A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of CTP-543 in Adult Patients With Moderate to Severe Alopecia Areata (THRIVE-AA1)
Phase: PHASE3
Conditions: Alopecia Areata
Sponsor: Concert Pharmaceuticals

Official Title: 
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the 
Efficacy and Safety of CTP-543 In Adult Patients With Moderate 
NCT Number: 
Document Dates: 
to Severe Alopecia Areata 
NCT04518995
Protocol Amendment 5:  28 April 2021  

CTP-543 
Protocol CP543.3001 
28 April 2021 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
1 
A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF CTP-543 IN ADULT PATIENTS 
WITH MODERATE TO SEVERE ALOPECIA AREATA 
INVESTIGATIONAL PRODUCT: 
CTP-543 
PROTOCOL NUMBER: 
CP543.3001 
ORIGINAL PROTOCOL: 
AMENDMENT 1: 
AMENDMENT 2: 
AMENDMENT 3 (North America): 
AMENDMENT 4 (North America): 
AMENDMENT 5 (North America): 
24 June 2020 
26 August 2020 
15 October 2020 
18 February 2021 
23 February 2021 
28 April 2021 
EudraCT NUMBER: 
CLINICALTRIALS.GOV IDENTIFIER 
(NCT Number): 
2020‐ 002704‐ 40 
NCT04518995 
IND NUMBER: 
131,423 
SPONSOR NAME / ADDRESS: 
Concert Pharmaceuticals, Inc. 
65 Hayden Avenue, Suite 3000N 
Lexington, MA 02421 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 

CTP-543 
Protocol CP543.3001 
28 April 2021 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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 / EMERGENCY CONTACT INFORMATION 
North American 
 Contact Information 
Name 
 MD 
Title 
 
Address 
 
 
 
Phone 
Facsimile 
Email 
 AND 
 

CTP-543 
Protocol CP543.3001 
28 April 2021 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
3 
 
 
CONCERT SIGNATURE PAGE 
 
PROTOCOL TITLE: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the 
Efficacy and Safety of CTP-543 in Adult Patients with Moderate to Severe Alopecia Areata 
Protocol Number: CP543.3001, Amendment 5 (North America) 
 
 
 
 
 
 
28-Apr-2021 
Sponsor Representative Signature 
dd mmm yyyy 
, MS, 
 
Printed Name of Sponsor Representative 
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable. 

CTP-543 
Protocol CP543.3001 
28 April 2021 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: CP543.3001 
 
 
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/Ethics Committee procedures, instructions from Concert 
representatives, the Declaration of Helsinki, International Council on Harmonization 
Good Clinical Practices Guidelines, and local regulations governing the conduct of 
clinical studies. 

CONFIDENTIAL & PROPRIETARY 
 
CTP-543 
28 April 2021 
Protocol CP543.3001 
Concert Pharmaceuticals, Inc. 
 
 
SUMMARY OF CHANGES: PROTOCOL CP543.3001; AMENDMENT 5 (28 APRIL 2021) 
 
Section 
Previous Text 
New Text 
Reason for Revision 
Synopsis/Inclusion 
Criteria/ 
8.1/Patient Inclusion 
Criteria 
5. 
If of reproductive age, female participants and female 
partners of male participants, willing and able to use a 
medically highly effective form of birth control from at least 
4 weeks prior to Baseline until at least 30 days following last 
dose of study drug. Examples of medically highly effective 
forms of birth control are: 
a. 
Confirmed infertility due to surgical procedure or 
post-menopausal (cessation of menses for at least 
12 months prior to screening) 
5. 
Female subjects are eligible to participate if at least one of the following 
conditions applies: 
a) Is a woman of childbearing potential (WOCBP) and using a medically 
highly effective form of birth control with a failure rate less than 1% per 
year from at least 4 weeks prior to Baseline until at least 30 days 
following last dose of study drug. Examples of medically highly 
effective birth control methods include: 
i. 
Combined (estrogen and progestogen containing) hormonal 
contraception (oral, patch, vaginal ring) 
ii. 
Progestogen-only hormonal contraception associated with 
inhibition of ovulation (oral, injectable, implantable) 
iii. 
Intrauterine device or intrauterine hormone-releasing system 
iv. 
Bilateral tubal occlusion 
v. 
Vasectomized partner or partner of the same sex 
vi. 
Double barrier method (any combination of physical and chemical 
methods) 
b) Is not a WOCBP: 
i. 
Premenopausal with one of the following: 
a. 
Documented hysterectomy; 
b. Documented bilateral salpingectomy; 
c. 
Documented bilateral oophorectomy. 
ii. 
Postmenopausal (cessation of menses for at least 12 months prior 
to screening) 
Postmenopausal is defined as no menses for at least 12 months 
prior to screening without an alternative medical cause. 
Criteria modified for 
consistency with 
European protocol for 
CP543.3001. Inclusion 
criteria remains 
unchanged, just 
expanded upon for 
clarity. 
b. 
Confirmed infertility of sexual partner or partner 
of the same sex 
c. 
Implants of levonorgestrel in females 
d. 
Oral contraceptive (combined, patch, vaginal 
ring, injectable, implant) in females 
e. 
Double-barrier method (any combination of 
physical and chemical methods) 
f. 
Intrauterine device with a failure rate less than 
1% per year 
8.3/Patient 
Withdrawal Criteria 
• Experience an intolerable adverse event: such events include, but are 
not limited to, adverse events ≥ Grade 4*, bone marrow-related 
events, a ≥ Grade 3* cardiac event (*CTCAE v5.0 criteria); 
• 
Experience an intolerable adverse event, including but not limited to 
bone marrow related events characterized by protocol specified 
hematologic abnormalities, or a ≥ Grade 3 cardiac event, or a ≥ Grade 4 
(other) adverse event (CTCAE v5.0 criteria) considered possibly related to 
study drug. Because laboratory abnormalities can occasionally occur that 
do not in themselves pose an unacceptable risk to subject safety (e.g., CK 
elevations with exercise, laboratory errors or artifacts), the occurrence of 
a ≥ Grade 4 laboratory abnormality, or any laboratory abnormality of 
concern to the Investigator, will be discussed with the Medical Monitor 
and a determination will be made, based on a reassessment of risk-benefit 
for the subject, whether the subject should discontinue randomized 
treatment. Documentation on the determination will be maintained in the 
study files 
Modified criteria for 
clarity 
9.2.1/Dose 
Patients who withdraw consent and therefore are discontinued from the 
study should undergo an Early Termination Visit and subsequent 
Safety Follow up Visit as appropriate per Section 8.3.1 Patient 
Withdrawal Procedures, and associated adverse events followed as 
described in Section 11 Adverse Events. 
Patients who withdraw consent and therefore are discontinued from the study 
Clarified Safety follow- 
Interruption Safety 
should undergo an Early Termination Visit and associated adverse events 
up will not occur for 
Criteria and 
should be followed as described in Section 11 Adverse Events. 
patients who Withdraw 
Management 
Consent during study 
conduct. 

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CONFIDENTIAL & PROPRIETARY 
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1. 
SYNOPSIS 
 
Name of Sponsor/Company: 
Concert Pharmaceuticals, Inc. 
Name of Investigational Product: 
CTP-543 
Name of Active Ingredient: 
Deuterated ruxolitinib 
Title of Study: 
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of CTP- 
543 in Adult Patients with Moderate to Severe Alopecia Areata 
Study center(s): Multicenter study; approximately 70 sites (North America and European Union) 
Studied period (years): 
Estimated date first patient first visit: October 2020 
Estimated date last subject last visit: February 2022 
Phase of development: 3 
Objectives: 
The overall objectives of the study are to assess the efficacy and safety following administration of 
CTP-543 in adult patients with moderate to severe alopecia areata. 
The primary objectives of the study are to assess: 
• 
The efficacy of CTP-543 on regrowth of hair following 24 weeks of treatment 
• 
The safety of CTP-543 following 24 weeks of treatment. 
The secondary objectives of the study are to assess: 
• 
Clinician- and patient-reported impression of the severity and improvement of alopecia areata 
• 
Patient-reported satisfaction with their scalp hair 
• 
Patient-reported levels of anxiety and depression 
• 
Changes in eyebrows and eyelashes. 
Methodology: 
This is a double-blind, randomized, placebo-controlled multicenter study to evaluate the efficacy and 
safety of CTP-543 in adult patients with moderate to severe alopecia areata. Patients will be between 
18 and 65 years of age and experiencing an episode of hair loss associated with alopecia areata lasting 
at least 6 months and not exceeding 10 years. Patients not currently being treated for alopecia areata or 
with other treatments that might affect hair regrowth or immune response must have at least 50% hair 
loss as measured by SALT at Screening and Baseline. 
An independent Data Monitoring Committee (DMC) will perform regular safety assessments based on 
a review of cumulative safety data. The DMC may advise study and/or treatment arm cessation due to 
intolerability at any time. 
The Screening Period may last up to 28 days prior to initiation of study drug. The Treatment Period is 
a 24-week, double-blind, placebo-controlled period. Following the 24-week Treatment Period, patients 
will have the opportunity to continue receiving treatment in an Open-Label Extension study. If a 
patient does not wish to continue into the Open-Label Extension study, they will complete treatment at 
Week 24 and return in 4 weeks for the Post-Treatment Safety Follow-up to assess safety following 
treatment completion. 

CTP-543 
Protocol CP543.3001 
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Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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Extension study, they will complete treatment at Week 24 and return in 4 weeks for the Post-Treatment 
Safety Follow-up to assess safety following treatment completion. 
Number of patients (planned): 
Approximately 700 patients are planned to be randomized in the study. Patients will be randomized in 
a 3:5:2 ratio (12 mg BID:8 mg BID:placebo). 
Diagnosis and main criteria for inclusion: 
Patients eligible for enrollment in the study must meet all of the following inclusion criteria and none 
of the exclusion criteria. 
Inclusion Criteria: 
1. Written informed consent, and authorization for release and use of protected health 
information. 
2. Between 18 and 65 years of age, inclusive, at the time of informed consent. 
3. Definitive diagnosis of alopecia areata with a current episode of scalp hair loss lasting at least 
6 months and not exceeding 10 years at the time of Screening. Total disease duration greater 
than 10 years is permitted. 
4. At least 50% scalp hair loss, as defined by a SALT score ≥50, at Screening and Baseline. 
5. Female subjects are eligible to participate if at least one of the following conditions applies: 
a) Is a woman of childbearing potential (WOCBP) and using a medically highly effective 
form of birth control with a failure rate less than 1% per year from at least 4 weeks prior to 
Baseline until at least 30 days following last dose of study drug. Examples of medically 
highly effective birth control methods include: 
i. Combined (estrogen and progestogen containing) hormonal contraception 
(oral, patch, vaginal ring) 
ii. Progestogen-only hormonal contraception associated with inhibition of 
ovulation (oral, injectable, implantable) 
iii. Intrauterine device or intrauterine hormone-releasing system 
iv. Bilateral tubal occlusion 
v. Vasectomized partner or partner of the same sex 
vi. Double barrier method (any combination of physical and chemical methods) 
b) Is not a WOCBP: 
i. 
Premenopausal with one of the following: 
a. Documented hysterectomy; 
b. Documented bilateral salpingectomy; 
c. Documented bilateral oophorectomy. 
ii. 
Postmenopausal (cessation of menses for at least 12 months prior to 
screening) 
Postmenopausal is defined as no menses for at least 12 months prior to 
screening without an alternative medical cause. 
6. Male participants must: 
a. Agree to use, with their partners, one of the highly effective contraceptive methods 
listed in Inclusion Criterion 5, from Baseline until at least 30 days following last dose 
of study drug. 
b. Refrain from donating sperm during the study and for at least 30 days after the end of 
the study. 
7. Willing to comply with the study visits and requirements of the study protocol. 

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Exclusion Criteria: 
1. History or presence of hair transplants. 
2. Treatment with other medications or agents within 1 month of Baseline or during the study that 
may affect hair regrowth or immune response, including but not limited to: corticosteroids 
administered orally, intravenously or intramuscularly, or applied to areas of skin affected by 
alopecia (intranasal and inhaled corticosteroids are allowed, eye and ear drops containing 
corticosteroids are also allowed); oral retinoids, oral cyclines (minocin, tetracycline); platelet- 
rich plasma injections; topical application to affected areas of retinoids, anthralin, squaric acid, 
diphenylcyclopropenone, or minoxidil. 
3. Treatment with systemic immunosuppressive medications including but not limited to 
methotrexate, cyclosporine, azathioprine, chloroquine derivatives, etanercept, JAK inhibitors 
within 3 months of Screening or during the study. 
NOTE: Patients previously treated with a Janus Kinase inhibitor more than 3 months prior to 
Screening may be allowed to enter the study at the discretion of the PI, if their previous 
treatment with a JAK inhibitor was well tolerated, and subsequent JAK treatment would not be 
thought to put the subject at risk. Consultation with the Medical Monitor may be warranted 
should questions arise with regard to prior tolerability. 
4. Treatment with biologics (e.g., adalimumab, atlizumab, canakinumab, certolizumab, 
fontolizumab, golimumab, infliximab, mepolizumab, rituximab, secukinumab, tocilizumab, 
ustekinumab) within 6 months of Screening or during the study. 
5. 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. 
6. Known history of moderate to severe androgenic alopecia or female pattern hair loss prior to 
alopecia areata. 
7. Unwilling to maintain a consistent hair style, including shampoo and hair products (including 
hair dye, process, and timing to hair appointments), and to refrain from weaves or extensions 
throughout the course of the study, or shaving of scalp hair for 2 weeks preceding a SALT 
assessment. 
8. Use of adhesive wigs, other than banded perimeter wigs, during the study. 
9. History of a lymphoproliferative disease or malignancy, other than non-melanoma skin cancer 
or cervical carcinoma. Patients with 3 or more basal or squamous cell carcinomas diagnosed 
in the past 2 years are excluded. 
10. History of solid organ or hematological transplantation. 
11. Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection 
or a positive SARS-CoV-2 test result within 2 weeks prior to Baseline. 
12. Abnormal levels of thyroid stimulating hormone at Screening, defined as <0.9 x the lower 
limit of normal (LLN) and >1.5 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 ≤100 x 109/L or ≥ 600 x 109/L 
b. Absolute neutrophil count ≤1.5 x 109/L 
c. Hemoglobin levels ≤10.5 g/dL for females, or hemoglobin levels ≤12.0 g/dL for males 
14. Screening blood level of hemoglobin A1c ≥7.5% (58 mmol/mol, 9.3 mmol/L). 
15. Abnormal liver function at Screening, defined as ≥2 × ULN of serum alanine transaminase, 
serum aspartate transaminase, and serum alkaline phosphatase, or ≥1.5 x ULN total bilirubin 
(unless isolated Gilbert’s syndrome). 

