect non-melanoma skin cancers including basal cell, 
squamous cell and Merkel cell carcinoma.  Exams will be performed as indicated in the Schedule 
of Events.  Brief physical examinations including abdominal palpation, head, eyes, ears, nose 
and throat assessment, and periodic skin examinations will be performed at all other intermediate 
visits as specified in Table 1.  


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9.9. 
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.   
9.10. 
Clinical Laboratory Assessments 
Clinical laboratory assessments are presented in Table 5 Clinical laboratory samples will be 
collected prior to study drug administration 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.  Subjects who do not qualify to participate in the study due to a screening laboratory 
value abnormality can repeat the test once within the original screening time window without 
resulting in screen failure, if the investigator believes there is a reasonable possibility that the 
subject would be eligible if re-tested. 
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 a medical history 
or an adverse event in the eCRF and may 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) 
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 
9.11. 
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 (i.e., 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.   
Laboratory results deemed Abnormal and clinically significant by the investigator will be 
recorded as an adverse event in the eCRF and should be fully investigated and repeated for 
verification.   
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);

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);


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
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 
handled by telephone. 
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


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
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 
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 


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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. 
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.  


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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: 
  
Name: 
, MD 
Telephone (24H/7D):  
 
Email: 
  
 
Serious Adverse Event Reporting Contact Information: 
 
Email: 
 
Fax: 
 
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. 
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 confidence 
intervals 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: 
 4, 8, 12, 16, 20, and 24 in the Treatment Period 
 Relative Change in SALT scores from baseline at Weeks: 
 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: 
 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 modified Intent-to-Treat (mITT) Population will include all patients who receive study drug 
and have at least 1 post-treatment SALT assessment.  Patients will be summarized according to 
study drug regimen to which they were randomized. A Per Protocol Population may be defined 
prior to blind break if >10% of patients have clinically significant protocol deviations.  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. 


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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. 
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.   
All treatment group comparisons for efficacy are for estimation purposes and no formal 
inferential testing will be performed.  
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, the confidence interval(s) for 
the dosing regimen difference at Week 24 will be calculated.  For categorical measures (e.g. 
proportion of responders), the confidence interval(s) 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. 


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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 
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 PCS laboratory values 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. 


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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. 
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

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


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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).   
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. 


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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.   
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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CONFIDENTIAL & PROPRIETARY 
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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 
individuals and the delegation of responsibilities, such as identifying those individuals who are 
authorized to make or change entries on eCRFs. 


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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.  
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: 


CTP-543 
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Protocol CP543.2003 
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
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, or local regulations will be applied, whichever retention period is longer.  
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. 


CTP-543 
 
 
 
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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. 


CTP-543 
 
 
 
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Protocol CP543.2003 
 
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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. 
Levy (2015) 
Levy LL, Urban J, King BA.Treatment of recalcitrant atopic dermatitis 
with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad 
Dermatol (2015) 73:395.   
Liu (2018) 
Liu LY, King BA. Tofacitinib for the Treatment of Severe Alopecia 
Areata in Adults and Adolescents. Journal of Investigative Dermatology 
Symposium Proceedings (2018) 19, S18eS20.  
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. 


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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. 
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. 


















CTP-543 
08 April 2019 
Protocol CP543.2003, 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 
CP543.2003, Protocol Amendment #1 
08 April 2019 
The main purpose of this amendment #1 (to original dated 15 February 2019), is to include 
United States to study centers on page 6 as the study will be conducted in Canada and United 
States. Additionally, a typo was corrected on page 35, Section 8.4.2. to change the 24 mg QD 
regimen (2 x 24 mg QD in AM) to (2 x 12 mg QD in the AM).   

