Clinical trial NCT04896385
Conditions: Vitiligo
Keywords: Vitiligo depigmenting disorder topical JAK inhibitor
Sponsor: Incyte Corporation
Start date: 2021-06-23; Completion date: 2023-07-10
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of the study is to evaluate the Mechanism Of Action (MOA) of ruxolitinib cream in vitiligo by assessing the change in biomarkers.

Detailed description:

Arms: arm 1: Ruxolitinib cream will be administered twice a day (BID) for 24 weeks arm 2: Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.
Interventions: intervention 1: Ruxolitinib cream intervention 2: Vehicle Cream
Intervention descriptions: intervention 1: Ruxolitinib cream is a topical formulation applied as a thin film to affected areas. intervention 2: Vehicle cream is matching in appearance to ruxolitinib cream and is to be applied in the same manner as ruxolitinib cream.

Protocol documents:
Prot_000.pdf: 
Official Title:          A Randomized, Double-Blind, Vehicle-Controlled Study 
to Evaluate the Mechanism of Action of Ruxolitinib Cream for 
Vitiligo (TRuE-V MOA)
NCT Number:          NCT04896385 
Document Date: 
Original Protocol: 03-March-2021 


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Protocol INCB 18424-214 
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Clinical Study Protocol 
TITLE PAGE 
INCB 18424-214 
A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the 
Mechanism of Action of Ruxolitinib Cream for Vitiligo 
(TRuE-V MOA) 
Product: 
Ruxolitinib Cream 
IND Number: 
 
EudraCT Number: 
2021-000361-32 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
03 MAR 2021 
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 18424-214 Protocol (dated 03 MAR 2021) 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 ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
2. 
INTRODUCTION ......................................................................................................17 
2.1. 
Background .................................................................................................................17 
2.2. 
Study Rationale ...........................................................................................................18 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Dose ..................................................................................................19 
2.3. 
Benefit/Risk Assessment ............................................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................21 
4. 
STUDY DESIGN .......................................................................................................22 
4.1. 
Overall Design ............................................................................................................22 
4.2. 
Overall Study Duration ...............................................................................................22 
4.3. 
Study Termination ......................................................................................................23 
5. 
STUDY POPULATION .............................................................................................23 
5.1. 
Inclusion Criteria ........................................................................................................23 
5.2. 
Exclusion Criteria .......................................................................................................24 
5.3. 
Lifestyle Considerations .............................................................................................26 
5.4. 
Screen Failures ............................................................................................................26 
5.5. 
Replacement of Participants .......................................................................................26 
6. 
STUDY TREATMENT ..............................................................................................27 
6.1. 
Study Treatments Administered .................................................................................27 
6.1.1. 
Application During the Double-Blind, Vehicle-Controlled Treatment Period ..........28 
6.1.2. 
Application During the Open-Label Treatment Extension Period .............................28 
6.2. 
Preparation, Handling, and Accountability ................................................................29 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................30 
6.4. 
Study Treatment Compliance .....................................................................................30 
6.5. 
Dose Modifications .....................................................................................................30 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................30 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................31 
6.6. 
Concomitant Medications and Procedures .................................................................32 
6.6.1. 
Permitted Medications and Procedures ......................................................................32 
6.6.2. 
Restricted Medications and Procedures ......................................................................32 
6.6.3. 
Prohibited Medications and Procedures .....................................................................33 
6.7. 
Treatment After the End of the Study .........................................................................33 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................34 
7.1. 
Discontinuation of Study Treatment ...........................................................................34 
7.1.1. 
Reasons for Discontinuation .......................................................................................34 
7.1.2. 
Discontinuation Procedures ........................................................................................34 
7.2. 
Participant Withdrawal From the Study .....................................................................35 
7.3. 
Lost to Follow-Up.......................................................................................................35 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................36 
8.1. 
Administrative and General Procedures .....................................................................36 
8.1.1. 
Informed Consent Process ..........................................................................................36 
8.1.2. 
Screening Procedures ..................................................................................................37 
8.1.3. 
Interactive Response Technology Procedure ..............................................................37 
8.1.4. 
Distribution of Reminder Cards and Diaries ..............................................................37 
8.1.5. 
Demography and Medical History ..............................................................................38 
8.1.5.1. 
Demographics and General Medical History .............................................................38 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................38 
 