CTP-543 
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16. Abnormal renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 using the 
CKD-EPI 2009 equation) at Screening. 
17. Patient has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B 
core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening, or known history of human 
immunodeficiency virus infection. Subjects who test positive for HCV but who are in 
remission (sustained virologic response as evidenced by undetectable HCV RNA level using a 
sensitive assay≥ 12 weeks after completion of HCV therapy) are allowed inclusion in the 
study. 
18. Vaccination with a live attenuated vaccine during the study or up to 6 weeks prior to 
randomization. 
19. History of previous active disease due to M. tuberculosis (TB) without documentation of 
successful treatment; OR, patient has a positive result from a Tuberculin Skin Test (TST) or a 
QuantiFERON-TB Gold (QFT) test performed at Screening. 
NOTE: If the patient has a positive QFT result at Screening and: (1) has no history of 
successful treatment for either active disease or latent infection due to M. tuberculosis, or (2) 
currently resides in an area with low prevalence of tuberculosis, or (3) has no lifetime history 
of occupational or household exposure to person(s) with tuberculosis, then the initial Screening 
QFT result may be a false-positive. In this instance, a second Screening test for latent TB 
infection should be obtained – either: (1) a repeat QFT test or (2) a Tuberculin Skin Test 
(TST). The repeat QFT test must be negative or the TST should show <15mm induration 
(considered negative TST) before being considered eligible for the study. 
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 drug. 
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 drug. 
27. Clinically significant medical condition, psychiatric disease, or social condition, as determined 
by the Investigator, that may unfavorably alter the risk-benefit of study participation, adversely 
affect study compliance, or confound interpretation of study results. 
Investigational product, dosage and mode of administration: 
CTP-543 will be dosed orally as tablets at doses of 8 mg or 12 mg every 12 hours during the Treatment 
Period. 
Reference therapy, dosage and mode of administration: 
Matching placebo will be dosed orally as tablets every 12 hours during the Treatment Period 
Duration of treatment: 

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28 April 2021 
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Patients will receive up to 24 weeks of study drug. 
Duration of study participation: 
Upon completion of the 24-week Treatment Period, patients will be eligible to either enroll in the 
Open-Label Extension study or complete treatment and exit the study following the 4-week Safety 
Follow-up visit. Patients will participate in the study for up to 32 weeks if they decide not to enroll in 
the Open-Label Extension study (4-week Screening, 24-week Treatment, 4-week Safety Follow-up). 
Otherwise study duration will be up to approximately 28 weeks. 
Criteria for evaluation: 
Primary Efficacy Endpoint 
 
The primary efficacy endpoint will be the percentage of patients achieving an absolute SALT 
score ≤20 at Week 24. 
Key Secondary Endpoints 
 
Percentage of responders (defined as “satisfied” or “very satisfied”) on the Hair Satisfaction 
Patient Reported Outcome (SPRO) scale at Week 24 
 
Percentage of patients achieving an absolute SALT score of ≤20 at Week 20, 16, 12 and 8 
For the primary efficacy analysis and in a hierarchical fashion within each dose level, key secondary 
efficacy analysis, a ≤ 0.025 (two-sided) alpha-level will be allocated to each dose for comparison with 
placebo to adjust for multiplicity of testing associated with two doses. Additional testing for secondary 
endpoints, in the order specified (see Section 12.4.3) (within each dose versus placebo) will continue to 
be tested at 0.025, in an alpha-level protected fashion, until not significant at 0.025. Nominal p-values 
will be reported for all tests, irrespective.  Testing will be performed only for the Treatment Period. 
Secondary Endpoints 
 
Relative change in SALT scores from Baseline at Weeks 4, 8, 12, 16, 20, and 24 
 
Percentage of responders (defined as “much improved” or “very much improved”) using the 
CGI-I at Weeks 12, 16, 20, and 24 
 
Percentage of responders (defined as “much improved” or “very much improved”) using the 
PGI-I at Weeks 12, 16, 20, and 24 
 
Change from Baseline in the CGI-S at Weeks 12, 16, 20,  and 24 
 
Change from Baseline in the PGI-S at Weeks 12, 16, 20, and 24 
 
Percentage of patients achieving at least a 75% relative reduction in SALT score from Baseline 
at Weeks 12 and 24 
 
Percentage of patients achieving at least a 90% relative reduction in SALT score from Baseline 
at Weeks 12 and 24 
 
Change from Baseline on the Brigham Eyebrow Tool for Alopecia (BETA) score at Weeks 12 
and 24 
 
Change from Baseline on the Brigham Eyelash Tool for Alopecia (BELA) score at Weeks 12 
and 24 
 
Percentage of responders (defined as “satisfied” or “very satisfied”) on the Hair Satisfaction 
Patient Reported Outcome (SPRO) scale at Weeks 12, 16, and 20 
 
Change from Baseline in the Hair Satisfaction Patient Reported Outcome (SPRO) scale at 
Weeks 12, 16, 20, and 24 
 
Percentage of patients achieving a ≥ 2-point change from Baseline in the Hair Satisfaction 
Patient Reported Outcome (SPRO) scale at Weeks 12, 16, 20, and 24 
 
Change from Baseline on the individual items of the Hair Quality Patient Reported Outcome 
(QPRO) scale at Weeks 12, 16, 20, and 24 

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 
Change from Baseline in the depression scale of the Hospital Anxiety and Depression Scale 
(HADS) at Week 24 
 
Change from Baseline in the anxiety scale of the Hospital Anxiety and Depression Scale 
(HADS) at Week 24 
 
Percentage of patients achieving an absolute SALT score of ≤20 at Weeks 8 and 4 
 
Percentage of patients achieving an absolute SALT score of ≤10 at Week 24 
There is no additional control for Type-1 error for the secondary endpoints. 
Additional exploratory statistical analyses to further assess for treatment effect will be outlined in the 
Statistical Analysis Plan finalized prior to database lock for the Primary Efficacy Analysis. 
Safety 
Safety and tolerability of CTP-543 will be assessed by evaluating adverse events, vital signs, 
concomitant medications, and clinical laboratory results, as well as physical examinations. 
Statistical methods: 
Sample Size: 
Power is calculated for the Primary Efficacy Endpoint for the chi-square test using a 2-sided 
significance level of 0.025. Based on Phase 2 results, the percentage of patients achieving an absolute 
SALT score ≤20 at Week 24 is assumed to be 40%, 25%, and 10% for the CTP-543 12 mg, CTP-543 
8 mg BID, and placebo groups, respectively. Patients will be randomized in a 3:5:2 ratio with a total 
N of approximately 700 patients (i.e., 210 for 12 mg BID, 350 for 8 mg BID, and 140 for placebo). 
These sample sizes will provide >99% power for the comparison of CTP-543 12 mg BID versus 
placebo and approximately 94% power for the comparison of CTP-543 8 mg BID versus placebo. 
Efficacy Analyses: 
The Efficacy Population will include all patients who are randomized in the study and dispensed study 
drug during the Treatment Period. The primary efficacy endpoint will be the proportion of patients 
achieving an absolute SALT score of ≤20 at Week 24. Pairwise treatment group differences from 
placebo will be assessed with the Cochran-Mantel-Haenszel test using baseline scalp hair loss (partial 
vs complete/near-complete) as the stratification factor, for each active treatment group versus placebo. 
Data will be summarized by active treatment versus placebo-treated patients (i.e., by treatment group). 
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. 
The final efficacy analysis will be conducted when all patients in the study have had the opportunity to 
complete Week 24. Additional details for statistical methods will be provided in the Statistical 
Analysis Plan. 
Safety Analyses: 
The Safety Population will include all patients who receive study drug during the Treatment Period. 
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. Adverse events, vital sign measurements, physical examination 
findings, clinical laboratory information, and concomitant medications will be tabulated and 
summarized by treatment and dose level. By-patient listings will be provided for any deaths, serious 
adverse events, and adverse events leading to discontinuation of treatment. 

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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
 
SUMMARY OF CHANGES: PROTOCOL CP543.3001; AMENDMENT 5 (28 APRIL 
2021)   .............................................................................................................................5 
1. 
SYNOPSIS ............................................................................................................... 6 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .............. 13 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................... 18 
4. 
INTRODUCTION .................................................................................................. 19 
4.1. 
Overview of Alopecia Areata .................................................................................. 19 
4.2. 
Scientific Rationale for the Study............................................................................ 19 
4.3. 
Nonclinical Information for CTP-543 ..................................................................... 20 
4.4. 
Clinical Information for CTP-543 ........................................................................... 20 
4.4.1. 
Clinical Studies of CTP-543 in Healthy Subjects .................................................... 20 
4.4.2. 
Clinical Studies of CTP-543 in Patients with Alopecia Areata ................................ 21 
5. 
ETHICS.................................................................................................................. 23 
5.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) ...................................... 23 
5.2. 
Written Informed Consent ...................................................................................... 23 
6. 
STUDY OBJECTIVES ........................................................................................... 24 
6.1. 
Primary Objectives ................................................................................................. 24 
6.2. 
Secondary Objectives ............................................................................................. 24 
7. 
OVERALL STUDY DESIGN ................................................................................ 25 
7.1. 
Study Design .......................................................................................................... 25 
7.2. 
Number of Patients and Sites .................................................................................. 27 
7.3. 
Method of Treatment Assignment and Blinding ...................................................... 27 
7.4. 
Rationale for Study Design, Doses, and Primary Endpoint ...................................... 27 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ............................................ 31 
8.1. 
Patient Inclusion Criteria ........................................................................................ 31 
8.2. 
Patient Exclusion Criteria ....................................................................................... 32 
8.3. 
Patient Withdrawal Criteria..................................................................................... 34 
8.3.1. 
Patient Withdrawal Procedures ............................................................................... 35 
8.4. 
Emergency Unblinding of Treatment Assignment ................................................... 35 
8.5. 
Criteria for Study Termination ................................................................................ 35 

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9. 
DESCRIPTION OF STUDY TREATMENTS ........................................................ 37 
9.1. 
Description of Treatments ....................................................................................... 37 
9.2. 
Dose-Adjustment Criteria ....................................................................................... 37 
9.2.1. 
Dose Interruption Safety Criteria and Management ................................................. 37 
9.3. 
Treatment Compliance ............................................................................................ 39 
9.4. 
Study Drug Materials and Management .................................................................. 39 
9.4.1. 
Physical Description of Study Drug ........................................................................ 39 
9.4.2. 
Study Drug Packaging, Labeling, and Storage......................................................... 40 
9.4.3. 
Study Drug Preparation and Administration ............................................................ 40 
9.4.4. 
Study Drug Return and Disposal ............................................................................. 40 
9.4.5. 
Study Drug Accountability ..................................................................................... 40 
9.5. 
Concomitant Medications and Procedures ............................................................... 41 
10. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 43 
10.1. 
Demographic Characteristics and Medical History .................................................. 43 
10.2. 
Severity of Alopecia Tool (SALT) .......................................................................... 43 
10.3. 
Photographs ............................................................................................................ 44 
10.4. 
Global Impression Scales ........................................................................................ 44 
10.4.1. 
Clinical Global Impression of Severity (CGI-S) ...................................................... 44 
10.4.2. 
Clinical Global Impression of Improvement (CGI-I) ............................................... 45 
10.4.3. 
Patient Global Impression of Severity (PGI-S) ........................................................ 45 
10.4.4. 
Patient Global Impression of Improvement (PGI-I) ................................................. 45 
10.5. 
Hair Satisfaction and Hair Quality Patient Reported Outcomes ............................... 45 
10.6. 
HADS..................................................................................................................... 45 
10.7. 
BETA ..................................................................................................................... 46 
10.8. 
BELA ..................................................................................................................... 46 
10.9. 
Vital Signs, Weight, and Height .............................................................................. 46 
10.10. 
Physical Examination ............................................................................................. 46 
10.11. 
Electrocardiogram .................................................................................................. 47 
10.12. 
Clinical Laboratory Assessments ............................................................................ 47 
10.13. 
Unscheduled Visit .................................................................................................. 48 
11. 
ADVERSE EVENTS .............................................................................................. 49 
11.1. 
Definition of Adverse Event ................................................................................... 49 
11.2. 
Evaluation of Adverse Events ................................................................................. 50 
11.2.1. 
Serious Adverse Event ............................................................................................ 50 

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11.2.2. 
Severity/Intensity .................................................................................................... 51 
11.2.3. 
Relationship to Study Drug ..................................................................................... 51 
11.2.4. 
Duration ................................................................................................................. 52 
11.2.5. 
Action Taken .......................................................................................................... 52 
11.2.6. 
Outcome ................................................................................................................. 52 
11.3. 
Follow-Up .............................................................................................................. 52 
11.4. 
Pregnancy ............................................................................................................... 53 
11.5. 
Recording Adverse Events ...................................................................................... 53 
11.6. 
Reporting Adverse Events....................................................................................... 53 
11.6.1. 
Reporting Serious Adverse Events .......................................................................... 53 
11.6.2. 
Reporting Urgent Safety Issues ............................................................................... 54 
12. 
STATISTICAL METHODS ................................................................................... 55 
12.1. 
Sample Size Rationale ............................................................................................ 55 
12.2. 
Endpoints ............................................................................................................... 55 
12.2.1. 
Efficacy .................................................................................................................. 55 
12.2.2. 
Safety ..................................................................................................................... 56 
12.3. 
Analysis Populations .............................................................................................. 56 
12.3.1. 
Treatment Period .................................................................................................... 56 
12.4. 
Analyses ................................................................................................................. 56 
12.4.1. 
Disposition and Baseline Characteristics ................................................................. 57 
12.4.2. 
Efficacy .................................................................................................................. 57 
12.4.3. 
Multiplicity ............................................................................................................. 58 
12.4.4. 
Missing Data for SALT-based endpoints ................................................................ 59 
12.4.5. 
Multiple Imputation ................................................................................................ 60 
12.4.5.1. 
Analysis of Imputed Datasets .................................................................................. 60 
12.4.5.2. 
Tipping Point Analyses ........................................................................................... 60 
12.4.6. 
Study Drug Exposure .............................................................................................. 61 
12.4.7. 
Safety ..................................................................................................................... 61 
12.4.8. 
Interim Analyses ..................................................................................................... 63 
13. 
REGULATORY CONSIDERATIONS ................................................................... 64 
13.1. 
Good Clinical Practice ............................................................................................ 64 
13.2. 
Sponsor’s Responsibilities ...................................................................................... 64 
13.3. 
Investigator’s Responsibilities ................................................................................ 65 
13.4. 
Protocol Amendments............................................................................................. 66 

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13.5. 
Audits and Inspections ............................................................................................ 67 
13.6. 
Quality Control and Quality Assurance ................................................................... 67 
14. 
DATA HANDLING AND RECORDKEEPING ..................................................... 68 
14.1. 
Confidentiality ........................................................................................................ 68 
14.2. 
Patient Data Protection ........................................................................................... 68 
14.3. 
Data Collection ....................................................................................................... 68 
14.4. 
Case Report Form Completion ................................................................................ 69 
14.5. 
Database Management, Data Clarification, and Quality Assurance ......................... 69 
14.6. 
Inspection of Records ............................................................................................. 69 
14.7. 
Retention of Records .............................................................................................. 70 
15. 
PUBLICATION POLICY....................................................................................... 71 
16. 
LIST OF REFERENCES ........................................................................................ 72 
17. 
APPENDICES ........................................................................................................ 73 
17.1. 
Clinical Laboratory Assessments ............................................................................ 73 
17.2. 
Severity of Alopecia Tool (SALT) .......................................................................... 74 
17.3. 
Global Impression Scales ........................................................................................ 75 
17.3.1. 
Clinical Global Impression of Severity (CGI-S) ...................................................... 75 
17.3.2. 
Clinical Global Impression of Improvement (CGI-I) ............................................... 75 
17.3.3. 
Patient Global Impression of Severity (PGI-S) ........................................................ 76 
17.3.4. 
Patient Global Impression of Improvement (PGI-I) ................................................. 76 
17.4. 
Patient Reported Outcome ...................................................................................... 77 
17.4.1. 
Satisfaction of Hair Patient Reported Outcome (SPRO) .......................................... 77 
17.4.2. 
Quality of Hair Patient Reported Outcome (QPRO) ................................................ 78 
17.5. 
Hospital Anxiety and Depression Scale (HADS) ..................................................... 79 

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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ........................................................................ 18 
Table 2: 
Schedule of Assessments ........................................................................................ 29 
Table 3: 
Selected Hematologic Thresholds for Dose Interruption.......................................... 38 
Table 4: 
SARS-CoV-2 Dose Interruption Criteria ................................................................. 39 
Table 5: 
Investigational Product ........................................................................................... 39 
 
LIST OF FIGURES 
Figure 1: 
Study Design .......................................................................................................... 26 

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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1: 
Abbreviations and Specialist Terms 
 
Abbreviation or Specialist Term 
Explanation 
BID 
Twice daily dosing 
CFR 
Code of Federal Regulations 
CGI-I 
Clinician Global Impression of Improvement 
CGI-S 
Clinician Global Impression of Severity 
CTCAE 
Common terminology criteria for adverse events 
CYP3A4 
Cytochrome P450 3A4 
DMP 
Data Management Plan 
EC 
Ethics Committee 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HADS 
Hospital Anxiety and Depression Scale 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
IRB 
Institutional Review Board 
JAK 
Janus kinase 
LLN 
Lower Limit of Normal 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
MedDRA 
Medical Dictionary for Regulatory Activities 
PCS 
Potentially clinically significant 
PGI-I 
Patient Global Impression of Improvement 
PGI-S 
Patient Global Impression of Severity 
QPRO 
Quality of Hair Patient Reported Outcome 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected for heart rate (Fridericia’s method) 
SALT 
Severity of Alopecia Tool 
SPRO 
Satisfaction of Hair Patient Reported Outcome 
STAT 
Signal transducers and activators of transcription 
TEAE 
Treatment-emergent adverse events 
ULN 
Upper Limit of Normal 

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4. 
INTRODUCTION 
4.1. 
Overview of Alopecia Areata 
Alopecia areata (AA) is an autoimmune disorder characterized by patches of non-scarring 
alopecia affecting scalp or scalp and body hair. Alopecia Areata is clinically heterogeneous, 
affects males and females, and has a prevalence rate of approximately 0.2% of the United States 
population (Safavi, 1992; Benigno, 2020). 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). 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), Health Canada, or any Competent Authority in the European Union 
indicating a significant unmet medical need. 
4.2. 
Scientific Rationale for the Study 
Recent advances in the understanding of the pathogenesis of AA have shown Janus kinase (JAK) 
inhibitors to be a promising novel therapy. 
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 a murine model of AA, CD81 T cells were 
shown to be central in AA, causing up-regulation of interleukin-15 in hair follicles and 
ultimately production of interferon-gamma, which targets the hair follicle for attack (Xing, 
2014). As downstream regulators of interferon-gamma and interleukin-15, JAK inhibitors have 
been shown to eliminate the interferon signature and reverse disease. 
CTP-543 is a selective JAK inhibitor. 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 
determined. CTP-543 was found to have potent and selective inhibitory activity for intracellular 
JAK1 and JAK2 (IC50 (nM) = 4.7 and 20, respectively) signaling. 