SAP_003.pdf: 
Official Title: 
NCT Number: 
Document Date: 
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
NCT03941548 
SAP Version 1: 08 January 2020 


Concert Pharmaceuticals, Inc. – Protocol #: CP543.2003 
Clinical Study Report 
Confidential and proprietary. Permission should be obtained before any reproduction. 
16.1.9 Documentation of Statistical Methods 
CP543.2003 Statistical Analysis Plan V1.0, 08 January 2020 










STATISTICAL ANALYSIS PLAN,  
Final v1.0 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 5 of 39 
8 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................ 17 
9 
SURGICAL AND MEDICAL HISTORY ........................................................................... 19 
10 
PRIOR AND CONCOMITANT MEDICATIONS ............................................................. 19 
11 
STUDY TREATMENT EXPOSURE AND TREATMENT COMPLIANCE ................. 20 
12 
EFFICACY ANALYSIS ........................................................................................................ 20 
12.1 
Primary Efficacy Endpoint Analysis ............................................................................ 20 
12.2 
Secondary Efficacy Endpoint Analyses ........................................................................ 21 
12.2.1 
Responder Analysis: Proportion of patients achieving at 
least a 90%, 75%, and 50% in relative change from Baseline 
in SALT score at Weeks 4, 8, 12, 16, 20, and 24 ..........................21 
12.2.2 
Absolute change in SALT score from Baseline to Weeks 4, 
8, 12, 16, 20, and 24, and relative change in SALT score 
from Baseline to Weeks 4, 8, 12, 16, and 20 .................................21 
12.2.3 
Change in satisfaction of hair coverage as reported by the 
patient .............................................................................................22 
12.3 
Exploratory Efficacy Endpoint Analyses ..................................................................... 22 
12.3.1 
Change in patient’s eyebrows as measured by the patient’s 
Visual Analog Scale (VAS) ...........................................................22 
12.3.2 
Change in satisfaction of hair coverage quality as reported 
by patient ........................................................................................23 
12.4 
Other Efficacy Endpoint Analyses ............................................................................... 23 
12.4.1 
Proportion of Subjects with a Total SALT Score ≤ 10, 20, 
and 25 .............................................................................................23 
12.4.2 
Global Impression Scales ...............................................................23 
12.5 
Summary of Efficacy Endpoint Analyses .................................................................... 26 
13 
SAFETY/TOLERABILITY ANALYSIS ............................................................................. 31 
13.1 
Adverse Events ............................................................................................................... 31 
13.2 
Clinical Laboratory ........................................................................................................ 32 
13.3 
Vital Signs ....................................................................................................................... 33 
13.4 
Physical Examination .................................................................................................... 33 
13.5 
Electrocardiogram ......................................................................................................... 33 
14 
APPENDICES ........................................................................................................................ 34 


STATISTICAL ANALYSIS PLAN,  
Final v1.0 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 6 of 39 
 
 
ABBREVIATIONS 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
ATC 
Anatomic therapeutic chemical 
BID 
Twice daily 
BRS 
Back quadrant raw score 
CGI-I 
Clinical Global Impression of Improvement 
CGI-S 
Clinical Global Impression of Severity 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRO 
Clinical research organization 
CS 
Clinically significant 
CTCAE 
Common terminology criteria for adverse events 
ECG 
Electrocardiogram 
ET 
Early termination 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
LOCF 
Last Observation Carried Forward 
LRS 
Left quadrant raw score 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
NCS 
Not clinically significant 
PCS 
Potentially clinically significant 
PGI-I 
Patient Global Impression of Improvement 
PGI-S 
Patient Global Impression of Severity 
PP 
Per protocol 
PPD 
Purified protein derivative 
PT 
Preferred term 
QD 
Once daily 
































