Clinical trial NCT04797650
Conditions: Alopecia Areata
Keywords: Alopecia Hair loss Hair disease CTP-543
Sponsor: Concert Pharmaceuticals
Start date: 2021-06-10; Completion date: 2022-06-29
Enrollment: 517 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the safety and effectiveness of an investigational study drug (called CTP-543) in adults (18 years and older) who have 50% or greater scalp hair loss.

Detailed description:

Arms: arm 1: Participants received CTP-543 matched placebo tablets, orally, twice daily (BID) for up to 24 weeks. arm 2: Participants received CTP-543 8 mg tablets, orally, BID for up to 24 weeks. arm 3: Participants received CTP-543 12 mg tablets, orally, BID for up to 24 weeks.
Interventions: intervention 1: CTP-543 matching placebo intervention 2: CTP-543
Intervention descriptions: intervention 1: Administered as tablets. intervention 2: Administered as tablets.

Protocol documents:
SAP_002.pdf: 
Official Title: 
NCT Number: 
Document Date: 
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
NCT04797650 
SAP Version 1.0 : 30 June 2022


Clinical Study Report 
Concert Pharmaceuticals, Inc. 
16.1 Study Information 
Study CP543.3002 
1 
9.
DOCUMENTATION OF STATISTICAL METHODS
CP543.3002, Statistical Analysis Plan, Version 1.0, 29 June 2022 
 


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STATISTICAL ANALYSIS PLAN 
 
STUDY 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: 
CP543.3002 
 
 
 
SPONSOR: 
Concert Pharmaceuticals, Inc. 
IND NUMBER: 
131,423 
PREPARED BY: 
 
 
 
 
 
 
 
 
This document is confidential and proprietary to Concert Pharmaceuticals, Inc. This study is being conducted in 
compliance with good clinical practice, including the archiving of essential documents. Acceptance of this 
document constitutes agreement by the recipient that no unpublished information contained herein will be 
reproduced, published, or otherwise disclosed without the prior written approval of Concert Pharmaceuticals, Inc., 
except that this document may be disclosed to appropriate Institutional Review Boards under the condition that 
they keep the information confidential. 
 
 
 
 


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ACKNOWLEDGEMENT AND SIGNATURE SHEET 
 
 
 Project Statistician Approval 
Concert Approval 
Signature and Date 
Signature and Date 
 
 
 
 


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VERSION HISTORY 
 
SAP Version 
Version Date 
Change(s) 
Rationale 
1.0 
2022-06-29 
First version 
 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS .......................................................................................8 
2. 
PURPOSE OF THE ANALYSES ..............................................................................10 
3. 
PROTOCOL SUMMARY ..........................................................................................11 
4. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS ..............................13 
5. 
ANALYSIS SAMPLES ..............................................................................................16 
6. 
STUDY SUBJECTS ...................................................................................................17 
6.1. 
Disposition of Subjects ...............................................................................................17 
6.2. 
Demographic and Other Baseline Characteristics ......................................................18 
6.3. 
Prior and Concomitant Medications ...........................................................................19 
6.4. 
Medical History ..........................................................................................................19 
7. 
STUDY OPERATIONS .............................................................................................20 
7.1. 
Protocol Deviations ....................................................................................................20 
7.2. 
Randomization ............................................................................................................20 
7.3. 
Measures of Treatment Compliance ...........................................................................20 
8. 
ENDPOINT EVALUATION .....................................................................................22 
8.1. 
Overview of Efficacy Analysis Methods ....................................................................22 
8.1.1. 
Multicenter Studies .....................................................................................................22 
8.1.2. 
Assessment Time Windows ........................................................................................22 
8.1.3. 
Timing of Analyses .....................................................................................................22 
8.1.4. 
Multiple Comparisons/Multiplicity ............................................................................23 
8.2. 
Primary Endpoint ........................................................................................................23 
8.2.1. 
Computation of the Primary Endpoint ........................................................................23 
8.2.2. 
Primary Analysis of the Primary Endpoint .................................................................24 
8.2.3. 
Sensitivity Analyses of the Primary Analysis ............................................................25 
8.2.4. 
Secondary Analyses of the Primary Endpoint ............................................................26 
8.3. 
Key Secondary Endpoints ...........................................................................................26 
8.3.1. 
Satisfaction of Hair Patient Reported Outcome (SPRO) at Week 24 .........................27 
8.3.2. 
SALT Score ≤ 20 at Weeks 20, 16, 12, and 8 ............................................................28 
8.4. 
Secondary Endpoints ..................................................................................................28 
8.4.1. 
Secondary SALT Endpoints .......................................................................................29 
8.4.2. 
Secondary SPRO Endpoints .......................................................................................29 


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8.4.3. 
Clinical Global Impression of Improvement (CGI-I) .................................................29 
8.4.4. 
Clinical Global Impression of Severity (CGI-S) ........................................................30 
8.4.5. 
Patient Global Impression of Improvement (PGI-I) ...................................................30 
8.4.6. 
Patient Global Impression of Severity (PGI-S) ..........................................................30 
8.4.7. 
Brigham Eyebrow Tool for Alopecia (BETA) ...........................................................30 
8.4.8. 
Brigham Eyelash Tool for Alopecia (BELA) .............................................................31 
8.4.9. 
Quality of Hair Patient Reported Outcome (QPRO) ..................................................31 
8.4.10. 
Hospital Anxiety and Depression Scale (HADS) .......................................................31 
8.5. 
Other Endpoints ..........................................................................................................31 
8.6. 
Examination of Subgroups .........................................................................................32 
9. 
SAFETY EVALUATION ..........................................................................................33 
9.1. 
Overview of Safety Analysis Methods .......................................................................33 
9.2. 
Extent of Exposure .....................................................................................................33 
9.3. 
Adverse Events ...........................................................................................................33 
9.4. 
Deaths, Serious Adverse Events, and Other Significant Adverse Events ..................35 
9.5. 
Clinical Laboratory Evaluation ...................................................................................36 
9.6. 
Vital Signs, Physical Findings, and Other Observations Related to Safety ...............37 
9.6.1. 
Vital Signs ..................................................................................................................37 
9.6.2. 
Physical Examinations ................................................................................................37 
9.6.3. 
Other Safety Measures ................................................................................................38 
10. 
PHARMACOKINETIC EVALUATION ...................................................................39 
11. 
OTHER ANALYSES .................................................................................................40 
12. 
INTERIM ANALYSES AND DATA MONITORING .............................................41 
13. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL .....................42 
14. 
REFERENCES ...........................................................................................................44 
15. 
APPENDIX .................................................................................................................45 
15.1. 
Study Flow Chart ........................................................................................................45 
15.2. 
Schedule of Events .....................................................................................................46 
15.3. 
Random Seeds for Multiple Imputation .....................................................................48 
15.4. 
Standardized MedDRA Query Values for COVID-19 ...............................................49 
16. 
ATTACHMENTS .......................................................................................................50 
 


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LIST OF TABLES 
Table 1: 
List of Abbreviations ....................................................................................................8 
Table 2: 
Analysis Windows for Unscheduled and Early Termination Visits ...........................22 
 
 
 


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LIST OF FIGURES 
Figure 1: Hierarchical Testing .......................................................................................................27 
 


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1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations 
Abbreviation 
Term 
ANCOVA 
Analysis of Covariance 
ATC 
Anatomical-Therapeutic-Chemical 
BELA 
Brigham Eyelash Tool for Alopecia 
BETA 
Brigham Eyebrow Tool for Alopecia 
BID 
Twice daily dosing 
CGI-I 
Clinician Global Impression of Improvement 
CGI-S 
Clinician Global Impression of Severity 
CI 
Confidence interval 
CSR 
Clinical study report 
CTCAE 
Common terminology criteria for adverse events 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FCS 
Fully conditional specification 
FDA 
Food and Drug Administration 
HADS 
Hospital Anxiety and Depression Scale  
IQR 
Interquartile range 
LS 
Least squares 
MAR 
Missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
MMRM 
Mixed effect model of repeated measures 
MNAR 
Missing not at random 
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 
SALT 
Severity of Alopecia Tool 
SAP 
Statistical analysis plan 
SPRO 
Satisfaction of Hair Patient Reported Outcome  


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TEAE 
Treatment-emergent adverse events 
WHO 
World Health Organization 
 


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2. 
PURPOSE OF THE ANALYSES 
This statistical analysis plan (SAP) provides a detailed description of the strategy and statistical 
methodology to be used for analysis of data from the North American CP543.3002 protocol 
dated 23FEB2021 and the European Union CP543.3002 protocol dated 12MAR2021. The 
statistical analyses outlined within both versions of the protocol are aligned. 
 
The purpose of the SAP is to describe the pre-specified statistical approaches to the analysis of 
study data prior to database lock.  This analysis plan is meant to supplement the study protocol. 
If differences occur between analyses described in the SAP and the current protocol, those found 
in this SAP will assume primacy.  Any deviations from this plan will be described in the Clinical 
Study Report (CSR). 


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3. 
PROTOCOL SUMMARY 
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 Severity of Alopecia Tool (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.  The study design diagram can be 
found in Appendix 15.1. 
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 meeting all inclusion 
criteria and none of the exclusion criteria will be randomized to twice-daily treatment with either 
12 mg CTP-543, 8 mg CTP-543 or placebo.  Patients will be randomized in a 1:2:1 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).  
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 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.  Other baseline assessments will include patient and clinician global impression 
of disease severity (PGI-S and CGI-S), Patient Reported Outcome for Satisfaction (SPRO) and 
Hair Quality (QPRO), the Hospital Anxiety and Depression Scale (HADS), and assessments for 
eyelash and eyebrow involvement.  The schedule of assessments can be found in Appendix 15.2. 
The double-blind, placebo-controlled Treatment Period will last 24 weeks.  Assessment of 
treatment response using SALT for efficacy will occur at 4, 8, 12, 16, 20 and 24 weeks.   
Patient safety will be monitored throughout the trial by the Investigator and supported by regular 
review by the Medical Monitor and DMC.  Chemistry and hematology laboratory values will be 
assessed under fasted conditions bi-weekly for the first month of the treatment period, followed 
by every 4 weeks through the remainder of the study.  Lipid levels will be assessed every 4 
weeks throughout the Treatment Period.  In light of the COVID-19 pandemic, challenges in the 


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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.  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 be followed for safety and 
efficacy assessments until Week 24, unless they withdraw consent.  Patients may withdraw 
consent at any time. 
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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4. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS 
The following is a list of general analysis and reporting conventions to be applied to this study, 
unless otherwise specified.  Departures from these general policies will be described, if 
applicable, in the appropriate sections of this SAP.  When this situation occurs, the rules set forth 
in the specific section take precedence over the general policies. 
All data displays (tables, listings, and figures) will have a header showing the sponsor company 
name, protocol number, page number, and display status (i.e. “DRAFT” or “FINAL”), as well as 
a footer indicating file name and run date/time.  Summary tables and data listings will be 
summarized by active treatment versus placebo-treated patients (i.e., by treatment group) for 
efficacy and exposure, and by treatment group and overall otherwise. All data for analysis will 
be listed by-patient.  
Categorical variables will be summarized using counts (n) and percentages (%) and will be 
presented in the form “n (xx.x).”  If a count is 0, no percentage will be shown. If a percentage is 
100%, 100 will be shown.  To ensure completeness, summaries for categorical variables will 
include all categories, even if no patients had a response in a particular category. Unless 
otherwise specified, the denominator for each percentage will be based on the number of patients 
in the population being summarized (header n).  Percentages will be rounded to one decimal 
place.    
Continuous variables will be summarized using mean, standard deviation, minimum, maximum, 
median, and number of patients.  The minimum and maximum will be the same precision as the 
original collected data. The mean and median will be reported to an additional level of precision 
than the original observations, and the standard deviation will be reported to two additional 
levels of precision than the original observations.  The precision for some original collected data 
and derived variables are longer than required for clinical interpretation (eg, >15 decimals). In 
these situations, the number of decimal places will be determined by the table of precision 
included as an attachment. 
Results of statistical models (ie, least-squares means, confidence intervals, risk differences) will 
be rounded to one additional decimal place from the original data, or a maximum of two decimal 
places. Standard error will be reported to an additional level of precision. Results which cannot 
be determined will be displayed as “NA”, “NE”, or similar. 
For tests of hypothesis of treatment group differences, the associated p-value will be reported.  
All p-values will be rounded to four decimal places after assignment of statistical significance; p-
values that round to 0.0000 or are reported by SAS as zero will be presented as “≤0.0001”; p-
values that round to 1 or are reported by SAS as 1 will be presented as “>0.9999”.  P-values 
which are significant at a 0.05, 0.025, 0.01, 0.001, or 0.0001 level will be marked with asterisks. 
P-values which cannot be determined will be displayed as “NA”. P-values are descriptive for 
outcomes and analyses not included in the multiplicity algorithm. 
Date of last dose is collected on the Treatment Discontinuation/Completion eCRF page. For 
patients with missing or partial date of last dose, the date of last dose (ie, treatment end date) will 
be imputed. Date of last dose will be imputed as follows:  


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• Derive the number of tablets taken at the last visit as the dispensed amount minus the 
returned amount. For treatment compliance (Section 7.3) and exposure (Section 9.2), if 
the returned amount is missing, it will be assumed that zero tablets were taken. 
Otherwise, it will be assumed that 60 tables were taken. 
• An estimated date of possible last dose will be calculated by adding the number of tablets 
taken divided by 2 to the visit date associated with the last visit where drug accountability 
was collected.  
• If there is a partial date of last dose, missing day will be imputed using the day from 
treatment start date, or the last day of the month if that month has fewer days than the 
treatment start month. 
• Treatment end date will be the minimum of the partial date of last dose, calculated 
estimated date of possible last dose, and collected study discontinuation/completion date. 
Summary tables and data listings:  
• Unless otherwise specified, no preliminary rounding will be performed; rounding will 
only occur after analysis.  
• Data from patients excluded from an analysis population will be presented in the data 
listings but will not be included in the calculation of summary statistics, where 
applicable. 
• Data from each patient will be separated by a blank line.  Within a data listing, if a 
descriptive item appears line after line (e.g., repetition of a patient number, date, visit, 
etc.), only the first occurrence will be displayed (e.g., in Listing of Vital Signs, patient 
number, date and visit will only be displayed on first row when presenting all parameters 
collected at same visit).  Repetition of actual results or outcomes (e.g., adverse events, lab 
results, vital sign values, etc.) will not be collapsed.  
• Data listings will be sorted by treatment, patient, and date and/or time of assessment, as 
applicable. 
• When change from baseline or change to baseline is calculated, baseline is the last 
observation obtained prior to first dosing of the study drug. 
• Unless otherwise noted, values reported as greater than or less than some quantifiable 
limit (e.g., “< 2.0”) will be summarized as using the numeric equivalent in summary 
tables and figures (e.g. “<2.0” will be analyzed as 2.0). The reported value will be used in 
listings.  
Mock tables and data listings will be provided as attachments to this analysis plan.  Minor 
changes to the mocks after formal SAP approval will not necessitate re-approval unless changes 
to the text of the SAP are required. 
All statistical deliverables will be produced, validated, and reviewed for accuracy/consistency in 
accordance with 
 standard operating procedures and the processes described in the 
statistical validation plan. 


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SAS® (SAS Institute, Cary, North Carolina) statistical software, version 9.4 or later, will be used 
for all analyses.  Adverse Events and Medical History will be coded in Medical Dictionary for 
Regulatory Activities (MedDRA) Version 23.1. Concomitant medications will be coded in 
World Health Organization (WHO) Drug Version 2020-SEP and Anatomical-Therapeutic-
Chemical (ATC) classification and preferred term. 
 


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5. 
ANALYSIS SAMPLES 
The Efficacy Population will include all patients who are randomized in the study and dispensed 
study drug during the Treatment Period and were not treated at site 102. It was determined by the 
Sponsor during the course of the study that site 102 would be early terminated due to continued 
failure to comply with study procedures.  The decision to exclude subjects treated at site 102 was 
made prior to unblinding.  
The Modified Efficacy Population will include all patients who are randomized in the study and 
dispensed study drug during the Treatment Period. This population will include subjects from 
site 102 and will be used for sensitivity analyses of the primary and key secondary endpoints. 
The Pharmacokinetic Population will include all patients who receive study drug and have at 
least 1 pharmacokinetic sample taken during the Treatment Period.  Patients who receive placebo 
will be excluded from the Pharmacokinetic Population. 
The Safety Population will include all patients who receive study drug during the Treatment 
Period. The Safety Population will include patients from site 102. 
The Per Protocol Population will include all patients in the Efficacy Population who were dosed 
according to protocol and have no major protocol deviations.  Further details on the 
identification of major protocol deviations are provided in Section 7.1. 
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 if the patient 
received that treatment for more than 50% of doses.  


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6. 
STUDY SUBJECTS 
6.1. 
Disposition of Subjects 
Disposition will be summarized by randomized treatment group and overall for all patients 
screened in the study.  The following disposition information will be summarized (percentages 
based on the number randomized, with the exception of the reasons for discontinuation): 
• The number of patients screened. Patients who rescreened will be counted only once. 
• The number of patients randomized. 
• The number and percentage of randomized patients within the Efficacy, Modified 
Efficacy, Pharmacokinetic, Safety, and Per Protocol Populations. 
• The number and percentage of patients who completed treatment, defined as patients with 
either “Complete-Entering Open Label” or “Complete” noted for the question “Subject 
Status” on the Treatment Discontinuation/Completion electronic case report form (eCRF) 
page.  
• The number and percentage of patients who completed treatment and enrolled in the 
Open Label Extension, defined as patients with “Complete-Entering Open Label” noted 
for the question “Subject Status” on the Study Treatment Discontinuation/Completion 
eCRF page. 
• The number and percentage of patients who completed treatment and completed the 
follow-up visit (for those patients who did not enroll in the Open Label Extension), 
defined as patients with “Complete” noted for the question “Subject Status” on the 
Treatment Discontinuation/Completion eCRF page. 
• The number and percentage of patients who prematurely discontinued treatment and the 
frequency and percentage of each discontinuation reason.  The denominator for the 
percentage of each discontinuation reason will be the number of patients who 
discontinued treatment. 
• The number and percentage of patients who prematurely discontinued treatment due to 
the COVID-19 pandemic and the frequency and percentage of each discontinuation 
reason.  The denominator for percentage of patients who prematurely discontinued 
treatment due to COVID-19 will be the number of patients who discontinued treatment. 
The denominator for the percentage of each COVID-19 discontinuation reason will be the 
number of patients who discontinued treatment due to the COVID-19 pandemic. 
• The number and percentage of patients who completed the study, defined as patients with 
either “Complete-Entering Open Label” or “Complete” noted for the question “Subject 
Status” on the Study Discontinuation/Completion eCRF page.  
• The number and percentage of patients who completed the study and enrolled in the Open 
Label Extension, defined as patients with “Complete-Entering Open Label” noted for the 
question “Subject Status” on the Study Discontinuation/Completion eCRF page. 


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• The number and percentage of patients who completed the study (for those patients who 
did not enroll in the Open Label Extension), defined as patients with “Complete” noted 
for the question “Subject Status” on the Study Discontinuation/Completion eCRF page. 
• The number and percentage of patients who prematurely discontinued the study and the 
frequency and percentage of each discontinuation reason.  The denominator for the 
percentage of each discontinuation reason will be the number of patients who 
discontinued the study. 
• The number and percentage of patients who prematurely discontinued the study due to 
the COVID-19 pandemic and the frequency and percentage of each discontinuation 
reason.  The denominator for percentage of patients who prematurely discontinued the 
study due to COVID-19 will be the number of patients who discontinued the study. The 
denominator for the percentage of each COVID-19 discontinuation reason will be the 
number of patients who discontinued the study due to the COVID-19 pandemic. 
The number and percentage of patients randomized within each treatment group and overall will 
also be summarized by investigative site. 
Disposition and patient visits will also be presented for each patient in patient data listings. 
Patient data listings will list date of informed consent, date of first/last treatment, date of end of 
treatment/early treatment termination, date of end of study/early study termination, and reasons 
for treatment or study discontinuation.  A Kaplan Meier curve of time to early treatment 
termination for any reason will also be presented for the Safety Population.  Patients who have 
completed treatment will be censored at date of last treatment, or 24 weeks.  Screen failures will 
be provided in a separate listing. Rescreened patients who later enrolled will not be listed as 
screen failures. 
6.2. 
Demographic and Other Baseline Characteristics 
Demographic characteristics (ie, sex, ethnic origin, race, age, and calculated body mass index) 
will be collected at the Screening Visit, between Day -28 and -1, and detailed on the eCRF.  
Demographic characteristics will be summarized using descriptive statistics for all randomized 
patients by treatment group and overall.  
Baseline characteristics will be summarized using descriptive statistics for all randomized 
patients by treatment group and overall and will include the following:  
• baseline total SALT score 
• Alopecia areata classification (randomization strata via IWRS): partial scalp hair loss 
(SALT ≥ 50 and < 95); complete or near-complete scalp hair loss (SALT ≥ 95) 
• duration of current episode in years (calculated as: [date of randomization – date of 
current episode onset + 1] / 365.25) 
• current nail involvement: yes; no (collected via eCOA system as ‘HAND IMAGE 
CAPTURE’) 
• nasal hair involvement: yes; no (collected on the Physical Examinations eCRF page) 
• eyebrow involvement: yes; no (collected as part of the BETA assessment) 


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• eyelash involvement: yes; no (collected as part of the BELA assessment) 
• whether the patient has experienced any past and/or concomitant diseases, conditions, or 
exposures to serious infections such as HIV, or past surgeries: yes; no (collected via the 
Medical History Summary eCRF page) 
Other co-morbidities may be identified and included as baseline characteristics.  
All demographics and baseline characteristics will also be listed within a by-patient data listing 
for all randomized patients. 
6.3. 
Prior and Concomitant Medications 
Concomitant medications will be recorded in the eCRF from Screening through study 
completion at Week 24 or the Follow-Up Visit at Week 28.  All medications will be coded using 
the WHO Drug Dictionary Version 2020-SEP. 
Medications are classified as prior if the medication started and stopped prior to the first dose 
date of study drug or as concomitant if used on or after the first dose date of study drug.  
Prior and concomitant medications will be summarized with counts and percentages separately 
for the Safety Population by treatment group and overall, WHO Drug ATC classification level 2 
and preferred term.  For each summary, a subject will be counted only once for each medication.  
Partial and completely missing dates will be imputed for the purposes of classifying concomitant 
medications as follows: 
• Partial dates will be imputed following the same algorithm as in Section 9.3 for 
Treatment-emergent adverse events (TEAEs). 
• For an entirely missing stop date (ie day, month, and year are missing), the medication 
will be treated as ongoing.  
Prior and concomitant medications will also be listed by-patient. 
6.4. 
Medical History 
Medical history will be coded with the MedDRA terminology Version 23.1 and summarized as 
counts and percentages for the Safety Population by treatment group and overall, system organ 
class, and preferred term.  A patient will be counted only once for each condition.  Conditions 
will be listed, including the verbatim investigator description of the relevant medical condition, 
the coded terms (system organ class, preferred term), start date, end date, and whether or not the 
condition is ongoing. 


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7. 
STUDY OPERATIONS 
7.1. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or International 
Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use 
Good Clinical Practice requirements.  The noncompliance may be either on the part of the 
participant, the investigator, or the study site staff.  Protocol deviations will be recorded on the 
source documents and with an explanation for the deviation.  All protocol deviations will also be 
recorded as specified in the monitoring plan. 
Protocol deviations will be identified by site staff, through medical reviews, and by clinical 
research associates during site monitoring.  A data review will be conducted before database lock 
by the sponsor to classify protocol deviations as minor or major.  Deviations that may alter or 
confound interpretation of the study results will be classified as major deviations.  Protocol 
deviations will be summarized as counts and percentages by treatment group and overall, 
deviation severity, and category for all randomized patients.  Patients will be counted once for 
each category within each level of severity. Deviations will also be presented by patient in a data 
listing for all randomized patients. 
7.2. 
Randomization 
Approximately 440 patients are planned to be randomized in the study.  Patients will be 
randomized in a 1:2:1 ratio (12 mg BID:8 mg BID:placebo) to each of three study arms:  
• CTP-543 12 mg BID 
• CTP-543 8 mg BID 
• Placebo BID 
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. 
A by-patient listing of randomized treatment group and randomization number will be presented. 
7.3. 
Measures of Treatment Compliance 
Patients will strive for 100% compliance with the daily dosing schedule.  Treatment compliance 
will be summarized as percent of planned dose received for each dosing regimen.  Percent of 
planned dose received will be calculated for the entire treatment period as follows: 
100*(Tablets Dispensed-Tablets Returned)/(Tablets Expected) 
Tablets Expected is defined as the time on treatment multiplied by the expected number of pills 
taken daily (x2 for the 12 mg BID group; x2 for the 8 mg BID group; x2 for the placebo group), 
where time on treatment is defined as treatment end date – treatment start date + 1.  Dose 


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interruptions will be ignored in this calculation.  Derived patient compliance, compliance per the 
eCRF (80% or higher versus less than 80%), and dosing exceptions will be listed in by-patient 
data listings. 
For patients who roll over into one of the open label extension studies, it will be assumed that 
only 1 dose of study drug was administered for the last dose of study drug. For patients who do 
not roll over, it will be assumed that 2 doses of study drug were administered for the last dose of 
study drug. 


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8. 
ENDPOINT EVALUATION 
8.1. 
Overview of Efficacy Analysis Methods 
8.1.1. 
Multicenter Studies 
Patients will be enrolled at up to 60 sites; site identifiers will be included on by-patient listings. 
8.1.2. 
Assessment Time Windows 
The visit schedule for all study assessments is provided in Appendix 15.2.  Patients will be 
considered completed for efficacy analyses after Week 24 (Visit 9).  Patients will either complete 
treatment at Week 24 and have a safety follow-up visit at Week 28 (Visit 10) prior to exiting the 
study, or if eligible, may enroll into an open-label extension study of CTP-543 at their Week 24 
visit. 
Unscheduled visits and early termination visits will be reassigned based on the analysis windows 
in the below table and the schedule of events. Assessments may only be re-assigned to visits 
where they were to be collected per the schedule of events. The latest assessment in a window 
will be selected as the visit used in summaries, unless otherwise specified.  All visits will be 
included in by-patient data listings. 
Table 2: 
Analysis Windows for Unscheduled and Early Termination Visits 
 
Safety Analyses 
Efficacy Analyses 
Nominal Visit 
Lower 
Target 
Upper 
Lower 
Target 
Upper 
Screening 
-28 
-1 
-1 
-28 
-1 
-1 
Visit 2-Day 1 
1 
1 
1 
1 
1 
1 
Visit 3-Week 2 
2 
15 
22 
12 
15 
18 
Visit 4-Week 4 
23 
29 
43 
26 
29 
32 
Visit 5-Week 8 
44 
57 
71 
54 
57 
60 
Visit 6-Week 12 
72 
85 
99 
82 
85 
88 
Visit 7-Week 16 
100 
113 
127 
110 
113 
116 
Visit 8-Week 20 
128 
141 
155 
138 
141 
144 
Visit 9-Week 24 
156 
169 
183 
166 
169 
172 
Visit 10-Week 28 
184 
197 
211 
194 
197 
200 
 
8.1.3. 
Timing of Analyses 
All final, planned analyses will be performed after the last patient has completed all study 
assessments, all relevant study data have been processed and integrated into the analysis 
database, and the database has been locked.  
Any post hoc, exploratory analyses completed to support planned study analysis, which were not 
identified in this SAP, will be documented and reported in appendices to the CSR.  Any results 
from these unplanned analyses (post hoc) will also be clearly identified in the text of the CSR. 


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8.1.4. 
Multiple Comparisons/Multiplicity 
Hierarchical testing will be used to control for multiple comparisons (Figure 1).  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.  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 each dose, 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. 
All other statistical tests outside of the hierarchy will be carried out at a two-sided significance 
level of ≤ 0.05.  Nominal p-values will be presented without adjustment for multiple 
comparisons. 
8.2. 
Primary Endpoint 
The primary efficacy endpoint is the percentage of patients achieving an absolute SALT score of 
≤20 at Week 24 (i.e., the binary endpoint denoting a SALT score ≤ 20). 
8.2.1. 
Computation of the Primary Endpoint 
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. A total SALT score equal to 0% indicates complete hair 
growth. A total SALT score equal to 100% indicates complete hair loss. An example of the 
SALT assessment can be found in Appendix 17.2 of protocol. The overall total SALT score is 
calculated in the eCOA system and will not re-derived. SALT scores are considered missing if 
the overall total could not be calculated. The primary endpoint is derived by categorizing the 
individual overall SALT scores at Week 24 (≤ 20 versus > 20).  
A multiple imputation (MI) approach will be used to estimate missing SALT scores.   
One hundred independent imputations will be done with SAS® PROC MI using the Fully 
Conditional Specification (FCS) regression method. The FCS method combines both the 
monotone and arbitrary missing data patterns into one procedure, imputing missing values with a 
sequential regression approach. 
For the primary efficacy analysis, missing SALT scores will be imputed under a missing at 
random (MAR) assumption. This assumes that patients who have missing data would have 
similar SALT scores as other patients in their respective treatment arm who have complete data.   
Any missing post-baseline SALT scores will be imputed to better inform the estimates of Week 
24 missing SALT scores. Patients who have discontinued treatment but remain on study will not 
have their SALT scores censored, but any arbitrary missing SALT scores after the patient 
discontinued treatment will be imputed in the same manner. Utilizing the FCS method, missing 


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SALT scores will be imputed in a sequential manner using regression models with baseline 
SALT score and the observed or imputed values of previous visits as covariates. Imputations will 
be implemented separately for each treatment under the assumption that different treatments may 
have distinct posterior distributions.   
In addition, 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. 
Multiple imputation will be done using the Efficacy Population and will not be repeated 
separately for the Per Protocol Population. Multiple imputation will be repeated for the Modified 
Efficacy Population.  
8.2.2. 
Primary Analysis of the Primary Endpoint 
Pairwise treatment group differences from placebo will be assessed with the Mantel-Haenszel 
test (common risk difference) using baseline scalp hair loss (partial vs complete/near-complete) 
as the stratification factor, for each active treatment group versus placebo. 
For each imputed dataset, treatment differences will be assessed using the Mantel-Haenszel 
estimate of a common risk difference, with the variance estimator (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 following SAS options for PROC 
FREQ will be used to estimate a common risk difference, confidence intervals, and p-values by 
imputation for placebo compared to each dose separately: 
proc freq data = < > ; 
by IMPUTATION; 
tables STRATA*TREATMENT*RESPONSE / commonriskdiff(cl=mh test=mh); 
run; 
The observed number and percentage of patients with an absolute SALT score ≤ 20 among non-
imputed data will be reported by treatment group along with the appropriate p-value, the 
combined treatment differences, combined standard errors, and 95% confidence intervals (CI). 
This analysis will be completed for the Efficacy Population and the Per Protocol Population. The 
analysis utilizing the Per Protocol Population is considered supportive. The results may also be 
displayed graphically.  


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8.2.3. 
Sensitivity Analyses of the Primary Analysis 
Sensitivity analyses of the primary efficacy endpoint will be conducted to evaluate the 
robustness of study results under different assumptions and imputation algorithms. For the 
primary endpoint categorized as absolute SALT score ≤ 20 at Week 24, the following sensitivity 
analyses will be performed for the Efficacy Population only. 
Sensitivity 1: Multiple imputation; missing not at random (MNAR)  
This sensitivity analysis is an implementation of a pattern mixture model that draws from 
different populations based on the reason for withdrawal from study. Patients who discontinued 
the study early due to a treatment-emergent adverse event (including COVID-19) or due to lack 
of efficacy will be considered MNAR. Treatment-emergent adverse event and lack of efficacy 
are reasons collected under “If 'Withdrew Consent', specify reason” on the Study 
Discontinuation/Completion eCRF page.   
For patients who discontinued the study early due to a treatment-emergent adverse event or lack 
of efficacy, SALT scores missing after discontinuation will be imputed using the control arm. 
This assumes that patients, regardless of treatment, who discontinue the study early for those 
reasons would have similar SALT scores to placebo patients with complete data.  
For patients who discontinued the study due to reasons other than treatment-emergent adverse 
event or lack of efficacy, missing SALT scores after subjects discontinue the study early will be 
multiply imputed from subjects within the same treatment group who have complete data at that 
time. Terms will include baseline values and the weekly data through the time point being 
imputed. 
The proportion of patients who have a SALT score ≤ 20 will be calculated for each imputed 
dataset. The primary analysis, as described in Section 8.2.2, will be repeated for the Efficacy 
Population using the MI with MNAR assumption datasets. 
Sensitivity 2: Tipping point 
Additionally, a tipping point analysis 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 tipping point analysis will use the primary MAR 
assumption datasets, where all imputed values are adjusted. 
The tipping point analysis will apply delta adjustments for both treated and placebo.  For the 
tipping point analyses, δT values (adjustments for treated patients) 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 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. 


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Sensitivity 3: Modified Efficacy Population 
A third sensitivity analysis will be done utilizing the Modified Efficacy Population. The primary 
analysis will be repeated, as described in Section 8.2.2.  
8.2.4. 
Secondary Analyses of the Primary Endpoint 
No secondary analyses specified. 
8.3. 
Key Secondary Endpoints 
The below figure displays the order of testing of the key secondary endpoints.  See also Section 
8.1.4. 
 
 
 
 
 
 
 
 


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Figure 1: Hierarchical Testing 
 
 
8.3.1. 
Satisfaction of Hair Patient Reported Outcome (SPRO) at Week 24  
The first key secondary endpoint is the percentage of responders per the SPRO at Week 24.  The 
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 SPRO responses 
are on a scale of 1-5, where 1 = very satisfied, 2 = satisfied, 3 = neither satisfied nor dissatisfied, 
4 = dissatisfied, and 5 = very dissatisfied.  An example of the SPRO assessment can be found in 
Appendix 17.4.1 of the protocol. 
A responder is defined as patients with answers of “very satisfied” or “satisfied” at Week 24 on 
the SPRO.  This endpoint will be assessed similar to the primary analysis of the primary 
endpoint, according to Section 8.2.2.     


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Missing data will be imputed similarly to the primary endpoint according to Section 8.2.1. 
However, since the SPRO scale is ordinal, the FCS logistic regression method will be used in 
lieu of the FCS regression method. The missing SPRO scores will be imputed in a sequential 
manner using logistic regression models with baseline SALT score, baseline SPRO score, and 
the observed or imputed SPRO values of previous visits as covariates.  
The observed number and percentage of SPRO responders by treatment group will be reported 
along with the appropriate p-values.  Both CTP-543 doses will be tested in parallel against 
placebo with a ≤ 0.025 alpha level.  This analysis will be completed for the Efficacy Population, 
the Per Protocol Population, and the Modified Efficacy Population.  The Per Protocol Population 
will be considered supportive. The analysis utilizing the Modified Efficacy Population is 
considered a sensitivity analysis. If the primary endpoint is unsuccessful, nominal p-values will 
be reported.  
8.3.2. 
SALT Score ≤ 20 at Weeks 20, 16, 12, and 8 
 
The next key secondary endpoints are the percentage of patients achieving an absolute SALT 
score of ≤20 (i.e., the binary endpoint denoting a SALT score ≤ 20) at Weeks 20, 16, 12, and 8.  
Missing data will be imputed according to Section 8.2.1.  These endpoints will be assessed 
according to Section 8.2.2.  If the primary endpoint and first key secondary endpoint are 
unsuccessful, nominal p-values for the SALT key secondary endpoints will be reported.  This 
analysis will be completed for the Efficacy Population, the Per Protocol Population, and the 
Modified Efficacy Population. The Per Protocol Population will be considered supportive.  The 
analysis utilizing the Modified Efficacy Population is considered a sensitivity analysis.  
8.4. 
Secondary Endpoints 
All statistical tests outside of the hierarchy defined in Section 8.1.4 and Section 8.3 will be 
carried out at a two-sided significance level of ≤ 0.05.  Nominal p-values will be presented. 
Analyses will be performed using the Efficacy Population. 
Missing values will not be imputed for efficacy endpoints that are not derived from SALT or 
SPRO scores. 
For the secondary endpoints of proportions of patients achieving specified improvement criteria 
(hereinafter, “secondary responder endpoints”), 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.  Observed counts and percentages of 
responders will be summarized by treatment group and the p-values reported. Secondary 
responder endpoints derived from SALT or SPRO scores will be analyzed similarly to the 
primary endpoint according to Section 8.2.2. 
For the secondary endpoints of absolute or relative changes (hereinafter, “continuous secondary 
endpoints”), treatment differences will be assessed with a mixed-effect model of repeated 
measures (MMRM).  Model covariates are described in applicable sections below.  Treatment 
group comparisons at each visit will be based on least squares (LS) mean estimates.  An 
unstructured covariance matrix will be used to model the within-subject errors.  Should the 
model fail to converge, an alternative autoregressive covariance matrix will be used instead.  The 
Kenward-Roger approximation will be used to estimate the denominator degrees of freedom.  
Assuming that the data are MAR, the estimates of the treatment differences calculated from the 


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MMRM described above are unbiased.  Standard descriptive statistics will be reported for each 
time point on the values and changes from baseline along with the LS means, standard errors, 
95% CIs and differences between treatment groups reported with LS means, standard errors, and 
95% CIs.  
8.4.1. 
Secondary SALT Endpoints 
 
The following secondary SALT responder endpoints will be assessed: 
• 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 
• Percentage of patients achieving an absolute SALT score of ≤20 at Week 4 
• Percentage of patients achieving an absolute SALT score of ≤10 at Week 24  
In addition, the continuous secondary SALT endpoint of relative change in SALT score from 
baseline at Weeks 4, 8, 12, 16, 20, and 24 will be assessed with a MMRM.  The model will 
include fixed factors for treatment group, study visit, and treatment by study visit interaction, 
with baseline SALT score as a covariate. Imputed values will not be used for the MMRM. 
Relative reduction is based on relative change from baseline.   
Relative change in SALT score is derived as percent change of the follow-up SALT score, where 
baseline SALT score is the denominator (i.e. absolute change divided by the baseline score, 
multiplied by 100). 
8.4.2. 
Secondary SPRO Endpoints 
The following secondary SPRO responder endpoints will be assessed: 
• Percentage of responders at Weeks 12, 16, and 20, where responders is defined as “very 
satisfied” or “satisfied” 
• Percentage of patients achieving a ≥ 2-point change from baseline in the SPRO scale at 
Weeks 12, 16, 20, and 24 
In addition, the continuous secondary SPRO endpoint of change from baseline at Weeks 12, 16, 
20, and 24 will be assessed with a MMRM.  The model will include fixed factors for treatment 
group, study visit, and treatment by study visit interaction, with baseline SALT score and 
baseline SPRO score as covariates. Imputed SPRO values will not be used for the MMRM. 
8.4.3. 
Clinical Global Impression of Improvement (CGI-I) 
The CGI-I will be assessed by the Investigator at Weeks 12, 16, 20, and 24.  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 assessment can be found in Appendix 
17.3.2 of the protocol.  


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The secondary CGI-I responder endpoint of percentage of responders (defined as “much 
improved” or “very much improved”) at Weeks 12, 16, 20, and 24 will be assessed. 
8.4.4. 
Clinical Global Impression of Severity (CGI-S) 
The CGI-S will be assessed by the Investigator and will consider the severity of the patient’s 
alopecia areata at the time of assessment.  The Investigator may select one of 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 for the duration of the 
study.  An example of the CGI-S assessment can be found in Appendix 17.3.1 of the protocol.  
The continuous secondary endpoint of change from baseline in the CGI-S at Weeks 12, 16, 20, 
and 24 will be assessed with a MMRM.  The model will include fixed factors for treatment 
group, study visit, and treatment by study visit interaction, with baseline SALT score and 
baseline CGI-S score as covariates.  
8.4.5. 
Patient Global Impression of Improvement (PGI-I) 
The PGI-I will be assessed by the patient at Weeks 12, 16, 20, and 24.  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 
assessment can be found in Appendix 17.3.4 of the protocol.  
The secondary PGI-I responder endpoint of percentage of responders (defined as “much 
improved” or “very much improved”) at Weeks 12, 16, 20, and 24 will be assessed. 
8.4.6. 
Patient Global Impression of Severity (PGI-S)  
The PGI-S 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 
assessment can be found in Appendix 17.3.3 of the protocol.  
The continuous secondary endpoint of change from baseline in the PGI-S at Weeks 12, 16, 20, 
and 24 will be assessed with a MMRM.  The model will include fixed factors for treatment 
group, study visit, and treatment by study visit interaction, with baseline SALT score and 
baseline PGI-S score as covariates.  
8.4.7. 
Brigham Eyebrow Tool for Alopecia (BETA) 
The 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. 
The continuous secondary endpoint of change from baseline in the BETA at Weeks 12 and 24 
will be assessed with a MMRM.  The model will include fixed factors for treatment group, study 
visit, and treatment by study visit interaction, with baseline SALT score and baseline BETA 
score as covariates.     


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8.4.8. 
Brigham Eyelash Tool for Alopecia (BELA) 
The 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 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.    
The continuous secondary endpoint of change from baseline in the BELA at Weeks 12 and 24 
will be assessed with a MMRM.  The model will include fixed factors for treatment group, study 
visit, and treatment by study visit interaction, with baseline SALT score and baseline BELA 
score as covariates. 
8.4.9. 
Quality of Hair Patient Reported Outcome (QPRO) 
The QPRO questionnaire is a 4-item assessment which provides additional details on key 
attributes of patient hair and helps provide context to the SPRO response.  Like the SPRO, the 
QPRO responses are on a scale of 1-5, where 1 = very satisfied, 2 = satisfied, 3 = neither 
satisfied nor dissatisfied, 4 = dissatisfied, and 5 = very dissatisfied.  An example of the QPRO 
assessment can be found in Appendix 17.4.2 of the protocol. 
The continuous secondary endpoints of change from baseline each individual item for QPRO at 
Weeks 12, 16, 20, and 24 will be assessed with a MMRM.  The model will include fixed factors 
for treatment group, study visit, and treatment by study visit interaction, with baseline SALT 
score and baseline QPRO item score as covariates.  
8.4.10. 
Hospital Anxiety and Depression Scale (HADS) 
The 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 assessment 
can be found in Appendix 17.5 of the protocol. 
The continuous secondary endpoints of change from baseline in HADS-A at Week 24 and 
change from baseline in HADS-D at Week 24 will be assessed with an ANCOVA.  The model 
will include fixed factors for treatment group with baseline SALT score and baseline HADS 
score (HADS-A or HADS-D as appropriate) as covariates.   
8.5. 
Other Endpoints 
A KM plot of time to first instance of post-baseline SALT ≤20 will also be included. Patients 
who do not meet the responder criteria will be censored at treatment end date or 24 weeks if the 
treatment end date extends beyond 24 weeks. Stratified log-rank statistics will be computed by 
randomization strata for CTP-543 8mg v. placebo and CTP-543 12mg v. placebo separately. The 
p values will be displayed with the KM plot. These p values are descriptive and are not part of 
the hierarchy outlined in Section 8.1.4 (Figure 1). 
No other efficacy endpoints are specified. 


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8.6. 
Examination of Subgroups 
No subgroup analyses are planned. 


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9. 
SAFETY EVALUATION 
 
9.1. 
Overview of Safety Analysis Methods 
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 (ie, as 
treated), should it differ from the randomized treatment arm.  Safety assessments will be 
summarized by treatment group and overall.  All safety endpoints will be listed in by-patient data 
listings. 
9.2. 
Extent of Exposure 
Study drug exposure will be summarized for each treatment group.  The number of days on 
which study drug was dosed (at least partially), the number of days in the study, percent of 
planned doses received, and total cumulative dose will be summarized for each treatment group.  
The number of days on which study drug was dosed (at least partially) will be calculated as 
(treatment end date – treatment start date + 1) minus the total number of days with a dosing 
exception per the Dosing Exceptions eCRF page of partial dose (counted as 1 day missed), 
missed dose (counted as 1 day missed), or dose interruption (counted as 1 day missed). The 
number of days in the study will be calculated as (treatment end date – treatment start date + 1). 
Total cumulative dose will be calculated as the total number of tablets taken multiplied by 8 mg, 
12 mg, or 0 mg for each applicable treatment.  
The number and percentage of subjects with at least one dose interruption will also be 
summarized, where dose interruption is defined as a value of “Dose interruption” for the 
question “Reason for Exception” on the Dosing Exceptions eCRF page. The sponsor may review 
the free text field associated with the “Reason for Exception” prior to database lock in order to 
identify reasons related to the dose interruption criteria outlined in Protocol Section 9.2.1. Should 
these reasons be identified, the definition of dose interruption would be refined based on those 
findings. 
Drug compliance will also be summarized, per Section 7.3.  
9.3. 
Adverse Events 
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. 


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Adverse events will be coded using MedDRA version 23.1 and summarized by treatment group, 
system organ class, and preferred term.   
An adverse event reported after informed consent, but before the first dose of study drug (i.e., 
Day 1), will be considered a pre-treatment adverse event.  Treatment-emergent adverse events 
will be defined as any adverse event that occurs after administration of the first dose of study 
drug. Adverse events will be limited to those collected within this protocol (ie, for rollover 
subjects, AEs collected under the protocol of the rollover study will not be in this study). The 
number and percentage of patients who report TEAEs will be summarized by treatment group, 
system organ class, and preferred term.  
Treatment emergent adverse events will also be summarized by intensity as well as relationship 
to study drug.   
Partial dates will be imputed for the purposes of defining TEAEs as follows: 
• For a missing start day where the month and year are present, the start day will be set to 
the first day of the month, unless 1) the first day of the month is before the date of 
administration of study drug and the month and year are the same as the month and year 
of the date of administration of study drug, and 2) the end date is on or after the date of 
administration of study drug or the end date is completely missing, in which case the start 
day will be set to the first day of administration of study drug. 
• For a missing start day and month where the year is present, the start day and month will 
be set to January 1st, unless 1) January 1st is before the date of administration of study 
drug, and 2) the end date is on or after the date of administration of study drug or the end 
date is completely missing, in which case the start day and month will be set to that of the 
first date of administration of study drug. 
• For an entirely missing start date (ie day, month, and year are missing), the start date will 
be set to the date of administration of study drug unless the stop date is prior to the date 
of administration of study drug, in which case the start date will be set to the stop date. 
• For a missing end day where the month and year are present, the end day will be set to 
the last day of the month, unless the month and year are the same as the month and year 
of the last visit date for the patient, in which case the end day will be set to that of the 
patient's last visit date. 
• For a missing end day and month where the year is present, the end day and month will 
be set to the patient's last visit date, unless the year of the patient's last visit date is greater 
than the end year, in which case the end day and month will be set to December 31st. 
• For an entirely missing stop date (i.e. day, month, and year are missing), the stop date 
will be imputed as the patient’s last visit date. 
Patients who report the same preferred term on multiple occasions will be counted once for the 
preferred term: under the highest severity when summarized by severity and under the closest 
relationship to study drug when summarized by relationship.  Missing severity or relationship 
will not be imputed.  If a patient reports multiple preferred terms for a system organ class, the 
patient will be counted only once for that system organ class. 


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The number and percentage of patients who experience TEAEs and the total number of TEAEs 
will be summarized by treatment group and overall 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 
Additionally, TEAEs will be summarized by treatment group and overall and 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. 
By-patient listings will include all adverse events. TEAEs will be flagged. 
9.4. 
Deaths, Serious Adverse Events, and Other Significant Adverse 
Events 
A serious adverse event is an adverse event 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. 
Serious adverse events will be summarized according to Section 9.3.  


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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.  
9.5. 
Clinical Laboratory Evaluation 
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.   
Clinical laboratory variables will be presented in 4 ways.  First, change from baseline to the 
minimum post-baseline value, maximum 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.  Only post-baseline values on treatment will be eligible.  The Follow-up Visit will 
be excluded from possible minimum, maximum, or final post-baseline values. 
This analysis will be repeated with outlying values removed from eligibility for minimum and 
maximum values. An outlier is defined using the interquartile range (IQR). The IQR is equal to 
the third quartile minus the first quartile and will be calculated by visit and treatment group for 
each numeric parameter. The IQR will be multiplied by a constant of 1.5. Any value which is 
above 1.5 times IQR plus the third quartile or below 1.5 times IQR minus the first quartile will 
be considered an outlier and will be removed from eligibility for minimum, maximum, or final 
post-baseline values. 
Second, shift tables will summarize by treatment group and active overall 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: minimum post-baseline value and maximum post-baseline value. 
Only post-baseline values on treatment will be eligible. Patients will only be reported in the shift 
tables if they have both a baseline and 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.  Laboratory values will be graded using 
CTCAE version 5.0, for those values included.  CTCAE grades will be based solely on numeric 
results and without regard to other symptoms based on clinical judgment. For laboratory 
parameters whose CTCAE grading is independent of baseline criteria, treatment-emergent PCS 
laboratory values are those in which the baseline value is not PCS and the post-baseline value is 
PCS. For laboratory parameters whose CTCAE grading is dependent upon baseline criteria, any 
post-baseline grading of Grade 3 or Grade 4 will be considered treatment-emergent.  The number 
and percentage of patients with treatment-emergent PCS laboratory values will be summarized 
by treatment group and overall for each clinical laboratory variable subject to CTCAE grading. 
For this analysis, the visit with the highest CTCAE grade value within a window will be selected. 


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Finally, the mean and mean change from baseline by visit will be summarized by treatment 
group and overall. 
These analyses will be repeated for serum chemistry results, hematology results, and lipid results 
(where lipid tests include total cholesterol, low-density lipoprotein, high-density lipoprotein, 
triglycerides).  Laboratory results will also be listed.  Reference ranges for each clinical 
laboratory parameter will also be summarized in a data listing. 
Box plots of hemoglobin, platelets, and neutrophils will also be provided with dose interruption 
limits included as reference lines (see Protocol Section 9.2.1). 
Pregnancy test results will be listed only. 
9.6. 
Vital Signs, Physical Findings, and Other Observations Related to 
Safety 
9.6.1. 
Vital Signs 
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.   
Height will only be measured at the Screening Visit.  Weight and vital signs will be measured 
according to the Schedule of Assessments (Appendix 15.2).  Weight and height will be used to 
calculate the patient’s body mass index at Screening.   
The mean and mean change from baseline to each scheduled assessment will be summarized 
descriptively by treatment group and overall for each vital sign variable specified in the 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, defined as for 
laboratory values in Section 9.5, will be summarized descriptively by treatment group and 
overall.  A listing of vital signs by patient will also be provided. 
9.6.2. 
Physical Examinations 
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 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. Complete physical exams will be performed at screening, baseline, 
Week 24, and Week 28. The presence or absence of nasal hair will be summarized as counts and 
percentages by treatment group at baseline and Week 24 for the Safety Population.   
Brief physical examinations will include assessment for active signs and symptoms of infection, 
including tuberculosis, skin examinations for non-melanoma skin, and an evaluation for PML 


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symptoms such as facial droop, general weakness, clumsiness, trouble speaking, personality 
changes, memory problems, and vision changes. Physical examinations will be performed 
according to the Schedule of Events (Appendix 15.2).  
A listing of the date and type of physical examinations performed will be provided. The listing 
will include presence or absence of nasal hair. Deteriorations from baseline on physical 
examination will be coded as adverse events and summarized as such. 
9.6.3. 
Other Safety Measures 
9.6.3.1. 
12-Lead Electrocardiogram 
Twelve-lead electrocardiograms (ECG) will be performed at the screening visit, Week 12, 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 (Frederica’s correction), QRS, RR 
intervals will be collected.  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.  
The mean and mean change from baseline to each scheduled assessment will be summarized 
descriptively by treatment group and overall for each ECG variable specified in the protocol. 
A listing of ECG results will be provided. A listing of abnormal ECG findings will also be 
provided. 
 


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10. 
PHARMACOKINETIC EVALUATION 
Sparse PK sampling was performed in this study in order to contribute to a cross study 
population PK analysis.  Covariates from this study and others will include age, gender, race, 
weight (or BMI), for the population PK analysis of CTP-543.  Exposure-response relationships 
for both efficacy and safety parameters will also be assessed. This population PK analysis will be 
described in a separate analysis plan and a separate population PK report will be generated.  The 
data will not be summarized in the CP543.3002 final clinical study report. 
A by-patient listing of whether PK sampling was performed will be included in the final clinical 
study report. 


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11. 
OTHER ANALYSES 
In light of the COVID-19 pandemic and recommendations in the FDA guidance document 
“Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency”, 
the following additional listings and summaries will be provided: 
• Listing of patients affected by COVID-19 related study disruption, defined as missed or 
remote visits or assessments indicated per the eCRF. 
• Listing of dosing exceptions related to COVID-19. 
• Summary and listing of protocol deviations related to COVID-19, per Section 7.1. 
• Summary of TEAEs related to COVID-19 by system organ class and preferred term and 
TEAEs related to COVID-19 leading to study drug discontinuation by system organ 
class and preferred term, per Section 9.3. Relationship to COVID-19 will be determined 
using the Standard MedDRA Query for COVID-19 (Appendix 15.4) and may also 
include preferred terms related to vaccinations if the collected term indicates relation to 
COVID-19 (ex: Vaccination complication, Vaccination site pain). Terms may be 
reviewed by the sponsor prior to database lock to finalize the list of preferred terms. 
• Listing of TEAEs related to COVID-19. 
• Listing of prior and concomitant medications related to COVID-19, where relationship 
to COVID-19 is defined by the question “Related to COVID-19?” on the Prior and 
Concomitant Medications CRF page. 
• Summary of number and percentage of randomized subjects with missed visits due to 
COVID-19. 


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12. 
INTERIM ANALYSES AND DATA MONITORING 
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. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL 
The following changes to the protocol were made:  
• Protocol Section 12.3.1 Analysis Populations 
o The Modified Efficacy Population was added as an analysis population. The 
Modified Efficacy Population is defined as the protocol defines the Efficacy 
Population. The SAP updates the definition of the Efficacy Population to exclude 
site 102 due to repeated and persistent non-compliance with the study procedures. 
o The text “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” was amended to add additional information in the event 
that a patient is given only a portion of the incorrect treatment.  
• Protocol Section 12.4.1 Disposition and Baseline Characteristics 
o This section of the protocol does not distinguish treatment discontinuation from 
study discontinuation. The SAP adds detail and specifies that both treatment and 
study discontinuation, as well as reasons for discontinuation for both treatment 
and study will be summarized in line with FDA feedback and the eCRF. 
• Protocol Section 12.4.2  
o Primary Efficacy Endpoint 
 The protocol uses the general umbrella term “Cochran-Mantel-Haenszel 
test” to describe the primary analysis. The SAP specifies “Mantel-
Haenszel common risk difference” in reference to analyses which use 
multiple imputation. This is in line with Protocol Section 12.4.5.1. 
Analysis of Imputed Datasets and was done to avoid confusion with 
stratified CMH tests utilized for non-imputed data. 
o Other Efficacy Endpoints 
 The protocol specifies that analyses of HADS will use an MMRM. The 
SAP updates this analysis to use an ANCOVA as the questionnaire was 
only collected at one post-baseline visit. 
• Protocol Section 12.4.5 – Multiple Imputation 
o The protocol states, “Missing values will be imputed with a sequential regression 
approach under the assumption of multivariate normality.” The SAP removes the 
phrase “under the assumption of multivariate normality” as it is not necessarily 
applicable when using the FCS method.  
o The protocol states that the discriminant function will be used for classification 
variables. The logistic function was specified for SPRO imputation because it is 
ordinal rather than nominal. 
o The SAP adds multiple imputation for the Modified Efficacy Population, which 
will include site 102. The primary multiple imputation for the Efficacy Population 
will not include site 102. 


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• Protocol Section 12.4.5.2 – Tipping Point Analyses 
o The protocol states that “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 SAP specifies only one 
tipping point analysis due to the following:  
 This statement assumes that the primary imputation method would employ 
an MNAR assumption. It was determined that MAR would be reasonable 
upon blinded review of reasons for missing data, as prespecified in 
Protocol Section 12.4.4.  
 To test the MAR assumption, an additional sensitivity analysis employing 
an MNAR assumption was added.  
 The values that will be MNAR for the MNAR sensitivity analysis are 
study discontinuations due to TEAEs or lack of efficacy. These values will 
be imputed using the control arm. As such, adjusting these values would 
shift those patients to be worse than placebo. As placebo in this study is a 
true placebo, this is not a realistic or informative shift. 
o The protocol states, “Missing values will not be imputed for efficacy endpoints 
which are not derived from SALT scores.” The SAP adds multiple imputation for 
the SPRO endpoints because SPRO at Week 24 is an alpha-controlled key 
secondary endpoint and the treatment of missing data should align with the 
treatment of missing data for the other alpha-controlled endpoints. 
• Protocol Section 12.4.8 Safety  
o Adverse Events 
 The protocol states that “Proportions for adverse events that are gender-
specific (e.g., dysmenorrhea) will be based on the number of patients from 
that gender.” The SAP specifies that the proportion of adverse events will 
be based on the number of patients in the safety population, even gender-
specific adverse events. This change is in line with previous studies in this 
program and generally accepted conventions. 
o Clinical Laboratory 
 Two additional presentations of labs were added to the SAP in light of 
outliers seen in blinded data review throughout the study (IQR) and to 
observe values over time (by visit summaries). 
• Other changes: 
o Analyses for COVID-19 were added in Section 11 of the SAP. 
o Log-rank statistics related to the primary endpoint were added as an Other 
Efficacy Endpoint. This analysis is descriptive only. 
 


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14. 
REFERENCES 
FDA. (2020). Guidance for Industry: Statistical Considerations for Clinical Trials During the 
COVID-19 Public Health Emergency. 