38 
 
38 
 
.38 
 
38 
8.3. 
Safety Assessments .....................................................................................................39 
8.3.1. 
Adverse Events ...........................................................................................................39 
8.3.2. 
Physical Examinations ................................................................................................40 
8.3.3. 
Vital Signs ..................................................................................................................40 
8.3.4. 
Electrocardiograms .....................................................................................................40 
8.3.5. 
Laboratory Assessments .............................................................................................41 
8.3.5.1. 
Pregnancy Testing ......................................................................................................42 


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8.3.5.2. 
Serology ......................................................................................................................42 
8.4. 
42 
8.5. 
Pharmacodynamic and Translational Assessments ....................................................42 
8.5.1. 
Skin Biopsy .................................................................................................................43 
8.5.2. 
43 
8.5.3. 
Immunohistology and Other Imaging Techniques .....................................................44 
8.6. 
Unscheduled Visits .....................................................................................................44 
8.7. 
End of Treatment and/or Early Termination ..............................................................44 
8.8. 
Safety Follow-Up ........................................................................................................44 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................45 
9.1. 
Definition of Adverse Event .......................................................................................45 
9.2. 
Definition of Serious Adverse Event ..........................................................................46 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........47 
9.4. 
Reporting of Serious Adverse Events .........................................................................49 
9.5. 
Events of Clinical Interest ..........................................................................................50 
9.5.1. 
Adverse Events of Special Interest .............................................................................50 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................50 
9.7. 
Pregnancy ...................................................................................................................51 
9.8. 
Warnings and Precautions ..........................................................................................51 
9.9. 
Product Complaints ....................................................................................................51 
9.10. 
Treatment of Overdose ...............................................................................................52 
10. 
STATISTICS ..............................................................................................................52 
10.1. 
Sample Size Determination ........................................................................................52 
10.2. 
Populations for Analysis .............................................................................................52 
10.3. 
Level of Significance ..................................................................................................53 
10.4. 
Data Handling Definitions and Conventions ..............................................................53 
10.4.1. 
Day 1 ...........................................................................................................................53 
10.4.2. 
Study Day ...................................................................................................................53 
10.4.3. 
Baseline Value ............................................................................................................53 
10.4.4. 
Handling of Missing and Incomplete Data .................................................................53 
10.5. 
Statistical Analyses .....................................................................................................53 


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10.5.1. 
Baseline, Demographics, Disease History, and Prior and Concomitant 
Medication ..................................................................................................................53 
10.5.2. 
Disposition of Participants ..........................................................................................53 
10.5.3. 
Exposure and Study Drug Compliance .......................................................................54 
 
54 
10.5.5. 
Safety Analysis ...........................................................................................................54 
10.5.6. 
Translational Analyses ................................................................................................55 
 
55 
10.6. 
Interim Analysis ..........................................................................................................55 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................55 
11.1. 
Investigator Responsibilities .......................................................................................55 
11.2. 
Data Management .......................................................................................................56 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................58 
11.4. 
Financial Disclosure ...................................................................................................58 
11.5. 
Publication Policy .......................................................................................................59 
11.6. 
Study and Site Closure................................................................................................59 
12. 
REFERENCES ...........................................................................................................60 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................61 
APPENDIX B. WHO CLASSIFICATION OF TOPICAL CORTICOSTEROIDS ...................62 
APPENDIX C. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................63 
APPENDIX D. PROTOCOL AMENDMENT SUMMARY OF CHANGES ...........................65 
 
LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................10 
Table 2: 
Key Study Design Elements .......................................................................................10 
Table 3: 
Schedule of Activities:  Double-Blind, Vehicle-Controlled Treatment Period 
(Day 1 to Week 24) .....................................................................................................12 
Table 4: 
Schedule of Activities:  Open-Label Treatment Extension (Week 28 to 
Week 52) .....................................................................................................................15 
Table 5: 
Objectives and Endpoints ...........................................................................................21 
Table 6: 
Study Treatment Information .....................................................................................27 


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Table 7: 
Guidelines for Interruption and Restarting of Study Drug .........................................31 
Table 8: 
Required Laboratory Analytes ....................................................................................41 
Table 9: 
Populations for Analysis .............................................................................................52 
Table 10: Safety Analyses ..........................................................................................................54 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................11 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
COVID-19 
coronavirus disease 2019 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXCL 
C-X-C motif chemokine ligand 
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 
F-BSA 
facial body surface area 
F-VASI 
facial Vitiligo Area Scoring Index 
F-VASI50/75 
50%/75% improvement in facial Vitiligo Area Scoring Index 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IB 
Investigator's Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification 
IEC 
independent ethics committee 