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There is evidence that CTP-543 has benefit in patients with moderate to severe alopecia areata. 
Three Phase 2 clinical studies of CTP-543 have been conducted in patients with moderate to 
severe alopecia areata. The first Phase 2 study was a double-blind, randomized, placebo- 
controlled, dose-ranging clinical trial. The overall objectives of the study were to assess the 
safety and efficacy of a 24-week regimen of administration of 4, 8, or 12 mg BID CTP-543 
compared with matching placebo in adult patients with moderate to severe alopecia areata. The 
primary efficacy endpoint was the proportion of responders, defined as patients achieving at least 
a 50% relative reduction in SALT score at Week 24 relative to Baseline. The primary efficacy 
endpoint was met in both the 8 mg BID group and 12 mg BID groups. The difference between 
the 4 mg BID group and the placebo group was not statistically significant. The 8 mg BID and 
12 mg BID doses also produced significant results vs placebo when other analyses of SALT data 
(i.e., percentage of patients achieving SALT ≤ 20) were conducted as well as analyses of patient 
and clinician reported global impression. The 8 mg BID and 12 mg BID doses were further 
assessed in two additional Phase 2 dose regimen clinical trials (see Section 4.4.2) in which once- 
daily versus twice-daily dosing with CTP-543 were assessed. 
The definitive dose-ranging study (CP543.2001) and the completed dose regimen studies 
(CP543.2002 and CP543.2003) demonstrated that both the 8 mg BID and 12 mg BID doses of 
CTP-543 are effective and generally well tolerated. Consequently, both of these doses will be 
studied in this Phase 3 registration study in adult patients with alopecia areata. 
Summaries of all clinical studies conducted to-date can be found in Section 4.4 below. Further 
details are provided in the current CTP-543 Investigator’s Brochure. 
 
4.3. 
Nonclinical Information for CTP-543 
A series of nonclinical studies were performed with CTP-543, which evaluated the in vitro and in 
vivo pharmacokinetic (PK) and metabolism properties, safety pharmacology, toxicology and 
toxicokinetics, and genotoxicity. All safety pharmacology and toxicology studies considered 
necessary for human safety assessment were conducted in compliance with Good Laboratory 
Practice regulations. 
Further details of the nonclinical studies for CTP-543 are described in the Investigator’s 
Brochure. 
 
4.4. 
Clinical Information for CTP-543 
4.4.1. 
Clinical Studies of CTP-543 in Healthy Subjects 
To date, five Phase 1 studies have been completed in healthy subjects, evaluating the safety, 
tolerability, and PK profile of single and multiple ascending doses of CTP-543: a single dose 
crossover study of CTP-543 versus ruxolitinib; a food effect study of CTP-543; a mass-balance 
study, and a drug-drug interaction (DDI) study with oral contraceptive (OC). A brief description 
of these studies is described below. Further details of the Phase 1 studies for CTP-543 are 
described in the Investigator’s Brochure. 
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 subjects. 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 

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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 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. CTP-543 was generally well 
tolerated in these studies and showed a dose proportional PK profile. 
Study CP543.1002 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 or 16 mg of CTP-543 in Period 1 who then crossed over to the alternate treatment 
for Period 2. CTP-543 was generally well tolerated in this study and showed an increase in PK 
parameters compared to ruxolitinib. 
Study CP543.1003 was a cross-over study to characterize and compare the relative 
bioavailability and PK profile of CTP-543 and metabolites under both fed and fasted conditions. 
A total of 14 subjects were enrolled and received single oral doses of 16 mg CTP-543. The 
administration of 16 mg CTP-543 under fed conditions resulted in a statistically significant 
decrease (approximately 40%) in peak exposure but not in total exposure compared to 
administration under fasted conditions. Single oral doses of 16 mg CTP-543 appeared to be well 
tolerated in both fasted and fed conditions. 
Study CP543.1004 assessed the absorption, metabolism, excretion, and mass balance of oral 
[14C]-CTP-543 in healthy adult male subjects. The study showed that there are no circulating 
metabolites above 10% of drug related material. Additionally, all metabolites in excreta are 
below 25% of drug related material. No adverse events were reported in this study. 
Study CP543.1005 was a 2-period, fixed-sequence study to determine the effect of multiple 
doses of CTP-543 on single dose pharmacokinetics (PK) of the components of a combination 
OC, ethinyl estradiol (EE) and levonorgestrel (LNG). Multiple oral doses of 12 mg CTP-543 
administered BID on Days 1 – 8 had no impact on EE overall and peak exposures following 
coadministration with a single dose of combination OC (0.03 mg EE / 0.15 mg LNG). Multiple 
oral doses of 12 mg CTP-543 administered BID on Days 1 - 8 increased LNG overall and peak 
exposures by approximately 17% and 16%, respectively, following coadministration with a 
single dose of combination OC (0.03 mg EE / 0.15 mg LNG) compared to Combination OC 
alone. This small increase in LNG exposure is not expected to impact the efficacy or safety of 
the OC. Overall, there were no new findings and AEs reported were consistent with previously 
reported safety data from other CTP-543 studies. 
 
4.4.2. 
Clinical Studies of CTP-543 in Patients with Alopecia Areata 
Three Phase 2 studies in patients with moderate to severe AA have been completed. An Open- 
Label Extension study is currently ongoing. Qualifying patients from the completed Phase 2 
trials were eligible to enroll in the Open-Label Extension study and continue to receive either 8 
mg BID or 12 mg BID CTP-543 for an additional 108 weeks. For full details of these studies, 
please see the CTP-543 Investigator’s Brochure. 
Study CP543.2001 was a double-blind, randomized, placebo-controlled Phase 2 dose ranging 
study to evaluate the safety and efficacy of CTP-543 in adult patients with moderate to severe 
alopecia areata. A total of 149 adults with moderate to severe alopecia areata were enrolled 

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across three cohorts. Patients were sequentially randomized to receive one of three doses of 
CTP-543 (4, 8, 12 mg twice daily) or placebo for 24 weeks. 
The overall objectives of the study were to assess the safety and efficacy of a 24-week regimen 
of administration of 4, 8, or 12 mg BID CTP-543 compared with matching placebo in adult 
patients with moderate to severe alopecia areata. The primary efficacy endpoint was the 
proportion of responders, defined as patients achieving at least a 50% relative reduction in SALT 
score, from Baseline at Week 24. The primary efficacy endpoint was met in both the 8 mg BID 
group and the 12 mg BID group. The difference between the 4 mg BID group and the placebo 
group was not statistically significant. 
The primary efficacy endpoint result was supported by results of exploratory endpoints utilizing 
SALT as well as clinician-based assessments and patient reported outcomes. The 8 mg BID and 
12 mg BID groups differentiated from placebo on various SALT analyses and had significant 
improvements in alopecia areata as measured by the CGI-I and PGI-I compared with the placebo 
group. 
The improvements in alopecia areata symptoms observed in the CTP-543 treatment groups were 
progressive over time through 24 weeks and appeared to be dose responsive. Significant 
differences from placebo were noted as early as 12 weeks into treatment. 
CTP-543 was generally well tolerated in all Cohorts. 
Study CP543.2002 was a randomized, open-label study to evaluate the efficacy and tolerability 
of two dosing regimens (8 mg BID versus 16 mg QD) of CTP-543 in adult patients with 
moderate to severe alopecia areata. Fifty-seven patients were randomized to receive 
CTP-543 either 8 mg BID or 16 mg QD over a 24-week treatment period.  The trial measured the 
relative change in SALT score between Week 24 and Baseline. Efficacy results in the 8 mg BID 
arm were consistent with the previously-reported 8 mg BID results from the CP543.2001 trial 
and showed superiority of the 8 mg BID dose group over the 16 mg QD dose group. Treatment 
was generally well tolerated in both arms of the study. 
CP543.2003 was a randomized, open-label study to evaluate the efficacy and tolerability of two 
dosing regimens (12 mg BID versus 24 mg QD) of CTP-543 in adult patients with moderate to 
severe alopecia areata. Sixty-six patients were randomized to receive CTP-543 either 12 mg 
BID or 24 mg QD over a 24-week treatment period. The trial measured the relative change in 
SALT score between Week 24 and Baseline. The primary outcome for the CP543.2003 study 
was the relative change in SALT score for each dose regimen from Baseline at Week 24. 
Following 24 weeks of dosing, subjects in the 12 mg BID dose group had a 60% relative change 
to Baseline in total SALT score at Week 24 compared to 52% in the 24 mg QD dose group. 
CTP-543 was generally well tolerated in both 24 mg/day dosing regimens. 
Both dose regimen studies support the continued use of the BID dosing regimen in the Phase 3 
program. 
Study CP543.5001 is an Open-Label Extension study in patients with alopecia areata who were 
previously enrolled in a qualifying clinical trial with CTP-543 and completed through the 24- 
week Treatment Period. Patients will receive daily treatment with CTP-543 at a dose of 8 mg 
BID or 12 mg BID for up to 164 weeks in this study. Previously qualifying CTP-543 clinical 
trials include: Cohort 3 from Study CP543.2001, Study CP543.2002, and Study CP543.2003. 
Taken together, the safety results of the Phase 2 clinical trials performed to-date appeared to 
show an overall acceptable risk-benefit profile for CTP-543. 

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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 Council on Harmonisation (ICH) 
guidelines and directives. Compliance with these regulations also constitutes compliance with 
the ethical principles described in the current revision of the Declaration of Helsinki and 
applicable local regulatory requirements and law. 
The Investigator is responsible for protecting the rights, safety, and welfare of patients under 
his/her care, and for the control of the medications under investigation. All ethical, regulatory, 
and legal requirements must be met before the first patient is enrolled in the study. 
 
5.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) 
The Institutional Review Board (IRB)/Ethics Committee (EC) will meet all regulatory authority 
requirements governing IRBs/ECs according to local regulations (e.g., 21 CFR Part 56, ICH E6). 
The study protocol and any amendments, the Sponsor’s approved informed consent form(s) 
(ICF), patient information sheets, patient recruitment materials, and other appropriate documents 
must be submitted to the IRB/EC by delegated study personnel 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) or Investigator dependent upon who is 
responsible for the initial submission. 
Any advertisements used to recruit patients for the study will be reviewed by the Sponsor and the 
IRB/EC 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/EC, must follow the Protection of Human 
Subjects regulations listed in the Code of Federal Regulations, Title 21, Part 50 or Directive 
2001/20/EC, and local country regulations. 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/EC and by the Sponsor. 
The ICF must not be altered without the prior agreement of the relevant IRB/EC and the 
Sponsor. 

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6. 
STUDY OBJECTIVES 
The overall objectives of the study are to assess the efficacy and safety of CTP-543 in adult 
patients with moderate to severe alopecia areata. 
 
6.1. 
Primary Objectives 
The primary objectives of the study are to assess: 
 The efficacy of CTP-543 on regrowth of hair following 24 weeks of treatment 
 The safety of CTP-543 following 24 weeks of treatment. 
6.2. 
Secondary Objectives 
The secondary objectives of the study are to assess: 
 Clinician- and patient-reported impression of the severity and improvement of alopecia 
areata 
 Patient-reported satisfaction with their scalp hair 
 Patient-reported levels of anxiety and depression 
 Changes in eyebrows and eyelashes. 

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7. 
OVERALL STUDY DESIGN 
7.1. 
Study Design 
This is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the efficacy 
and safety of CTP-543 in adult patients with moderate to severe alopecia areata. Patients will 
require a definitive diagnosis of alopecia areata by the Investigator based on clinical evaluation 
involving physical examination and medical history. The patient’s alopecia areata will be 
classified by the Investigator into one of two categories defined for this study: 
1) Partial scalp hair loss (SALT score ≥ 50 and < 95); 
2) Complete or near-complete scalp hair loss (SALT ≥ 95). 
Patients will be between 18 and 65 years of age and experiencing a current episode of hair loss 
associated alopecia areata lasting at least 6 months and not exceeding 10 years. Total disease 
duration may exceed the duration of the current episode. Patients will require at least 50% hair 
loss as measured by the SALT assessment at Screening and Baseline, and should not be treated 
concurrently for alopecia areata or with other treatments that might affect hair regrowth. 
An independent Data Monitoring Committee (DMC) will perform regular safety assessments. 
The DMC will convene to review accumulated safety data at regular intervals specified in the 
DMC Charter. The DMC will determine if there are adequate safety data to support continuation 
of a particular dose group or individual patient and may advise study and/or treatment arm 
cessation due to intolerability at any time. 
The Screening Period may last up to 28 days prior to initiation of study drug. The Treatment 
Period is a 24-week, double-blind, placebo-controlled period to define efficacy and safety for 
CTP-543. Following the 24-week Treatment Period, patients will have the opportunity to 
continue receiving treatment in an Open-Label Extension study. If a patient does not wish to 
continue into the Open-Label Extension study, they will complete treatment at Week 24 and 
return in 4 weeks for the Post-Treatment Safety Follow-up to assess safety following treatment 
completion. 

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Screening 
Up to 4 Weeks 
CTP-543, 8 mg BID 
Randomization 
CTP-543, 12 mg BID 
Placebo 
Figure 1: 
Study Design 
 
 
 
 
 
OR 
 
 
 
 
Patients will provide appropriately-obtained informed consent prior to initiating any screening 
procedures. Patients meeting initial screening criteria will be eligible to continue to the Day 1 
visit for review of eligibility and baseline assessments, including SALT assessment, physical 
examination, clinical laboratory assessments, and vital signs. Patients will be randomized in a 
3:5:2 ratio (12 mg BID:8 mg BID:placebo). Randomization will be stratified by scalp hair loss 
into one of the following two categories: 1) Partial scalp hair loss (SALT ≥ 50 and < 95); 2) 
Complete or near-complete scalp hair loss (SALT ≥ 95). 
The double-blind, placebo-controlled Treatment Period for each group will last 24 weeks. 
Assessment of treatment response using SALT will occur at 4, 8, 12, 16, 20 and 24 weeks. All 
SALT assessments will be performed with a live physical examination of the patient by 
qualified, trained site personnel. Photographs of the scalp will be used to provide a visual record 
at the time of SALT assessments. Photographs of the eyebrows and eyelashes will be taken at 
Baseline, Week 12, and Week 24 as outlined in Table 2. Photographs of hands will be taken at 
the same timepoints as eyebrows and eyelashes to document nail involvement in those patients 
for whom it applies. The primary efficacy analysis will be conducted when all patients have 
completed Week 24. 
Enrolled patients will take the first dose of study drug in the clinic on Day 1 and will be 
instructed to take study drug daily approximately every 12 hours without regard to food, for the 
duration of the Treatment Period. Patients should take study drug in the clinic on all Study Visit 
Days after clinical laboratory blood draws are completed. All efficacy, patient and clinician 
reported outcomes, and laboratory and safety assessments will be conducted according to the 
Schedule of Assessments (Table 2). 
Patient safety will be monitored throughout the study by the Investigator and appropriate staff, 
and supported by regular review by the Medical Monitor, and DMC. Chemistry, hematology, 
and lipid laboratory values will be monitored closely for the duration of the study. Chemistry 
and hematology laboratory values will be assessed bi-weekly for the first month of the treatment 
period, followed by every 4 weeks through the remainder of the study. Lipid levels (fasted) will 
Safety Follow-Up 
4 Weeks 
Treatment Period 
24 Weeks 
Study Duration: Up to a Total of 32 Weeks 
Open-Label Extension 

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be assessed every 4 weeks throughout the Treatment Period. In light of the COVID-19 
pandemic, challenges in the conduct of study visits may arise from quarantines, site closures, 
and/or travel limitations. To ensure the safety of trial participants and to minimize risk to trial 
integrity, alternative methods for drug dispensation and assessments, including telemedicine 
visits and clinical laboratory blood draws at a local laboratory or via a Home Health Care 
agency, may be offered for those trial participants who may no longer have access to the 
investigational site. Additional information will be documented in study manuals. Significant 
cytopenias or other hematologic abnormalities will be managed by severity through dose 
interruption or discontinuation, and signs and symptoms of infection will be closely monitored 
and treated promptly. Patients who experience intolerable symptoms during treatment may 
discontinue treatment at the judgement of the Investigator, but will continue in the study and 
complete all assessments unless they withdraw consent. Patients may withdraw consent at any 
time. 
 
7.2. 
Number of Patients and Sites 
Approximately 700 patients are planned to be randomized in the study at approximately 70 study 
centers. 
 
7.3. 
Method of Treatment Assignment and Blinding 
Patients will be randomized in a 3:5:2 ratio (12 mg BID:8 mg BID:placebo). Randomization will 
be stratified by scalp hair loss into one of the following two categories: 1) Partial scalp hair loss 
(SALT ≥ 50 and < 95); 2) Complete or near-complete scalp hair loss (SALT ≥ 95). The 
randomization schedule will be generated prior to study start. 
All study patients, Investigators, and site study staff will be blinded to study drug assignment for 
the duration of the study. Tablets and packaging of CTP-543 and placebo will be identical in 
appearance. 
 
7.4. 
Rationale for Study Design, Doses, and Primary Endpoint 
Double-blind, randomized, placebo-controlled studies are considered optimal for obtaining 
unbiased estimates of the efficacy and safety of investigational products. The Severity of 
Alopecia Tool (SALT) (Olsen, 2004) was introduced as part of investigative guidelines 
published by the National Alopecia Areata Foundation is widely used to assess the extent of the 
scalp surface hair loss in AA. The SALT has been used as the hair loss measurement scale in all 
the studies of CTP-543 in patients with alopecia areata to date. The 24-week duration of the 
Treatment Period has been shown to be sufficient in establishing hair regrowth with CTP-543 
and to significantly differentiate active doses from placebo as well as differentiate between doses 
of CTP-543. 
The selection of the 8 mg and 12 mg BID doses of CTP-543 for this study is supported by the 
efficacy and safety of CTP-543 observed in the completed and analyzed Phase 2 CP543.2001, 
CP543.2002, and CP543.2003 studies. Analysis of the primary efficacy endpoint in CP543.2001 
showed that the proportions of responders (patients achieving at least a 50% relative reduction in 
SALT score from Baseline at Week 24) were significantly greater in the 8 mg BID group and 
12 mg BID group compared with the placebo group (P <0.001 for both) and compared with the 
4 mg BID group (P = 0.030 and P = 0.003, respectively).  For the analysis performed on the 
efficacy population, 9.3% of patients in the placebo group and 21.4% of patients in the 4 mg BID 

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group were responders, compared with 47.4% in the 8 mg BID group and 58.3% in the 12 mg 
BID group. Results also showed a significantly greater proportion of responders in the 8 mg 
BID and 12 mg BID groups which had at least 50%, 75%, and 90% relative reduction in SALT 
score by Week 24 compared with both the placebo group and the 4 mg BID group. 
Additionally, both the 8 mg BID group and the 12 mg BID group had significantly greater 
proportions of patients who achieved an absolute SALT score ≤20 at Week 24 compared with 
the placebo group. Achieving a SALT score ≤ 20 has been reported by AA patients and 
clinicians to represent clinically-meaningful treatment success for AA (Wyrwich, 2020). In the 
Wyrwich study, qualitative interviews were conducted in the US with hair expert dermatologists 
and AA patients who had experienced ≥50% scalp hair loss. The clinicians judged that 80% 
scalp hair represented treatment success. Adult and adolescent AA patients participating in the 
study perceived that, short of 100% scalp hair, the presence of ~70-90% scalp hair (median 80%) 
represented treatment success. Nearly all queried clinicians and patients in this study agreed that 
for patients with ≥ 50% scalp hair loss, successful treatment would be hair regrowth resulting in 
≤ 20% scalp hair loss. 
Therefore, based on the efficacy and safety data observed in the CP543.2001, CP543.2002, and 
CP543.2003 studies, 8 mg BID and 12 mg BID of CTP-543 will be assessed further for efficacy 
and safety in the Phase 3 program in patients with moderate to severe alopecia areata. This 
Phase 3 study will employ SALT as the hair loss assessment tool and the primary efficacy 
endpoint will be the percentage of patients who achieve a SALT score ≤ 20, as this represents a 
clinically-meaningful treatment success for patients with AA. 

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Table 2: 
Schedule of Assessments 
 
Event1 
Screening 
Baseline/ 
Randomization 
Treatment Period4 
Safety 
Follow-Up 
Day -28 to Day -12 
(Visit 1) 
Day 13 
(Visit 2) 
Week 2 
(Visit 3) 
Week 4, 8, 12 
(Visit 4, 5, 6) 
Week 16, 20 
(Visit 7, 8) 
Week 24 
(Visit 9)/ ET 
Visit 
Week 28 
(Visit 10)5 
Informed consent 
X 
Eligibility assessment 
X 
X 
Demographics 
X 
Medical history 
X 
X 
Randomization 
X 
Complete physical examination 
X 
X 
X 
X 
Brief physical examination 
X 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
X 
Pregnancy test6 
X 
X 
X 
X 
X 
X 
Tuberculosis test 
X 
Clinical laboratory testing7,8 
X9 
X 
X10 
X 
X 
X 
X 
HBV and HCV test 
X 
12-lead electrocardiogram 
X 
X12 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
Severity of Alopecia Tool assessment11 
X 
X 
X 
X 
X 
Photographs of the scalp 
X 
X 
X 
X 
X 
Photographs of eyebrows, eyelashes, and hands 
X 
X12 
X 
Eyebrow Assessment (BETA) 
X 
X12 
X 
Eyelash Assessment (BELA) 
X 
X12 
X 
Patient Reported Outcome Scales: SPRO and QPRO 
X 
X12 
X 
X 
Patient and Clinical Global Impression of Improvement (PGI-I, 
CGI-I11) 
X12 
X 
X 
Patient and Clinical Global Impression of Severity (PGI-S, CGI-S11) 
X 
X12 
X 
X 
Hospital Anxiety and Depression Scale (HADS) 
X 
X 
Dispense study drug13 
X 
X 
X 
Study drug accountability 
X 
X 
X 
Adverse events14 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications14 
X 
X 
X 
X 
X 
X 
X 

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6 Serum pregnancy test only for females of childbearing potential 
7 Includes hematology, serum chemistry, and lipids (fasted) performed by the central 
lab. 
8 Collected pre-dose. 
9 Will include thyroid stimulating hormone and hemoglobin A1c at Screening only. 
10 Will include hematology and serum chemistry only. 
11 Should be performed by the same rater for the patient for the duration of the study. 
12 Performed at Week 12 only. 
13 Due to COVID-19, Direct to Patient (DTP) shipping services may be warranted in 
cases where a patient is not able to attend in clinic visits or a site is closed. 
14 Collection is ongoing. 
HBV = hepatitis B virus; HCV = hepatitis C virus 
1 Due to the COVID-19 pandemic, patient study visits may be performed remotely when 
the provider and patient are not able to be physically present in the clinic. Study personnel 
should strive to perform assessments per the schedule of events above with the 
understanding that all assessments may not be able to be performed (ECGs, vitals, SALT 
assessments). 
2 Randomization/Day 1 may occur any time after eligibility has been confirmed. 
3 All subsequent visits and week increments should be based on the date of Visit 2 (Day 1). 
4 All visit windows are ±2 days. 
5 The Safety Follow-Up Visit is intended for those patients who do not roll over into the 
Open-Label Extension. 

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8. 
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. 
 
8.1. 
Patient Inclusion Criteria 
1. Written informed consent, and authorization for release and use of protected health 
information. 
2. Between 18 and 65 years of age, inclusive, at the time of informed consent. 
3. Definitive diagnosis of alopecia areata with a current episode of scalp hair loss lasting at 
least 6 months and not exceeding 10 years at the time of Screening. Total disease 
duration greater than 10 years is permitted. 
4. At least 50% scalp hair loss, as defined by a SALT score ≥50, at Screening and Baseline. 
5. Female subjects are eligible to participate if at least one of the following conditions applies: 
a) Is a woman of childbearing potential (WOCBP) and using a medically highly effective form 
of birth control with a failure rate less than 1% per year from at least 4 weeks prior to 
Baseline until at least 30 days following last dose of study drug. Examples of medically 
highly effective birth control methods include: 
i. 
Combined (estrogen and progestogen containing) hormonal contraception (oral, 
patch, vaginal ring) 
ii. Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable) 
iii. Intrauterine device or intrauterine hormone-releasing system 
iv. Bilateral tubal occlusion 
v. Vasectomized partner or partner of the same sex 
vi. Double barrier method (any combination of physical and chemical methods) 
b) Is not a WOCBP: 
i. 
Premenopausal with one of the following: 
a. Documented hysterectomy; 
b. Documented bilateral salpingectomy; 
c. Documented bilateral oophorectomy. 
ii. 
Postmenopausal (cessation of menses for at least 12 months prior to screening) 
Postmenopausal is defined as no menses for at least 12 months prior to 
screening without an alternative medical cause. 
6. Male participants must: 
a. Agree to use, with their partners, one of the highly effective contraceptive methods 
listed in Inclusion Criterion 5, from Baseline until at least 30 days following last dose 
of study drug. 
b. Refrain from donating sperm during the study and for at least 30 days after the end of 
the study. 
7. Willing to comply with the study visits and requirements of the study protocol. 

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8.2. 
Patient Exclusion Criteria 
1. History or presence of hair transplants. 
2. Treatment with other medications or agents within 1 month of Baseline or during the 
study that may affect hair regrowth or immune response, including but not limited to: 
corticosteroids administered orally, intravenously or intramuscularly, or applied to areas 
of skin affected by alopecia (intranasal and inhaled corticosteroids are allowed, eye and 
ear drops containing corticosteroids are also allowed); oral retinoids, oral cyclines 
(minocin, tetracycline); platelet-rich plasma injections; topical application to affected 
areas of retinoids, anthralin, squaric acid, diphenylcyclopropenone, or minoxidil. 
3. Treatment with systemic immunosuppressive medications including but not limited to 
methotrexate, cyclosporine, azathioprine, chloroquine derivatives, etanercept, JAK 
inhibitors within 3 months of Screening or during the study. 
NOTE: Patients previously treated with a Janus Kinase inhibitor more than 3 months 
prior to Screening may be allowed to enter the study at the discretion of the PI, if their 
previous treatment with a JAK inhibitor was well tolerated, and subsequent JAK 
treatment would not be thought to put the subject at risk. Consultation with the Medical 
Monitor may be warranted should questions arise with regard to prior tolerability. 
4. Treatment with biologics (e.g., adalimumab, atlizumab, canakinumab, certolizumab, 
fontolizumab, golimumab, infliximab, mepolizumab, rituximab, secukinumab, 
tocilizumab, ustekinumab) within 6 months of Screening or during the study. 
5. 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. 
6. Known history of moderate to severe androgenic alopecia or female pattern hair loss 
prior to alopecia areata. 
7. Unwilling to maintain a consistent hair style, including shampoo and hair products 
(including hair dye, process, and timing to hair appointments), and to refrain from weaves 
or extensions throughout the course of the study, or shaving of scalp hair for 2 weeks 
preceding a SALT assessment. 
8. Use of adhesive wigs, other than banded perimeter wigs, during the study. 
9. History of a lymphoproliferative disease or malignancy, other than non-melanoma skin 
cancer or cervical carcinoma. Patients with 3 or more basal or squamous cell carcinomas 
diagnosed in the past 2 years are excluded. 
10. History of solid organ or hematological transplantation. 
11. Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive 
infection or a positive SARS-CoV-2 test result within 2 weeks prior to Baseline. 
12. Abnormal levels of thyroid stimulating hormone at Screening, defined as <0.9 x the 
lower limit of normal (LLN) and >1.5 x the upper limit of normal (ULN). 

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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 ≤100 x 109/L or ≥ 600 x 109/L 
b) Absolute neutrophil count ≤1.5 x 109/L 
c) Hemoglobin levels ≤10.5 g/dL for females, or hemoglobin levels ≤12.0 g/dL for 
males 
14. Screening blood level of hemoglobin A1c ≥7.5% (58 mmol/mol, 9.3 mmol/L). 
15. Abnormal liver function at Screening, defined as ≥2 × ULN of serum alanine 
transaminase, serum aspartate transaminase, and serum alkaline phosphatase, or ≥1.5 x 
ULN total bilirubin (unless isolated Gilbert’s syndrome). 
16. Abnormal renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2 using 
the CKD-EPI 2009 equation) at Screening. 
17. Patient has positive results for hepatitis B surface antigens (HBsAg), antibodies to 
hepatitis B core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening, or known 
history of human immunodeficiency virus infection. Subjects who test positive for HCV 
but who are in remission (sustained virologic response as evidenced by undetectable 
HCV RNA level using a sensitive assay≥ 12 weeks after completion of HCV therapy) are 
allowed inclusion in the study. 
18. Vaccination with a live attenuated vaccine during the study or up to 6 weeks prior to 
randomization. 
19. History of previous active disease due to M. tuberculosis (TB) without documentation of 
successful treatment; OR, patient has a positive result from a Tuberculin Skin Test (TST) 
or a QuantiFERON-TB Gold (QFT) test performed at Screening. 
NOTE: If the patient has a positive QFT result at Screening and: (1) has no history of 
successful treatment for either active disease or latent infection due to M. tuberculosis, or 
(2) currently resides in an area with low prevalence of tuberculosis, or (3) has no lifetime 
history of occupational or household exposure to person(s) with tuberculosis, then the 
initial Screening QFT result may be a false-positive. In this instance, a second Screening 
test for latent TB infection should be obtained – either: (1) a repeat QFT test or (2) a 
Tuberculin Skin Test (TST). The repeat QFT test must be negative or the TST should 
show <15mm induration (considered negative TST) before being considered eligible for 
the study. 
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 drug. 
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. 

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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 drug. 
27. Clinically significant medical condition, psychiatric disease, or social condition, as 
determined by the Investigator, that may unfavorably alter the risk-benefit of study 
participation, adversely affect study compliance, or confound interpretation of study 
results. 
 
8.3. 
Patient Withdrawal Criteria 
For all patients, it is the intent that patients who discontinue study medication (at any time) for 
any reason will continue to be followed for all protocol-planned study visits through the 
completion of the 24-week treatment period, and will have all endpoints (including efficacy) 
collected accordingly. 
The Investigator, Sponsor, or its designee may decide a patient should discontinue treatment at 
any time and for any reason.  In addition, patients will discontinue randomized treatment if they: 
 Experience an intolerable adverse event, including but not limited to bone marrow 
related events characterized by protocol specified hematologic abnormalities, or a ≥ 
Grade 3 cardiac event, or a ≥ Grade 4 (other) adverse event (CTCAE v5.0 criteria) 
considered possibly related to study drug. Because laboratory abnormalities can 
occasionally occur that do not in themselves pose an unacceptable risk to subject 
safety (e.g., CK elevations with exercise, laboratory errors or artifacts), the 
occurrence of a ≥ Grade 4 laboratory abnormality, or any laboratory abnormality of 
concern to the Investigator, will be discussed with the Medical Monitor and a 
determination will be made, based on a reassessment of risk-benefit for the subject, 
whether the subject should discontinue randomized treatment. Documentation on the 
determination will be maintained in the study files; 
 Require a medication that is prohibited by the protocol. However, under certain 
circumstances, and in consultation with the Medical Monitor, short-term use of a 
prohibited medication may not necessitate withdrawal of treatment when its use is 
unlikely to unfavorably alter the risk-benefit of subject participation; 
 In the opinion of the Investigator, have any medically appropriate reason; 
 Become pregnant; 
 Have a serious adverse event associated with a SARS-CoV-2 infection; 

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 The Investigator believes that further treatment is undesirable or the risk-benefit 
profile has become unfavorable. 
Furthermore, dose interruptions lasting more than 21 days may require treatment discontinuation 
on a case by case basis following consultation with the Medical Monitor. 
In addition, 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 withdraws consent and requests to stop participating in the study. Patients who withdraw 
or are withdrawn from the study will not be replaced. 
 
8.3.1. 
Patient Withdrawal Procedures 
If a patient withdraws consent from further participation in 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. 
 
8.4. 
Emergency Unblinding of Treatment Assignment 
In the case of a medical requirement to break the blind to determine appropriate treatment for an 
adverse event, unblinding of a patient’s treatment assignment can be achieved through the study- 
specific Interactive Web Response System. If possible, the Investigator should discuss the 
circumstances with the Medical Monitor(s) prior to accessing unblinding information. In the 
event of a blind break, the Medical Monitor(s) will be notified through the electronic data 
capture system. The patient for whom the blind is broken should be subsequently withdrawn 
from the study. The details regarding the process of breaking the blind are outlined in the 
Medical Monitoring Plan and the Pharmacy Manual. 
 
8.5. 
Criteria for Study Termination 
The DMC will review cumulative safety data at regular intervals throughout the study. Should 
safety signals arise that suggest treatment with CTP-543 poses an unjustified risk to patients, 
termination of the study or modification of dosing arms may occur upon Sponsor review of the 
DMC recommendation. The DMC may call for unscheduled data review meetings at any time to 
ensure appropriate safety monitoring. 
Events that could trigger an unscheduled review may include, but are not limited to: 
High frequency of dose interruptions 
High frequency of, or a trend in, SAEs 
High frequency of Grade 3/4 adverse events 
Trend in organ system-specific moderate and/or severe adverse events 
High frequency of patient discontinuation of treatment due to adverse events 
The Sponsor will notify Investigators of any recommendation of study termination by the DMC. 
The Sponsor will notify Investigators of recommendation for study modification as necessary to 
protect patient safety including appropriate instructions for removing patients from treatment, 
while maintaining the blind. 

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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. The Sponsor reserves 
the right to discontinue the study at any time for clinical or administrative reasons. 

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9. 
DESCRIPTION OF STUDY TREATMENTS 
9.1. 
Description of Treatments 
Patients will be stratified by extent of scalp hair loss and randomized to CTP-543 or placebo in a 
3:5:2 ratio (12mg BID:8 mg BID: placebo). 
Treatments arms will include: 
 12 mg CTP-543 every 12 hours 
 8 mg CTP-543 every 12 hours 
 Placebo every 12 hours 
For each treatment arm, patients will take the first dose of study drug in the clinic on Day 1 of 
the Treatment Period and will be instructed to take study drug approximately every 12 hours (± 3 
hours) without regard to food for the duration of the study. 
 
9.2. 
Dose-Adjustment Criteria 
No individualized dose adjustment is allowed during the Treatment Period except in the event of 
intolerability, for which a dose interruption or patient discontinuation may occur at the 
judgement of the Investigator in consultation with the Medical Monitor (see Section 9.2.1 below 
for details). 
The DMC will review cumulative safety data throughout the study in accordance with the DMC 
Charter. If the DMC determines that the high dose of CTP-543 should be stopped for safety 
reasons, patients receiving treatment at that dose will move to the low dose of CTP-543 at the 
patient’s next visit. If an immediate hazard is suspected, patients without an imminent visit may 
have an Unscheduled Visit for potential dose adjustment to maintain the blind. In the event of 
CTP-543 treatment arm cessation and dose adjustment to the low dose of CTP-543 treatment, the 
blind will be maintained and individual patient treatment modifications will not be disclosed. 
 
9.2.1. 
Dose Interruption Safety Criteria and Management 
Patients who experience hematologic adverse events as described in Table 3, significant clinical 
laboratory abnormality, or adverse events that may reflect an unfavorable risk-benefit profile 
may have their dose interrupted at the discretion of the Investigator. The Medical Monitor(s) 
should be consulted whenever possible prior to decisions for dose interruption. 
Patients who withdraw consent and therefore are discontinued from the study should undergo an 
Early Termination Visit and associated adverse events should be followed as described in 
Section 11 Adverse Events. 
Hematology parameters will be assessed bi-weekly for the first 4 weeks of the Treatment Period, 
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 Unscheduled Visit within 
72 hours, except in severe cases (i.e.: neutrophil counts below 0.5 x 109/L) 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. 

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subject should discontinue treatment permanently. Signs and symptoms include, but are not 
limited to: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or 
body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or 
vomiting, diarrhea, trouble breathing, persistent pain or pressure in the chest, new confusion, 
inability to wake or stay awake, bluish lips or face. 
Subjects who have signs or symptoms consistent with SARS-CoV-2 infection should be tested 
for SARS-CoV-2 and do not have to dose interrupt unless the test result is positive. Subjects 
who have a positive SARS-CoV-2 test (antigen or antibody) but do not have any signs or 
symptoms consistent with SARS-CoV-2 infection are not required to dose interrupt. 
Table 4: 
SARS-CoV-2 Dose Interruption Criteria 
 
SARS-CoV-2 Test Result 
SARS-CoV-2 Symptoms 
Dose Interruption 
Positive 
Yes 
Yes 
Positive 
No 
No 
Negative 
Yes 
No 
 
9.3. 
Treatment Compliance 
At each scheduled study visit after randomization, the Investigator or designee will interview the 
patient regarding treatment compliance and compare the number of dispensed versus returned 
study drug tablets. Patients should strive for 100% compliance with the daily dosing schedule. 
Retraining on treatment compliance should occur for patients with less than 80% compliance at 
any visit and the Sponsor should be notified. 
 
9.4. 
Study Drug Materials and Management 
Please consult the Pharmacy Manual for a complete description of the study drug and 
requirements for storage, handling, dispensing, accountability, returns and destruction. 
 
9.4.1. 
Physical Description of Study Drug 
Study drug will include CTP-543 and matching placebo. Details regarding formulation and 
dosage are presented in Table 5. 
Table 5: 
Investigational Product 
 
Investigational Product 
(CTP-543 or Placebo) 
Product Name: 
CTP-543 or Matching placebo 
Dosage Form: 
Tablet 
Dosage Strength of CTP-543 
8 mg, 12 mg 
Route of Administration 
Oral 
Physical Description 
White, capsule-shaped tablets 

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9.4.2. 
Study Drug Packaging, Labeling, and Storage 
Study drug will be packaged and labeled by an appropriately qualified vendor. Each patient will 
receive one 60 count bottle of study medication at each 4-week study visit. Details of the 
packaging, labeling and dispensing instructions can be found in the Pharmacy Manual. 
The label(s) for the investigational product and placebo will include the required caution 
statements and/or regulatory statements, as applicable per local regulations. 
Adequate supplies of study drug will be provided to each site by the sponsor or designee. Study 
drug should be stored in the original container 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 bottle at room temperature as 
stated on the package label. No special handling procedures are required. Due to the COVID-19 
pandemic, Direct to Patient (DTP) shipping services may be warranted in cases where a patient is 
not able to attend in clinic visits or a site is closed. Additional information can be found in the 
Pharmacy Manual. 
9.4.3. 
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 for the duration 
of the Treatment Period. 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 without 
regard to food. Patients should be instructed to take one tablet in the morning and one tablet in 
the evening, approximately 12 hours apart. If a dose is missed, the patient should skip the 
missed dose and resume dosing at the next scheduled dose. The patient should not take two 
doses at the same time. Deviations from prescribed dosing should be discussed at each visit for 
assessment of compliance and retraining when necessary. 
 
9.4.4. 
Study Drug Return and Disposal 
The Sponsor (or designee) will review with the Investigator and relevant site personnel the 
process for study treatment return, disposal, and/or destruction, including responsibilities for the 
site versus the Sponsor (or designee). Specific requirements for destruction or return are defined 
in the Pharmacy Manual. 
 
9.4.5. 
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. 

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9.5. 
Concomitant Medications and Procedures 
All medications, including over-the-counter therapies (e.g., vitamins, herbal, and nutritional 
supplements) and vaccinations (including the SARS-CoV-2 vaccination), taken at the time of the 
Screening Visit through the Follow-Up Visit will be recorded in the patient’s source 
documentation and documented in the eCRF. Additionally, any prior janus kinase (JAK) 
inhibitor use or live virus vaccinations (including Herpes Zoster) will be recorded. 
To date, there is no clear evidence of any safety concern for receipt of a SARS-CoV-2 vaccine 
during the treatment period. Existing data on JAK inhibitors and vaccines, including the SARS- 
CoV-2 vaccine, are insufficient to conclude whether JAK inhibitors, including CTP-543, have an 
effect on vaccine effectiveness, though data to date do not suggest that a major effect is likely. 
Subjects considering enrollment in the CP543.3001 trial may wish to receive their vaccine(s) 
before entering the trial. As subject and public health are paramount, SARS-CoV-2 vaccination 
should not be delayed or withheld for subjects already enrolled in the CTP-543 trial. 
Knowledge about the vaccines and virus is continually growing. The Sponsor or 
 will notify 
sites as new information is obtained that might further inform vaccine-related questions during 
the study. Please also carefully read the product information (package insert) for the vaccine 
being used, noting any specific precautions or warnings for concomitant administration with 
JAK inhibitors or immunosuppressants. 
Any concomitant medication deemed necessary for the wellbeing of the patient may be given at 
the discretion of the Investigator. Use of medications that are prohibited per protocol will 
require patient withdrawal from the study. However, under certain circumstances, and in 
consultation with the Medical Monitor, short-term use of a prohibited medication may not 
necessitate withdrawal when its use is unlikely to unfavorably alter the risk-benefit of subject 
participation or confound the study endpoints. 
The following treatments are not permitted during the study: 
 Medications that may affect hair regrowth or immune response (such as: 
corticosteroids administered orally, by injection, or applied to areas of skin affected 
by alopecia; platelet-rich injections; topical application to affected areas of anthralin, 
squaric acid, diphenylcyclopropenone, or minoxidil; 
 Chronic or long-term 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); 
 NOTE: a short course of steroid treatment for acute treatment of a condition 
during the trial may be allowed following discussion with the Medical Monitor 
 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) dosed for systemic exposure; 

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 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. 
 Live vaccines including (but are not limited to) the measles, mumps, and rubella 
(MMR) vaccine; intranasal flu vaccine; and Zostavax (but not Shingrix) for herpes 
zoster. 

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10. 
STUDY ASSESSMENTS AND PROCEDURES 
The schedule of assessments and procedures is presented in Table 2 and should be referenced for 
details regarding the collection of each assessment at each visit. Due to the COVID-19 
pandemic, patient safety and some other assessments outlined below may be performed remotely 
if travel restrictions, quarantine, and/or site closures are presented and the Principal Investigator 
and the patient are not able to be physically present in the clinic. 
10.1. 
Demographic Characteristics and Medical History 
Demographic characteristics [i.e., sex, ethnic origin, date of birth (as appropriate per local 
regulations), and calculated body mass index] will be collected at the Screening Visit, between 
Day -28 and -1, and detailed on the eCRF. 
The patient’s alopecia areata will be classified by scalp hair loss into one of two categories 
defined for this study: 
1) Partial scalp hair loss (SALT ≥ 50 and < 95); 
2) Complete or near-complete scalp hair loss (SALT ≥ 95). 
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 and any prior janus kinase (JAK) 
inhibitor use, 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 for each dose group. 
Medical history should be thoroughly probed for potential exposure to serious infections such as 
HIV, history or vaccination against herpes zoster or other recent live virus vaccinations, prior 
SARS-CoV-2 infection, as well as cancer risk due to the potential immunosuppressive properties 
and known adverse events associated with JAK inhibitors. 
 
10.2. 
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 loss that quantifies 
the amount of scalp surface without hair in a pre-specified quadrant of the scalp (right side, top, 
left side, back), that is further summed after applying a quadrant-specific multiplier indicative of 
scalp surface area contribution, to provide an overall score of total hair loss. The SALT 
assessment will occur via live examination of the patient during clinic visits. If a patient is 
unable to attend an in-person clinic visit due to COVID-19, a SALT assessment will not be 
performed. Missed assessments will be recorded in the eCRF as due to COVID-19. 

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SALT will be used to determine efficacy for the study. To reduce variability, one rater should 
perform the SALT assessment for the patient for the duration of the study. All investigators 
using the SALT will be trained prior to use. Please consult the associated Site Operations 
Manual for additional details regarding SALT scoring and training requirements for this study. 
An example of the SALT assessment tool is provided in Section 17.2. 
10.3. 
Photographs 
Photographs of the scalp will be used to provide a visual record at the time of Baseline 
assessment of SALT as well as potential changes in SALT scores throughout the study. Scalp 
photographs will correspond to the 4 defined quadrants of the SALT assessment and will be 
taken when SALT assessments are performed.  Photographs of the scalp will be used to support 
rater training and continued monitoring throughout the course of the trial. However, no formal 
analyses will be performed on the photographs. 
Photographs of the eyebrows and eyelashes will be taken at Baseline, Week 12, and Week 24 as 
outlined in Table 2. A formal analysis via photographs will be performed for those patients with 
eyebrow and/or eyelash involvement. 
A photograph of the hands will be taken at the same timepoints as eyebrows and eyelashes to 
document potential changes for those with nail involvement throughout the study compared to 
Baseline. No formal analyses of nail involvement will occur. 
If a patient is unable to attend an in-person clinic visit due to COVID-19, photographs will not be 
performed. Missed assessments will be recorded in the eCRF as due to COVID-19. 
 
10.4. 
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 7-point Likert scale measuring either disease state severity or 
improvement after treatment. 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. 
In this study, the Global Impression Scale of Severity and the Global Impression Scale of 
Improvement will be performed by both the clinician and the patient at selected times during the 
study as indicated in Table 2. 
 
10.4.1. 
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 seven numeric choices representing “Among the most extreme hair loss” to 
“Normal, no hair loss”. To reduce variability, one rater should perform the CGI-S assessment 
for the patient. An example of the CGI-S is provided in Section 17.3.1. If a patient is unable to 
attend an in-person clinic visit due to COVID-19, the CGI-S will not be performed. Missed 
assessments will be recorded in the eCRF as due to COVID-19. 

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10.4.2. 
Clinical Global Impression of Improvement (CGI-I) 
The Clinical Global Impression Scale of Improvement will be assessed by the Investigator. 
Compared to the patient’s alopecia areata prior to treatment at Baseline, the patient’s current 
state of alopecia areata will be assessed according to the Investigator’s perceived change. 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 Section 17.3.2. If a 
patient is unable to attend an in-person clinic visit due to COVID-19, the CGI-I will not be 
performed. Missed assessments will be recorded in the eCRF as due to COVID-19. 
 
10.4.3. 
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/her alopecia areata at the time of assessment. The Patient may select one of 
seven numeric choices representing “Among the most extreme hair loss” to “Normal, no hair 
loss”. An example of the PGI-S is provided in Section 17.3.3. If a patient is unable to attend an 
in-person clinic visit due to COVID-19, the PGI-S should be performed via a virtual visit with 
video capability. 
10.4.4. 
Patient Global Impression of Improvement (PGI-I) 
The Patient Global Impression Scale of Improvement will be assessed by the patient. Compared 
to the patient’s alopecia areata prior to treatment at Baseline, the patient’s current state of 
alopecia areata will be assessed according to his/her perceived change. 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 Section 17.3.4. If a patient is unable to attend an in-person 
clinic visit due to COVID-19, the PGI-I should be performed via a virtual visit with video 
capability. 
 
10.5. 
Hair Satisfaction and Hair Quality Patient Reported Outcomes 
The Hair Satisfaction Patient Reported Outcome (SPRO) is a single item questionnaire answered 
by the patient designed to measure how satisfied alopecia areata patients are with their hair at the 
time of the assessment. The Hair Quality Patient Reported Outcome (QPRO) questionnaire 
provides additional details on key attributes of their hair and to help provide context to the SPRO 
response. The SPRO and QPRO are provided in Section 17.4. If a patient is unable to attend an 
in-person clinic visit due to COVID-19, the SPRO and QPRO should be performed via a virtual 
visit with video capability. 
 
10.6. 
HADS 
The Hospital Anxiety and Depression Scale (HADS) is a 14-item measure designed to assess 
anxiety and depression symptoms in medical patients. Items are rated on a 4-point severity 
scale. The HADS produces two scales, one for anxiety (HADS–A) and one for depression 
(HADS–D). An example of the HADS is provided in Section 17.5. If a patient is unable to 
attend an in-person clinic visit due to COVID-19, the HADS should be performed via a virtual 
visit with video capability. 

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10.7. 
BETA 
The Brigham Eyebrow Tool for Alopecia (BETA) is a clinician-rated scale that assesses the total 
eyebrow hair present. The scale is used for each eyebrow in which the Individual Eyebrow 
Score is derived by assessment of density (D) x surface area (SA). An expert panel will perform 
central readings based on photographs of the eyebrows and will provide a score for each patient 
with eyebrow involvement. The BETA will be performed at Baseline, Week 12, and Week 24. 
Additional detail on how to take the photographs for the central read of the BETA will be 
outlined in a separate study manual. If a patient is unable to attend an in-person clinic visit due 
to COVID-19, the BETA may not be performed due to the inability to take photographs of the 
eyebrows. Missed assessments will be recorded in the eCRF as due to COVID-19. 
 
10.8. 
BELA 
The Brigham Eyelash Tool for Alopecia (BELA) is a clinician-rated scale that assesses the total 
eyelash hair present. The scale is used for each eye in which the Total Eyelash Score is derived 
by assessment of density (D) and distribution on the right and left eye. An expert panel will 
perform central readings based on photographs of the eyelashes and will provide a score for each 
patient with eyelash involvement. The BELA will be performed at Baseline, Week 12, and 
Week 24.   Additional detail on how to take the photographs for the central read of the BELA 
will be outlined in a separate study manual. If a patient is unable to attend an in-person clinic 
visit due to COVID-19, the BELA may not be performed due to the inability to take photographs 
of the eyelashes. Missed assessments will be recorded in the eCRF as due to COVID-19. 
10.9. 
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 temperature. 
Weight will be measured per institution standard of care. Patients should wear light clothing, 
empty pockets of heavy objects, 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 
according to the Schedule of Assessments. Weight and height will be used to calculate the 
patient’s body mass index at Screening. Refer to the Schedule of Assessments for assessment 
timepoints (Table 2). 
In the event a patient is unable to attend an in-clinic visit due to COVID-19, vital signs may be 
performed by a Home Health Care agency. 
 
10.10. 
Physical Examination 
Per the Schedule of Assessments (Table 2) a complete physical examination will consist of an 
examination of all major organ systems to include, but not be limited to, chest auscultation, 
abdominal auscultation and palpation, head, eyes, ears, nose and throat. An assessment for 
active signs and symptoms of infection including tuberculosis, and skin examinations for non- 
melanoma skin cancers, will be performed. Evaluation for progressive multifocal 
leukoencephalopathy (PML) symptoms such as facial droop, general weakness, clumsiness, 
trouble speaking, personality changes, memory problems, and vision changes will be assessed. 

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Additionally, an assessment for the presence or absence of nasal hair will be performed during 
complete physical exams. 
Per the Schedule of Assessments (Table 2), brief physical examinations will include assessment 
for active signs and symptoms of infection, including tuberculosis, skin examinations for non- 
melanoma skin cancers, and an evaluation for progressive multifocal leukoencephalopathy 
(PML) symptoms such as facial droop, general weakness, clumsiness, trouble speaking, 
personality changes, memory problems, and vision changes. 
If telemedicine visits are warranted due to COVID-19, the focus of a virtual physical exam 
should be on evaluation of safety, including assessing for active signs and symptoms of 
infection, exposure to TB, and inquiry on changes to skin lesions and/or moles indicative of skin 
cancers and signs and symptoms of PML. 
 
10.11. 
Electrocardiogram 
Twelve-lead electrocardiograms will be performed at the screening visit and end of study 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. A 
central reading center will be used to read all ECGs and determine QT/QTc intervals. The 
Investigator should indicate review of the electrocardiogram report by signing and dating the 
report. If a patient is unable to attend an in-person clinic visit due to COVID-19, an ECG may 
not be performed. Missed assessments will be recorded in the eCRF as due to COVID-19. 
 
10.12. 
Clinical Laboratory Assessments 
Clinical laboratory assessments are presented in Section 17.1. Clinical laboratory samples 
should be collected at the beginning of each clinic visit and just prior to a dose on all Study Visit 
Days and will be processed by a central laboratory. In the event a patient is unable to attend an 
in-clinic visit due to COVID-19, clinical laboratory blood draws may be performed by a Home 
Health Care agency or a local laboratory. Patients should try to have laboratory blood draws 
performed in the morning and dose study drug after clinical laboratory blood draws are 
completed. 
The results of clinical laboratory tests conducted at the Screening Visit (and prior to dosing) 
must be assessed by the Investigator to determine each patient’s eligibility for participation in the 
study. The Investigator should indicate review of the laboratory reports throughout the study by 
signing and dating each report. 
All clinical laboratory results that fall outside the reference range will be interpreted by the 
Investigator as Abnormal, not clinically significant, or Abnormal, clinically significant. 
Laboratory results deemed Abnormal, clinically significant will be recorded as an adverse event 
in the eCRF (see additional criteria outlined in Section 11.1). Clinically significant laboratory 
abnormalities indicative of hematologic or other effects requiring intervention should be 
discussed with the Medical Monitor(s). 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. 

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10.13. 
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, for suspicion of tuberculosis, 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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11. 
ADVERSE EVENTS 
11.1. 
Definition of Adverse Event 
An adverse event is any untoward medical occurrence that may appear or worsen in a patient 
during the course of a study. It may be a new intercurrent illness, a worsening concomitant 
illness, an injury, or any concomitant impairment of the patient’s health, including laboratory test 
values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in 
the frequency or intensity of a pre-existing condition) should be considered an adverse event. A 
diagnosis or syndrome should be recorded on the adverse event page of the eCRF rather than the 
individual signs or symptoms of the diagnosis or syndrome. A worsening of the condition under 
study, alopecia areata, will not be reported as an adverse event. 
All patients will be monitored for adverse events during the study.  Assessments may include 
monitoring of the following parameters: the patient’s clinical symptoms, laboratory, physical 
examination findings, or findings from other tests and/or procedures. 
An adverse event reported after informed consent, but before the first dose of study drug (ie, 
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. 
An abnormal laboratory value is considered to be an adverse event if the abnormality: 
 Is considered clinically significant; OR 
 results in discontinuation from the study; OR 
 is judged by the Investigator to be of significant clinical importance requiring 
treatment, modification/interruption of investigational product dose, or any other 
therapeutic intervention. 
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the adverse event eCRF. If the abnormality was not a part of 
a diagnosis or syndrome, then the laboratory abnormality should be recorded as the adverse 
event. If possible, the laboratory abnormality should be recorded as a medical term and not 
simply as an abnormal laboratory result (e.g., record thrombocytopenia rather than decreased 
platelets). 
Vaccine-related AEs (e.g. fever, fatigue, headache) resulting directly from the vaccination may 
occur. The temporal relationship of the event(s) to the vaccination should be clearly described 
and the PI should consider whether these AEs are “unlikely” to be, or are “not related” to study 
medication. 

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11.2. 
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. 
 
11.2.1. 
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); 
 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). 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. 

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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. 
 
11.2.2. 
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) 
(v5.0) should be used to grade the severity/intensity of all events. These criteria will be provided 
in the Site Operations Manual. If a CTCAE criterion does not exist, the Investigator should 
grade the severity according to the following criteria: 
 Grade 1 (mild): does not interfere with the patient’s usual function 
 Grade 2 (moderate): interferes to some extent with patient's usual function 
 Grade 3 (severe): interferes significantly with patient's usual function 
 Grade 4 (life-threatening): results in a threat to life or in an incapacitating disability 
 Grade 5 (death): results in death 
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is 
based on patient/event outcome or action criteria associated with events that pose a threat to a 
patient’s life or functioning. 
Seriousness, not severity, serves as a guide for defining regulatory obligations. 
 
11.2.3. 
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: 
Related for Regulatory Reporting Assessment: 
 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. 

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 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). 
Unrelated for Regulatory Reporting Assessment: 
 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. 
 
11.2.4. 
Duration 
For all adverse events whether or not considered serious, the Investigator will provide a record of 
the start and stop dates of the event. Every effort should be made to resolve all adverse events 
with continued follow-up with the patient until appropriate resolution can be achieved. If an 
event is unresolved at the end of the study it will be recorded as ongoing. 
 
11.2.5. 
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. 
 
11.2.6. 
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). 
 
11.3. 
Follow-Up 
Adverse events, severe adverse events and serious adverse events, including clinically significant 
laboratory tests, electrocardiograms, or physical examination findings, will be followed, 
regardless of causality, 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 

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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. 
 
11.4. 
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 in EDC 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 pregnancy occurs in a female patient, then study drug should be discontinued immediately. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
should be reported as an adverse event or serious adverse event if reporting criteria are met. 
Spontaneous abortion, and any congenital anomaly or birth defect in the patient’s (or male 
patient’s partner’s) newborn should be reported as an SAE. 
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. 
 
11.5. 
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. 
11.6. 
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 completion 
of the safety follow-up visit, as applicable. 
 
11.6.1. 
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/EC. 

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United States and Canada 
 and Emergency Contact Information: 
 
 MD 
Telephone: 
 
Facsimile: 
 
Email: 
 AND 
 
 
 
Serious Adverse Event Reporting Contact Information: 
 Safety Group Email:
 
Serious Adverse Event Help Line: 
 
Serious Adverse Event Fax Line: 
 
 
11.6.2. 
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(s)] 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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12. 
STATISTICAL METHODS 
12.1. 
Sample Size Rationale 
Power is calculated for the Primary Efficacy Endpoint for the chi-square test using a 2-sided 
significance level of 0.025. Based on Phase 2 results, the percentage of patients achieving an 
absolute SALT score ≤20 at Week 24 is assumed to be 40%, 25%, and 10% for the CTP-543 12 
mg, CTP-543 8 mg BID, and placebo groups, respectively. Patients will be randomized in a 
3:5:2 ratio with a total N of approximately 700 patients (i.e., 210 for 12 mg BID, 350 for 8 mg 
BID, and 140 for placebo BID). These sample sizes will provide >99% power for the 
comparison of CTP-543 12 mg BID versus placebo and approximately 94% power for the 
comparison of CTP-543 8 mg BID versus placebo. 
 
12.2. 
Endpoints 
12.2.1. 
Efficacy 
Primary Efficacy Endpoint 
 The primary efficacy endpoint will be the percentage of patients achieving an absolute 
SALT score of ≤20 at Week 24. 
Key Secondary Endpoints 
1. Percentage of responders (defined as “satisfied” or “very satisfied”) on the Hair 
Satisfaction Patient Reported Outcome (SPRO) scale at Week 24 
2. Percentage of patients achieving an absolute SALT score of ≤20 at Week 20, 16, 12 and 8 
 
See Section 12.4.3 for details on multiple comparisons control for Primary and Key Secondary 
Endpoints. 
 
Secondary Endpoints 
 Relative change in SALT scores from Baseline at Weeks 4, 8, 12, 16, 20, and 24 
 Percentage of responders (defined as “much improved” or “very much improved”) using 
the CGI-I at Weeks 12, 16, 20, and 24 
 Percentage of responders (defined as “much improved” or “very much improved”) using 
the PGI-I at Weeks 12, 16, 20, and 24 
 Change from Baseline in the CGI-S at Weeks 12, 16, 20, and 24 
 Change from Baseline in the PGI-S at Weeks 12, 16, 20, and 24 
 Percentage of patients achieving at least a 75% relative reduction in SALT score from 
Baseline at Weeks 12 and 24 
 Percentage of patients achieving at least a 90% relative reduction in SALT score from 
Baseline at Weeks 12 and 24 

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 Change from Baseline on the Brigham Eyebrow Tool for Alopecia (BETA) score at 
Weeks 12 and 24 
 Change from Baseline on the Brigham Eyelash Tool for Alopecia (BELA) score at 
Weeks 12 and 24 
 Percentage of responders (defined as “satisfied” or “very satisfied”) on the SPRO scale at 
Weeks 12, 16, and 20 
 Change from Baseline in the SPRO scale at Weeks 12, 16, 20 and 24 
 Percentage of patients achieving a ≥ 2-point change from Baseline in the SPRO scale at 
Weeks 12, 16, 20, and 24 
 Change from Baseline on the individual items of the Hair Quality Patient Reported 
Outcome (QPRO) scale at Weeks 12, 16, 20 and 24 
 Change from Baseline in the depression scale of the Hospital Anxiety and Depression 
Scale (HADS) at Week 24 
 Change from Baseline in the anxiety scale of the Hospital Anxiety and Depression Scale 
(HADS) at Week 24 
 Percentage of patients achieving an absolute SALT score of ≤20 at Weeks 8 and 4 
 Percentage of patients achieving an absolute SALT score of ≤10 at Week 24 
Additional exploratory statistical analyses to further assess for treatment effect will be outlined 
in the Statistical Analysis Plan finalized prior to database lock for the Primary Efficacy Analysis 
 
12.2.2. 
Safety 
Safety and tolerability of CTP-543 will be assessed by evaluating adverse events, vital signs, 
concomitant medications, and clinical laboratory results, as well as physical examinations. 
 
12.3. 
Analysis Populations 
12.3.1. 
Treatment Period 
The Efficacy Population will include all patients who are randomized in the study and dispensed 
study drug during the Treatment Period. 
The Safety Population will include all patients who receive study drug during the Treatment 
Period. 
The Per Protocol Population will include all patients in the Efficacy Population who were dosed 
according to protocol and have no major protocol deviations. Inclusion in the Per Protocol 
Population will be determined prior to breaking the study blind. 
In the event patients incorrectly receive treatment associated with a different treatment group, 
they will be analyzed “as randomized” for efficacy and “as treated” for safety. 
 
12.4. 
Analyses 
For the Treatment Period, data will be summarized by active treatment versus placebo-treated 
patients (i.e., by treatment group). All data for analysis will be listed by patient. 

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Continuous measures will be summarized descriptively (mean, standard deviation, median, 
minimum value, and maximum value) and categorical measures will be presented as number and 
percentage. 
Additional details for statistical methods will be provided in the Statistical Analysis Plan. 
 
12.4.1. 
Disposition and Baseline Characteristics 
Disposition will be summarized by randomized treatment group. The number and percentage of 
patients, who are randomized, treated, prematurely discontinued, (overall and by reason for 
discontinuation), and complete the study will be summarized. 
Baseline characteristics will be summarized by treatment group. 
The number of patients in each treatment group will be summarized for each investigative site 
for the Treatment Period. Medical history will be coded with the Medical Dictionary for 
Regulatory Activities (MedDRA) terminology and summarized by system organ class and 
preferred term. Prior and concomitant medications will be summarized separately by World 
Health Organization Drug Dictionary Anatomical-Therapeutic-Chemical classification and 
preferred term. 
12.4.2. 
Efficacy 
The primary analysis targets an effect of treatment (response rates at 24 weeks) among subjects 
given the opportunity for treatment who are dispensed study drug. The treatment policy strategy 
is used for the intercurrent event of discontinuation of study treatment (either temporarily or 
permanently) and so the response rates at 24 weeks are of interest, irrespective of continued 
therapy, in line with the intent-to-treat principle. 
For the primary efficacy analysis and the key secondary efficacy analysis, a 0.025 (two-sided) 
alpha-level will be allocated to each dose for comparison with placebo to adjust for multiplicity 
of testing associated with two doses. Additional secondary endpoints will be tested in the 
following order (see Section 12.4.3) and be considered statistically significant and alpha-level 
protected if they (and all prior endpoints in the hierarchy for that dose versus placebo) achieve 
statistical significance at the 0.025 level of significance. Irrespective, nominal p-values will be 
provided. Testing will be performed only for the Treatment Period. Missing values will be 
handled as specified in Section 12.4.4. 
Primary Efficacy Endpoint 
The primary efficacy endpoint will be the proportion of patients achieving an absolute SALT 
score ≤ 20 at Week 24. Pairwise treatment group differences from placebo will be assessed with 
the Cochran-Mantel-Haenszel test using baseline scalp hair loss (partial vs complete/near- 
complete) as the stratification factor, for each active treatment group versus placebo. 

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Other Efficacy Endpoints 
For proportions of patients achieving specified improvement criteria (eg, CGI-I and PGI-I 
responders), pairwise treatment group differences from placebo at each scheduled evaluation will 
be assessed with the Cochran-Mantel-Haenszel test using baseline scalp hair loss as the 
stratification factor. 
Absolute and/or relative changes in SALT score, SPRO score, CGI-S and PGI-S values, BELA 
and BETA score, QPRO scores, and HADS anxiety and depression scores, will be assessed with 
a mixed effects repeated measures (MMRM) model. The model will include fixed factors for 
treatment group, study visit, and treatment by study visit interaction, with baseline SALT score 
as a covariate. Treatment group comparisons at each visit will be based on least squares mean 
estimates. An unstructured covariance structure will be used to model the within-subject errors. 
The Kenward-Roger approximation will be used to estimate denominator degrees of freedom. 
 
12.4.3. 
Multiplicity 
Hierarchical testing will be used to control for multiple comparisons. For the primary efficacy 
analysis and the key secondary efficacy analyses, a ≤0.025 (two-sided) alpha-level will be 
allocated to each dose for comparison with placebo to adjust for multiplicity of testing associated 
with two doses. The below figure displays the order of testing of the key secondary endpoints. 
Once p>0.025 is observed for a treatment group comparison, inference for additional endpoints 
is no longer alpha-level protected for that dose group, however nominal p-values will still be 
reported. 
Subsequently, conditional upon significance (≤ 0.025) for the primary endpoint and first key 
secondary endpoint for both doses, a linear hierarchical testing approach with ≤ 0.025 (two- 
sided) alpha-level will be used to test the remaining key secondary endpoint comparisons versus 
placebo. Once p>0.025 is observed for a treatment group comparison, inference for additional 
endpoints is no longer alpha-level protected for that dose group, however nominal p-values will 
still be reported. 

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12.4.4. 
Missing Data for SALT-based endpoints 
Prior to database lock, the classification of the missing data pattern for missing SALT scores will 
be finalized based on blinded data review and documented as either considered to be missing at 
random (MAR) or potentially missing not at random (MNAR), consistent with general categories 
of reasons for missingness. Subjects with missing data due to COVID-19 will have data 
reviewed to determine the specific limitation imposed by COVID-19 leading to the inability to have 
captured the protocol-specified assessments. For example, missing at random will be considered 
plausible for COVID-19 related reasons such as site closures and travel limitations. In general, 
however, if a MAR assumption is not considered plausible, MNAR will be assumed. Patterns of 
missing values across visits will be listed and summarized with numbers and percentages by 
treatment and visit. 

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12.4.5. 
Multiple Imputation 
A multiple imputation (MI) approach will be used to estimate missing SALT scores. Analyses of 
the multiply imputed datasets will be performed for both the primary endpoint (percentage of 
subjects with absolute SALT scores ≤ 20) as well as key secondary endpoints employing SALT 
scores, between each dose and placebo, using the MMRM approach. 
The imputation will be implemented separately for each treatment, under the assumption that 
different treatments may have distinct posterior distributions. Missing values will be imputed 
with a sequential regression approach under the assumption of multivariate normality. Missing 
SALT scores will be imputed in a sequential manner using regression models with a number of 
predictor variables. Covariates to be included are the baseline SALT score, in addition to the 
observed or imputed values of the previous time points. 
One hundred independent imputations will be done with SAS® PROC MI using the Fully 
Conditional Specification (FCS) regression method for all imputed continuous variables and the 
discriminant function method for all imputed classification variables, if needed. For each 
continuous variable, all other variables are used as covariates, and for each imputed classification 
variable, all other continuous variables are used as covariates. The FCS method combines both 
the monotone and arbitrary missing data patterns into one procedure. 
 
12.4.5.1. Analysis of Imputed Datasets 
For the analysis of the primary endpoint (i.e., the binary endpoint denoting a SALT score ≤ 20) 
the individual SALT scores will be categorized (≤ 20 versus > 20) and analyzed using a Mantel- 
Haenszel test (comparing each dose to placebo, separately). For each imputed dataset, treatment 
differences will be assessed using the Mantel-Haenszel estimate of a common risk difference, 
with the variance estimator due to Sato (used to construct confidence limits for the Mantel- 
Haenszel estimate of the common risk difference in the SAS FREQ Procedure). The resulting 
100 estimates of the treatment differences and standard errors will then be combined using SAS 
PROC MIANALYZE. 
 
12.4.5.2. Tipping Point Analyses 
 
For the primary endpoint categorized as absolute SALT score ≤ 20, tipping point sensitivity 
analyses will be conducted for each dose compared to placebo at week 24 if the result of the MI 
analysis is statistically significant at the alpha ≤ 0.025 level, in favor of treatment, for the given 
dose. 
 