STATISTICAL ANALYSIS PLAN,  
Final v1.0 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 22 of 39 
12.2.3 Change in satisfaction of hair coverage as reported by the patient 
The patient satisfaction hair coverage questionnaire will be assessed by the patient. The patient 
might select one of the five numeric choices representing “very dissatisfied” (0) to “very 
satisfied” (4).  For consistency with the satisfaction of hair coverage quality questionnaire (see 
Section 12.3), responses to the satisfaction of hair coverage questionnaire will be rated 1 (“very 
dissatisfied”) to 5 (“very satisfied”) in the summaries and by-patient data listing. Missing data will 
not be imputed. 
Responses to patient satisfaction question will also be summarized based on the mITT analysis 
population by category, visit, and dosing regimen using count and percentage.   
The patient satisfaction hair coverage will be further categorized as ‘satisfied’ (i.e., including 
responses of ‘somewhat satisfied’, ‘mostly satisfied’, and ‘very satisfied’) or ‘dissatisfied’ (i.e., 
including responses of ‘dissatisfied’ and ‘very dissatisfied’). A shift table will be presented for 
change in satisfaction of hair coverage (satisfied vs. dissatisfied) as reported by the patient based 
on the mITT analysis population for each scheduled visit and each dosing regimen.  
No supportive and subgroup analyses will be performed. 
Patient satisfaction of hair coverage data will be displayed in a by-subject data listing. 
12.3 Exploratory Efficacy Endpoint Analyses 
12.3.1 Change in patient’s eyebrows as measured by the patient’s Visual Analog Scale (VAS) 
The VAS is a distinct 100-millimeter line anchored on the left end at full degree of impairment 
(no eyebrow) and on the right end at no degree on impairment (full eyebrow). 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.  To assess the degree of impairment, the VAS analysis 
value will be computed by subtracting the VAS recorded value from 100. Missing data will not be 
imputed. 
The VAS for each eyebrow will be summarized based on the mITT analysis population by visit 
and dosing regimen using descriptive statistics.  The change and percent change from Baseline in 
VAS will also be summarized similarly for each eyebrow.  Difference of the means in change and 
percent change from Baseline between the two dosing regimens will be provided along with a two-
sided 90% CI at each visit for each eyebrow. 
No supportive and subgroup analyses will be performed for this endpoint.  


STATISTICAL ANALYSIS PLAN,  
Final v1.0 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 23 of 39 
12.3.2 Change in satisfaction of hair coverage quality as reported by patient 
The patient satisfaction hair coverage quality questionnaire will be assessed by the patient. For 
each of the 7 questions, the patient might select one of the five numeric choices representing “very 
dissatisfied” (1) to “very satisfied” (5). Missing data will not be imputed. 
A similar analysis approach as outlined for the change in satisfaction of hair coverage secondary 
efficacy endpoint (refer to Section 12.2.3) will be used for the change in satisfaction of hair 
coverage quality total score.  No supportive and subgroup analyses will be performed for this 
endpoint. 
12.4 Other Efficacy Endpoint Analyses 
12.4.1 Responder Analysis: Proportion of patients achieving at least 80% in relative change 
from Baseline in SALT score at Weeks 4, 8, 12, 16, 20, and 24 
The proportion of patients achieving at least 80% in relative change from Baseline in SALT score 
at Weeks 4, 8, 12, 16, 20, and 24, frequency and proportion will be summarized and analyzed 
similarly to the proportion of patients achieving at least a 90%, 75%, and 50% relative change 
from Baseline in SALT score at Weeks 4, 8, 12, 16, 20, and 24 (refer to Section 12.2.1). 
12.4.2 Proportion of Subjects with a SALT Score ≤ 10 and ≤ 20 at Weeks 12 and 24 
The number and percentage of subjects with a SALT score ≤ 10 and ≤ 20 at Weeks 12 and 24 will 
be summarized based on the mITT analysis population by visit and dosing regimen.  The difference 
in percentages along with the two-sided Wald 90% CI will also be provided at each visit. 
No supportive and subgroup analyses will be performed for this endpoint. 
12.4.3 Global Impression Scales 
The global impression scales employ a Likert scale measuring either disease severity or 
improvement after treatment. In this study, the global impression scales of severity and 
improvement will be performed by both the clinician and patient. The global impression scale of 
severity should consider the condition of the patient at the time of the assessment while the global 
impression scale of improvement should consider the condition of the patient at the time of the 
assessment compared to Baseline. 
Clinical Global Impression of Severity (CGI-S) 
The CGI-S will be assessed by the Investigator and will consider the severity of the patient’s 
alopecia areata at the time of assessment. The Investigator may select one of the five numeric 
choices representing “Extremely severe” to “Not at all severe”. Missing data will not be imputed. 