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Abbreviations and 
Special Terms 
Definition 
IFN-γ 
interferon gamma 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent to treat 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOA 
mechanism of action 
PBMC 
peripheral blood mononuclear cell 
 
 
QD 
once daily 
RNA 
ribonucleic acid 
RNAseq 
ribonucleic acid sequencing 
RSI 
reference safety information 
SAE 
serious adverse event 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SPF 
sun protection factor 
T4 
thyroxine 
T-BSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
TSH 
thyroid-stimulating hormone 
T-VASI 
total body Vitiligo Area Scoring Index 
T-VASI50/75 
50%/75% improvement in total body Vitiligo Area Scoring Index 
ULN 
upper limit of normal 
UV 
ultraviolet 
VASI 
Vitiligo Area Scoring Index 
WHO 
World Health Organization 
 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the 
Mechanism of Action of Ruxolitinib Cream for Vitiligo (TRuE-V MOA) 
Protocol Number:  INCB 18424-214 
Objectives and Endpoints: 
Table 1 presents the primary and secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the change in immune biomarkers in 
participants with vitiligo. 
• Percentage change from baseline in immune 
biomarkers, including CXCL10, at Week 4, Week 12, 
and Week 24. 
Secondary 
• To correlate the change in key serum and skin 
biomarkers of vitiligo to efficacy. 
• Correlation of key skin inflammatory biomarkers of 
vitiligo in target lesions to efficacy readouts at 
Week 12 and Week 24. 
• To assess the safety and local tolerability of 
ruxolitinib cream. 
• The frequency and severity of AEs. 
Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table. 
Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of patients with vitiligo 
Population 
Male and female participants aged ≥ 18 years of age who have nonsegmental vitiligo 
with depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA 
on nonfacial areas, and ≥ 3 T-VASI.  Total body vitiligo area (facial and nonfacial) 
should not exceed 50% BSA. 
Number of 
Participants 
Approximately 60 participants will be randomized 2:1 (ruxolitinib cream 1.5% 
BID:vehicle BID). 
Study Design 
Randomized, double-blind, vehicle-controlled, with an open-label treatment extension. 
Estimated Duration 
of Study 
Participation 
Screening:  Up to 42 days. 
Double-blind period:  24 weeks. 
Open-label period:  28 weeks. 
Safety follow-up:  30 days after last application of study drug or last study visit. 
Total:  Up to approximately 63 weeks. 
DSMB 
No 
Coordinating 
Principal 
Investigator 
To be determined 


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Treatment Groups and Duration: 
This is a randomized, double-blind, vehicle-controlled study with an open-label treatment 
extension period in adult participants (age ≥ 18 years) with nonsegmental vitiligo who have 
depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial 
areas, and ≥ 3 T-VASI.  Total body involved vitiligo area (facial and nonfacial) should not 
exceed 50% BSA.  Approximately 60 participants will be randomized 2:1 to receive initial 
double-blind study treatment (ruxolitinib cream 1.5%:vehicle) administered BID for 24 weeks 
(see Figure 1).  Participants will be stratified by age (≤ 40 years old and > 40 years old).  During 
the double-blind treatment period, the participant's randomized treatment will be applied to 
depigmented areas on the face and body up to 20% T-BSA (facial and nonfacial). 
After completion of the Week 24 assessments from the double-blind treatment period, eligible 
participants will be offered the opportunity to continue the study in the 28-week open-label 
treatment extension period in which all participants will receive open-label ruxolitinib cream 
1.5%, administered BID.  To be eligible for the open-label treatment extension period, 
participants must have completed the baseline and Week 24 visit assessments, be compliant with 
study procedures, and not have any safety issues.  The total treated area in the open-label 
treatment extension period should not exceed 20% BSA (facial and nonfacial). 
Figure 1 presents the study design schema.  The SoA is detailed in Table 3 (for the double-blind 
treatment period) and Table 4 (for the open-label treatment extension period).  Adherence to the 
study design requirements, including those specified in the SoA, is essential and required for 
study conduct. 
Figure 1: 
Study Design Schema 
 
 
 