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15. 
APPENDIX 
15.1. 
Study Flow Chart 
 
 


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15.2. 
Schedule of Events 
 
 
 
Screening 
Baseline/ 
Randomization 
Treatment Period4 
Safety 
Follow-Up 
Day -28 to Day -12 
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 
Event1 
(Visit 1) 
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 
Pharmacokinetic Sampling for Population Pharmacokinetics  
 
X 
 
X12 
 
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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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. 
6 For females of childbearing potential, a serum pregnancy test will be performed at 
Screening.  Throughout the Treatment Period, and at the safety follow-up (if 
applicable), urine pregnancy tests will be performed.   
7 Includes fasted hematology, serum chemistry, and lipids 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, Site to Subject (STS) or Direct to Subject (DTS) 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. 


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15.3. 
Random Seeds for Multiple Imputation 
The following list of numbers will be used in order for programming tasks that require random 
seeds.  If additional numbers are required, programming will return to the start of the list and add 
one to each value for additional seeds. 
 
30788490 
59846961 
71245840 
79609234 
26047018 
81338379 
15768979 
78450241 
50892929 
29239796 
32909600 
93095742 
49221436 
83257824 
24006875 
48041342 
20079591 
24767358 
60535539 
91978466 
 
 
 


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15.4. 
Standardized MedDRA Query Values for COVID-19 
 
Scope 
Preferred Term 
Preferred Term Code 
Narrow Asymptomatic COVID-19 
10084459 
Narrow Coronavirus infection 
10051905 
Narrow Coronavirus test positive 
10070255 
Narrow COVID-19 
10084268 
Narrow COVID-19 immunisation 
10084457 
Narrow COVID-19 pneumonia 
10084380 
Narrow COVID-19 prophylaxis 
10084458 
Narrow COVID-19 treatment 
10084460 
Narrow Exposure to SARS-CoV-2 
10084456 
Narrow Multisystem inflammatory syndrome in children 
10084767 
Narrow Occupational exposure to SARS-CoV-2 
10084394 
Narrow SARS-CoV-2 antibody test positive 
10084491 
Narrow SARS-CoV-2 carrier 
10084461 
Narrow SARS-CoV-2 sepsis 
10084639 
Narrow SARS-CoV-2 test false negative 
10084480 
Narrow SARS-CoV-2 test positive 
10084271 
Narrow SARS-CoV-2 viraemia 
10084640 
Narrow Suspected COVID-19 
10084451 
Broad 
Antiviral prophylaxis 
10049087 
Broad 
Antiviral treatment 
10068724 
Broad 
Coronavirus test 
10084353 
Broad 
Coronavirus test negative 
10084269 
Broad 
Exposure to communicable disease 
10049711 
Broad 
Pneumonia viral 
10035737 
Broad 
SARS-CoV-2 antibody test 
10084501 
Broad 
SARS-CoV-2 antibody test negative 
10084509 
Broad 
SARS-CoV-2 test 
10084354 
Broad 
SARS-CoV-2 test false positive 
10084602 
Broad 
SARS-CoV-2 test negative 
10084273 
 


Concert Pharmaceuticals, Inc. 
Statistical Analysis Plan – CP543.3002 
Page 50 of 50 
Version Date: 2022-06-29 
Version: 1.0  
 
16. 
ATTACHMENTS 
 

Prot_000.pdf: 


CTP-543 
23 February 2021 
Protocol CP543.3002 
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: 
CP543.3002 
ORIGINAL PROTOCOL 
(NORTH AMERICA):  
23 February 2021 
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 
 
23 February 2021 
Protocol CP543.3002 
 
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 
 
23 February 2021 
Protocol CP543.3002 
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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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:  CP543.3002 
 
 
 
 
 
Sponsor Representative Signature  
 
dd mmm yyyy 
 
 
Printed Name of Sponsor Representative 
 
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable.   
 
 
 
Electronically signed by
Reason
Date  Feb 23, 2021 09 58 EST
23-Feb-2021


CTP-543 
 
23 February 2021 
Protocol CP543.3002 
 
Concert Pharmaceuticals, Inc. 
CONFIDENTIAL & PROPRIETARY 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number:  CP543.3002 
 
 
 
 
 
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. 
 
 
 


CTP-543 
 
23 February 2021 
Protocol CP543.3002 
 
Concert Pharmaceuticals, Inc. 
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 50 sites (North America and European Union)  
Studied period (years):  
Estimated date first patient first visit: April 2021 
Estimated date last subject last visit: June 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. 




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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 440 patients are planned to be randomized in the study.  Patients will be randomized in 
a 1:2:1 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. 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 
b. Post-menopausal (cessation of menses for at least 12 months prior to screening)  
c. Infertility of sexual partner or partner of the same sex 
d. Implants of levonorgestrel in females 
e. Contraceptive (combined oral, patch, vaginal ring, injectable, implant) in females 
f. Double-barrier method (any combination of physical and chemical methods) 
g. Intrauterine device with a failure rate less than 1% per year 
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. 
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.  


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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). 
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.   


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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:  
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  


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 
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  
 
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.  


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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 continuity-corrected 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%, 26%, and 9% for the 12 mg BID CTP-
543, 8 mg BID CTP-543, and placebo groups, respectively.  Patients will be randomized in a 1:2:1 
ratio with a total N of approximately 440 patients (i.e., 110 for 12 mg BID, 220 for 8 mg BID, and 110 
for placebo).  These sample sizes will provide >99% power for the comparison of CTP-543 12 mg BID 
versus placebo and approximately 92% 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. 
Population Pharmacokinetic Analyses: 
CTP-543 population PK analysis will be conducted using sparse PK sampling in a subset of patients.  
Population PK analysis will include the evaluation of various covariates that may include the effects of  
age, gender, race, and weight (or BMI) on the PK of CTP-543.  Exposure-response relationships for 
both efficacy and safety parameters will also be assessed.  
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  
 
1. 
SYNOPSIS ...................................................................................................................5 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............12 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................17 
4. 
INTRODUCTION ......................................................................................................18 
4.1. 
Overview of Alopecia Areata .....................................................................................18 
4.2. 
Scientific Rationale for the Study ...............................................................................18 
4.3. 
Nonclinical Information for CTP-543 ........................................................................19 
4.4. 
Clinical Information for CTP-543 ..............................................................................19 
4.4.1. 
Clinical Studies of CTP-543 in Healthy Subjects .......................................................19 
4.4.2. 
Clinical Studies of CTP-543 in Patients with Alopecia Areata ..................................20 
5. 
ETHICS ......................................................................................................................22 
5.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) ........................................22 
5.2. 
Written Informed Consent ..........................................................................................22 
6. 
STUDY OBJECTIVES ..............................................................................................23 
6.1. 
Primary Objectives .....................................................................................................23 
6.2. 
Secondary Objectives .................................................................................................23 
7. 
OVERALL STUDY DESIGN ....................................................................................24 
7.1. 
Study Design ...............................................................................................................24 
7.2. 
Number of Patients and Sites ......................................................................................26 
7.3. 
Method of Treatment Assignment and Blinding ........................................................26 
7.4. 
Rationale for Study Design, Doses, and Primary Endpoint........................................26 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................30 
8.1. 
Patient Inclusion Criteria ............................................................................................30 
8.2. 
Patient Exclusion Criteria ...........................................................................................30 
8.3. 
Patient Withdrawal Criteria ........................................................................................33 
8.3.1. 
Patient Withdrawal Procedures ...................................................................................33 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................34 
8.5. 
Criteria for Study Termination ...................................................................................34 
9. 
DESCRIPTION OF STUDY TREATMENTS ..........................................................35 
9.1. 
Description of Treatments ..........................................................................................35 


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9.2. 
Dose-Adjustment Criteria ...........................................................................................35 
9.2.1. 
Dose Interruption Safety Criteria and Management ...................................................35 
9.2.2. 
Pharmacokinetic Criteria for Stopping Doses ............................................................37 
9.3. 
Treatment Compliance ................................................................................................37 
9.4. 
Study Drug Materials and Management .....................................................................37 
9.4.1. 
Physical Description of Study Drug ...........................................................................37 
9.4.2. 
Study Drug Packaging, Labeling, and Storage ...........................................................38 
9.4.3. 
Study Drug Preparation and Administration ..............................................................38 
9.4.4. 
Study Drug Return and Disposal ................................................................................38 
9.4.5. 
Study Drug Accountability .........................................................................................38 
9.5. 
Concomitant Medications and Procedures .................................................................39 
10. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................41 
10.1. 
Demographic Characteristics and Medical History ....................................................41 
10.2. 
Severity of Alopecia Tool (SALT) .............................................................................41 
10.3. 
Photographs ................................................................................................................42 
10.4. 
Global Impression Scales ...........................................................................................42 
10.4.1. 
Clinical Global Impression of Severity (CGI-S) ........................................................42 
10.4.2. 
Clinical Global Impression of Improvement (CGI-I) .................................................43 
10.4.3. 
Patient Global Impression of Severity (PGI-S) ..........................................................43 
10.4.4. 
Patient Global Impression of Improvement (PGI-I) ...................................................43 
10.5. 
Hair Satisfaction and Hair Quality Patient Reported Outcomes ................................43 
10.6. 
HADS .........................................................................................................................43 
10.7. 
BETA ..........................................................................................................................44 
10.8. 
BELA ..........................................................................................................................44 
10.9. 
Pharmacokinetic Assessments ....................................................................................44 
10.10. 
Vital Signs, Weight, and Height .................................................................................44 
10.11. 
Physical Examination .................................................................................................45 
10.12. 
Electrocardiogram .......................................................................................................45 
10.13. 
Clinical Laboratory Assessments ...............................................................................45 
10.14. 
Unscheduled Visit .......................................................................................................46 
11. 
ADVERSE EVENTS..................................................................................................47 
11.1. 
Definition of Adverse Event .......................................................................................47 
11.2. 
Evaluation of Adverse Events ....................................................................................48 
11.2.1. 
Serious Adverse Event ................................................................................................48 