STATISTICAL ANALYSIS PLAN,  
Final v1.0 
 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 28 of 39 
Efficacy Endpoint 
Collection Time 
Method  
Exploratory 
 
 
Change from Baseline in 
VAS for Eyebrows to 
Week 24 
Baseline and Week 24 
Descriptive statistics by visit and dosing regimen for each eyebrow 
separately with difference in means and two-sided 90% CI (t-distribution) 
for each post-baseline visit 
• Main analysis: with no imputation based on mITT analysis population  
• No supportive and subgroup analyses 
Change from Baseline in 
satisfaction of hair 
coverage quality to Week 
24 
Baseline and Week 24 
Descriptive statistics by visit and dosing regimen with difference in means 
and two-sided 90% CI (t-distribution) for each post-baseline visit 
• Main analysis: with no imputation based on mITT analysis population  
• No supportive and subgroup analyses 
Other 
 
 
Responder (80%) in 
relative change from 
Baseline in SALT score at 
Weeks 4, 8, 12, 16, 20, and 
24 
Baseline and Weeks 4, 
8, 12, 16, 20, and 24 
Count and proportion of subjects by visit and dosing regimen for each 
responder definition separately with difference in proportions and two-sided 
Wald 90% CI for each post-baseline visit 
• Main analysis: using LOCF imputation based on mITT analysis 
population 
• Supportive analysis: using LOCF imputation based on PP analysis 
population, if applicable 
• Subgroup analyses: using LOCF imputation based on mITT analysis 
population within each subtype of alopecia areata at Baseline 












STATISTICAL ANALYSIS PLAN,  
Final v1.0 
 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 34 of 39 
14 APPENDICES 
Appendix 1 
Table 1 provides a description of the procedures planned at each visit. 
 




STATISTICAL ANALYSIS PLAN,  
Final v1.0 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 36 of 39 
ET=Early termination; HBV= hepatitis B virus; HCV = hepatitis C virus; PPD = 
purified protein derivative. 
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 for subsequent visits.  
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 For females of childbearing potential, a serum pregnancy test will be performed at 
all visits aside from the randomization visit where a urine pregnancy test will be 
performed. 
6 If PPD (skin test) is performed, subject will need to return to the clinic 24-48 hours after 
placement for PPD reading.  
7 Includes hematology and serum chemistry.  
8 When possible, collect 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, when possible, for the patient for the duration of 
the study. 
12 For participants who authorize photographs to be taken of their scalp involvement and/or 
eye and nail involvement.  
13 Will be conducted at Visit 6 (Week 8) only.  
14 Collection is ongoing. 


STATISTICAL ANALYSIS PLAN,  
Final v1.0 
 
Protocol Number CP543.2003 
Sponsor: Concert Pharmaceuticals, Inc. 
 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date : 03-Jun-2018 
 Proprietary & Confidential 
Page 37 of 39 
Appendix 2 
Output Conventions 
TLF will be generated using SAS® and will be displayed on letter size paper with landscape 
orientation, 1-inch margins, and 9-point Courier New font. 
All TLFs will include a header section comprised of the Sponsor’s name, the protocol number, the 
delivery description, the data cut-off date (if applicable), the TLF number, the TLF title, the 
analysis population, and the page number (Page X of Y). The footer section will include the TLF 
footnotes, the CRO’s name, the date and time of the execution of the program, and the name of 
the program. 
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.   
Mean and median will be displayed to one more decimal place than the original value; SD and CI 
will be displayed to two more decimal places than the original value; minimum and maximum will 
keep the same number of decimal places as the original value. If derived parameters are to be 
summarized, the number of decimals of the derived values is to be chosen on a case-by-case basis, 
but the rule above applies. 
For categorical summary tables, percentages will be reported to one decimal place. Percentages 
between 0 and 0.1 (both exclusive) will be displayed as “<0.1”. Percentages between 99.9 and 
100.0 (both exclusive) will be displayed as “>99.9”. For each dosing regimen, the denominator for 
each percentage will be the number of patients within the population, unless otherwise specified. 
Listings will be ordered by dose regimen, patient number, parameter (where applicable), date, 
and visit (where applicable). Imputed dates and imputed missing data will not be presented in the 
listings. 
All statistical deliverables will be produced, validated, and reviewed for accuracy/consistency in 
accordance with 
 standard operating procedures.    
Dates & Times Format 
Date and time (if available) will be presented in the format yyyy-mm-dd/hh:mm. 
Presentation of Treatment Arms 
When applicable, study treatments will be represented as follows in the different outputs: