Conditions: NonSegmental Vitiligo
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 171
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of INCB054707 over a 24-week placebo-controlled double-blind treatment period, followed by a 28-week double-blind extension period in participants with nonsegmental vitiligo.

Detailed description:

Arms:
arm 1: Participants will receive INCB054707 Dose A for 24 weeks (Period 1) followed by INCB054707 Dose C for 28 weeks (Period 2). arm 2: Participants will receive INCB054707 Dose B for 52 weeks (Period 1 + Period 2). arm 3: Participants will receive INCB054707 Dose C for 52 weeks (Period 1 + Period 2). arm 4: Participants will receive placebo for 24 weeks (Period 1) followed by INCB054707 Dose C for 28 weeks (Period 2).

Interventions: intervention 1: INCB054707 intervention 2: Placebo
Intervention descriptions: intervention 1: INCB054707 will be administered once daily intervention 2: Placebo or INCB054707 will be administered once daily

Protocol document:
Prot_000.pdf: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging 
Study of the Efficacy and Safety of INCB054707 Followed by an Extension  
NCT Number:      NCT04818346 
Document Date:  Clinical Study Protocol Version 5: 12-July-2022 
Official Title:       
Period in Participants With Vitiligo  


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TITLE PAGE 
Clinical Study Protocol 
 
 
INCB 54707-205 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Ranging Study of the Efficacy and Safety of INCB054707 
Followed by an Extension Period in Participants With Vitiligo 
 
Product: 
INCB054707 
IND Number: 
 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
16 NOV 2020 
Amendment 1: 
19 AUG 2021 
Amendment 2: 
09 FEB 2022 
Amendment 3: 
19 MAY 2022 
Amendment 4: 
12 JUL 2022 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 54707-205 Protocol Amendment 4 (dated 12 JUL 2022) and agree to 
conduct the study as outlined.  I agree to maintain the confidentiality of all information received 
or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................9 
1. 
PROTOCOL SUMMARY ..........................................................................................13 
2. 
INTRODUCTION ......................................................................................................22 
2.1. 
Background .................................................................................................................22 
2.2. 
Study Rationale ...........................................................................................................23 
2.2.1. 
Scientific Rationale for Study Design ........................................................................24 
 
24 
 
....................................................25 
2.3. 
Benefit/Risk Assessment ............................................................................................25 
2.3.1. 
Clinical Studies ...........................................................................................................26 
2.3.2. 
Benefit Assessment .....................................................................................................28 
2.3.3. 
Benefit-Risk Conclusion .............................................................................................28 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................29 
4. 
STUDY DESIGN .......................................................................................................33 
4.1. 
Overall Design ............................................................................................................33 
4.2. 
Overall Study Duration ...............................................................................................33 
4.3. 
Study Termination ......................................................................................................34 
5. 
STUDY POPULATION .............................................................................................34 
5.1. 
Inclusion Criteria ........................................................................................................34 
5.2. 
Exclusion Criteria .......................................................................................................35 
5.3. 
Lifestyle Considerations .............................................................................................38 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................39 
5.4. 
Screen Failures ............................................................................................................39 
5.5. 
Replacement of Participants .......................................................................................39 
5.6. 
Data Safety Monitoring Board ....................................................................................39 
6. 
STUDY TREATMENT ..............................................................................................40 
6.1. 
Study Treatments Administered .................................................................................40 
6.2. 
Preparation, Handling, and Accountability ................................................................42 


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6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................43 
6.4. 
Study Treatment Compliance .....................................................................................43 
6.5. 
Dose Modifications .....................................................................................................43 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................43 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................46 
6.6. 
Concomitant Medications and Procedures .................................................................46 
6.6.1. 
Permitted Medications and Procedures ......................................................................47 
6.6.2. 
Restricted Medications and Procedures ......................................................................47 
6.6.3. 
Prohibited Medications and Procedures .....................................................................47 
6.7. 
Treatment After the End of the Study .........................................................................48 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................49 
7.1. 
Discontinuation of Study Treatment ...........................................................................49 
7.1.1. 
Reasons for Discontinuation .......................................................................................49 
7.1.2. 
Discontinuation Procedures ........................................................................................49 
7.2. 
Participant Withdrawal From the Study .....................................................................50 
7.3. 
Lost to Follow-Up.......................................................................................................50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................51 
8.1. 
Administrative and General Procedures .....................................................................51 
8.1.1. 
Informed Consent Process ..........................................................................................51 
8.1.2. 
Screening Procedures ..................................................................................................52 
8.1.3. 
Interactive Response Technology Procedure ..............................................................52 
8.1.4. 
Distribution of Reminder Cards and Diaries ..............................................................52 
8.1.5. 
Demography and Medical History ..............................................................................52 
8.1.5.1. 
Demographics and General Medical History .............................................................52 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................53 
 
53 
 
53 
8.2.2. 
Vitiligo Area Scoring Index ........................................................................................53 
 
54 
 
54 
 
55 


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8.2.6. 
Photography ................................................................................................................55 
8.2.6.1. 
Definition of Targeted Nonfacial Vitiligo Depigmented Areas .................................56 
 
56 
 
56 
 
57 
 
57 
 
57 
 
57 
 
58 
 
58 
 
58 
 
58 
 
58 
 
59 
 
59 
 
59 
8.3. 
Safety Assessments .....................................................................................................59 
8.3.1. 
Adverse Events ...........................................................................................................60 
8.3.2. 
Physical Examinations ................................................................................................60 
8.3.3. 
Vital Signs ..................................................................................................................61 
8.3.4. 
Electrocardiograms .....................................................................................................61 
8.3.5. 
Laboratory Assessments .............................................................................................61 
8.3.5.1. 
Pregnancy Testing ......................................................................................................64 
8.3.5.2. 
Serology ......................................................................................................................64 
8.3.5.3. 
Tuberculosis Screening ...............................................................................................65 
 
66 
 
66 
 
66 
 
67 
8.6. 
Unscheduled Visits .....................................................................................................67 
8.7. 
End of Treatment and/or Early Termination ..............................................................67 
8.8. 
Follow-Up ...................................................................................................................67 
8.8.1. 
Safety Follow-Up ........................................................................................................68 


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68 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................69 
9.1. 
Definition of Adverse Event .......................................................................................69 
9.2. 
Definition of Serious Adverse Event ..........................................................................70 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........71 
9.4. 
Reporting of Serious Adverse Events .........................................................................73 
9.5. 
Events of Clinical Interest ..........................................................................................74 
9.5.1. 
Adverse Events of Special Interest .............................................................................74 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................75 
9.7. 
Pregnancy ...................................................................................................................75 
9.8. 
Warnings and Precautions ..........................................................................................76 
9.9. 
Product Complaints ....................................................................................................76 
9.10. 
Treatment of Overdose ...............................................................................................76 
10. 
STATISTICS ..............................................................................................................77 
10.1. 
Sample Size Determination ........................................................................................77 
10.2. 
Populations for Analysis .............................................................................................77 
10.3. 
Level of Significance ..................................................................................................77 
10.4. 
Statistical Analyses .....................................................................................................78 
10.4.1. 
Primary Analysis ........................................................................................................79 
10.4.2. 
Secondary Analysis ....................................................................................................79 
10.4.3. 
Safety Analyses ..........................................................................................................79 
 
80 
 
80 
 
80 
 
80 
10.5. 
Interim Analysis ..........................................................................................................80 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................81 
11.1. 
Investigator Responsibilities .......................................................................................81 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................82 
11.2. 
Data Management .......................................................................................................82 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................84 


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11.4. 
Financial Disclosure ...................................................................................................84 
11.5. 
Publication Policy .......................................................................................................84 
11.6. 
Study and Site Closure................................................................................................85 
12. 
REFERENCES ...........................................................................................................86 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................89 
APPENDIX B. LIST OF STRONG/MODERATE SYSTEMIC CYP3A4 
INHIBITORS AND STRONG SYSTEMIC CYP3A4 INDUCERS..........................91 
 
 
92 
 
93 
APPENDIX E. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................96 
APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................99 
 


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LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................13 
Table 2: 
Key Study Design Elements .......................................................................................14 
Table 3: 
Schedule of Activities (Placebo-Controlled Period) ...................................................16 
Table 4: 
Schedule of Activities (Extension Period) ..................................................................19 
 
27 
Table 6: 
Objectives and Endpoints ...........................................................................................29 
Table 7: 
Exclusionary Laboratory Values ................................................................................37 
Table 8: 
Study Treatment Information .....................................................................................41 
 
44 
 
 
46 
 
55 
 
55 
Table 13: Required Laboratory Analytes ....................................................................................63 
 
66 
 
.67 
Table 16: Populations for Analysis .............................................................................................77 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................15 
Figure 2: 
Control of the Overall Type I Error Rate ....................................................................78 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
anti-HBc 
antibody to hepatitis B core antigen 
AST 
aspartate transaminase 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
COVID-19 
coronavirus disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
EOT 
end of treatment 
EOT1 
end of treatment during the placebo-controlled period 
EOT2 
end of treatment during the extension period 
 
 
 
 
F-BSA 
facial body surface area 
FDA 
Food and Drug Administration 
 
 
FSH 
follicle-stimulating hormone 


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Abbreviations and 
Special Terms 
Definition 
F-VASI 
Facial Vitiligo Area Scoring Index 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GGT 
gamma-glutamyl transferase 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HCVAb 
hepatitis C virus antibody 
HDL 
high-density lipoprotein 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HS 
hidradenitis suppurativa 
hsCRP 
high-sensitivity C-reactive protein 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IFN 
interferon 
INR 
international normalized ratio 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent-to-treat 
JAK 
Janus kinase 
LDL 
low-density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effect model for repeated measures 
OTC 
over-the-counter 
PDE-4 
phosphodiesterase-4 


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Abbreviations and 
Special Terms 
Definition 
PPD 
purified protein derivative 
PT 
prothrombin time 
QALY 
quality-adjusted life year 
QD 
once daily 
QFT-GIT 
QuantiFERON®-TB Gold In-Tube test 
RDW 
red blood cell distribution width 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
schedule(s) of activities 
SOP 
standard operating procedure 
STAT 
signal transducer and activator of transcription 
T4 
thyroxine 
TB 
tuberculosis 
T-BSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
TSH 
thyroid-stimulating hormone 
T-VASI 
Total Body Vitiligo Area Scoring Index 
T-VASI50
 
≥ 50%
 improvement in total body Vitiligo Area Scoring Index 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
UV 
ultraviolet 
VASI 
Vitiligo Area Scoring Index 
WBC 
white blood cell 


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Abbreviations and 
Special Terms 
Definition 
WOCBP 
women of childbearing potential 
WONCBP 
women of nonchildbearing potential 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging 
Study of the Efficacy and Safety of INCB054707 Followed by an Extension Period in 
Participants With Vitiligo 
Protocol Number:  INCB 54707-205 
Objectives and Endpoints: 
Table 1 presents the primary and key secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of INCB054707. 
Percent change from baseline in Total Vitiligo 
Area Scoring Index (T-VASI) at Week 24. 
Key Secondary 
To further determine the efficacy of 
INCB054707. 
Proportion of participants achieving T-VASI50 at 
Week 24.  
T-VASI50 is defined as 50% or greater reduction 
in the Total Vitiligo Area Scoring Index. 
Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table. 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of adult patients with vitiligo. 
Population 
Men or women aged 18 to 75 years with nonsegmental vitiligo who have 
depigmented areas including T-BSA ≥ 8%, T-VASI ≥ 8, F-BSA ≥ 0.5%, 
and F-VASI ≥ 0.5.   
Number of Participants 
Approximately 160 participants will be randomized 1:1:1:1 to receive 1 of 
3 doses of INCB054707 or placebo.   
The 28-week double-blind extension period will include all participants 
who successfully complete the placebo-controlled period. 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, 
dose-ranging, multicenter study to evaluate the efficacy and safety of 
INCB054707 (15, 45, and 75 mg QD) over a 24-week treatment period, 
followed by a 28-week double-blind extension period (45 mg and 75 mg 
QD) and a 24-week follow-up period.  Participants will be stratified based 
on total BSA involvement (8%-20% and > 20%). 
Estimated Duration of 
Study Participation 
Screening:  Up to 32 days 
Placebo-controlled period (double-blind):  24 weeks 
Extension period (double-blind):  28 weeks 
Safety follow-up:  4 weeks after last dose of study drug 
 
 
Total:  Up to approximately 80 weeks (19 months) 
DSMB 
Yes (external) 
Coordinating Principal 
Investigator 
, MD 
Treatment Groups and Duration: 
The study design is shown in Figure 1.  The SoA for the placebo-controlled and extension 
periods are detailed in Table 3 and Table 4, respectively.  


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Figure 1: 
Study Design Schema 
 
 
Participants will be screened for up to 32 days prior to the first dose of INCB054707 on Day 1.  
Stratification will be based on total BSA involvement, with 2 strata:  8% to 20% and > 20%.  
Approximately 160 participants will take oral INCB054707 (15 mg, 45 mg, or 75 mg) or placebo 
QD in a blinded manner for 24 weeks.  Following completion of the Week 24 visit, participants 
will enter the 28-week double-blind extension period with 45 mg QD (for participants who 
received 45 mg during the placebo-controlled period) or 75 mg (for participants who received 
placebo, 15 mg, or 75 mg during the placebo-controlled period), with a safety follow-up visit 
scheduled 4 weeks after the last dose of study drug, 
 
 
Efficacy will be assessed via changes in the 
, 
T-VASI 
 photography, 
  
 
 
 
Participants will be assessed for safety and tolerability by monitoring the frequency and severity 
of AEs and performing physical examinations, ECGs, vital signs measurements, and clinical 
laboratory assessments at various timepoints during the study. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix E. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 


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Table 3: 
Schedule of Activities (Placebo-Controlled Period) 
Visit Day (Range) 
Screening 
Treatment (Placebo-Controlled Period) 
Notes 
Days 
−32 to −1 
Baseline 
(Day 1) 
Wk 2 
(± 3 d) 
(Remote 
Visit) 
Wk 4 
(± 3 d) 
Wk 6 
(± 3 d) 
(Remote 
Visit) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 16 
(± 3 d) 
Wk 20 
(± 3 d) 
Wk 24 
(± 3 d) 
(EOT1) 
Remote visits may be 
performed in-clinic at the 
discretion of the investigator. 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Section 8.1.1 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
Section 5.1 and Section 5.2 
Demographic data, 
general medical history, 
and vitiligo medical and 
treatment history 
X 
 
 
 
 
 
 
 
 
 
Section 8.1.5 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.6 and Section 8.1.5 
Contact IRT 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Section 8.1.3 
Randomization  
 
X 
 
 
 
 
 
 
 
 
Section 6.3 and Section 8.1.3 
Distribute reminder cards 
and diaries 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Section 8.1.4 
Dispense study drug 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Section 6.2 
Collect study drug and 
review diary cards 
 
 
 
X 
 
X 
X 
X 
X 
X 
Section 8.1.4 
Assess study drug 
compliance 
 
 
 
X 
 
X 
X 
X 
X 
X 
Section 6.4 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.3.1 
Comprehensive physical 
examination 
X 
X 
 
 
 
 
 
 
 
X 
Section 8.3.2 
Height 
X 
 
 
 
 
 
 
 
 
 
Section 8.3.2 
Weight 
X 
X 
 
 
 
 
 
 
 
X 
Section 8.3.2 
Targeted physical 
examination 
 
 
 
X 
 
X 
X 
X 
X 
 
Section 8.3.2 
Vital signs 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Section 8.3.3 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
X 
Section 8.3.4 
Efficacy assessments 


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Table 3: 
Schedule of Activities (Placebo-Controlled Period) (Continued) 
Visit Day (Range) 
Screening 
Treatment (Placebo-Controlled Period) 
Notes 
Days 
−32 to −1 
Baseline 
(Day 1) 
Wk 2 
(± 3 d) 
(Remote 
Visit) 
Wk 4 
(± 3 d) 
Wk 6 
(± 3 d) 
(Remote 
Visit) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 16 
(± 3 d) 
Wk 20 
(± 3 d) 
Wk 24 
(± 3 d) 
(EOT1) 
Remote visits may be 
performed in-clinic at the 
discretion of the investigator. 
Efficacy assessments (continued) 
T-VASI 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Section 8.2.2 
Photography of the face 
X 
X 
 
 
 