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11.2.2. 
Severity/Intensity ........................................................................................................49 
11.2.3. 
Relationship to Study Drug ........................................................................................49 
11.2.4. 
Duration ......................................................................................................................50 
11.2.5. 
Action Taken ..............................................................................................................50 
11.2.6. 
Outcome ......................................................................................................................50 
11.3. 
Follow-Up ...................................................................................................................50 
11.4. 
Pregnancy ...................................................................................................................51 
11.5. 
Recording Adverse Events .........................................................................................51 
11.6. 
Reporting Adverse Events ..........................................................................................51 
11.6.1. 
Reporting Serious Adverse Events .............................................................................51 
11.6.2. 
Reporting Urgent Safety Issues ..................................................................................52 
12. 
STATISTICAL METHODS .......................................................................................53 
12.1. 
Sample Size Rationale ................................................................................................53 
12.2. 
Endpoints ....................................................................................................................53 
12.2.1. 
Efficacy .......................................................................................................................53 
12.2.2. 
Safety ..........................................................................................................................54 
12.2.3. 
Pharmacokinetic .........................................................................................................54 
12.3. 
Analysis Populations ..................................................................................................54 
12.3.1. 
Treatment Period ........................................................................................................54 
12.4. 
Analyses ......................................................................................................................55 
12.4.1. 
Disposition and Baseline Characteristics ....................................................................55 
12.4.2. 
Efficacy .......................................................................................................................55 
12.4.3. 
Multiplicity .................................................................................................................56 
12.4.4. 
Missing Data for SALT-based endpoints ...................................................................57 
12.4.5. 
Multiple Imputation ....................................................................................................58 
12.4.5.1. 
Analysis of Imputed Datasets .....................................................................................58 
12.4.5.2. 
Tipping Point Analyses...............................................................................................58 
12.4.6. 
Population Pharmacokinetics ......................................................................................59 
12.4.7. 
Study Drug Exposure ..................................................................................................59 
12.4.8. 
Safety ..........................................................................................................................59 
12.4.9. 
Interim Analyses .........................................................................................................61 
13. 
REGULATORY CONSIDERATIONS......................................................................62 
13.1. 
Good Clinical Practice ................................................................................................62 
13.2. 
Sponsor’s Responsibilities ..........................................................................................62 


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13.3. 
Investigator’s Responsibilities ....................................................................................63 
13.4. 
Protocol Amendments ................................................................................................64 
13.5. 
Audits and Inspections ................................................................................................64 
13.6. 
Quality Control and Quality Assurance ......................................................................65 
14. 
DATA HANDLING AND RECORDKEEPING .......................................................66 
14.1. 
Confidentiality ............................................................................................................66 
14.2. 
Patient Data Protection ...............................................................................................66 
14.3. 
Data Collection ...........................................................................................................66 
14.4. 
Case Report Form Completion ...................................................................................67 
14.5. 
Database Management, Data Clarification, and Quality Assurance ...........................67 
14.6. 
Inspection of Records .................................................................................................67 
14.7. 
Retention of Records ..................................................................................................68 
15. 
PUBLICATION POLICY ..........................................................................................69 
16. 
LIST OF REFERENCES ............................................................................................70 
17. 
APPENDICES ............................................................................................................71 
17.1. 
Clinical Laboratory Assessments ...............................................................................71 
17.2. 
Severity of Alopecia Tool (SALT) .............................................................................72 
17.3. 
Global Impression Scales ...........................................................................................73 
17.3.1. 
Clinical Global Impression of Severity (CGI-S) ........................................................73 
17.3.2. 
Clinical Global Impression of Improvement (CGI-I) .................................................73 
17.3.3. 
Patient Global Impression of Severity (PGI-S) ..........................................................74 
17.3.4. 
Patient Global Impression of Improvement (PGI-I) ...................................................74 
17.4. 
Patient Reported Outcome ..........................................................................................75 
17.4.1. 
Satisfaction of Hair Patient Reported Outcome (SPRO) ............................................75 
17.4.2. 
Quality of Hair Patient Reported Outcome (QPRO) ..................................................76 
17.5. 
Hospital Anxiety and Depression Scale (HADS) .......................................................77 
 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................17 
Table 2: 
Schedule of Assessments ............................................................................................28 
Table 3: 
Selected Hematologic Thresholds for Dose Interruption ...........................................36 
Table 4: 
SARS-CoV-2 Dose Interruption Criteria ....................................................................37 
Table 5: 
Investigational Product ...............................................................................................37 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................25 
 
  


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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 and one 
Phase 2 trial is currently ongoing.  An Open-Label Extension study (CP543.5001) and a Phase 3 
study (CP543.3001) are currently ongoing.   
Study CP543.3001 is a double-blind, randomized, placebo-controlled trial in 700 patients with 
moderate to severe alopecia areata being conducted in the US, Canada, and select EU countries. 
For more 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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Lipid levels will 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 440 patients are planned to be randomized in the study.  Approximately 50 sites 
total will be identified in North America and select EU  countries.   
7.3. 
Method of Treatment Assignment and Blinding 
Patients will be randomized in a 1:2:1 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. This same primary endpoint is 
currently being used in the ongoing Phase 3 study, CP543.3001. 
 
 
 


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Table 2: 
Schedule of Assessments 
 
Screening 
Baseline/ 
Randomization 
Treatment Period4 
Safety 
Follow-Up 
Day -28 to Day -12 
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 
Event1 
(Visit 1) 
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 
Pharmacokinetic Sampling for Population Pharmacokinetics  
 
X 
 
X12 
 
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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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. 
6 For females of childbearing potential, a serum pregnancy test will be performed at 
Screening.  Throughout the Treatment Period, and at the safety follow-up (if 
applicable), urine pregnancy tests will be performed.   
7 Includes fasted hematology, serum chemistry, and lipids 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, Site to Subject (STS) or Direct to Subject (DTS) 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. 


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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. 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 
b. Post-menopausal (cessation of menses for at least 12 months prior to screening)  
c. Infertility of sexual partner or partner of the same sex 
d. Implants of levonorgestrel in females 
e. Contraceptive (combined oral, patch, vaginal ring, injectable, implant) in females 
f. Double-barrier method (any combination of physical and chemical methods) 
g. Intrauterine device with a failure rate less than 1% per year 
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. 
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 


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(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). 


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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. 
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. 


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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: 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); 
 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;  
 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.   


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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.  
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 
1:2:1 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 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. 
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 
9.2.2. 
Pharmacokinetic Criteria for Stopping Doses 
There are no pharmacokinetic criteria for stopping study drug doses. 
 
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, or 
greater than 100% 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 


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Dosage Strength of CTP-543 
8 mg, 12 mg 
Route of Administration 
Oral 
Physical Description 
White, capsule-shaped tablets 
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, Site to Subject (STS) or Direct to Subject (DTS) 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 


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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. 
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 this CP543.3002 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 
 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); 


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 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; 
 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. 
Pharmacokinetic Assessments 
Whole blood (4 mL each) will be collected in K2EDTA vacutainer collection tubes to evaluate 
plasma concentrations of CTP-543.   
The exact time of blood collection as well as the exact time of the preceding dose will be 
recorded.  To document the preceding dose time, patients should be instructed to record the last 
dosing time prior to the Week 12 and 24 visits directly on their dosing bottles.  All attempts to 
adhere to the pharmacokinetic schedule should be made.  However, the inability to follow the 
schedule or to obtain/process a sample will not be considered a protocol deviation. 
Instructions for harvesting and preparing plasma samples prior to freezing and additional 
procedures for blood sample collection will be provided in separate study laboratory manual. 
10.10. 
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).  


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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.   
10.11. 
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. 
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. 
10.12. 
Electrocardiogram 
Twelve-lead electrocardiograms will be performed at the screening visit, Week 12, 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. 
10.13. 
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.      


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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.   
10.14. 
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, 
pharmacokinetic and pharmacodynamic tests).  However, hospitalization or 
prolonged hospitalization for a complication of such procedures remains a reportable 
serious adverse event. 
 Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an adverse event. 
 A procedure that is planned (i.e., planned prior to the starting of treatment on study); 
must be documented in the source document and the eCRF.  Hospitalization or 
prolonged hospitalization for a complication remains a reportable serious adverse 
event. 
 An elective treatment of or an elective procedure for a pre-existing medical condition 
that does not worsen.  
 Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above. 


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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 
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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. 
United States and Canada 
 and Emergency Contact Information: 
 
 


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, 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 continuity-corrected 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%, 26%, and 9% for the 
CTP-543 12 mg, CTP-543 8 mg BID, and placebo groups, respectively.  Patients will be 
randomized in a 1:2:1 ratio with a total N of approximately 440 patients (i.e., 110 for 12 mg BID, 
220 for 8 mg BID, and 110 for placebo BID).  These sample sizes will provide >99% power for 
the comparison of CTP-543 12 mg BID versus placebo and approximately 92% 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. 
12.2.3. 
Pharmacokinetic 
CTP-543 population PK analysis will be conducted using sparse PK samples in a subset of 
patients.  Pharmacokinetic samples will be collected per the schedule of assessments (Table 2).  
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 Pharmacokinetic Population will include all patients who receive study drug and have at 
least 1 pharmacokinetic sample taken during the Treatment Period.  Patients who receive placebo 
will be excluded from the Pharmacokinetic Population. 
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. 


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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. 
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. 


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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. 
Population Pharmacokinetics 
Population PK analysis will include the evaluation of various covariates including age, gender, 
race, weight (or BMI), on the PK of CTP-543.  Exposure-response relationships for both efficacy 
and safety parameters will also be assessed.  
12.4.7. 
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. 
12.4.8. 
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.   


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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. 
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 


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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 
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.   
12.4.9. 
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.   
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. 
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 


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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 
Pregnancy Testing 
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) serum (screening) and urine 
(Treatment Period and Safety Follow-
up Visit, if applicable) 
Serology 
Lipids  
Other 
Hepatitis B Surface Antigen (HBsAg) 
Hepatitis C Virus Antibodies (HCV 
Ab) 
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
Triglycerides 
Tuberculosis 
Thyroid stimulating hormone