The patterns of interest for the tipping point analysis will consider two cases and will estimate 
tipping points for values where only missing values not at random (MNAR) are adjusted and also 
where all missing values are adjusted (i.e., two separate tipping point analyses). 
The tipping point analyses will use the imputed datasets generated for the primary analysis with 
the delta adjustments for both treated and placebo. For the tipping point analysis, δT values 
(adjustments for treated subjects) will represent a percentage difference between the imputed 
value and baseline and can vary from 0% to 100% of the difference for subjects with an imputed 
SALT score less than baseline, or zero otherwise. For the placebo arm, δP values will represent a 
percentage difference between the imputed value and 0 hair loss. Accordingly, the maximum 

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delta value of 100% provides for an adjusted imputed value equal to either baseline (for treated 
subjects, representing non-response) or zero hair loss for placebo, representing response. 
Tipping points will therefore be provided for combinations of δT and δP to provide a range of 
assumptions about hypothetical improvements on placebo missing data values and reduction in 
efficacy for treated imputed values such that there is no longer evidence of efficacy. 
 
Missing values will not be imputed for efficacy endpoints which are not derived from SALT 
scores. 
 
12.4.6. 
Study Drug Exposure 
Study drug exposure will be summarized for each treatment group. The number of days on 
which study drug was dosed will be summarized for each treatment group. 
The total number of days on study drug will exclude dose interruptions. The total number of 
days of exposure to study drug will be summarized with the mean, standard deviation, median, 
minimum, and maximum number of days on the dose. Drug compliance will also be 
summarized. 
 
12.4.7. 
Safety 
All safety summaries will be descriptive with no statistical hypothesis testing and based on the 
Safety Population. Patients will be summarized according to the study drug received (i.e., as 
treated), should it differ from the randomized treatment arm. 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 (refer to Section 11.1). 
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 through to the final study 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. 

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Proportions for adverse events that are gender-specific (e.g., dysmenorrhea) will be based on the 
number of patients from that gender. 
The number and percentage of patients who experience TEAEs will be summarized by treatment 
group 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. Treatment-emergent adverse events that result in dose 
interruption will also be identified. 
Additionally, treatment-emergent adverse events will be summarized by time interval: 0 to 12 
weeks, and 12 to 24 weeks. For each time interval, an incidence table will summarize only 
TEAEs with an onset date within the interval and a prevalence table will summarize all TEAEs 
that have an onset date within the interval or continue into the interval. Differences between the 
incidence and prevalence tables can provide insight into the duration of TEAEs as well as the 
recurrence of TEAEs. A preferred term for an individual patient will be reported in multiple 
time intervals if there are multiple adverse event reports. The denominator for each time interval 
will be the number of patients who received at least 1 dose of study drug within the interval. 
Clinical Laboratory 
Clinical laboratory variables will be presented in 3 ways. First, change from Baseline to the 
smallest post-baseline value, largest post-baseline value, and final value will be summarized. 
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, shift tables will summarize the number and percentage of patients with categorical 
changes from baseline defined by the laboratory normal reference range for each laboratory 
parameter (Below reference range, Within reference range, and Above reference range). The 
baseline category will be cross-tabulated with post-baseline category (3 × 3 table). The 
post-baseline category will be assigned and summarized in 2 ways for each laboratory parameter: 
smallest post-baseline value and largest post-baseline value. 
Third, 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 

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are those in which the baseline value is not PCS and the post-baseline value is PCS. The number 
and percentage of patients with treatment-emergent PCS laboratory values will be summarized 
by treatment group for each clinical laboratory variable. 
Vital Signs 
The mean change from baseline to each scheduled assessment will be summarized descriptively 
by treatment group 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. 
The number and percentage of patients with at least 1 PCS vital sign value will be summarized 
descriptively. 
 
12.4.8. 
Interim Analyses 
An independent Data Monitoring Committee (DMC) will perform regular safety assessments 
based on a review of cumulative safety data. The DMC may advise study and/or treatment arm 
cessation due to intolerability at any time. There are no plans to perform interim efficacy 
analyses or to discontinue the study early due to demonstration of efficacy differences. 
Therefore, no adjustment of Type I error is required for interim analyses. 

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13. 
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. 
13.1. 
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 (R2) and in 
accordance with the general ethical principles outlined in the Declaration of Helsinki. The study 
will receive approval from the IRB/EC 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. 
 
13.2. 
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. 
During the study, a monitor from Concert Pharmaceuticals or its representative will have regular 
contacts with the investigational site, for the following: 
 Provide information and support to the Investigator(s) 
 Confirm that facilities remain acceptable 
 Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 

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 Perform source data verification. This includes a comparison of the data in the case 
report forms with the patient’s medical records at the hospital or practice, and other 
records relevant to the study. This will require direct access to all original records for 
each patient (e.g., clinic charts). 
 Record and report any protocol deviations. 
 Due to the COVID-19 pandemic and the possibility for site closures and/or travel 
restrictions, source data verification may be performed remotely. 
 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/EC by designated study personnel. 
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. 
 
13.3. 
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. Patients who fail screening must have the reason(s) recorded in the patient’s source 
documents. 
The Investigator or designee should inform the IRB/EC 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/EC and Regulatory Agencies, 
as required per country regulations. Where applicable, a progress report will be sent to the 
IRB/EC and the protocol will be reviewed annually (e.g., re-approved) or more frequently, as 
required by the IRB/EC or local regulations. 

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The Investigator will maintain a copy of all correspondence with/from the IRB/EC, including 
copies of approved documents. The Investigator will also maintain a copy of the IRB/EC 
membership list with occupation and qualification (or a statement confirming compliance with 
GCP requirements for committee composition). 
In the US, the Investigator or designee 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. 
In the EU, the Sponsor or designee is responsible for notifying the EC/RA of the conclusion of 
the clinical study within 90 days of completion of the study, per the EU Directive. In cases 
where a study is terminated early, notification must be made within 15 days of the early 
termination. The final study report must be submitted within 1 year after study completion. 
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. 
 
13.4. 
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/EC. Except for 
administrative amendments, Investigators must await IRB/EC approval of protocol amendments 
before implementing the change(s). The Sponsor will ensure submission of any protocol 
amendments to the appropriate regulatory agencies and Ethics Committees. 
Trial conduct may be impacted in light of the COVID-19 pandemic. Challenges may arise (e.g., 
quarantines, site closures, travel limitations, interruptions to the supply chain for the 
investigational product, etc.) leading to difficulties in meeting protocol-specified procedures, 
including administering or using the investigational product or adhering to protocol-mandated 
visits and laboratory/diagnostic testing. Taking into consideration Regulatory Agency guidance, 
amendments to protocol defined criteria may be implemented without IRB approval or before 
filing an amendment to the IND/CTA in order to minimize or eliminate immediate hazards or to 
protect the life and well-being of research participants (e.g., to limit exposure to COVID-19). 
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/EC notified within 5 days or per local regulations. 
When, in the judgment of the chairman of the local IRB/EC, 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. 

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13.5. 
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/site 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. 
 
13.6. 
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 will be instituted for this study. All audit findings 
will be summarized and placed on file with appropriate documentation of response/resolution. 
In light of the COVID-19 pandemic, patient safety will be ensured by maintaining compliance 
with Good Clinical Practice (GCP) and minimizing risks to patient safety and data integrity. 
These efforts include additional risk mitigation strategies and appropriate documentation of 
protocol deviations occurring prior to implementation of protocol amendments. 

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14. 
DATA HANDLING AND RECORDKEEPING 
14.1. 
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/EC is expressly 
permitted, IRB/EC 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. 
 
14.2. 
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. 
14.3. 
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. 

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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. 
 
14.4. 
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. 
 
14.5. 
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. 
 
14.6. 
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 

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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: 
 Information to confirm that the patient exists [e.g., initials, date of birth (applicable 
per local regulations), 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. In light of the COVID-19 pandemic, 
source document verification may occur remotely. Additional detail on remote source document 
verification will be provided in the study plans. 
 
14.7. 
Retention of Records 
Clinical Investigators must retain study records from investigational drug studies 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 the 
appropriate regulatory authority is notified. 
The Investigator must maintain all study documentation as confidential, and take measures to 
prevent accidental or premature destruction of these documents. 
The Investigator must notify the Sponsor prior to destroying any study essential documents. 
If the Investigator can no longer ensure archiving, he/she shall inform the Sponsor. The relevant 
records shall be transferred to a mutually agreed upon designee. 

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15. 
PUBLICATION POLICY 
The results of this study may be published in a medical publication, journal, or another public 
dissemination, or may be presented at a medical conference or used for teaching purposes. 
Additionally, this study and its results may be submitted for inclusion in all appropriate health 
authority study registries, as well as publication on health authority study registry websites, as 
required by local health authority regulations. Selection of first authorship will be based on 
several considerations, including, but not limited to study participation, contribution to the 
protocol development, and analysis and input into the manuscript, related abstracts, and 
presentations in a study. 

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16. 
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. 
Benigno (2020) 
Benigno M, Anastassopoulos KP, Mostaghimi A, Udall M, Daniel SR, et al. A 
Large Cross-Sectional Survey Study of the Prevalence of Alopecia Areata in 
the United States. Clinical, Cosmetic and Investigational Dermatology. 2020; 
13:259-266. 
Bilgic (2013) 
Bilgiç Ö, Bilgiç A, Bahali K, Bahali AG, Gürkan A, Yilmaz 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. 
Ghoreschi (2009) 
Ghoreschi K., Laurence A., O’Shea JJ. Janus kinases in immune cell 
signaling. Immunol Rev. 2009;228(1):273-87. 
Jakafi (2020) 
Jakafi prescribing information. Incyte Corporation. Wilmington, DE. 2020. 
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. 
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. 
Sato (1989) 
Sato, T. On the Variance Estimator of the Mantel-Haenszel Risk 
Difference. Biometrics (1989). 45:1323– 1324. Letter to the editor. 
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. 
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. 
Wyrwich (2020) 
Wyrwich KW, Kitchen H, Knight S, et al. The Alopecia Areata Investigator’s 
Global Assessment (AA-IGATM) Scale: A Measure for Evaluating Clinically 
Meaningful Success in Clinical Trials. British Journal of Dermatology. 2020 
Jan; doi.org/10.1111/bjd.18883. 
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. 

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17. 
APPENDICES 
17.1. 
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 
C-Reactive Protein (CRP) 
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 (Fasted) 
Other 
Hepatitis B Surface Antigen (HBsAg) 
Hepatitis C Virus Antibodies (HCV 
Ab) 
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
Tuberculosis 
Thyroid stimulating hormone 
Triglycerides 

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17.3. 
Global Impression Scales 
17.3.1. 
Clinical Global Impression of Severity (CGI-S) 
How would you rate the severity of the patient’s alopecia areata at this time: 
 
1. Normal, no hair loss 
 
2. Borderline hair loss 
 
3. Mild hair loss 
 
4. Moderate hair loss 
 
5. Marked hair loss 
 
6. Severe hair loss 
 
7. Among the most extreme hair loss 
 
17.3.2. 
Clinical Global Impression of Improvement (CGI-I) 
Compared to the patient’s alopecia areata prior to treatment at Baseline, the patient’s current 
state of alopecia areata is: 
 
1. Very Much Improved 
 
2. Much Improved 
 
3. Minimally Improved 
 
4. No Change 
 
5. Minimally Worse 
 
6. Much Worse 
 
7. Very Much Worse 

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17.3.3. 
Patient Global Impression of Severity (PGI-S) 
 
How would you rate the severity of your alopecia areata at this time: 
 
1. Normal, no hair loss 
 
2. Borderline hair loss 
 
3. Mild hair loss 
 
4. Moderate hair loss 
 
5. Marked hair loss 
 
6. Severe hair loss 
 
7. Among the most extreme hair loss 
 
 
17.3.4. 
Patient Global Impression of Improvement (PGI-I) 
 
Compared to my alopecia areata prior to treatment at Baseline, my current state of alopecia 
areata is: 
 
1. Very Much Improved 
 
2. Much Improved 
 
3. Minimally Improved 
 
4. No Change 
 
5. Minimally Worse 
 
6. Much Worse 
 
7. Very Much Worse 

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17.4. 
Patient Reported Outcome 
17.4.1. 
Satisfaction of Hair Patient Reported Outcome (SPRO) 
How satisfied are you with the hair on your scalp today? 
5 Very dissatisfied 
4 Dissatisfied 
3 Neither satisfied nor dissatisfied 
2 Satisfied 
1 Very satisfied 

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17.4.2. 
Quality of Hair Patient Reported Outcome (QPRO) 
For the next set of questions, please choose the best answer that represents how you feel today. 
 
1. How satisfied are you with the 
thickness of the hair on your 
scalp? 
5
Very 
dissatisfied 
4
Dissatisfied 
3
Neither 
satisfied nor 
dissatisfied 
2
Satisfied 
1
Very 
satisfied 
2. How satisfied are you with the 
evenness of the hair on your 
scalp? 
5
Very 
dissatisfied 
4
Dissatisfied 
3
Neither 
satisfied nor 
dissatisfied 
2
Satisfied 
1
Very 
satisfied 
5
4
3
2
1
3. How satisfied are you with your 
Very 
Dissatisfied 
Neither 
Satisfied 
Very 
eyebrows? 
dissatisfied 
satisfied nor 
satisfied 
dissatisfied 
5
4
3
2
1
4. How satisfied are you with your 
Very 
Dissatisfied 
Neither 
Satisfied 
Very 
eyelashes? 
dissatisfied 
satisfied nor 
satisfied 
dissatisfied 

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10.9/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.   
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 temperature.   
Amended text to allow for 
contactless temperature  
monitoring of patients.  
17.4.2./Quality of 
Hair Patient Reported 
Outcome (QPRO) 
Updated the QPRO 
questions 1 and 2 to remove 
‘coverage.  

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10.10/Physical 
Examination 
A complete physical examination will include an examination of all 
major organ systems to include, but not be limited to, chest 
auscultation, abdominal auscultation and palpation, head, eyes, ears, 
nose and throat.  Assessment for active signs and symptoms of 
infection including tuberculosis, and skin examinations for non-
melanoma skin cancers, will be performed as indicated in the 
Schedule of Assessments.  Brief physical examinations will include 
assessment for active signs and symptoms of infection, including 
tuberculosis, and skin examinations for non-melanoma skin cancers 
and will be performed at all other intermediate visits as specified in 
Table 2. 
If telemedicine visits are warranted due to COVID-19, the focus of 
a virtual physical exam should be on evaluation of safety, including 
assessing for active signs and symptoms of infection, exposure to 
TB, and inquiry on changes to skin lesions and/or moles indicative 
of skin cancers. 
Per the Schedule of Assessments (Table 2) a complete physical examination 
will consist of an examination of all major organ systems to include, but not be 
limited to, chest auscultation, abdominal auscultation and palpation, head, 
eyes, ears, nose and throat.  An assessment for active signs and symptoms of 
infection including tuberculosis, and skin examinations for non-melanoma skin 
cancers, will be performed.  Evaluation for progressive multifocal 
leukoencephalopathy (PML) symptoms such as facial droop, general 
weakness, clumsiness, trouble speaking, personality changes, memory 
problems, and vision changes will be assessed. Additionally, an assessment 
for the presence or absence of nasal hair will be performed during 
complete physical exams.   
Per the Schedule of Assessments (Table 2), brief physical examinations will 
include assessment for active signs and symptoms of infection, including 
tuberculosis, skin examinations for non-melanoma skin cancers, and an 
evaluation for progressive multifocal leukoencephalopathy (PML) 
symptoms such as facial droop, general weakness, clumsiness, trouble 
speaking, personality changes, memory problems, and vision changes. 
If telemedicine visits are warranted due to COVID-19, the focus of a virtual 
physical exam should be on evaluation of safety, including assessing for active 
signs and symptoms of infection, exposure to TB, and inquiry on changes to 
skin lesions and/or moles indicative of skin cancers and signs and symptoms 
of PML. 
Language added for 
evaluation for progressive 
multifocal 
leukoencephalopathy (PML) 
and presence or absence of 
nasal hairs during physical 
exams.   

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12.4.2/Efficacy 
(Statistical Methods) 
12.4.3 Multiplicity 
For the primary efficacy analysis and the first key secondary 
efficacy analysis, a 0.025 (two-sided) alpha-level will be allocated 
to each dose for comparison with placebo to adjust for multiplicity 
of testing associated with two doses. Testing will be performed only 
for the Treatment Period.  Missing values will be handled as 
specified in Section 12.4.4.  
Pairwise treatment group differences from placebo will be assessed 
with the Cochran-Mantel-Haenszel test using baseline scalp hair 
loss (partial vs complete/near-complete) as the stratification factor. 
For proportions of patients achieving specified improvement 
criteria (eg, CGI-I and PGI-I responders), pairwise treatment group 
differences from placebo at each scheduled evaluation will be 
assessed with the Cochran Mantel Haenszel test using baseline 
scalp hair loss as the stratification factor.  Missing values will not 
be imputed for other efficacy endpoints. 
Absolute and/or relative changes in SALT score, SPRO score, 
CGI-S and PGI-S values, BELA and BETA score, QPRO scores, 
and HADS anxiety and depression scores, will be assessed with a 
mixed effects repeated measures (MMRM) model.  The model will 
include fixed factors for treatment group, study visit, and treatment 
by study visit interaction, with baseline SALT score as a covariate 
and patient as a random effect.  Treatment group comparisons at 
each visit will be based on least squares mean estimates.  An 
unstructured covariance structure will be used to model the within-
subject errors.  The Kenward-Roger approximation will be used to 
estimate denominator degrees of freedom 
Hierarchical testing will be used to control for multiple 
comparisons. For the primary efficacy analysis and the first key 
secondary efficacy analysis, a 0.025 (two-sided) alpha-level will 
allocated to each dose for comparison with placebo to adjust for 
multiplicity of testing associated with two doses.   
For the primary efficacy analysis and the first key secondary efficacy analysis, 
a 0.025 (two-sided) alpha-level will be allocated to each dose for comparison 
with placebo to adjust for multiplicity of testing associated with two doses. 
The primary analysis targets an effect of treatment (response rates at 24 
weeks) among subjects given the opportunity for treatment who are 
dispensed study drug.  The treatment policy strategy is used for the 
intercurrent event of discontinuation of study treatment (either 
temporarily or permanently) and so the response rates at 24 weeks are of 
interest, irrespective of continued therapy, in line with the intent-to-treat 
principle.  
For the primary efficacy analysis and the first key secondary efficacy analysis, 
a 0.025 (two-sided) alpha-level will be allocated to each dose for comparison 
with placebo to adjust for multiplicity of testing associated with two doses.  
Additional secondary endpoints will be tested in the following order (see 
Section 12.4.3) and be considered statistically significant and alpha-level 
protected if they (and all prior endpoints in the hierarchy for that dose 
versus placebo) achieve statistical significance at the 0.025 level of 
significance.  Irrespective, nominal p-values will be provided.  Testing will 
be performed only for the Treatment Period.  Missing values will be handled as 
specified in Section 12.4.4 
Pairwise treatment group differences from placebo will be assessed with the 
Cochran-Mantel-Haenszel test using baseline scalp hair loss (partial vs 
complete/near-complete) as the stratification factor, for each active treatment 
group versus placebo. 
For proportions of patients achieving specified improvement criteria (eg, CGI-I 
and PGI-I responders), pairwise treatment group differences from placebo at 
each scheduled evaluation will be assessed with the Cochran Mantel Haenszel 
test using baseline scalp hair loss as the stratification factor.  Missing values 
will not be imputed for other efficacy endpoints. 
Absolute and/or relative changes in SALT score, SPRO score, CGI-S and PGI-
S values, BELA and BETA score, QPRO scores, and HADS anxiety and 
depression scores, will be assessed with a mixed effects repeated measures 
(MMRM) model.  The model will include fixed factors for treatment group, 
study visit, and treatment by study visit interaction, with baseline SALT score 
as a covariate and patient as a random effect.  Treatment group comparisons 
at each visit will be based on least squares mean estimates.  An unstructured 
covariance structure will be used to model the within-subject errors.  The 
Kenward-Roger approximation will be used to estimate denominator degrees 
of freedom 
Hierarchical testing will be used to control for multiple comparisons. For the 
primary efficacy analysis and the first key secondary efficacy analyses, a 
0.025 (two-sided) alpha-level will be allocated to each dose for comparison 
with placebo to adjust for multiplicity of testing associated with two doses.  
Section updated to reflect 
modifications to primary 
endpoint analysis, missing 
data, adjustment for 
multiplicity, and tipping 
point analysis.  

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12.4.4 Missing Data 
for SALT-based 
endpoints 
12.4.5 Multiple 
Imputation 
12.4.5.1 Analysis of 
Imputed Datasets 
12.4.5.2 Tipping 
Point Analyses 
primary endpoint and first key secondary endpoint for each dose, a 
linear hierarchical 
-sided) alpha-
level will be used to test the remaining key secondary endpoint 
comparisons versus placebo. Once p>0.05 is observed for a 
treatment group comparison, inference for additional   endpoints is 
no longer alpha-level protected for that dose group, however 
nominal p-values will still be reported. 
Prior to database lock, the classification of the missing data pattern 
for missing SALT scores will be finalized based on blinded data 
review and documented as either considered to be missing at 
random (MAR) or potentially missing not at random (MNAR).  
Patterns of missing values across visits will be listed and 
summarized with numbers and percentages by treatment and visit.  
If the percentage of subjects with missing SALT score data at Week 
performed, otherwise a multiple imputation (MI) approach will be 
used to estimate SALT scores. 
For the analysis of the primary endpoint (i.e., the binary endpoint 
de
- 
Haenszel test (comparing each dose to placebo, separately). For ach 
imputed dataset, treatment differences will be assessed on the 
natural logarithm scale using the log of the Mantel-Haenszel 
estimate of the adjusted Odds Ratio with a standard error using the 
Greenland and Robins (1985) variance estimate (used to construct 
confidence limits for the Mantel-Haenszel estimate of the adjusted 
Odds Ratio in the SAS FREQ Procedure). The resulting 100 
estimates of the treatment differences and standard errors will then 
be combined using SAS PROC MIANALYZE. 
The pattern of interest for the tipping point analysis is missing 
values not at random (MNAR) for the CTP-543 treatment arms 
only. Subjects from the CTP-543 treatment arms, who have a 
MNAR value at a given visit, might have, on average, their 
observed values of the other subjects. 
The below figure displays the order of testing of the key secondary 
endpoints.  
and first key secondary endpoint for both doses, a linear hierarchical testing 
25 (two-sided) alpha-level will be used to test the 
remaining key secondary endpoint comparisons versus placebo. Once p>0.025 
is observed for a treatment group comparison, inference for additional   
endpoints is no longer alpha-level protected for that dose group, however 
nominal p-values will still be reported. 
Prior to database lock, the classification of the missing data pattern for missing 
SALT scores will be finalized based on blinded data review and documented as 
either considered to be missing at random (MAR) or potentially missing not at 
random (MNAR), consistent with general categories of reasons for 
missingness.  Subjects with missing data due to COVID-19 will have data 
reviewed to determine the specific limitation imposed by COVID-19 
leading to the inability to have captured the protocol-specified 
assessments. For example, missing at random will be considered plausible 
for COVID-19 related reasons such as site closures and travel limitations. 
In general, however, if a MAR assumption is not considered plausible, 
MNAR will be assumed.  Patterns of missing values across visits will be listed 
and summarized with numbers and percentages by treatment and visit.  
A multiple imputation (MI) approach will be used to estimate missing SALT 
scores. 
For the analysis of the primary endpoint (i.e., the binary endpoint denoting a 
> 20) and analyzed using a Mantel-Haenszel test (comparing each dose to
placebo, separately).  For each imputed dataset, treatment differences will be
assessed using the Mantel-Haenszel estimate of a common risk difference,
with the variance estimator due to Sato (used to construct confidence limits
for the Mantel-Haenszel estimate of the common risk difference in the SAS
FREQ Procedure).  The resulting 100 estimates of the treatment differences
and standard errors will then be combined using SAS PROC MIANALYZE.
The patterns of interest for the tipping point analysis will consider two cases 
and will estimate tipping points for values where only missing values not at 
random (MNAR) are adjusted and also where all missing values are 
adjusted (i.e., two separate tipping point analyses).  
The tipping point analyses will use the imputed datasets generated for the 
primary analysis with the delta adjustments for both treated and placebo.  

CTP-543
15 October 2020
Protocol CP543.3001
Concert Pharmaceuticals, Inc.
CONFIDENTIAL & PROPRIETARY 
 10 
The tipping point analysis will use the imputed datasets generated 
for the primary analysis with the delta adjustment. For the tipping 
between the imputed value and baseline and can vary from 0% to 
100% of the difference for subjects with an imputed SALT score 
less than baseline, or zero otherwise. Accordingly, the maximum 
delta value of 100% provides for an adjusted imputed value equal to 
baseline, if the imputed value otherwise represent improvement 
from baseline. This necessarily equates to a non-response for that 
subject with respect to the primary endpoint.  
If during the course of delta change, the study conclusions change 
-sided) alpha-level 
(favorable to not favorable) for a given dose at Week 24, a tipping 
point is reached.  
The increments of delta can start at about 5% of the difference 
between the imputed value and baseline, and may decrease to 1% 
with the intent to refine the grid around the tipping points. 
For the tipping point analysis, 
T values (adjustments for treated subjects) will 
represent a percentage difference between the imputed value and baseline and 
can vary from 0% to 100% of the difference for subjects with an imputed 
SALT score less than baseline, or zero otherwise.  
P 
values will represent a percentage difference between the imputed value 
and 0 hair loss.  Accordingly, the maximum delta value of 100% provides for 
an adjusted imputed value equal to either baseline (for treated subjects, 
representing non-response) or zero hair loss for placebo, representing 
response. 
T 
P to provide a range of assumptions about hypothetical 
improvements on placebo missing data values and reduction in efficacy for 
treated imputed values such that there is no longer evidence of efficacy. 

CTP-543
18 February 2021
Protocol CP543.3001
Concert Pharmaceuticals, Inc.
CONFIDENTIAL & PROPRIETARY 
6 
1/Synopsis/ 
Exclusion Criteria 
8.2/Patient Exclusion 
Criteria 
2. Treatment with other medications or agents
within 1 month of Baseline 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);
oral retinoids, oral cyclines (minocin, tetracycline);
platelet-rich plasma injections; topical application
to affected areas of retinoids, anthralin, squaric
acid, diphenylcyclopropenone, or minoxidil.
11. Fever, inflammation, or systemic signs of 
illness suggestive of systemic or invasive infection
within 2 weeks prior to first dose of study drug.
14. Screening blood level of hemoglobin
(53 mmol/mol, 8.6 mmol/L).
17. Patient has positive results for hepatitis B 
surface antigens (HBsAg), antibodies to hepatitis B 
core antigens (anti-HBc), or hepatitis C virus
(HCV) at Screening, or known history of human
immunodeficiency virus infection.
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 prior to 
randomization, whichever is longer.
19. Positive TB test, or history of incompletely 
treated or untreated tuberculosis.
Note: TB test may be performed via a 
QuantiFERON-TB Gold test or a Tuberculin Skin
Test (TST).  If the TST is negative, patients can be 
randomized into the study, assuming they meet all 
other inclusion and 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 patient is eligible for 
randomization. 
2. Treatment with other medications or agents within 1 month of Baseline or during the study 
that may affect hair regrowth or immune response, including but not limited to: corticosteroids
administered orally, intravenously or intramuscularly, or applied to areas of skin affected by 
alopecia (intranasal and inhaled corticosteroids are allowed, eye and ear drops containing
corticosteroids are also allowed); oral retinoids, oral cyclines (minocin, tetracycline); platelet-
rich plasma injections; topical application to affected areas of retinoids, anthralin, squaric acid, 
diphenylcyclopropenone, or minoxidil.
11. Fever, inflammation, or systemic signs of illness suggestive of systemic or invasive 
infection, or a positive SARS-CoV-2 antigen test, within 2 weeks prior to first dose of study 
drug.
14. Screening blood level of hemoglobin A1c 
. 
17. Patient has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis 
B core antigens (anti-HBc), or hepatitis C virus (HCV) at Screening, or known history of human
immunodeficiency virus infection.  Subjects who test positive for HCV but who are in 
remission (sustained virologic response as evidenced by undetectable HCV RNA level 
in the study. 
18. Vaccination with a live attenuated vaccine during the study or up to 6 weeks prior to 
randomization. 
19. History of previous active disease due to M. tuberculosis (TB) without documentation
of successful treatment; OR, patient has a positive result from a Tuberculin Skin Test 
(TST) or a QuantiFERON-TB Gold (QFT) test performed at Screening.
NOTE: If the patient has a positive QFT result at Screening and: (1) has no history of
successful treatment for either active disease or latent infection due to M. tuberculosis, or
(2) currently resides in an area with low prevalence of tuberculosis, or (3) has no lifetime
history of occupational or household exposure to person(s) with tuberculosis, then the 
initial Screening QFT result may be a false-positive.  In this instance, a second Screening
test for latent TB infection should be obtained  either: (1) a repeat QFT test or (2) a
Tuberculin Skin Test (TST).  The repeat QFT test must be negative or the TST should 
show <15mm induration (considered negative TST) before being considered eligible for
the study. 
Exclusion criterion clarified 
Exclusion criterion clarified 
due to SARS-CoV-2 
Exclusion criteria modified 
Exclusion criterion clarified 
Exclusion criterion clarified 
Exclusion criterion clarified 

CTP-543
18 February 2021
Protocol CP543.3001
Concert Pharmaceuticals, Inc.
CONFIDENTIAL & PROPRIETARY 
7 
4.4.1/Clinical Studies 
of CTP-543 in 
Healthy Subjects 
Study CP543.1005 was a 2-period, fixed-sequence 
study to determine the effect of multiple doses of 
CTP-543 on single dose pharmacokinetics (PK) of 
the components of a combination OC, ethinyl 
estradiol (EE) and levonorgestrel (LNG).  
Preliminary pharmacokinetic data indicate that 
multiple oral doses of 12 mg CTP-543 
administered BID had no impact on ethinyl 
estradiol (EE) exposures following 
coadministration of a single dose of combination 
OC (0.03 mg EE / 0.15 mg levonorgestrel 
(LNG)).  Multiple oral doses of 12 mg CTP-543 
increased LNG exposures slightly following 
coadministration of a single dose of the 
combination OC. Specifically, coadministration 
of CTP-543 increased LNG AUC0-t, AUC0-inf, 
and Cmax by approximately 18%, 17%, and 
16%, respectively, relative to a single oral dose 
of combination OC administered alone.  This 
small increase in LNG exposure is not expected to 
impact the efficacy or safety of the OC.  Overall, 
there were no new findings and AEs reported were 
consistent with previously reported safety data 
from other CTP-543 studies. 
Study CP543 1005 was a 2-period, fixed-sequence study to determine the effect of multiple 
doses of CTP-543 on single dose pharmacokinetics (PK) of the components of a combination 
OC, ethinyl estradiol (EE) and levonorgestrel (LNG).  Multiple oral doses of 12 mg CTP-543 
administered BID on Days 1  8 had no impact on EE overall and peak exposures following 
coadministration with a single dose of combination OC (0.03 mg EE / 0.15 mg LNG). Multiple 
oral doses of 12 mg CTP-543 administered BID on Days 1 - 8 increased LNG overall and 
peak exposures by approximately 17% and 16%, respectively, following coadministration 
with a single dose of combination OC (0.03 mg EE / 0 15 mg LNG) compared to 
Combination OC alone.  This small increase in LNG exposure is not expected to impact the 
efficacy or safety of the OC.  Overall, there were no new findings and AEs reported were 
consistent with previously reported safety data from other CTP-543 studies. 
Completed study 
information updated  
4.4.2/Clinical Studies 
of CTP-543 in 
Patients with 
Alopecia Areata 
Study CP543.5001 is an Open-Label Extension 
study in patients with alopecia areata who were 
previously enrolled in a qualifying clinical trial 
with CTP-543 and completed through the 24-week 
Treatment Period.  Patients will receive daily 
treatment with CTP-543 at a dose of 8 mg BID or 
12 mg BID for up to 108164 weeks in this study.  
Previously qualifying CTP-543 clinical trials 
include: Cohort 3 from Study CP543.2001, Study 
CP543.2002, and Study CP543.2003. 
Study CP543 5001 is an Open-Label Extension study in patients with alopecia areata who were 
previously enrolled in a qualifying clinical trial with CTP-543 and completed through the 24-
week Treatment Period.  Patients will receive daily treatment with CTP-543 at a dose of 8 mg 
BID or 12 mg BID for up to 164 weeks in this study.  Previously qualifying CTP-543 clinical 
trials include: Cohort 3 from Study CP543.2001, Study CP543.2002, and Study CP543.2003.  
Duration of Open-label 
Extension trial updated 
8.3./Patient 
Withdrawal Criteria 
Experience an intolerable adverse event, 
Grade 4, including bone marrow-related events, or 
v5.0 criteria; 
Experience an intolerable adverse event: such events include, but are not limited to, 
-
v5.0 criteria); 
Have a serious adverse event associated with a SARS-CoV-2 infection; 
Modified criteria for clarity 
Added criteria in light of 
SARS-CoV-2 

CTP-543
18 February 2021
Protocol CP543.3001
Concert Pharmaceuticals, Inc.
CONFIDENTIAL & PROPRIETARY 
9 
10.1./Demographic 
Characteristics and 
Medical History 
Medical history should be thoroughly probed for 
potential exposure to serious infections such as 
HIV, history or vaccination against herpes zoster 
or other recent live virus vaccinations, as well as 
cancer risk due to the potential immunosuppressive 
properties and known adverse events associated 
with JAK inhibitors. 
Medical history should be thoroughly probed for potential exposure to serious infections such as 
HIV, history or vaccination against herpes zoster or other recent live virus vaccinations, prior 
SARS-CoV-2 infection, as well as cancer risk due to the potential immunosuppressive 
properties and known adverse events associated with JAK inhibitors. 
Clarified SARS-CoV-2 
infection should be 
documented  
11.1. Definition of 
Adverse Event 
NA 
Vaccine-related AEs (e.g. fever, fatigue, headache) resulting directly from the vaccination 
may occur.  The temporal relationship of the event(s) to the vaccination should be clearly 
described and the PI should consider whether th
Additional language added 
for AEs related in vaccines 
in light of the SARS-CoV-2 
vaccinations.