 
X 
 
 
X 
If photo quality at screening 
is not adequate, the 
photography may be 
repeated at Day 1.  The 
baseline photo is defined as 
the most adequate one either 
taken at screening or Day 1.  
(Section 8.2.6) 
Photography of nonfacial 
targeted areas 
X 
X 
 
 
 
 
X 
 
 
X 
The genitalia area should not 
be photographed.  If photo 
quality at screening is not 
adequate, the photography 
may be repeated at Day 1.  
The baseline photo is 
defined as the most adequate 
one either taken at screening 
or Day 1.  (Section 8.2.6) 


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Table 3: 
Schedule of Activities (Placebo-Controlled Period) (Continued) 
Visit Day (Range) 
Screening 
Treatment (Placebo-Controlled Period) 
Notes 
Days 
−32 to −1 
Baseline 
(Day 1) 
Wk 2 
(± 3 d) 
(Remote 
Visit) 
Wk 4 
(± 3 d) 
Wk 6 
(± 3 d) 
(Remote 
Visit) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 16 
(± 3 d) 
Wk 20 
(± 3 d) 
Wk 24 
(± 3 d) 
(EOT1) 
Remote visits may be 
performed in-clinic at the 
discretion of the investigator. 
Laboratory assessments 
Serum FSH (WONCBP 
only) 
X 
 
 
 
 
 
 
 
 
 
Section 8.3.5.1 and Table 13 
Serum pregnancy test 
(WOCBP) 
X 
 
 
 
 
 
 
 
 
X 
Section 8.3.5.1 and Table 13 
Urine pregnancy test 
(WOCBP) 
 
X 
 
X 
 
X 
X 
X 
X 
 
Section 8.3.5.1 and Table 13 
TB screening 
X 
 
 
 
 
 
 
 
 
 
Chest x-ray may be required 
for some participants.  
Section 8.3.5.3 and Table 13  
HIV testing 
X 
 
 
 
 
 
 
 
 
 
Section 8.3.5.2 and Table 13 
Hepatitis testing 
X 
 
 
 
 
 
 
 
 
 
Section 8.3.5.2 and Table 13 
Urinalysis 
X 
 
 
 
 
 
X 
 
 
X 
Table 13 
Hematology and blood 
chemistry assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table 13; at-home blood 
collection for remote visits 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
Reflexive testing during the 
study per Appendix D (also 
Table 13). 
Lipid panel 
 
X 
 
 
 
 
X 
 
 
X 
Table 13 
Thyroid function markers 
X 
 
 
 
 
 
X 
 
 
X 
Table 13 
Inflammation marker 
 
X 
 
 
 
 
X 
 
 
X 
Table 13 


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Table 4: 
Schedule of Activities (Extension Period) 
Visit Day (Range) 
Treatment (Extension Period) 
Safety 
Follow-Up 
Notes 
Wk 26 
(± 3 d) 
(Remote 
Visit) 
Wk 28 
(± 3 d) 
Wk 30 
(± 3 d) 
(Remote 
Visit) 
Wk 32 
(± 3 d) 
Wk 36 
(± 3 d) 
Wk 40 
(± 3 d) 
Wk 44 
(± 3 d) 
Wk 48 
(± 3 d) 
Wk 52 
(± 3 d) 
(EOT2) 
Wk 56 
(4 wks 
post last 
dose + 7 d) 
(EOS) 
Remote visits 
may be 
performed in-
clinic at the 
discretion of the 
investigator. 
Administrative procedures 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.6 and 
Section 8.1.5  
Contact IRT 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Section 8.1.3  
Distribute reminder 
cards and diaries 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Section 8.1.4 
Dispense study drug 
 
X 
 
X 
X 
X 
X 
X 
 
 
Section 6.2  
Collect study drug 
and review diary 
cards 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Section 8.1.4 
Assess study drug 
compliance 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Section 6.4 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.3.1 
Comprehensive 
physical 
examination 
 
 
 
 
 
 
 
 
X 
 
Section 8.3.2 
Weight 
 
 
 
 
 
 
 
 
X 
 
Section 8.3.2 
Targeted physical 
examination 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Section 8.3.2 
Vital signs 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Section 8.3.3 
12-lead ECG 
 
 
 
 
 
 
 
 
X 
 
Section 8.3.4 


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Table 4: 
Schedule of Activities (Extension Period) (Continued) 
Visit Day (Range) 
Treatment (Extension Period) 
Safety 
Follow-Up 
Notes 
Wk 26 
(± 3 d) 
(Remote 
Visit) 
Wk 28 
(± 3 d) 
Wk 30 
(± 3 d) 
(Remote 
Visit) 
Wk 32 
(± 3 d) 
Wk 36 
(± 3 d) 
Wk 40 
(± 3 d) 
Wk 44 
(± 3 d) 
Wk 48 
(± 3 d) 
Wk 52 
(± 3 d) 
(EOT2) 
Wk 56 
(4 wks 
post last 
dose + 7 d) 
(EOS) 
Remote visits 
may be 
performed in-
clinic at the 
discretion of the 
investigator. 
Efficacy assessments 
T-VASI 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.2.2 
Photography of the 
face 
 
 
 
 
X 
 
 
 
X 
 
Section 8.2.6 
Photography of 
nonfacial targeted 
areas  
 
 
 
 
X 
 
 
 
X 
 
Section 8.2.6 


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Table 4: 
Schedule of Activities (Extension Period) (Continued) 
Visit Day (Range) 
Treatment (Extension Period) 
Safety 
Follow-Up 
Notes 
Wk 26 
(± 3 d) 
(Remote 
Visit) 
Wk 28 
(± 3 d) 
Wk 30 
(± 3 d) 
(Remote 
Visit) 
Wk 32 
(± 3 d) 
Wk 36 
(± 3 d) 
Wk 40 
(± 3 d) 
Wk 44 
(± 3 d) 
Wk 48 
(± 3 d) 
Wk 52 
(± 3 d) 
(EOT2) 
Wk 56 
(4 wks 
post last 
dose + 7 d) 
(EOS) 
Remote visits 
may be 
performed in-
clinic at the 
discretion of the 
investigator. 
Laboratory assessments 
Serum pregnancy 
test (WOCBP) 
 
 
 
 
 
 
 
 
X 
X 
Section 8.3.5.1 
and Table 13 
Urine pregnancy 
test (WOCBP) 
 
X 
 
X 
X 
X 
X 
X 
 
 
Section 8.3.5.1 
and Table 13 
Urinalysis 
 
 
 
 
X 
 
 
X 
X 
 
Table 13 
Hematology and 
blood  
chemistry 
assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table 13; at-
home blood 
collection for 
remote visits. 
Coagulation 
 
X 
 
 
 
 
 
 
 
 
Reflexive testing 
during the study 
per Appendix D 
(also Table 13). 
Lipid panel 
 
 
 
 
X 
 
 
 
X 
 
Table 13 
Thyroid function 
markers 
 
 
 
 
X 
 
X 
 
X 
X 
Table 13 
Inflammation 
marker 
 
 
 
 
X 
 
 
 
X 
 
Table 13 
a Only for participants who consent to additional follow-up visits. 


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2. 
INTRODUCTION 
INCB054707 is an oral JAK inhibitor with selectivity for JAK1 that is currently under 
development for the treatment of patients with HS.  Proinflammatory cytokines are strongly 
implicated in the pathogenesis of several dermatologic diseases, such as HS, atopic dermatitis, 
plaque psoriasis, alopecia areata, and vitiligo.  
 
 
.  
 
 
 
 
2.1. 
Background 
Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to 
destruction of melanocytes and is estimated to affect 0.5% to 2% of the population worldwide 
(Krüger and Schallreuter 2012).  Prevalence is similar between men and women, and there is no 
known difference in presentation based on skin type or race.  Nearly 70% to 80% of patients 
develop vitiligo before 30 years of age, with almost 50% presenting before 20 years of age and 
25% presenting before 10 years of age (Bergqvist and Ezzedine 2020).  Generalized 
(nonsegmental) vitiligo is the most common type, accounting for up to 90% of cases (Taïeb and 
Picardo 2009).  Other autoimmune diseases such as thyroid disorders, type 1 diabetes mellitus, 
pernicious anemia, and Addison disease are often associated with vitiligo, and its natural course 
is generally unpredictable but often progressive.  
The pathogenesis of vitiligo appears to involve intrinsic defects within melanocytes and 
autoimmunity that targets these cells.  Melanocytes from patients with vitiligo are more 
vulnerable to intrinsic and/or extrinsic factors that induce a cellular stress response than those 
from healthy individuals (Rodrigues et al 2017, Speeckaert and van Geel 2017).  Melanocyte 
stress response activates innate immunity, which may represent the initiating vitiligo event.  The 
oxidative stress, cell damage, and cytokines secreted from innate immune cells trigger release of 
chemotaxis factors, such as CXCL9 and CXCL10, by keratinocytes and recruit cytotoxic CD8+ 
T cells to the skin.  Activated CD8+ T cells release proinflammatory IFN-γ, which triggers more 
CXCL9 and CXCL10 release from keratinocytes through JAK1- and JAK2-mediated signaling, 
leading to recruitment of more melanocyte-specific CD8+ cells that destroy melanocytes and 
result in skin depigmentation (Frisoli and Harris 2017).  Because IFN-γ signaling requires the 
JAK-STAT pathway, inhibition of JAK signaling may be an effective strategy for the treatment 
of patients with vitiligo. 
No drugs are currently approved for the treatment of patients with vitiligo.  In general, first-line 
treatment consists of off-label use of topical corticosteroids and calcineurin inhibitors.  
Second-line treatment consists of phototherapy (narrow-band UVB and psoralen plus UVA) and 
systemic corticosteroids (Bergqvist and Ezzedine 2020).  Less common therapies include 
surgical grafting techniques and depigmenting treatments.  The response to these therapies 
varies, can be time-intensive, can be slow, and often produces disappointing results if 
repigmentation is cosmetically unacceptable (Narayan et al 2020). 


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The chronic nature of vitiligo and lack of effective therapy can have a negative psychosocial 
impact on patients, with effects on quality of life similar to those of other dermatologic diseases, 
such as psoriasis and atopic dermatitis (Cupertino et al 2017).  Involvement of cosmetically 
sensitive areas, such as the face and hands, can have a major impact on self-esteem and 
eventually link to the psychological burden and quality of life; individuals with more than 25% 
of BSA involvement may have difficulties performing daily tasks, such as gardening, shopping, 
or clothing selection, and difficulty with socialization, such as participating in sports activities 
and initiating and maintaining romantic relationships (Silverberg and Silverberg 2013).  In some 
societies, affected individuals even face discrimination due to poor understanding and lack of 
acceptance of the disease (Yazdani Abyaneh et al 2014).  Approximately 75% of patients with 
vitiligo feel their appearance is moderately to severely intolerable, and 41% of patients feel that 
there is little they can do to improve their condition, with feelings of hopelessness increasing 
with time (Salzer and Schallreuter 1995).  Not surprisingly, 66% of patients report being 
distressed by their disease, and 92% have experienced stigmatization (Krüger and 
Schallreuter 2014).  Feelings of embarrassment and fear of rejection can cause patients with 
vitiligo to withdraw and lead to social isolation in both personal and professional relationships.  
A majority of patients with vitiligo have reported feelings of anxiety and embarrassment when 
meeting strangers or beginning a new sexual relationship (Porter et al 1990).  Additionally, 
clinical depression or depressive symptoms are associated with vitiligo.  Based on various 
meta-analyses, patients with vitiligo are approximately 5 times more likely to have depression 
than healthy controls, with vitiligo being considered one of the most psychologically devastating 
diseases in dermatology (Lai et al 2017, Osinubi et al 2018). 
 
  The largest published vitiligo 
study to date reported treatment of 157 participants (with at least 0.5% F-BSA and at least 
3% nonfacial BSA with depigmented areas) with topical administration of ruxolitinib (a JAK1/2 
inhibitor) cream for up to 52 weeks.  At Week 24, 50% of the participants treated with 
ruxolitinib 1.5% cream QD achieved F-VASI50 compared with 3% applying vehicle; 
additionally, 32% of the participants achieved T-VASI50 at Week 24 compared with 0% 
applying vehicle (Rosmarin et al 2020). 
 
 
 
2.2. 
Study Rationale 
Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to a loss of 
melanocytes.  The chronic nature of the disease, the lack of a uniform and effective therapy, and 
the unpredictable course of the disease have a profound psychosocial impact on patients, 
affecting their quality of life.  
 
 
 
  


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2.2.1. 
Scientific Rationale for Study Design 
INCB054707 is an oral small-molecule JAK1 inhibitor and has been evaluated in 36 participants 
with HS in 2 clinical studies with oral doses of up to 90 mg for 8 weeks.  During the treatment 
period, INCB054707-treated participants demonstrated improvement, characterized as decreased 
number of abscesses and inflammatory nodules, decreased HS-associated pain, and improved 
quality of life.  Observed AEs were mild to moderate in intensity and mostly unrelated to study 
medication, with no associated SAEs or withdrawals.  Immunological commonalities exist 
between HS and vitiligo, in which lesions have increased expression of lymphocyte-recruiting 
chemokines, including CXCL10 (Vossen et al 2019), and elevated IFN-γ levels (Banerjee 
et al 2017).  Treatment of patients with vitiligo for 24 weeks with the topical JAK1/2 inhibitor 
ruxolitinib cream demonstrated that inhibition of the JAK-STAT pathway leads to 
repigmentation (Rosmarin et al 2020).  
 
 
 
 
In the proposed study, the clinical safety and efficacy of 3 doses of INCB054707 (15, 45, and 
75 mg) compared with placebo will be evaluated in male and female adult participants with 
extensive vitiligo (T-BSA ≥ 8%, T-VASI ≥ 8, F-BSA ≥ 0.5%, and T-VASI ≥ 0.5) for 24 weeks, 
which is consistent with the duration of other systemic therapies and with narrow-band UVB 
phototherapy (Hamzavi et al 2004).  Efficacy will be assessed via changes in the 
 
 affected by vitiligo lesions, 
 and T-VASI, 
 and photography.  
 
 
 
 
 
With the goal of obtaining long-term efficacy and safety data for the compound (up to 52 weeks 
in total), after the 24-week placebo-controlled period, all participants will enter into a 
double-blind extension period for 28 weeks and will receive either 45 mg or 75 mg QD, followed 
by a 4-week safety follow-up period 
 
 to monitor safety and potential change in pigmentation after discontinuation or 
completion of treatment with INCB054707. 
It is expected that the outcome of this study will be instrumental in informing dose selection to 
be evaluated in a potential Phase 3 study in the future. 
 
 
 
 
 
 
 
 
 
 


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2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of INCB054707 may be found in the IB.  


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2.3.1. 
Clinical Studies 
Single doses of INCB054707 up to 405 mg and multiple doses of INCB054707 up to 120 mg 
QD for up to 10 days have been evaluated in 2 placebo-controlled studies in healthy participants.  
The most common TEAEs were mild to moderate headache in 31% of participants who received 
INCB054707 in the multiple-dose study; the events were not dose-dependent and resolved 
spontaneously following discontinuation of INCB054707.  Furthermore, decreases in platelet 
counts were observed among participants treated with INCB054707 at doses ≥ 60 mg QD.  The 
magnitude of the decrease was larger for participants treated with 120 mg QD compared with 
those who received 60 mg QD, suggesting a dose-related trend.  Of note, for the participants with 
a treatment-emergent decrease in platelet counts, the platelet counts remained within the normal 
range. 
In 2 clinical studies in participants with HS, INCB 54707-202 (15 mg only) and 
INCB 54707-203 (placebo and 30, 60, and 90 mg), QD doses of study drug were administered 
for up to 8 weeks.  Transient and asymptomatic thrombocytopenia was observed in 4 of 
8 participants who received INCB054707 90 mg QD after 4 weeks of exposure, which led to 
dose interruption for a maximum of 2 weeks, and resolved without medical intervention.  All 
participants returned to their normal dosing schedule after dose interruption and completed the 
study without clinical sequelae or re-emergence of thrombocytopenia.  Platelet count decreases 
have been transient and stabilize over time, as observed in studies with other JAK1 inhibitors for 
treatment of other dermatologic indications, such as abrocitinib in atopic dermatitis (Gooderham 
et al 2019) and itacitinib in plaque psoriasis (Bissonnette et al 2016).  Thrombocytopenia TEAEs 
were asymptomatic and judged as treatment-related.  Hemoglobin levels remained within normal 
limits and were mostly unchanged during the study, while neutrophil counts showed a mild 
dose-dependent decrease within normal limits.  Across the 2 studies, the most common TEAE 
was fatigue, observed in 6 of the 36 participants (17%).  Mild-to-moderate headache was 
observed in 11% (4 of 36) of the participants exposed to INCB054707 and in 22% (2 of 9) of the 
participants exposed to placebo.  No serious or fatal TEAEs were reported in the studies; more 
details are provided in the IB. 
Based on the available nonclinical and clinical data, the potential risks to participants are 
summarized in Table 5. 


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2.3.2. 
Benefit Assessment  
Based on the expected mode of action of INCB054707, participants randomly assigned to 1 of 
the 3 active treatment groups may experience clinically meaningful improvements in their 
vitiligo lesions during the placebo-controlled (24 weeks) period, and all participants will be 
offered drug therapy with 45 mg or 75 mg during the extension period (28 weeks). 
Vitiligo is characterized by a progressive loss of functional melanocytes and associated with 
auditory abnormalities, including SNHL, with a prevalence ranging from 4.0% to 68.8% when 
compared with healthy controls (de Jong et al 2017).  During embryogenesis, precursor 
melanocyte cells (melanoblasts) migrate to the dermis and also to the base of the cochlea, which 
is responsible for hearing high frequencies.  It appears that inner ear melanocytes are very 
important for cochlear hair cell function and normal hearing (Rahimi et al 2019).  
 
 
 
 
 
 
 
 
 
 
Participants will also contribute to the process of developing a novel anti-inflammatory agent 
expected to induce repigmentation in vitiligo, a disease with high unmet need and that is severely 
debilitating to participants' psychosocial well-being. 
2.3.3. 
Benefit-Risk Conclusion 
Currently, there are no approved drug therapies for vitiligo, and treatments are empirical and 
directed by the available clinical guidelines.  There are limited data on the effectiveness and 
long-term safety of current therapies, including topical or oral corticosteroids and calcineurin 
inhibitors.  Given the psychosocial burden and stigma caused by vitiligo, patients continue to 
need effective and safe treatments for their disease. 
Considering the safety measures initiated to minimize risk to participants in this study, the 
potential risks identified in association with INCB054707 are justifiable and appropriately 
balanced by the anticipated efficacy benefits expected to be afforded to participants. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 6 presents the objectives and endpoints. 
Table 6: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of INCB054707.  
• Percent change from baseline in Total Vitiligo 
Area Scoring Index (T-VASI) at Week 24. 
Key Secondary 
To further determine the efficacy of INCB054707. • Proportion of participants achieving T-VASI50 
at Week 24. 
T-VASI50 is defined as 50% or greater 
reduction in the Total Vitiligo Area Scoring 
Index. 
Secondary 
To evaluate the safety and tolerability of 
INCB054707. 
• Frequency and severity of AEs, including the 
results of physical examinations, vital signs, 
evaluation of clinical laboratory studies, and 
ECGs. 


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Table 6: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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Table 6: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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Table 6: 
Objectives and Endpoints (Continued) 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, multicenter, randomized, parallel-group, placebo-controlled, double-blind, 
dose-ranging study to evaluate the efficacy and safety of INCB054707 (15, 45, and 75 mg QD) 
over a 24-week treatment period followed by a 28-week double-blind extension period 
(INCB054707 45 mg and 75 mg QD), a 4-week safety follow-up period 
 
.  The study will enroll approximately 
160 men and women aged 18 to 75 years with nonsegmental vitiligo.  Figure 1 presents the study 
design schema, and Table 3 and Table 4 present the SoA for the placebo-controlled and 
extension periods, respectively. 
Participants will be screened for up to 32 days before the first dose of study drug.  Key entry 
criteria for participants are diagnosis of nonsegmental vitiligo, with depigmented areas including 
T-BSA ≥ 8%, T-VASI ≥ 8, F-BSA ≥ 0.5%, and F-VASI ≥ 0.5.  Screening will include 
assessments described in Table 3.  
Participants who meet all the study entry criteria and none of the exclusion criteria will return to 
the study site on Day 1 of dosing and be randomized in a 1:1:1:1 ratio to 1 of 4 treatment groups 
(placebo or INCB054707 15, 45, or 75 mg QD).  Participant randomization will be stratified 
based on total BSA involvement, with 2 strata: 8% to 20% and > 20%.  
Approximately 160 participants will take oral study drug (placebo, 15 mg, 45 mg, or 75 mg) QD 
in a blinded manner for 24 weeks.  Participants who complete the Week 24 visit will enter the 
28-week double-blind extension period with 45 mg QD (for participants who received 45 mg 
during the placebo-controlled period) or 75 mg (for participants who received placebo, 15 mg, or 
75 mg during the placebo-controlled period), with a 4-week safety follow-up period after the last 
dose of study drug 
. 
The external DSMB will review safety data throughout the study and may provide 
recommendations regarding changes in the study conduct (see Section 5.6).  
Participants will be assessed for safety and tolerability by monitoring the frequency and severity 
of AEs and performing physical examinations, ECGs, vital signs measurements, and clinical 
laboratory assessments at various timepoints during the study. 
 
 
 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix E. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF.  The end of the study is defined 
as the date of the last visit of the last participant in the study or the last scheduled procedure 
shown in the SoA (see Table 3 and Table 4) for the last participant in the study globally. 


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It is estimated that an individual will participate for approximately 19 months, including up to 
32 days for screening, continuous treatment for 52 weeks (including placebo-controlled and 
extension periods, as long as participants are receiving benefit and have not met any criteria for 
study withdrawal), 
 
A participant is considered to have completed the study if he/she has completed both the 
placebo-controlled and the extension periods of the study, including the Week 56 safety 
follow-up (EOS) visit (see Table 3 and Table 4).  A study is considered completed when the last 
participant's last visit has occurred. 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the IRB/IEC of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively if, for example, required by regulatory decision 
or upon advice of the DSMB (see Section 5.6).  If the study is terminated prematurely, the 
sponsor will notify the investigators, the IRBs and IECs, and the regulatory bodies of the 
decision and reason for termination of the study.  
5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign an ICF. 
2. Men and women aged 18 to 75 years at the time of consent. 
3. Clinical diagnosis of nonsegmental vitiligo, with depigmented areas including: 
a. T-BSA ≥ 8%, and 
b. T-VASI ≥ 8, and 
c. F-BSA ≥ 0.5%, and 
d. F-VASI ≥ 0.5. 
4. Removed during Protocol Amendment 1. 
5. Agreement to discontinue all agents and procedures used to treat vitiligo from screening 
through the final safety follow-up visit. 


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6. Agreement to use contraception, as follows (see Appendix A): 
a. Male participants and female participants of childbearing potential must agree to take 
appropriate precautions to avoid pregnancy (with at least 99% certainty) from 
screening through 90 days after the last dose of study drug.   
b. Male participants must refrain from donating sperm during this period.  Female 
participants must refrain from donating oocytes during this period.  
c. Permitted methods that are at least 99% effective in preventing pregnancy should be 
communicated to the participant and his/her understanding confirmed.  
Note:  This criterion does not apply to women of nonchildbearing potential (ie, surgically 
sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined 
as amenorrhea at least 12 months before screening, confirmed by FSH levels at 
screening).  
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Inability or unwillingness of the participant to sign the ICF. 
2. Other forms of vitiligo (eg, segmental) or other skin depigmentation disorders (eg, 
piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive 
macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor). 
3. Uncontrolled thyroid function at screening as determined by the investigator. 
Note:  If the participant has a history of thyroid disease and is on treatment, the 
participant must be on a stable thyroid regimen for at least 3 months prior to Day 1. 
4. Use of laser or light-based treatment (phototherapy), including tanning beds, within 
8 weeks prior to Day 1. 
5. Use of dihydroxyacetone (generally present in self-tanning products) within 4 weeks 
prior to Day 1.  
6. Current or past use of the depigmenting agent monobenzyl ether of hydroquinone, 
including Benoquin® (monobenzone). 
7. History of melanocyte-keratinocyte transplantation procedure (MKTP) or other surgical 
treatment for vitiligo. 
8. Spontaneous and significant repigmentation within 6 months prior to screening 
(eg, repigmentation without any treatment, and significant in amount as determined by 
the investigator). 
9. Women who are pregnant, considering pregnancy, or breastfeeding. 


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10. Concurrent conditions or history of other diseases, as follows: 
a. Thrombocytopenia, coagulopathy, platelet dysfunction, or history of thrombotic 
events. 
b. Any clinically significant medical condition other than vitiligo, as determined by the 
investigator, that is not adequately controlled with appropriate treatment OR may 
interfere with the course, severity, or assessments of this study. 
c. Any other active skin disease or condition that may interfere with the course, severity, 
or assessments of this study. 
d. Any bacterial, fungal, or viral infection that, based on the investigator's clinical 
assessment, makes the participant an unsuitable candidate for the study. 
e. Current herpes zoster infection, a history of disseminated herpes simplex, or a history 
of herpes zoster. 
f. History of malignancy, including melanoma, lymphoma, and leukemia within 5 years 
before Day 1, other than a successfully treated nonmetastatic cutaneous squamous 
cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix. 
g. Albinism. 
11. History of treatment failure for vitiligo, or any other inflammatory condition, with any 
systemic or topical JAK or TYK2 inhibitor (eg, ruxolitinib, tofacitinib, baricitinib, 
filgotinib, lestaurtinib, pacritinib, abrocitinib, brepocitinib). 
12. Current use of anticoagulants or medications known to cause thrombocytopenia. 
13. Receipt of medications or investigational drugs within the following interval before 
Day 1 (first administration of study drug): 
a. < 12 weeks or 5 half-lives (if known), whichever is longer, for any topical or systemic 
JAK or TYK2 inhibitor.  
b. < 12 weeks or 5 half-lives (if known), whichever is longer, for any investigational or 
experimental treatments. 
c. < 12 weeks or 5 half-lives (if known), whichever is longer, for systemic 
immunosuppressive or immunomodulating biologic drugs (eg, adalimumab, 
etanercept, infliximab, golimumab, certolizumab, ustekinumab, secukinumab, 
brodalumab, ixekizumab, risankizumab, guselkumab, bimekizumab, iscalimab, 
bermekimab, rituximab, anakinra). 
d. < 6 weeks for live vaccine, or planning to receive live vaccine during the course of 
the study or within 6 weeks after the last dose of study drug. 
e. < 4 weeks for systemic immunosuppressive or immunomodulating small-molecule 
drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, dapsone, 
azathioprine).  
Note 1:  Use of corticosteroid inhalers and intranasal sprays is allowed.  
Note 2:  Use of oral corticosteroids for nondermatologic conditions (eg, asthma 
exacerbation, bronchitis) is allowed for no longer than 7 days, if deemed acceptable 
by the investigator and the sponsor. 
Note 3:  Use of topical corticosteroids for dermatologic disease other than vitiligo (eg, 
atopic dermatitis or psoriasis) is allowed for areas not being treated for vitiligo.  The 
total BSA involvement for other dermatologic diseases, outside of the areas treated 
for vitiligo, must not exceed 10%. 


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f. < 3 weeks for any oral or topical PDE-4 inhibitor (eg, apremilast, crisaborole). 
g. < 2 weeks for any topical drug applied onto vitiligo lesions. 
h. < 2 weeks for any OTC therapies used for vitiligo treatment. 
i. < 2 weeks or 5 half-lives (if known), whichever is longer, for strong and moderate 
systemic CYP3A4 inhibitors and strong systemic CYP3A4 inducers.  Examples 
include but are not limited to the following (see Appendix B for details):  
erythromycin, rifampicin/rifampin, ciprofloxacin, some azole antifungals (eg, 
ketoconazole, fluconazole), nefazodone, St John's wort, diltiazem, mibefradil, 
verapamil, grapefruit/grapefruit juice, and Seville oranges. 
j. < 1 week for antiplatelet drugs.  
Note:  Low-dose acetylsalicylic acid (≤ 100 mg QD) is permitted for the purpose of 
cardiovascular prophylaxis at the discretion of the investigator. 
14. Laboratory values at screening defined in Table 7. 
Table 7: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
Hematology 
a 
Platelets 
< 150 × 109/L 
b 
Hemoglobin 
< 10 g/L 
c 
ANC 
< 1.5 × 109/L 
d 
WBC 
≤ 3.0 × 109/L 
Hepatic 
e 
ALT 
≥ 2 × ULN 
f 
AST 
≥ 2 × ULN 
g 
Total bilirubin 
≥ 1.5 × ULN 
(Note:  unless clinical diagnosis of Gilbert's syndrome) 
h 
Alkaline phosphatase 
≥ 2× ULN 
Renal 
j 
Serum creatinine 
> 1.25 × ULN 
Coagulation 
l 
PT 
> ULN 
m 
INR 
> ULN 
15. Evidence of HBV or HCV infection or risk of reactivation.  Participants cannot be 
positive for hepatitis B surface antigen, anti–hepatitis B core antibody, or HCV antibody; 
participants also cannot be positive for HBV DNA or HCV RNA in case these reflexive 
assessments are required to be performed. 
Note:  Participants with no prior history of HBV infection who have been vaccinated 
against HBV and who have a positive antibody (hepatitis B surface antibody) against 
HBsAg as the only evidence of prior exposure may participate in the study. 


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16. Known HIV infection. 
17. Evidence of active or latent or inadequately treated infection with Mycobacterium 
tuberculosis (ie, TB) as defined by the following: 
a. A positive QFT-GIT or positive Mantoux/PPD tuberculin skin test performed at or 
within the 12 weeks prior to Day 1 is exclusionary; a negative test is required for 
eligibility unless other criteria as described here are applicable.  It is recommended 
that participants with a history of Bacille Calmette-Guérin vaccination be tested with 
the QFT-GIT, because the Mantoux/PPD tuberculin skin test may be positive due to 
vaccination.  A QFT-GIT or Mantoux/PPD tuberculin skin test is not required if the 
participant has previously received a documented adequate course of therapy for 
either latent or active TB infection. 
b. A history of either untreated or inadequately treated latent or active TB infection. 
c. If a participant has previously received an adequate course of therapy for either latent 
TB infection (9 months of isoniazid in a locale where rates of primary multidrug TB 
resistance are < 5% or an acceptable alternative regimen) or active TB infection (an 
acceptable multidrug regimen), neither a QFT-GIT nor a Mantoux/PPD tuberculin 
skin test is needed, but a chest x-ray(s) or other appropriate diagnostic image, 
performed within 3 months of Day 1, is required.  To be considered eligible for the 
study, the x-ray(s) must be negative for active TB infection as determined by a 
qualified radiologist.  Documentation of adequate treatment for TB and negative chest 
x-ray(s) results must be obtained prior to Day 1. 
d. A participant who is currently being treated for active TB infection is to be excluded. 
18. Known hypersensitivity or severe reaction to INCB054707 or excipients of INCB054707 
(refer to IB). 
19. Inability or unlikeliness of the participant to comply with the dose schedule and study 
evaluations, in the opinion of the investigator. 
20. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits; 
pose a significant risk to the participant; or interfere with interpretation of study data. 
5.3. 
Lifestyle Considerations 
Participants are not allowed to use tanning beds within 8 weeks prior to Day 1 and during the 
study.  
Participants are not allowed to use dihydroxyacetone (generally present in self-tanning products) 
within 4 weeks prior to Day 1 and during the study.  
Participants are allowed to use of bland emollients, camouflage makeups, or sunscreen agents. 


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5.3.1. 
Meals and Dietary Restrictions 
Participants must abstain from consumption of grapefruit or grapefruit juice (pomelos, exotic 
citrus fruits, grapefruit hybrids, or fruit juices) and of Seville oranges from 14 days before the 
start of study drug until after the final dose of study drug. 
Participants must abstain from consumption of dietary supplements containing St John's wort 
(Hypericum perforatum) from 14 days before the start of study drug until after the final dose of 
study drug. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study drug. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error.  Additionally, a participant who fails screening may 
repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status.  Participants who rescreen must reconsent and be assigned a new participant 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study.  However the COVID-19 global 
pandemic may present challenges to the normal conduct of this study, requiring the outline of 
potential mitigation strategies described in Appendix E. 
5.6. 
Data Safety Monitoring Board 
This study will use an external DSMB to monitor safety.  There will be 1 planned DSMB review 
following randomization of the initial 40 participants in the study and their respective completion 
of visit at Week 24, with at least 2 additional reviews at a time to be determined after the first 
assessment.  The DSMB members will be blinded to participants' treatment assignment for the 
initial safety review; however, the DSMB members may request unblinding at any time.  
Participants and investigators will remain blinded to each participant's treatment assignment 
during both the placebo-controlled and extension periods of the study.  The sponsor will remain 
blinded through completion of the placebo-controlled period.  The sponsor will be unblinded 
after the primary database lock, when all participants have completed the placebo-controlled, 
double-blind treatment period (Week 24 analysis). 
The voting members of the committee are external to the sponsor.  The members of the DSMB 
will not be involved with the study in any other way (eg, they cannot be study investigators) and 
will have no competing interests that could affect their roles with respect to the study. 
The DSMB will make recommendations to the sponsor regarding steps to ensure both participant 
safety and the continued ethical integrity of the study.  Specific details regarding composition, 
responsibilities, and governance, including the roles and responsibilities of the various members 
of the clinical study team, and requirements for the proper documentation of DSMB reports, 
minutes, and recommendations will be described in the DSMB charter that is reviewed and 
approved by all DSMB members. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatments Administered 
Information regarding study drug and administration is provided in Table 8.  Participants will 
record study drug administration in a daily diary.  Further information regarding study drug 
administration is provided in Appendix C. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix E. 


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6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatment must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator, and authorized site staff. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records).  Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including tablet counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol (see Appendix C).  
The investigator will also maintain records adequately documenting that the participants were 
provided the specified study drug.  These records should include dates, quantities, and any 
available batch or serial numbers or unique code numbers assigned to the investigational product 
and study participants. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional SOPs.  If 
local procedures mandate on-site destruction of the investigational supply, the site should (where 
local procedures allow) maintain the investigational supply until the study monitor inspects the 
accountability records in order to evaluate compliance and accuracy of accountability by the 
investigative site.  At sites where the study drug is destroyed before monitor inspection, the 
monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Pharmacy Manual. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix E. 


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6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT system (see 
Section 8.1.3).  Participant randomization will be stratified based on total BSA involvement 
(8%-20% and > 20%).  Once a randomization number has been assigned, it must not be 
reassigned.  Full details will be provided in the IRT Study Reference Manual. 
Study drug will be dispensed at study visits summarized in the SoA (see Table 3 and Table 4). 
Returned study drug should not be redispensed to participants. 
Participants and investigators will remain blinded to each participant's treatment assignment 
during both the placebo-controlled and extension periods of the study.  The sponsor will remain 
blinded through completion of the placebo-controlled period.  The sponsor will be unblinded 
after the primary database lock, when all participants have completed the placebo-controlled, 
double-blind treatment period (Week 24 analysis).  Emergency unblinding will occur if an AE 
requires the investigator to be made aware of the participant's treatment assignment (see 
emergency unblinding procedures in Section 9.6 and refer to the IRT Manual). 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with study drug will be monitored by the study site based on the drug accountability 
and reported in the eCRF.  Participants will be instructed to bring all unused study drug with 
them to study visits in order for site personnel to conduct tablet counts to assess study drug 
accountability.  
Participant' compliance must be within 80% to 120%, assessed at each study visit.  If outside of 
this range, it will be considered a protocol deviation.  Participants consistently noncompliant 
with the study drug may be withdrawn from the study.  The decision on withdrawal will be made 
by the investigator after consultation with the sponsor, and relevant correspondence will be 
archived in the site study file. 
6.5. 
Dose Modifications 
No dose modifications will be allowed during the study.  In some circumstances, it may be 
necessary to temporarily interrupt treatment with study drug as a result of AEs or laboratory 
abnormalities that have an unclear relationship to the study drug.  Further details are described in 
Section 6.5.1. 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Instructions for dose interruption or discontinuation of INCB054707 are outlined in Table 9 and 
Table 10; in addition to these guidance steps, safety concerns should be discussed with the 
sponsor (or representative) immediately upon occurrence or awareness. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the outline of potential mitigation 
strategies described in Appendix E. 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest. 
Table 9 and Table 10 provide specifics on further reasons for permanent discontinuation of study 
drug. 
See Section 7.1 for discontinuation procedures. 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including OTC or prescription medicines, vitamins, 
vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any prior medication 
received up to 12 weeks before Day 1, and 28 (+ 7) days after the last dose of study drug (or up 
to the EOS visit, whichever occurs last), will be recorded in the eCRF.  Any addition, deletion, or 
change in the dose of these medications will also be recorded. 
 
.  Only medications or 
treatments with a potential therapeutic impact on vitiligo, per discretion of the investigator or 
designee, will be prohibited 
 
. 
Concomitant treatments/procedures that are required to manage a participant's medical condition 
during the study will also be recorded in the eCRF.  The medical monitor should be contacted if 


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there are any questions regarding concomitant or prior therapy, restricted or prohibited 
medications, or procedures.  If visits at Week 2, Week 6, Week 26, and Week 30 are scheduled 
as remote, concomitant medications will also be assessed remotely, via a phone call conducted 
by the study site; otherwise information will be captured during in-clinic visit (see Table 3 and 
Table 4). 
6.6.1. 
Permitted Medications and Procedures 
The following are permitted during the study with application guidance.  Investigators and site 
staff are expected to use their best clinical judgement with these recommendations and adhere to 
the guidelines as closely as possible.  Please consult the sponsor if there are specific questions. 
• Participants may use bland emollients, camouflage makeups, and sunscreen agents.  
Note:  Emollients, camouflage makeups, or sunscreen agents may need to be removed 
prior to study assessment of the vitiligo lesions. 
• Concomitant oral vitamins, herbal supplements, and other skin products should be 
approved by the investigator and ideally should remain stable during the study. 
6.6.2. 
Restricted Medications and Procedures 
The following are restricted during the study under specified conditions: 
• Use of topical treatment for dermatologic disease other than vitiligo (eg, atopic 
dermatitis or psoriasis) is allowed for areas not being treated for vitiligo. 
 
 
• Use of oral corticosteroids for no longer than 7 days, if deemed acceptable by the 
investigator and the sponsor, is allowed for nondermatologic conditions (eg, asthma 
exacerbation, bronchitis). 
Note:  Use of corticosteroid inhalers and intranasal sprays is allowed. 
6.6.3. 
Prohibited Medications and Procedures 
The following medications are prohibited for all participants in the study: 
• Any topical or systemic JAK or TYK2 inhibitor other than INCB054707 
(eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib, abrocitinib, 
brepocitinib).  
• Any other investigational or experimental treatments, including those for vitiligo. 
• Systemic immunosuppressive or immunomodulating biologic drugs (eg, adalimumab, 
etanercept, infliximab, golimumab, certolizumab, ustekinumab, secukinumab, 
brodalumab, ixekizumab, risankizumab, guselkumab, bimekizumab, iscalimab, 
bermekimab, rituximab, anakinra). 
• Systemic immunosuppressive or immunomodulating small-molecule drugs (eg, oral 
or injectable corticosteroids, methotrexate, cyclosporine, dapsone, azathioprine). 


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• Systemic or topical PDE-4 inhibitors (eg, apremilast, crisaborole). 
• Other topical agents for vitiligo, including corticosteroids, vitamin D derivatives, and 
calcineurin inhibitors. 
• Conventional therapies with a potential therapeutic impact on vitiligo, per discretion 
of the investigator or designee. 
• Any phototherapy, including tanning beds. 
• Laser or surgical treatments for vitiligo. 
• Any topical drug applied onto vitiligo lesions. 
• Any OTC therapies used for vitiligo treatment. 
• Dihydroxyacetone (generally present in self-tanning products). 
• Treatment known to affect the course of vitiligo, such as skin bleaching treatments 
(eg, hydroquinone) or depigmenting agents (eg, monobenzone). 
• Anticoagulants, antiplatelet drugs, or medications known to cause thrombocytopenia. 
• Acetylsalicylic acid (aspirin). 
Note:  Low-dose acetylsalicylic acid (≤ 100 mg QD) is permitted for the purpose of 
cardiovascular prophylaxis at the discretion of the investigator. 
• Live vaccines (during the study and within 6 weeks after the last dose of study drug). 
• Strong and moderate systemic CYP3A4 inhibitors and strong systemic CYP3A4 
inducers within 2 weeks or 5 half-lives (if known).  Examples include but are not 
limited to the following (see Appendix B for details):  erythromycin, 
rifampicin/rifampin, ciprofloxacin, some azole antifungals (eg, ketoconazole, 
fluconazole), nefazodone, St. John's wort, diltiazem, mibefradil, verapamil, 
grapefruit/grapefruit juice, and Seville oranges. 
6.7. 
Treatment After the End of the Study 
Upon completion of the 52 weeks of treatment, participants will not be provided additional 
treatment within this study. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant becomes pregnant.  
• Consent is withdrawn.   
Note:  Consent withdrawn means that the participant has explicitly indicated that 
he/she does not want to be followed any longer; in this case, no further data, except 
data in the public domain, may be solicited from or collected on the participant.  
Participants may choose to discontinue study treatment and remain in the study. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
• Any AE of unacceptable severity as noted in Section 6.5. 
• Participant meets discontinuation criteria as described in Section 6.5. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's or sponsor's opinion, the sponsor should be consulted for instruction 
on handling the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit (EOT1 during the placebo-controlled period; EOT2 during the extension period) should be 
conducted.  Reasonable efforts should be made to have the participant return for a safety 
follow-up visit 4 weeks after last dose (EOS) 
 
.  These visits 
are described in Table 3 and Table 4. 
The last date of the last dose of study drug and the reason for discontinuation of study drug will 
be recorded in the eCRF. 


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If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The EOT visit should be performed and date recorded. 
• The status of the participant should be updated to EOT in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments.  
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.  When a participant is withdrawn from the study, the EOT visit 
procedures should be performed; if possible, the safety follow-up visit should also be conducted 
within 28 (+ 7) days of the last dose of study drug 
 
. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records.  If the 
participant withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 


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• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the countries in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection laws.  The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 


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• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
• Participants who are rescreened are required to sign a new ICF. 
8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is randomized in the 
study (Day 1).  Screening may not exceed 32 days.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
randomization or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error.  For screening assessments that are repeated, the most recent available result before 
randomization will be used to determine eligibility. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact the IRT to obtain the 
participant ID number during screening.  Upon determining that the participant is eligible for 
randomization, the IRT will be contacted to randomize the participant and obtain the treatment 
assignment.  Additionally, the IRT will be contacted at each regular study visit to dispense 
medication to the participant and to update the study drug supply.  Additional details are 
provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and Diaries 
Participants will be provided with a reminder card at each visit.  The reminder card will indicate 
the date/time of the next visit and will also remind the participant that they should not take their 
morning dose of study drug on the day of the visits at Week 4, Week 12, Week 24, and Week 36, 
because they will take it after blood draws for 
 have been 
completed.  
Participants will be instructed on the use of the diary.  
 
 
  Daily study drug administration will be 
recorded in the diary and verified by the study investigator/designee at study visits as shown in 
Table 3 and Table 4. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, Fitzpatrick scale score, 
nicotine use, medical and surgical history, and current illnesses.  Medical history will include 


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relevant medical or surgical treatment that is considered to be clinically significant by the 
investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A vitiligo medical and treatment history, including date of diagnosis, relevant disease 
characteristics, and prior treatments, including systemic treatments, phototherapy, and surgical 
procedures, will be collected at screening.  A medical or surgical history of other conditions 
related to vitiligo or relevant to the conduct of this clinical trial will also be collected at 
screening. 
8.2. 
Efficacy Assessments 
8.2.2. 
Vitiligo Area Scoring Index  
Areas affected by depigmentation due to vitiligo will be assessed using the VASI as shown in the 
SoA (see Table 3 and Table 4).  It is based on a composite estimate of the overall area of vitiligo 
patches at baseline and the degree of macular repigmentation within these patches over time. 
 
 
  
 
 
 
 
 
 
 
 
 


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The T-VASI is calculated using a formula that includes contributions from all body regions 
(possible range:  0-100) as follows: 
VASI = Σ [Hand Units] × [Residual Depigmentation] All Body Sites 
The body is divided into the following 6 separate and mutually exclusive sites:  (1) head/neck, 
(2) hands, (3) upper extremities (excluding hands), (4) trunk, (5) lower extremities (excluding 
feet), and (6) feet.  The percentage of vitiligo involvement is estimated in hand units (%BSA) by 
the same investigator during the entire course of the study.  Hand unit is based on the 
participant's hand size.  The investigator uses his/her hand to mimic the participant's hand size to 
evaluate %BSA vitiligo involvement.  The degree of depigmentation for each body site is 
determined and estimated to the nearest of the following percentages:  0, 10%, 25%, 50%, 
 
.  The T-VASI is then derived by multiplying the values assessed for the vitiligo 
involvement by the percentage of affected skin for each body site and summing the values of all 
body sites together (Hamzavi et al 2004). 


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8.2.6. 
Photography 
Photography of the face and/or body areas affected with vitiligo will be obtained at visits listed 
in Table 3 and Table 4. 


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All sites will use 2-dimensional photography to photograph facial and nonfacial (targeted) 
depigmented areas. 
8.2.6.1. 
Definition of Targeted Nonfacial Vitiligo Depigmented Areas   
At the baseline visit, depigmented nonfacial areas that are representative of the participant's 
overall disease will be selected as targeted nonfacial vitiligo depigmented areas.  These areas 
will be assessed, measured, and documented in the participant's medical record at each 
subsequent visit during the study (see Table 3 and Table 4).  A note should be made in the 
medical record, and the baseline photographs can be marked with the location of the targeted 
depigmented area.  The genitalia area should not be photographed. 
Photographic procedures will be standardized, and a full description of the methodology will be 
provided to the sites in a photography manual. 


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8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see Table 3 and Table 4).  
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix E. 


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8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
28 (+ 7) days after the last dose of study drug 
 
.  Adverse events that begin or 
worsen after informed consent should be recorded on the Adverse Events Form in the eCRF 
regardless of the assumption of a causal relationship with the study drug.  Conditions that were 
already present at the time of informed consent should be recorded on the Medical History Form 
in the eCRF.  Adverse events (including laboratory abnormalities that constitute AEs) should be 
described using a diagnosis whenever possible rather than by individual underlying signs and 
symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
considered related to the study drug/procedures, or caused the participant to discontinue the 
study drug.  Care will be taken not to introduce bias when detecting AEs and/or SAEs.  
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours.  The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
If visits at Week 2, Week 6, Week 26, and Week 30 are scheduled as remote, adverse events will 
also be assessed remotely, via a phone call conducted by the study site; otherwise information 
will be captured during in-clinic visit (see Table 3 and Table 4). 
8.3.2. 
Physical Examinations 
Physical examinations will be conducted at the timepoints listed in Table 3 and Table 4. 
A comprehensive physical examination will include height (at screening only) and body weight 
and assessment of the following organ or body systems:  skin; head, eyes, ears, nose, and throat; 
thyroid; lungs; cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes.  A 
brief neurologic examination will also be performed. 
A targeted physical examination should be conducted as indicated by symptoms reported by the 
participant, AEs, or other findings.  Abnormalities that are considered clinically significant in the 
judgment of the investigator (or designee) are to be reported as AEs. 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, a physician' assistant, or an advanced registered nurse practitioner, as local law 
permits. 


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8.3.3. 
Vital Signs 
Vital signs measurements (to be taken before blood collection for laboratory tests) include blood 
pressure, pulse, respiratory rate, and body temperature and will be obtained as outlined in the 
SoA (see Table 3 and Table 4).  If vital signs cannot be taken before blood collection for 
laboratory tests, there must be a minimum of 30 minutes from the completion of the blood 
collection procedures to the beginning of the vital signs collection.  Blood pressure and pulse 
will be taken with the participant in the recumbent, semirecumbent, or sitting position after 
5 minutes of rest.  Abnormal vital sign results identified at any time after the first dose of study 
drug constitute an AE if they are considered clinically significant in the judgment of the 
investigator. 
8.3.4. 
Electrocardiograms 
Single 12-lead ECGs will be obtained as outlined in the SoA (see Table 3 and Table 4) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals; if necessary, calculation of such parameters is also acceptable if the ECG machine does 
not perform it automatically.  All 12-lead ECGs will be performed with the participant in a 
recumbent or semirecumbent position after 5 minutes of rest.  Prolonged QTcF values of 
≥ 450 milliseconds are to be confirmed by performing 2 additional ECGs (within the next 
5 minutes) and averaging the results to determine the averaged value. 
Additional 12-lead ECGs may be performed at other visits as deemed clinically necessary.  
Electrocardiograms will be interpreted by the investigator at the site or designee, and the results 
will be used for immediate management of the participant's care.  The decision to include or 
exclude a participant or withdraw a participant from the study based on an ECG flagged as 
"Abnormal, Clinically Significant" is the responsibility of the investigator, in consultation with 
the sponsor's medical monitor, as appropriate.  Any abnormalities that are considered clinically 
significant in the judgment of the investigator are to be reported as AEs.  ECGs should be 
performed in line with local standards and results reported in the eCRF. 
8.3.5. 
Laboratory Assessments 
See Table 13 for the list of clinical laboratory tests to be performed and Table 3 and Table 4 for 
the laboratory assessment visit schedule.  A central laboratory will perform all clinical laboratory 
assessments for safety (ie, blood chemistries, hematology assessments, coagulation tests, 
endocrine function, and urinalysis), 
.  
 
  Additional testing may be required by the 
investigator or sponsor based on emerging safety data.  All Protocol-required laboratory 
assessments must be conducted in accordance with the Laboratory Manual and Table 3 and 
Table 4. 
If visits at Week 2, Week 6, Week 26, and Week 30 are scheduled as remote, blood collection 
will be conducted remotely (eg, participant's home or workplace); otherwise blood will be 
collected during in-clinic visit (see Table 3 and Table 4).  At-home sampling for additional 
laboratory assessments may also be conducted; see Appendix E for COVID-19–related guidance. 
Information regarding collection, processing, and shipping of samples for laboratory assessment 
is provided in the Laboratory Manual. 


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Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.  All laboratory tests with values considered clinically significantly 
abnormal during participation in the study (including any unscheduled testing within the 
24-week follow-up period) should be repeated until the values return to normal or baseline or are 
no longer considered clinically significant by the investigator or medical monitor. 
If screening laboratory assessments are performed more than 32 days before Day 1, then the tests 
must be repeated and eligibility confirmed before study drug administration on Day 1. 
Laboratory sample collection on Day 1 must be performed before study drug administration.  
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 


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Table 13: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology  
Urinalysis  
Serology / Infection 
Pregnancy Testing 
• Albumin 
• Alkaline phosphatase 
• ALT 
• AST 
• Bicarbonate or CO2 
• Blood urea nitrogen or urea 
• Calcium 
• Chloride 
• Creatine kinase 
• Creatinine 
• Glucose 
• GGT 
• Lactate dehydrogenase 
• Phosphate 
• Potassium 
• Sodium 
• Total bilirubin 
• Direct bilirubin (if total 
bilirubin is elevated above 
1.5  ULN) 
• Total protein 
Complete blood count, 
including: 
• Hemoglobin 
• Mean corpuscular volume 
• Hematocrit 
• Platelet count 
• Mean platelet volume  
• In samples with 
abnormalities in platelet 
count or size distribution 
(as indicated by an 
automated analyzer), a 
blood film should be 
examined. 
• Red blood cell count 
• Red blood cell distribution 
width (RDW) 
• WBC count 
Differential count (% and 
absolute values), including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
• Color and appearance 
• pH and specific 
gravity 
• Bilirubin 
• Glucose 
• Ketones 
• Leukocyte esterase 
• Nitrite 
• Occult blood 
• Protein 
• Microscopic 
evaluation (in case of 
abnormal urinalysis 
results) 
• HBsAg* 
• HBsAb 
• HBcAb* 
• HCVAb* 
• HIV 
• QuantiFERON-TB 
Gold test  
 
*Observation:  If either 
HBsAg or HBcAb is 
positive, a reflexive 
HBV DNA must be 
obtained.  If HCVAb is 
positive, a reflexive 
HCV RNA must be 
obtained. 
Pregnancy testing will be 
performed only for female 
participants.  Further instructions 
are provided in Section 8.3.5.1. 
• Serum FSH:  for confirmation 
of nonchildbearing status for 
WONCBP (screening only) 
• Serum pregnancy test 
(WOCBP):  to be performed 
at visits indicated in Table 3 
and Table 4.   
• Urine pregnancy test 
(WOCBP):  to be performed 
at visits indicated in Table 3 
and Table 4. 
Pregnancy tests (serum or urine) 
should be repeated if required by 
local regulations. 
Lipid Panel 
Coagulation 
Thyroid Function Markers 
• Total cholesterol 
• Triglycerides 
• LDL 
• HDL 
 
Observation:  Fasting is 
not required. 
• PT 
• INR 
• TSH 
• Free T4 
Inflammation Marker 
• hsCRP 
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data or to rule out a diagnosis. 
Note:  Alternative tests (ie, CO2 or CO2 Combining Power or HCO3) are also allowed as per regional standard of care. 


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8.3.5.1. 
Pregnancy Testing 
A serum FSH test will be required for all WONCBP during screening (before the first dose of 
study drug) for confirmation of nonchildbearing status.  Women of nonchildbearing potential are 
defined as surgically sterile with a hysterectomy and/or bilateral oophorectomy OR 
postmenopausal, defined as amenorrhea ≥ 12 months prior to screening. 
A serum pregnancy test will be required for all WOCBP during screening (before the first dose 
of study drug) and at the visits indicated in Table 3 and Table 4.  Urine pregnancy tests will be 
performed locally as outlined in Table 3 and Table 4, as medically indicated (eg, in case of loss 
of menstrual cycle, when pregnancy is suspected), or per country-specific requirement (note that 
country-required urine pregnancy testing will be outlined and communicated to investigational 
sites under separate cover).  If a urine pregnancy test is positive, the results should be confirmed 
with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, the participant should be immediately 
discontinued (see Section 7.1).  Additionally, Section 9.7 should be followed for reporting 
requirements. 
8.3.5.2. 
Serology 
Hepatitis B and C and HIV screening assessments will be performed at the screening visit to rule 
out infection; required analytes are shown in Table 13.  Generally, hepatitis and HIV tests should 
be performed early in the screening process due to the length of time needed to obtain the results.  
Additional tests may be performed if clinically indicated. 
Eligibility criteria for participants with a history of HCV infection should generally require 
participants to have completed curative antiviral treatment and require HCV viral quantitative 
RNA below the limit of quantification 12 weeks after the end of HCV therapy.  A patient who is 
HCVAb positive but HCV RNA negative due to prior treatment or natural resolution should be 
eligible. 
Reactivation of HBV can occur in chronic carriers of HBV infection (HBsAg-positive, 
undetectable or low HBV DNA, and normal ALT) who are not on HBV therapy or in individuals 
who have serologic evidence of a resolved prior HBV infection (ie, HBsAg-negative and 
anti-HBc–positive).  While HBsAg-negative, anti-HBc–positive patients are at lower risk of 
HBV reactivation compared with HBsAg-positive patients, risk of HBV reactivation should be 
considered in all participants. 
Participants with no prior history of HBV infection who have been vaccinated against HBV and 
who have a positive antibody against HBV surface antigen as the only evidence of prior 
exposure may participate in the study. 


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8.3.5.3. 
Tuberculosis Screening 
At the time of screening, all participants will undergo TB screening.  Depending on the TB status 
of the participant, different assessments may be performed. 
The QFT-GIT is the preferred testing method.  If the QFT-GIT cannot be performed, or if the 
results cannot be determined by the reference laboratory to be either positive or negative (eg, 
indeterminate), then participants may be screened using the PPD tuberculin skin test (Mantoux 
method; see Note 1) with approval of the medical monitor (or designee).  The QFT-GIT is an 
indirect test for Mycobacterium tuberculosis infection (including disease) and is intended for use 
in conjunction with risk assessment, radiography (see Note 2), and other medical and diagnostic 
evaluations. 
It is recommended that participants with a history of Bacille Calmette-Guérin vaccination be 
tested with the QFT-GIT, because the Mantoux/PPD tuberculin skin test may be positive due to 
vaccination.   
A QFT-GIT or Mantoux/PPD tuberculin skin test is not required if the participant has previously 
received a documented adequate course of therapy for either latent TB infection (eg, 9 months of 
isoniazid in a locale where rates of primary multidrug TB resistance are < 5% or an acceptable 
alternative regimen) or active TB infection (an acceptable multidrug regimen).  In such cases, a 
chest x-ray(s) or other appropriate diagnostic image, performed within 3 months of Day 1, is 
required (see Note 2).  To be considered eligible for the study, the x-ray(s) must be negative for 
active TB infection as determined by a qualified radiologist (see Note 2).  Documentation of 
adequate treatment for TB and negative chest x-ray(s) results must be obtained prior to Day 1.  
Note 1:  If the QFT-GIT cannot be performed, or if the results cannot be determined to be 
positive or negative (eg, indeterminate), then participants may be screened using the PPD 
tuberculin test (Mantoux method), with the approval of the medical monitor (or designee). 
Participants must have the PPD test administered and evaluated by a health care professional 
48 to 72 hours later in order to be eligible for the study, unless performed and documented within 
the past 3 months.  The test should be performed according to local standards with induration of 
< 5 mm required for inclusion. 
Note 2:  At the discretion of the investigator or medical monitor (or designee), participants may 
be required to have a chest x-ray (posterior-anterior and lateral views) or other appropriate 
diagnostic image (ie, computed tomography or magnetic resonance imaging) taken at screening, 
or previously taken within 3 months prior to Study Day 1, and read by a qualified radiologist to 
potentially distinguish between latent and active TB.  Documentation of adequate treatment for 
TB and negative chest x-ray(s) results must be obtained prior to Day 1. 


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8.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time at the investigator's (or designee's) discretion and 
appropriate clinical and laboratory tests may be performed as clinically indicated. 
If there is a potential clinically significant abnormality in hematology or chemistry assessments 
(particularly in platelet count) during the study, an unscheduled visit within the following week 
should occur to repeat laboratory assessments (further details are provided in Table 9 and 
Table 10).  The investigator must inform and consult the sponsor (or designee) regarding any 
hematologic abnormality. 
8.7. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues study drug, whether the participant is terminating 
the study early or the participant has completed the study, the EOT visit should be conducted.  If 
the EOT visit coincides with a regular study visit, the EOT evaluations will supersede those of 
that scheduled visit, and the data should be entered in the EOT visit in the eCRF.  The participant 
should be encouraged to return for the follow-up visits (EOS, 
). 
8.8. 
Follow-Up 
Adverse events and SAEs must be reported up until at least 28 (+ 7) days after the last dose of 
study drug 
 
, and ongoing AEs and SAEs must be followed up until toxicities 
resolve, return to baseline, or are deemed irreversible, whichever is longer.  Reasonable efforts 
should be made to have the participant return for the follow-up visit and report any AEs that may 


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occur during this period.  In exceptional cases when the participant cannot return to the site for 
the safety follow-up visit, the participant should be contacted by telephone for assessment of 
AEs and SAEs and the site should properly document the contact. 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit (EOS), which should occur 28 (+ 7 days) after the EOT visit (or after the last dose of study 
drug if the EOT visit was not performed). 
 
 
 
 
 


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9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug-related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. 
Additional Guidance for Events Meeting the Adverse Event Definition 
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug.  Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin, platelet count 
decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study drug (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy assessments. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent.  If the condition is present before 
entering the study, then it should be captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs.  This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) is not considered an SAE. 
d. Results in persistent or significant disability/incapacity 
• The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions.  This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle), that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
An important medical event is an event that may not result in death, be immediately life-threatening, or 
require hospitalization but may be considered serious when, based on appropriate medical judgment, 
the event may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definition.  Examples of such events include new invasive or 
malignant cancers, intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, development of 
drug dependency or drug abuse, or suspected transmission of an infectious agent via a medicinal 
product.  Secondary malignancies should always be considered SAEs. 


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9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF.  Conditions that were present at the time informed consent was 
given should be recorded on the Medical History Form in the eCRF.   
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Event Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested.  In this 
case, all participant identifiers, with the exception of the participant number, will be redacted by the 
site staff on the copies of the medical records before submission.  These records can be submitted to 
Incyte Pharmacovigilance by email/fax per the contact information listed in the Study Reference 
Manual or as per SAE completing guidelines.   
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information.  Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE.  When a clear diagnosis cannot be identified, each sign or 
symptom should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine the following: 
• The severity grade (CTCAE v5.0 Grade 1 to 5).  See below for further instructions on the assessment 
of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug:  suspected 
(yes) or not suspected (no).  See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit 
 
. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications). 


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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE.  
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB or Product Information for study drug, or 
marketed products, respectively, in making his/her assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report.  However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements.  Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
submit the updated causality assessment. 


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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the AE eCRFs until it has resolved or until it is 
judged to be permanent; assessment should be made at each visit (or more frequently if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology.   
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance (either via email/fax if paper SAE form is used or in the SAE EDC CRF) until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
See Appendix D for the management of potential Hy's Law cases. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedures), all SAEs 
occurring after the participant has signed the ICF through the last study visit (or up until the end 
of the safety follow-up period, whichever occurs later) must be reported to the sponsor (or 
designee) immediately, without undue delay but not later than within 24 hours of obtaining 
knowledge of its occurrence unless otherwise specified by the Protocol.  The investigator will 
submit any updated SAE data to the sponsor (or designee) immediately, without undue delay but 
not later than within 24 hours of it being available.  
Investigators are not obligated to actively seek SAE information after conclusion of study 
participation.  If the investigator learns of any SAE, including death, at any time after a 
participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, then the investigator must notify the sponsor (or 
designee) within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB for the study drug (new occurrence) and is 
thought to be related to the study drug, the sponsor or its designee may urgently require further 


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information from the investigator for expedited reporting to health authorities.  The sponsor or its 
designee may need to issue an Investigator Notification to inform all investigators involved in 
any study with the same drug that this SAE has been reported.  Suspected unexpected serious 
adverse reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC or as per national regulatory requirements 
in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation.  The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available.  The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual or as per the Incyte Reference Guide for 
Completing the Serious Adverse Event Report Form). 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Report Form.  Once the EDC system is functional, the 
SAE report should be retrospectively added to the EDC system and follow-up should be completed 
through the EDC.  The original copy of the Serious Adverse Event Report Form and the email or 
facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference Guide for 
Completing the Serious Adverse Report Form or Study Reference Manual for details and for the 
email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system.  The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation).  Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs.  
9.5. 
Events of Clinical Interest 
Not applicable. 
9.5.1. 
Adverse Events of Special Interest 
Not applicable. 


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9.6. 
Emergency Unblinding of Treatment Assignment 
In case of a medical emergency, for a participant's safety management, the procedure for 
emergency unblinding is provided to the investigator in the IRT Manual.  If a participant's 
treatment assignment is unblinded, the sponsor or its designee should be notified immediately by 
telephone for awareness. 
If an investigator, the site personnel performing assessments, or a participant is unblinded, then 
the participant must discontinue study drug unless there are ethical reasons to have the 
participant remain on the study treatment.  In these cases, the investigator must obtain specific 
approval from the sponsor's (or its designee's) medical monitor for the participant to continue in 
the study. 
9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only).  
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form or Study Reference Manual. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or its designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 


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9.8. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9.10. 
Treatment of Overdose 
There has been no clinical experience with overdose of INCB054707.  Treatment of overdose 
should consist of general supportive measures. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 16. 
Table 16: 
Populations for Analysis 
Population 
Description 
ITT  
The ITT population includes all randomized participants.  Treatment groups for 
this population will be defined according to the treatment assignment at 
randomization. 
Safety 
The safety population includes all participants who received at least 1 dose of 
study drug, Treatment groups for this population will be determined according to 
the actual treatment the participant received on Day 1. 
10.3. 
Level of Significance 
 
 
 
 
 
 


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10.4.1. 
Primary Analysis 
 
 
 
 
 
 
 
 
 
10.4.2. 
Secondary Analysis 
 
 
 
 
 
 
 
 
  
10.4.3. 
Safety Analyses 
Safety analyses will be conducted for the safety population.  A TEAE is any AE either reported 
for the first time or worsening of a pre-existing event after the first dose of study drug until the 
end of the safety follow-up period.  Analysis of AEs will be limited to TEAEs, but data listings 
will include all AEs regardless of their timing to study drug administration.  Adverse events will 
be tabulated by the MedDRA preferred term and system organ class.  Severity of AEs will be 
based on the National Cancer Institute CTCAE v5.0 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, then the AE will be considered treatment-related.  The incidence of AEs 
and treatment-related AEs will be tabulated.  
The clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned.  Laboratory test values outside the normal range will be assessed for 
severity based on the normal ranges for the clinical reference laboratory.  The incidence of 
abnormal laboratory values and shift tables relative to baseline will be tabulated.  Descriptive 
statistics and mean change from baseline will be determined for vital signs (blood pressure, 
pulse, respiratory rate, and body temperature) at each assessment time.  Descriptive statistics and 
mean change from baseline will be determined for each ECG parameter at each assessment time. 


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10.5. 
Interim Analysis 
No formal interim analysis is planned in this study.  However, preplanned analyses of safety 
(blinded data) will be provided to an external DSMB (see Section 5.6) as specified in the DSMB 
charter.  The process by which the DSMB will review data and make recommendations and 
decisions will be documented in the DSMB charter.  The SAP will describe the planned analyses 
in greater detail. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 


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11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study.  As part of his/her responsibilities, the coordinating principal investigator will review the 
final CSR.  Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system.  The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF.  The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements.  Other data outside the EDC system required in the study conduct 
of the Protocol such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and, as designated by the sponsor, will have their own data flow 
management plans, study charters, 
 as applicable. 
The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected, including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
 photographs, diary data), 
or as otherwise specified in the Protocol. 
• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants.  Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete.  Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail).  Source data are in general all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source data are contained in source 
documents (original records or certified copies).  


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• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed and 
available at the investigator's site.  Examples of source documents are original 
documents, data, and records (eg, hospital records, electronic hospital records, 
clinical and office charts, laboratory notes, memoranda, participants' diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm or magnetic 
media, x-rays, participants' files, and e-records/records kept at the pharmacy, at 
the laboratories, and at medico-technical departments involved in the clinical 
trial). 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, 
depending on the study.  Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, or copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor.  
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 


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11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 30 years after study completion unless local regulations require 
otherwise.  No records may be destroyed during the retention period without the written approval 
of the sponsor.  No records may be transferred to another location or party without written 
notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 


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are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.6. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
Banerjee A, McNish S, Shanmugam VK. Interferon-gamma (IFN-γ) is elevated in wound 
exudate from hidradenitis suppurativa. Immunol Invest 2017;46:149-158. 
 
 
 
Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatology 2020;236:571-592. 
 
 
 
Bissonnette R, Luchi M, Fidelus-Gort R, et al. A randomized, double-blind, placebo-controlled, 
dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, 
in patients with stable, chronic plaque psoriasis. J Dermatolog Treat 2016;27:332-338. 
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med 2009;28:586-604. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2014. 
Cupertino F, Niemeyer-Corbellini JP, Ramos-E-Silva M. Psychosomatic aspects of vitiligo. Clin 
Dermatol 2017;35:292-297. 
 
 
 
 
Frisoli ML, Harris JE. Vitiligo: mechanistic insights lead to novel treatments. J Allergy Clin 
Immunol 2017;140:654-662. 
Gooderham MJ, Forman SB, Bissonnette R et al. Efficacy and safety of oral Janus kinase 1 
inhibitor abrocitinib for patients with atopic dermatitis: a phase 2 randomized clinical trial. 
JAMA Dermatol 2019;155:1371-1379. 
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. Parametric modeling of narrowband 
UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. 
Arch Dermatol 2004;140:677-683. 
 
 
INCB054707 Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in 
children/adolescents and adults. Int J Dermatol 2012;51:1206-1212. 
Lai YC, Yew YW, Kennedy C, Schwartz RA. Vitiligo and depression: a systematic review and 
meta-analysis of observational studies. Br J Dermatol 2017;177:708-718. 


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Mehta CR, Patel NR. Exact logistic regression: theory and examples. Stat Med 
1995;14:2143-2160. 
Millum J, Grady C. The ethics of placebo-controlled trials: methodological justifications. 
Contemp Clin Trials 2013;36:510-514.  
Narayan VS, Uitentuis SE, Luiten RM, Bekkenk MW, Wolkerstorfer A. Patients' perspective on 
current treatments and demand for novel treatments in vitiligo [published online ahead of print 
September 7, 2020]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.16927. 
Osinubi O, Grainge MJ, Hong L, et al. The prevalence of psychological comorbidity in people 
with vitiligo: a systematic review and meta-analysis. Br J Dermatol 2018;178:863-878. 
Porter JR, Beuf AH, Lerner AB, Nordlund JJ. The effect of vitiligo on sexual relationships. J Am 
Acad Dermatol 1990;22:221-222. 
Rahimi H, Mozafari N, Bastaninejad S, Tehranchinia Z, Samani NA. Hearing status in patients 
with vitiligo. Clin Cosmet Investig Dermatol 2019;12:445-450. 
Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE, Vitiligo Working Group. New 
discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol 2017;77:1-13. 
Rosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: a 
randomised, controlled, phase 2 trial. Lancet 2020;396:110-120. 
Salzer BA, Schallreuter KU. Investigation of the personality structure in patients with vitiligo 
and a possible association with impaired catecholamine metabolism. Dermatology 
1995;190:109-115. 
Silverberg JI, Silverberg NB. Association between vitiligo extent and distribution and 
quality-of-life impairment. JAMA Dermatol 2013;149:159-164. 
Speeckaert R, van Geel N. Vitiligo: an update on pathophysiology and treatment options. Am J 
Clin Dermatol 2017;18:733-744. 
Taïeb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med 2009;360:160-169. 
 
 
Vallerand IA, Lewinson RT, Parsons LM, et al. Vitiligo and major depressive disorder: a 
bidirectional population-based cohort study. J Am Acad Dermatol 2019;80:1371-1379. 
 
 
 
 
 
 
 


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Vossen ARJV, van der Zee HH, Tsoi LC, et al. Novel cytokine and chemokine markers of 
hidradenitis suppurativa reflect chronic inflammation and itch. Allergy 2019;74:631-634. 
Yazdani Abyaneh MA, Griffith R, Falto-Aizpurua L, Nouri K. The dark history of white spots. 
JAMA Dermatol 2014;150:936. 
 
 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS 
Definitions 
 
Woman of Childbearing Potential (WOCBP) 
 
A woman is considered fertile following menarche and until becoming postmenopausal unless permanently 
sterile (see below). 
Women in the following categories are not considered WOCBP: 
• 
Premenarchal 
• 
Premenopausal female with 1 of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel's review of the participant's medical records, medical 
examination, or medical history interview. 
• 
Postmenopausal female 
− 
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
o 
A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy (HRT).  However, in the absence of 12 months of amenorrhea, 
confirmation with 2 FSH measurements in the postmenopausal range is required. 
− 
Female participants on HRT and whose menopausal status is in doubt will be required to use one of the 
nonhormonal highly effective contraception methods if they wish to continue their HRT during the 
study.  Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment. 
For male participants of reproductive potentiala 
The following methods during the protocol-defined timeframe in Section 5.1 are highly effective: 
• 
Use a male condom plus partner use of an additional contraceptive method when having penile-vaginal 
intercourse with a woman of childbearing potential who is not currently pregnant. 
• 
Vasectomy with medical assessment of the surgical success (verified by site personnel's review of the 
participant's medical records) 
• 
Sexual abstinenceb 
− 
Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a 
long-term and persistent basis) and agree to remain abstinent. 
The following are not acceptable methods of contraception: 
• 
Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method. 
• 
Male condom with cap, diaphragm, or sponge with spermicide. 
• 
Male and female condom cannot be used together. 
Note:  Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration. 


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For female participants who are WOCBP 
The following methods during the protocol-defined timeframe in Section 5.1 that can achieve a failure rate of less 
than 1% per year when used consistently and correctly are considered highly effective birth control methods: 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc 
− 
Oral 
− 
Intravaginal  
− 
Transdermal  
• 
Progestogen-only hormonal contraception associated with inhibition of ovulationc 
− 
Oral 
− 
Injectable  
− 
Implantabled  
• 
Intrauterine deviced 
• 
Intrauterine hormone-releasing systemd 
• 
Bilateral tubal occlusiond 
• 
Vasectomized partnerd,e 
• 
Sexual abstinenceb  
a If the male participant has a partner with childbearing potential, the partner should also use contraceptives. 
b In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatments.  The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the 
participant.  
c Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may reduce the 
efficacy of the contraception method. 
d Contraception methods that in the context of this guidance are considered to have low user dependency. 
,e Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of the 
surgical success. 
Source:  Clinical Trials Facilitation and Coordination Group 2014. 


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APPENDIX B. LIST OF STRONG/MODERATE SYSTEMIC CYP3A4 
INHIBITORS AND STRONG SYSTEMIC CYP3A4 
INDUCERS 
Strong and Moderate Systemic CYP3A4 Inhibitors 
Strong Systemic CYP3A4 Inducers 
• 
Erythromycin  
• 
Troleandomycin, Clarithromycin, Telithromycin   
• 
Ciprofloxacin  
• 
Ketoconazole, Fluconazole, Itraconazole, 
Voriconazole, Posaconazole 
• 
Nefazodone  
• 
Diltiazem 
• 
Mibefradil  
• 
Verapamil  
• 
Aprepitant, Casopitant  
• 
Grapefruit/grapefruit juice 
• 
Seville oranges 
• 
Indinavir, Atazanavir, Nelfinavir, Ritonavir, 
Saquinavir, Boceprevir, Danoprevir, Elvitegravir, 
Lopinavir, Paritaprevir, Saquinavir, Telaprevir, 
Tipranavir, Ombitasvir, Cobicistat 
• 
Idelalisib 
• 
Conivaptan 
• 
Crizotinib 
• 
Cyclosporine 
• 
Dronedarone 
• 
Fluvoxamine 
• 
Imatinib 
• 
Tofisopam 
• 
Rifampicin/rifampin  
• 
St John's wort 
• 
Phenytoin 
• 
Apalutamide 
• 
Carbamazepine 
• 
Bosentan 
• 
Efavirenz 
• 
Etravirine 
• 
Enzalutamide 
• 
Mitotane 
• 
Phenobarbital 
• 
Primidone 
Note:  Updated lists of CYP3A4 inhibitors/inducers can be found at Food and Drug Administration.  Drug 
Development and Drug Interactions:  Table of Substrates, Inhibitors and Inducers.  Available at: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-
inhibitors-and-inducers. 


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APPENDIX E. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical trials.  The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the investigational 
product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the trial.  Because of this risk and 
in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines: 
In addition to the remote visits already specified in the Protocol, the evolving situation of the 
pandemic may require further travel restrictions and isolation requirements, or the investigator's 
benefit/risk assessment may determine it to be unsafe for participants to attend study visits at the 
investigational site.  In such cases, the site staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video calls).  At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed.  Periodic on-site visits 
should be conducted whenever feasible, in addition to the mandatory on-site visits 
outlined below. 
• No efficacy assessments can be performed via telemedicine (video call, phone call, or 
via photography). 
• Laboratory sampling:  in order to support investigator oversight of participant safety 
and disease management, off-site laboratory sampling (in accordance with the SoA, 
see Table 3 and Table 4) may be allowed in 1 of 2 ways:  
− Use of home nursing services  
− Instruct the participant to undergo some laboratory tests at a local (nearby) 
hospital laboratory or facility closer to the participant's residence rather than at the 
investigational site.  In this case, the study physician will provide the participant 
with the list of parameters to be checked.  These tests should be performed at 
certified laboratories and copies of results provided to the site. 


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Mandatory On-Site Visits: 
The visits outlined below must be performed in person in order to capture the investigator's 
efficacy assessments
, even if the date that the participant 
eventually comes into the clinic deviates from the visit window.  
No efficacy assessments can be performed via telemedicine (video call, phone call, or 
photography). 
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic.  Further instructions 
will be provided if needed. 
During the placebo-controlled period, the following visits must be performed in person: 
• Screening 
• Day 1 (Baseline) 
• Week 12 visit 
• Week 24 visit 
During the extension period, the following visits must be performed in person: 
• Week 36 visit 
• Week 52 visit 
Investigational Medicinal Product Dispensation and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug via shipment 
to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study drug 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant.   
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the site monitor will continue to employ off-site monitoring practices such as routine 
communication methods (eg, phone calls, e-mails, video visits) with the sites to get information 
on trial progress, subject status, and information on issue resolution.  The study monitor may 
remotely review data entered into the EDC for accuracy and completeness.  If allowed by local 
regulations, remote source data verification may be implemented with agreement of the principal 
investigator and institution, as applicable. 


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If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training.  The study drug can be returned to the sponsor by the hospital pharmacy directly or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Other Considerations  
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight.  In such situations, the investigator is required to provide 
the local physician with a delegation letter listing all delegated activities.  The sponsor, through 
the study investigator or institution, will reimburse the local physician for the tests/procedures 
conducted outside of the standard of care. 
• In case of need, participants may refer to the local health care provider.  Participants will 
be requested to obtain certified copies of the source data at the local health facility with 
the outcome of the contact and provide those to the investigator for appropriate oversight.  
The investigator/delegate will be requested to enter any relevant information into the 
EDC. 
• Should COVID-19–related restrictions be localized and have an effect on a limited 
number of sites, the affected sites may utilize direct contracting of third parties to support 
continuous study conduct (eg, home nursing services, couriers, etc). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [nearby] laboratory tests). 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
19 AUG 2021 
Amendment 2 
09 FEB 2022 
Amendment 3 
19 MAY 2022 
Amendment 4 
12 JUL 2022 
Amendment 4 (12 JUL 2022) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to extend the follow up period for the study from 4 to 
24 weeks. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema; Table 4:  Schedule of Activities [Extension 
Period]); Section 2.2.1, Scientific Rationale for Study Design; Section 3, Objectives 
and Endpoints (Table 6:  Objectives and Endpoints); Section 4.1, Overall Design; 
Section 4.2, Overall Study Duration; Section 6.6, Concomitant Medications and 
Procedures; Section 7.1.2, Discontinuation Procedures; Section 7.2, Participant 
Withdrawal From the Study; Section 8.3.1, Adverse Events; Section 8.3.5, 
Laboratory Assessments; Section 8.7, End of Treatment and/or Early Termination; 
Section 8.8, Follow-Up; Section 9.3, Recording and Follow-Up of Adverse Events 
and/or Serious Adverse Events; Section 9.4, Reporting of Serious Adverse Events. 
Description of change:  
 
 
Rationale for change:  The follow-up period was extended to assess the change in 
pigmentation after completion of treatment with INCB054707. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 3 (19 MAY 2022) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to clarify the unblinding procedures for the sponsor. 
1. Section 5.6, Data Safety Monitoring Board; Section 6.3, Measures to Minimize Bias:  
Randomization and Blinding 
Description of change:  Revised the unblinding procedures for determining that the 
sponsor will be unblinded after the primary database lock, when all participants have 
completed the placebo-controlled, double-blind treatment period (Week 24 analysis). 
Rationale for change:  To clarify and describe the correct unblinding procedures after 
study primary endpoint completion and database lock (placebo-controlled period, 
Week 24 analysis). 


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Amendment 2 (09 FEB 2022) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to provide clarification on the management of creatine 
kinase elevations. 
1. Section 6.5.1, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug (Table 9:  Guidelines for Interrupting, Restarting, and Discontinuing of 
Study Drug) 
Description of change:  Added guidance to describe management of creatine kinase 
elevations. 
Rationale for change:  To clarify how creatine kinase elevations should be managed by 
investigators. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1 (19 AUG 2021) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to remove the inclusion criterion requiring previous 
vitiligo treatment and to permit in-clinic visits for the scheduled remote visits.  Additional 
changes are summarized below. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements) 
Description of change:  Added the name for the coordinating principal investigator. 
Rationale for change:  To update the coordinating principal investigator field in the 
table. 
2. Section 1, Protocol Summary [Table 3:  Schedule of Activities (Placebo-Controlled 
Period); Table 4:  Schedule of Activities (Extension Period)]; Section 6.6, 
Concomitant Medications and Procedures; Section 8.3.1, Adverse Events; 
Section 8.3.5, Laboratory Assessments 
Description of change:  Added clarification that in-clinic visits are permitted for the 
scheduled remote visits at Week 2, Week 6, Week 26, and Week 30. 
Rationale for change:  To allow principal investigators the choice of remote or in-clinic 
visits based on the most adequate option for each participant. 
3. Section 5.1, Inclusion Criteria 
Description of change:  Removed Inclusion Criterion 4, "History of prior vitiligo 
treatment with a total duration of at least 3 months." 
Rationale for change:  To align the inclusion criteria with the participant population, 
currently limited in terms of available treatments.  There are no approved therapies for 
vitiligo, and the currently prescribed therapies may not offer considerable benefit. 
4. Section 5.2, Exclusion Criteria (Table 7:  Exclusionary Laboratory Values) 
Description of change:  Removed "Conjugated (direct) bilirubin" and ≥ 1.2 × ULN from 
Exclusion Criterion 15g. 
Rationale for change:  To clarify that Exclusion Criterion 15g is only applicable to total 
bilirubin. 
5. Section 6.5.1, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug (Table 9:  Guidelines for Interrupting, Restarting, and Discontinuing of 
Study Drug) 
Description of change:  Added clarification for the number of times the study drug can 
be interrupted/restarted due to ALT and/or AST > 3.0 x ULN. 
Rationale for change:  To clarify that the study drug can only be interrupted/restarted up 
to 2 times. 


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6. Section 8.3.5, Laboratory Assessments (Table 13:  Required Laboratory Analytes) 
Description of change:  Creatine kinase will be included as one of the tests under the 
blood chemistries column. 
Rationale for change:  The inclusion of creatine kinase follows a request from the 
external DSMB members.  The recommendation was based on their expertise on other 
Janus kinase inhibitors. 
7. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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SAP_001.pdf: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging 
Study of the Efficacy and Safety of INCB054707 Followed by an Extension 
Official Title:      
Period in Participants With Vitiligo 
NCT Number:        NCT04818346 
Document Date:    Statistical Analysis Plan: 25-April-2022 


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TITLE PAGE 
Statistical Analysis Plan 
INCB 54707-205 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Ranging Study of the Efficacy and Safety of INCB054707 
Followed by an Extension Period in Participants With Vitiligo 
IND Number: 
 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 2 dated 09 FEB 2022 
CRF Approval Date: 
28 JAN 2022 
SAP Version: 
Original 
SAP Author: 
 
Biostatistics 
Date of Plan: 
25 APR 2022 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
3. 
STUDY DESIGN .......................................................................................................12 
3.1. 
Randomization ............................................................................................................12 
 
13 
 
14 
3.4. 
Schedule of Assessments ............................................................................................14 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................15 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................15 
4.1.1. 
Day 1 ...........................................................................................................................15 
4.1.2. 
Study Day ...................................................................................................................15 
4.1.3. 
Baseline Value ............................................................................................................15 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................16 
4.2. 
Variable Definitions ....................................................................................................17 
4.2.1. 
Body Mass Index ........................................................................................................17 
4.2.2. 
Prior and Concomitant Medication .............................................................................17 
5. 
STATISTICAL METHODOLOGY ...........................................................................18 
5.1. 
General Methodology .................................................................................................18 
5.2. 
Treatment Groups .......................................................................................................18 
5.3. 
Analysis Populations ..................................................................................................18 
5.3.1. 
All-Randomized Population .......................................................................................18 
5.3.2. 
Intent-to-Treat Population ..........................................................................................18 
5.3.3. 
Safety Population ........................................................................................................18 
5.3.4. 
Extension Evaluable Population .................................................................................19 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................19 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................19 


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6.1.1. 
Demographics and Baseline Characteristics ...............................................................19 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................19 
6.1.3. 
Medical History ..........................................................................................................20 
6.2. 
Disposition of Participant ...........................................................................................21 
6.3. 
Protocol Deviations ....................................................................................................21 
6.4. 
Exposure .....................................................................................................................21 
6.5. 
Study Drug Compliance .............................................................................................22 
6.6. 
Prior and Concomitant Medication .............................................................................23 
7. 
EFFICACY .................................................................................................................23 
7.1. 
General Considerations ...............................................................................................23 
 
23 
 
23 
 
23 
 
24 
 
24 
 
25 
 
26 
 
26 
 
26 
 
27 
 
27 
 
27 
 
27 
 
27 
 
28 
 
29 
 
30 
 
30 
 
31 
7.3. 
Efficacy Hypotheses ...................................................................................................31 
7.4. 
Analysis of the Primary Efficacy Parameter ..............................................................31 
7.4.1. 
Primary Efficacy Analysis ..........................................................................................31 
7.4.2. 
Subgroup Analyses for Primary Endpoint ..................................................................32 


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7.4.3. 
Sensitivity and Supportive Analyses for Primary Endpoint .......................................32 
7.5. 
Analysis of the Secondary Efficacy Parameters .........................................................32 
 
33 
8. 
SAFETY AND TOLERABILITY ..............................................................................34 
8.1. 
General Considerations ...............................................................................................34 
8.2. 
Adverse Events ...........................................................................................................34 
8.2.1. 
Adverse Event Definitions ..........................................................................................34 
8.2.2. 
Adverse Event Summaries ..........................................................................................34 
8.3. 
Clinical Laboratory Tests ...........................................................................................36 
8.3.1. 
Laboratory Value Definitions .....................................................................................36 
8.3.2. 
Laboratory Value Summaries .....................................................................................36 
8.3.3. 
Potentially Clinically Important Laboratory Values ...................................................36 
8.3.4. 
Potential Drug-Induced Liver Injury Events ..............................................................37 
8.4. 
Vital Signs ..................................................................................................................38 
8.5. 
Electrocardiograms .....................................................................................................38 
9. 
INTERIM ANALYSES ..............................................................................................39 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................39 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................39 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................39 
11. 
REFERENCES ...........................................................................................................40 
 
41 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Definition of Day 1 .....................................................................................................15 
Table 3: 
Definition of First and Last Dose Date .......................................................................22 
 
.25 
 
25 
Table 6: 
Criteria for Potentially Clinically Important Laboratory Values ................................37 
Table 7: 
Normal Ranges for Vital Sign Values ........................................................................38 
Table 8: 
Normal Ranges for Electrocardiogram Intervals ........................................................39 
Table 9: 
Statistical Analysis Plan Versions ..............................................................................39 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
 
13 
 
29 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BSA 
body surface area  
 
 
CI 
confidence interval 
 
 
CRF 
case report form 
 
 
CTCAE 
Common Terminology Criteria for Adverse Events 
DILI 
drug-induced liver injury 
 
 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
 
 
 
 
F-BSA 
facial body surface area 
FDA 
Food and Drug Administration 
 
 
 
 
F-VASI 
Facial Vitiligo Area Scoring Index 
 
 
 
 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effects model for repeated measures 
NCI 
National Cancer Institute 
NRI 
nonresponder imputation 
PC 
placebo-controlled 
 
 
 
 
PT 
preferred term  
PTA 
pure-tone average 


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Abbreviations and 
Special Terms 
Definition 
QALYs 
quality-adjusted life years 
QD 
once daily 
QTcF 
Fridericia's corrected QT interval 
SAP  
Statistical Analysis Plan  
 
 
 
 
SOC 
system organ class 
 
 
T-BSA 
total body surface area 
TEAE 
treatment-emergent adverse event  
 
 
 
 
T-VASI 
Total Vitiligo Area Scoring Index 
 
 
 
 
ULN 
upper limit of normal 
 
 
 
 
 
 
 
 
WHO 
World Health Organization 
 
 


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1. 
INTRODUCTION 
This is a Phase 2, multicenter, randomized, parallel-group, placebo-controlled, double-blind, 
dose-ranging study to evaluate the efficacy and safety of INCB054707 (15, 45, and 75 mg QD) 
over a 24-week treatment period, followed by a 28-week double-blind extension period 
(INCB054707 45 mg and 75 mg QD). A safety follow-up visit will be conducted approximately 
4 weeks after the last dose of study drug. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 54707-205 Protocol. 
 
 
 
 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 54707-205 Protocol Amendment 2 dated 09 FEB 2022 and CRFs 
approved 28 JAN 2022. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the efficacy of INCB054707. 
• Percent change from baseline in Total Vitiligo 
Area Scoring Index (T-VASI) at Week 24. 
Key Secondary 
To further determine the efficacy of INCB054707. • Proportion of participants achieving T-VASI50 
at Week 24. 
T-VASI50 is defined as 50% or greater 
reduction in the Total Vitiligo Area Scoring 
Index.  
Secondary 
To evaluate the safety and tolerability of 
INCB054707. 
• Frequency and severity of AEs, including the 
results of physical examinations, vital signs, 
evaluation of clinical laboratory studies, and 
ECGs.  


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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3. 
STUDY DESIGN 
This is a Phase 2, multicenter, randomized, parallel-group, placebo-controlled, double-blind, 
dose-ranging study to evaluate the efficacy and safety of INCB054707 (15, 45, and 75 mg QD) 
over a 24-week double-blind PC period followed by a 28-week double-blind extension period 
(INCB054707 45 mg and 75 mg QD). The study will enroll approximately 160 men and women 
aged 18 to 75 years with nonsegmental vitiligo, with depigmented areas including T-BSA ≥ 8%, 
T-VASI ≥ 8, F-BSA ≥ 0.5%, and F-VASI ≥ 0.5. 
Participants will be screened for up to 32 days before the first dose of study drug. Participants 
who meet all study entry criteria and none of the exclusion criteria will return to the study site on 
Day 1 of dosing and be randomized to 1 of 4 treatment groups. Participants will be stratified 
based on T-BSA involvement (8.0%-20.0% and > 20.0%). 
Participants will receive double-blinded study treatment of placebo or 1 of 3 doses of 
INCB054707 (15, 45, or 75 mg) QD for 24 weeks. Participants who complete the Week 24 will 
enter the 28-week double-blind extension period with 45 mg QD (for participants who received 
45 mg during the PC period) or 75 mg QD (for participants who received placebo, 15 mg, or 
75 mg during the PC period), with a safety follow-up visit scheduled 4 weeks after the last dose 
of study drug. 
The study schema is shown in Figure 1. 
Figure 1: 
Study Design Schema 
 
The primary analysis will occur after the primary database lock, when all participants have 
completed or discontinued from the PC, double-blind treatment period. 
The final analysis will occur when all participants have completed or withdrawn from the study. 
3.1. 
Randomization 
Approximately 160 participants will be randomized 1:1:1:1 to 1 of 3 INCB054707 treatment 
groups or the placebo group (approximately 40 participants per group). 
Participant randomization will be stratified based on T-BSA involvement (8.0%-20.0% and 
> 20.0%). 


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3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 2 dated 09 FEB 2022 for a full description of all study procedures 
and assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is defined in Table 2 for each period. Note that the treatment groups for each period are 
described in Section 5.2. 
Table 2: 
Definition of Day 1 
Treatment Period 
Treatment Group 
Day 1 
PC period 
Placebo 
INCB054707 15 mg 
INCB054707 45 mg 
INCB054707 75 mg 
The day the first dose of study drug (INCB054707 or 
placebo) is administered to the participants in the PC 
period. 
Extension period 
Placebo to INCB054707 75 mg 
INCB054707 15 mg to 75 mg 
INCB054707 45 mg 
INCB054707 75 mg 
The day the first dose of study drug (INCB054707 
45 mg or 75 mg) is administered to the participants in 
the extension period. 
Throughout study 
participation 
INCB054707 45 mg 
INCB054707 75 mg 
The day the first dose of study drug (INCB054707 
45 mg or 75 mg) is administered to the participants in 
the PC period. 
For randomized participants not treated with any study drug, Day 1 is defined as the day of 
randomization. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCB054707 or placebo in the PC period, unless otherwise defined. 
For randomized participants not treated with any study drug, baseline is defined as the last 
nonmissing assessment before or on the day of randomization for all parameters. 


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For participants who continue in the extension period, baseline is defined as follows: 
• For efficacy evaluation in the extension period, baseline is the last nonmissing 
measurement obtained before the first administration of study drug in the PC period, 
unless otherwise defined. 
• For safety evaluation in the extension period, baseline is the last nonmissing 
measurement obtained before the first administration of study drug in the extension 
period, unless otherwise defined.  
When scheduled assessments and unscheduled assessments occur on the same day and the time 
of the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Handling of Missing and Incomplete Dates 
In general, values for missing dates will not be handled unless methods for handling missing 
dates are specified in this section or relevant sections. The original reported dates collected in the 
eCRF should be used in all relevant listings. The following rules will be used for handling partial 
dates for analyses requiring dates. 
When calculating the time since diagnosis of nonsegmental vitiligo, a partial diagnosis date will 
be handled as follows in the calculation: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 
When the date of the last dose is used in deriving variables such as duration of treatment or 
TEAE flag, a missing or partial date of the last dose will be handled as follows: 
• If only the day is missing, then the earlier date of the last day of the month or the date 
that the participant discontinued treatment will be used. 
• If both the month and day are missing, then the earlier date of 31 DEC of the year or 
the date that the participant discontinued treatment will be used. 
• Otherwise, the date that the participant discontinued treatment will be used as the date 
of the last dose. 


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4.2. 
Variable Definitions 
The following variables will only be calculated if not reported in the eCRF. 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
Body mass index (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB054707 or placebo in the PC period. 
In the PC period, concomitant medication is defined as any nonstudy medication that is started 
accordingly: 
• Before the date of first administration of INCB054707 or placebo in the PC period 
and is ongoing throughout the study or ends on/after the date of first study drug 
administration during the PC period. 
• On/after the date of first administration of INCB054707 or placebo in the PC period 
and is ongoing or ends during the PC period. 
In the extension period, concomitant medication is defined as any nonstudy medication that is 
started accordingly: 
• Before the date of first administration of INCB054707 in the extension period and is 
ongoing throughout the study or ends on/after the date of first study drug 
administration during the extension period. 
• On/after the date of first administration of INCB054707 in the extension period and is 
ongoing or ends during the extension period. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB054707 or placebo. In the listing, it will be indicated whether 
a medication is only prior, only concomitant, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9.1 or later) will be used 
for the generation of all tables, graphs, and statistical analyses. Descriptive summaries for 
continuous variables will include but not be limited to the number of observations, mean, 
standard deviation, median, minimum, and maximum. Descriptive summaries for categorical 
variables will include the number and percentage of participants in each category. 
5.2. 
Treatment Groups 
This is a randomized, double-blind, placebo-controlled, dose-ranging study followed by a 
double-blind extension period. Table summaries, unless otherwise indicated, will present data by 
treatment group. The results will be summarized and presented separately for the PC period and 
the extension period, unless otherwise specified. 
For the PC period, the treatment groups will be placebo and INCB054707 15, 45, and 75 mg. 
For the extension period, the participants will be grouped as follows according to the treatment 
they received during the PC period: 
• Placebo to INCB054707 75 mg 
• INCB054707 15 mg to 75 mg 
• INCB054707 45 mg 
• INCB054707 75 mg 
5.3. 
Analysis Populations 
5.3.1. 
All-Randomized Population 
The all-randomized population will include all participants who were randomized. 
5.3.2. 
Intent-to-Treat Population 
All participants who were randomized to the study constitute the ITT population. Treatment 
groups for this population will be defined according to the treatment assignment at the time of 
randomization regardless of the actual study treatment the participant might apply during their 
participation in the PC period. 
The ITT population will be used for the summary of demographics, baseline characteristics, 
participant disposition, and analyses of all efficacy data in the PC period. 
5.3.3. 
Safety Population 
The safety population will include all participants who received at least 1 dose of INCB054707 
or placebo during the PC period. Treatment groups for this population will be determined 
according to the actual treatment the participant receives on Day 1 in the PC period regardless of 
assigned study treatment. 


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All safety analyses for the PC period will be conducted using the safety population. 
5.3.4. 
Extension Evaluable Population 
All analyses for the extension period will be conducted with the extension evaluable population, 
which includes all participants who received at least 1 dose of INCB054707 during the extension 
period. 
6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
Demographics, baseline characteristics, and disease history will be summarized by treatment 
group and overall. 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics will be summarized for the ITT population and the extension 
evaluable population: age, sex, race, ethnicity, weight, height, BMI, and BMI category 
(< 25 kg/m2, ≥ 25 to < 30 kg/m2, ≥ 30 to < 40 kg/m2, ≥ 40 to < 50 kg/m2, ≥ 50 kg/m2). 
The following demographics will be summarized for the ITT population only: tobacco use (never 
used, current user, former user). 
6.1.2. 
Baseline Disease Characteristics and Disease History 
The baseline disease characteristics and disease history summarized for all participants in the 
ITT population include but are not limited to the following: 
• Disease duration (years) 
• Fitzpatrick scale skin type (Type I, II, III, IV, V, VI) 
• Vitiligo family history 
• Prior therapy or surgery for vitiligo treatment 
• Selected comorbidities 
• Baseline F-BSA involvement 
• Baseline F-BSA involvement category ( 0.5%, > 0.5%-1.0%, > 1.0%-1.5%, 
> 1.5%-2.0%, > 2.0%-2.5%, > 2.5%-3.0%) 
 
 
 
 
 
 
 
 


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• Baseline T-BSA involvement 
• Baseline T-BSA involvement category ( 8.0%, > 8.0%-14.0%, > 14.0%-20.0%, 
> 20.0%-30.0%, > 30.0%-40.0%, > 40.0%-50.0%, > 50.0%-80.0%, > 80.0%) 
• Baseline T-BSA involvement stratification category (8.0%-20.0%, > 20.0%) 
• Baseline T-VASI score 
• Baseline T-VASI score category ( 8.0, > 8.0-14.0, > 14.0-20.0, > 20.0-30.0, 
> 30.0-40.0, > 40.0-50.0, > 50.0-80.0, > 80.0) 
 
 
 
 
 
• History of acne vulgaris (no/yes) 
• Currently having acne vulgaris (no/yes) 
• Vitiligo in genital area (no/yes) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: disease duration (years) will be calculated as follows: 
disease duration (years) = (date of randomization − date of diagnosis + 1) / 365.25. 
 
 
 
 
 
 
 
 
 
6.1.3. 
Medical History 
For participants in the ITT population, medical history will be summarized by assigned treatment 
group. This summary will include the number and percentage of participants with medical 
history for each body system/organ class as documented in the eCRF. 


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6.2. 
Disposition of Participant 
The number of participants enrolled by country and/or site will be summarized for the ITT 
population by treatment group and overall. 
The following will be summarized by treatment group and overall for the ITT population in the 
PC period: 
• Number (%) of participants who were randomized 
• Number (%) of participants who were treated in the PC period 
• Number (%) of participants who completed treatment in the PC period through 
Week 24 
• Number (%) of participants who discontinued study treatment in the PC period with a 
primary reason for discontinuation 
• Number (%) of participants who withdrew from the study in the PC period with a 
primary reason for withdrawal 
The following will be summarized by treatment group and overall for the extension evaluable 
population in the extension period: 
• Number (%) of participants who were treated in the extension period 
• Number (%) of participants who completed treatment in the extension period 
• Number (%) of participants who discontinued study treatment in the extension period 
with a primary reason for discontinuation 
• Number (%) of participants who completed the study 
• Number (%) of participants who withdrew from the study in the extension period 
with a primary reason for withdrawal 
6.3. 
Protocol Deviations 
Protocol deviations recorded will be summarized by treatment group and overall, for the ITT 
population in the PC period and the extension evaluable population in the extension period, and 
listed. 
6.4. 
Exposure 
For participants in the safety population in the PC period, the extension evaluable population in 
the extension period, and those who took INCB054707 45 mg or 75 mg throughout study 
participation, study drug exposure will be summarized by treatment group descriptively as the 
following: 
• Duration of treatment with study drug (days): date of last dose of study drug in the 
specific period – date of first dose of study drug in the specific period + 1. 
The date of first and last doses of study drug in each period are defined in Table 3. 


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Table 3: 
Definition of First and Last Dose Date 
Treatment Period 
Treatment Group 
First Dose Date 
Last Dose Date 
PC period 
Placebo 
INCB054707 15 mg 
INCB054707 45 mg 
INCB054707 75 mg 
Date that the first dose of 
study drug was 
administered to the 
participants in the PC 
period 
Date that the last dose of 
study drug was 
administered to the 
participants in the PC 
period 
Extension period 
Placebo to INCB054707 75 mg 
INCB054707 15 mg to 75 mg 
INCB054707 45 mg 
INCB054707 75 mg 
Date that the first dose of 
study drug was 
administered to the 
participants in the extension 
period 
Date that the last dose of 
study drug was 
administered to the 
participants in the extension 
period 
Throughout study 
participation 
INCB054707 45 mg 
INCB054707 75 mg 
Date that the first dose of 
study drug was 
administered to the 
participants in the PC 
period 
Date that the last dose of 
study drug was 
administered to the 
participants throughout 
study participation 
In addition, for the safety population in the PC period and the extension evaluable population in 
the extension period, average daily dose of INCB054707 and total actual dose of INCB054707 
will be summarized by treatment group descriptively as follows: 
• Average daily dose of INCB054707 (mg/day): total actual INCB054707 dose taken 
in the specific period (mg) / [duration of treatment with INCB054707 in the specific 
period (days) – number of interrupted days with INCB054707 in the specific period]. 
• Total actual dose of INCB054707 taken (mg): (total number of tablets dispensed in 
the specific period – total number of tablets returned in the specific period) × 
15 (mg/tablet) × pT 
in which pT denotes the proportion of INCB054707 among the 5 tablets taken daily 
with pT = 0 (0/5) for the placebo group, 1/5 for the INCB054707 15 mg group, 3/5 for 
the INCB054707 45 mg group, and 1 (5/5) for the INCB054707 75 mg group. 
The total number of tablets dispensed and returned in each period is based on information 
entered in the Drug Accountability eCRF. If there is dispensed drug that has not been returned, 
the actual dose taken starting from the dispense date of the unreturned drug will be imputed by 
the dose taken as reported in the Compliance eCRF. 
6.5. 
Study Drug Compliance 
For participants in the safety population and the extension evaluable population, the overall 
compliance (%) for INCB054707/placebo will be calculated for all participants as follows: 
compliance (%) = 100 × [total dose actually taken in the specific period] / [total prescribed 
dose in the specific period]. 
The total prescribed dose in the specific period is defined as the sum of the doses prescribed by 
the investigator accounting for dose interruptions during the specific period, and will be 
calculated as: [duration of treatment with study drug in the specific period − number of days with 
dose interruptions in the specific period] × 5 (tablets/day). 


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The total dose actually taken in the specific period will be calculated as: total number of tablets 
dispensed in the specific period − total number of tablets returned in the specific period (see 
Section 6.4 for details on total number of tablets dispensed and returned). 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
For the ITT population in the PC period, both prior and concomitant medications will be 
summarized by treatment group and overall. For the extension evaluable population in the 
extension period, only concomitant medication will be summarized by treatment group and 
overall.  All summaries will be by WHO drug class and WHO drug preferred term. 
7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
General Considerations 
All by-visit analyses for the extension evaluable population will include the follow-up period if 
the data are available, unless otherwise specified. 
Unless otherwise stated, the strata identified in the randomization process will be used in all 
efficacy analyses. 


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Total body VASI (T-VASI) is calculated using a formula that includes contributions from all 
body regions (possible range: 0-100) as follows: 
VASI =
∑
[Hand Units] × [Residual Depigmentation]
all body sites
 
The body is divided into the following 6 separate and mutually exclusive sites: (1) head/neck, 
(2) hands, (3) upper extremities (excluding hands), (4) trunk, (5) lower extremities (excluding 
feet), and (6) feet. The percentage of vitiligo involvement is estimated in hand units (%BSA) by 
the same investigator during the entire course of the study. Hand unit is based on the participant's 
hand size. The investigator uses their hand to mimic the participant's hand size to evaluate 
%BSA vitiligo involvement. The degree of depigmentation for each body site is determined and 
estimated to the nearest of the following percentages: 0%, 10%, 25%, 50%, 75%, 90%, or 100%. 
The T-VASI is then derived by multiplying the values assessed for the vitiligo involvement by 
the percentage of affected skin for each body site and summing the values of all body sites 
together (Hamzavi et al 2004). 
The T-VASI50 is defined as at least 50% reduction from baseline in T-VASI. 
 
 


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7.3. 
Efficacy Hypotheses 
The primary hypothesis is that INCB054707 75 mg is superior to placebo at Week 24 in mean 
percent change from baseline in T-VASI in participants with vitiligo. Assuming μT is the mean 
percent change from baseline at Week 24 in T-VASI in the INCB054707 75 mg group and μC is 
the mean percent change from baseline at Week 24 in T-VASI in the placebo group, the primary 
hypotheses of the study are as follows: 
• H0 (null hypothesis): μT = μC 
• HA (alternative hypothesis): μT ≠ μC 
7.4. 
Analysis of the Primary Efficacy Parameter 
The primary efficacy endpoint is the percent change from baseline in T-VASI at Week 24. 
7.4.1. 
Primary Efficacy Analysis 
 
 
 
 
 
 


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7.4.2. 
Subgroup Analyses for Primary Endpoint 
A subgroup will be formed based on the following participant characteristics and baseline 
variables for those participants whose data are available: 
• Baseline T-BSA involvement (8.0%-20.0%, > 20.0%) 
The primary efficacy endpoint will be summarized using descriptive statistics based on the ITT 
population for the subgroups defined above. 
7.4.3. 
Sensitivity and Supportive Analyses for Primary Endpoint 
Not applicable. 
7.5. 
Analysis of the Secondary Efficacy Parameters 
The key secondary efficacy endpoint is proportion of participants who achieve T-VASI50 at 
Week 24. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
8.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the PC period and the 
extension evaluable population in the extension period unless otherwise specified. Summary 
tables may be replaced with listings when appropriate. For instance, an AE frequency table may 
be replaced with a listing if it only contains a few unique PTs reported on relatively few 
participants. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first dose of study drug until the end of the safety follow-up. 
A TEAE in the PC period is any AE with a start time after the first dose of study drug in the PC 
period and until the end of the safety follow-up, or prior to the first dose in the extension period 
for participants who entered in to the extension period. 
A TEAE in the extension period is any AE with a start time after the first dose of study drug in 
the extension period until the end of the safety follow-up. 
For participants who took INCB054707 45 mg or 75 mg throughout study participation, a TEAE 
is any AE with a start time after the first dose of study drug in the PC period until the end of the 
safety follow-up. 
Analysis of AEs (as discussed below) will be limited to TEAEs, but data listings will include all 
AEs regardless of their timing in relation to study drug administration. For purposes of analysis, 
all AEs will be considered TEAEs unless the AE can unequivocally be defined as not 
treatment-emergent. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the NCI CTCAE v5.0. The CTCAE reporting guidelines and grading details are available 
on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. In addition, serious TEAEs will also be tabulated. 
8.2.2. 
Adverse Event Summaries 
Adverse events will be summarized by treatment group and overall INCB054707 dose groups for 
the safety population in the PC period. For the extension evaluable population in the extension 


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period and for participants who took INCB054707 45 mg or 75 mg throughout study 
participation, AEs will be summarized by treatment group and overall. 
An overall summary of AEs will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any treatment-related TEAEs 
• Number (%) of participants who temporarily interrupted study treatment because of 
TEAEs 
• Number (%) of participants who permanently discontinued study treatment because 
of TEAEs 
• Number (%) of participants who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if 10 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by MedDRA SOC and PT 
• Summary of TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of TEAEs by MedDRA SOC, PT, and maximum severity 
• Summary of TEAEs by MedDRA SOC, PT, and CTCAE grade category 
• Summary of Grade 3 or higher TEAEs by MedDRA SOC and PT 
• Summary of Grade 3 or higher TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of serious TEAEs by MedDRA SOC and PT 
• Summary of serious TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of Grade 3 or higher treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related serious TEAEs by MedDRA SOC and PT 
• Summary of TEAEs with a fatal outcome by MedDRA SOC and PT 
• Summary of TEAEs leading to dose interruption by MedDRA SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by MedDRA SOC and 
PT 
• Summary of TEAEs requiring concomitant medications by MedDRA SOC and PT 


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8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
Laboratory values, change from baseline values, and percent change from baseline values will be 
summarized descriptively by visit, and non-numeric test values will be tabulated when necessary. 
Baseline will be determined according to Section 4.1.3. The last record before study drug 
administration in the highest priority will be considered the baseline record. For baseline 
laboratory candidates with the same date and time in the same priority category, additional rules 
may be provided after consultation with the medical monitor to delineate which value will be 
defined as baseline. 
8.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in SI 
units. All tests with numeric values will have a unique unit per test. Any laboratory test results 
and associated normal ranges from local laboratories will be converted to SI units. 
When there are multiple laboratory nonmissing values for a participant's particular test at a 
scheduled visit, central laboratory values have higher priority over local laboratory values. If a 
tie still exists, the laboratory value with the smallest laboratory sequence number will be used in 
by-visit summaries. In addition, box-and-whisker plots will be provided for creatine kinase, 
hemoglobin, hematocrit, platelet count, high sensitivity C-reactive protein, lymphocyte absolute 
count, neutrophil absolute count, white blood cell count, total cholesterol, HDL, LDL, and 
HDL/LDL ratio. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low (but never high), normal, high (but never 
low), and both low and high will be calculated for each test. This shift summary will be produced 
for each test. The denominator for the percentage calculation will use the number of participants 
in the baseline category (ie, low, high, normal, missing) as the denominator for the percentage in 
each of the categories during the study. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5. Shift tables will also be presented showing change in CTCAE grade from baseline to 
the worst grade postbaseline. Separate summaries for abnormally high and abnormally low 
laboratory values will be provided when the laboratory parameter has both high and low grading 
criteria. The denominator for the percentage calculation will be the number of participants in the 
baseline category. The number of participants who experienced worsening of laboratory 
abnormalities will be summarized by maximum severity. 
8.3.3. 
Potentially Clinically Important Laboratory Values 
Criteria for potentially clinically important laboratory values are listed in Table 6. 


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8.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including blood pressure, pulse, respiratory rate, and body temperature will be summarized 
descriptively. Baseline will be determined according to Section 4.1.3. 
Normal ranges for vital sign values are defined in Table 7. For participants exhibiting vital sign 
abnormalities, the abnormal values will be listed along with their assigned treatment group. Alert 
vital signs are defined as an absolute value outside the defined range and percentage change 
greater than 25%. Note that the definition of alert vital signs does not apply to body temperature. 
The abnormal values for participants exhibiting alert vital sign abnormalities will be listed. 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QT, QRS, and QTcF intervals will be obtained for each 
participant during the study. Values at each scheduled visit, change, and percentage change from 
baseline will be summarized for each ECG parameter. Baseline will be determined as the 
average of all nonmissing values before the first administration of INCB054707 or placebo. 
Normal ranges for ECG values are defined in Table 8. Electrocardiogram values will also be 
considered abnormal if the absolute percentage change from baseline is more than 25% (30% for 
QRS interval). Participants exhibiting ECG abnormalities will be listed with study visit and 
assigned treatment group. Abnormal values for participants with alert ECG values, defined as 
both the absolute value and the percentage change from baseline being outside normal ranges, 


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will be identified and listed. Outliers of QT and QTcF values, defined as absolute values 
> 450 milliseconds, > 500 milliseconds, or change from baseline > 30 milliseconds, will be 
summarized. 
9. 
INTERIM ANALYSES 
There are no planned, formal interim analyses for this study. An external DMC will be charged 
with evaluating interim safety results. The sponsor will remain blinded, and DMC decisions will 
be communicated through sponsor management as dictated in the DMC charter. Additional 
operational details of the interim analyses, including tables, figures, and listings provided to the 
DMC, will be documented in the DMC charter. Additional safety analyses may be performed at 
the discretion of the DMC chair. 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 9. 
Table 9: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
25 APR 2022 
10.1. 
Changes to Protocol-Defined Analyses 
 
 
 
 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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11. 
REFERENCES 
 
 
 
 
 
 
 
 
 
 
 
 
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med 2009;28:586-604. 
 
 
Food and Drug Administration. Guidance for Industry: Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation. 2009. 
Hamzavi I, Jain H, McLean D, Shapiro J, Zeng H, Lui H. Parametric modeling of narrowband 
UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. 
Arch Dermatol 2004;140:677-683. 
 
 
 
Mehta CR, Patel NR. Exact logistic regression: theory and examples. Stat Med 1995;14:2143-
2160. 
 
 
 
 
 
 
 
 
 
 


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Figures 


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