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Table 3: 
Schedule of Activities:  Double-Blind, Vehicle-Controlled Treatment Period (Day 1 to Week 24) 
Procedure 
Screening 
Double-Blind, Vehicle-Controlled Treatment 
Notes 
Days 
−42 to −1 
Day 1 
(Baseline) 
Wk 4 
(± 3 d) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 18 
(± 7 d) 
Wk 24a 
(EOT1) 
(± 7 d) 
Administrative procedures 
 
Informed consent 
X 
 
 
 
 
 
 
 
Contact IRT 
X* 
X 
X 
X 
X 
X 
X 
*Entry of age into the IRT will be required at screening. 
Inclusion and exclusion 
criteria 
X 
X 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
General and disease medical 
history 
X 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
 
Application of study drug at 
site 
 
X 
X 
X 
X 
X 
X* 
At each study visit, starting at Day 1, the participant 
should apply the study drug under direct supervision of the 
site staff.  
*At the Week 24 visit, study drug is only applied by 
participants continuing in the open-label treatment 
extension period.  
Dispense (D) and return (R) 
study drug and 
reminder/diary cards 
 
D 
R/D 
R/D 
R/D 
R/D 
R/D* 
All tubes of study drug will be weighed before being 
dispensed.  All returned tubes of study drug will be 
weighed. 
*At the Week 24 visit, study drug and diary cards are only 
dispensed to participants continuing in the open-label 
treatment extension period. 
Collect study drug and 
collect/review study drug 
diary cards 
 
 
X 
X 
X 
X 
X 
 
Assess compliance 
 
 
X 
X 
X 
X 
X 
 


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Table 3: 
Schedule of Activities:  Double-Blind, Vehicle-Controlled Treatment Period (Day 1 to Week 24) (Continued) 
Procedure 
Screening 
Double-Blind, Vehicle-Controlled Treatment 
Notes 
Days 
−42 to −1 
Day 1 
(Baseline) 
Wk 4 
(± 3 d) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 18 
(± 7 d) 
Wk 24a 
(EOT1) 
(± 7 d) 
Safety assessments 
 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
 
Comprehensive physical 
examination 
X 
 
 
 
 
 
X 
 
Targeted physical 
examination 
 
X 
X 
X 
X 
X 
 
See Section 8.3.2. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECG 
X 
 
 
 
 
 
 
12-Lead ECG performed within 2 months before baseline 
is acceptable. 
 
Laboratory assessments 
 
Hematology and chemistry 
assessments 
X 
X 
X 
X 
X 
X 
X 
 
Serology 
X 
 
 
 
 
 
 
Serology includes hepatitis and HIV assessments. 
Thyroid testing 
X 
 
 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
FSH 
X* 
 
 
 
 
 
 
*FSH is only measured for confirmation of nonchildbearing 
status of women who are postmenopausal, defined as having 
amenorrhea for at least 12 months without an alternative 
medical cause before screening.  
Pregnancy testing 
X* 
X 
X 
X 
X 
X 
X 
*Female participants of childbearing potential will have a 
serum test at the screening and safety follow-up visits.  A 
urine test will be conducted at all other visits.  A positive 
urine test must be confirmed by a serum test. 


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Table 3: 
Schedule of Activities:  Double-Blind, Vehicle-Controlled Treatment Period (Day 1 to Week 24) (Continued) 
Procedure 
Screening 
Double-Blind, Vehicle-Controlled Treatment 
Notes 
Days 
−42 to −1 
Day 1 
(Baseline) 
Wk 4 
(± 3 d) 
Wk 8 
(± 3 d) 
Wk 12 
(± 3 d) 
Wk 18 
(± 7 d) 
Wk 24a 
(EOT1) 
(± 7 d) 
 translational assessments 
 
Serum biomarker sampling 
 
X 
X 
 
X 
 
X 
 
Skin biopsy:  lesional vitiligo 
skin (identified at baseline 
[Day 1])  
 
X 
 
 
X 
 
X 
For lesional skin, 
 per timepoint will be taken 
from the inside edge of an active vitiligo lesion, and the 
sampling area should be entirely contained within lesional 
skin. 
See Section 8.5.1.  
Skin biopsy:  nonlesional 
 
X 
 
 
 
 
 
For nonlesional skin, 
 will be taken at baseline 
(Day 1) from uninvolved skin adjacent to the lesional area 
selected for biopsy. 
Note:  Unscheduled visits may occur at any time at the investigator's discretion, and appropriate clinical and laboratory tests may be performed, as clinically indicated. 
a Week 24 is considered the first visit of the open-label period. 
 
 


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Table 4: 
Schedule of Activities:  Open-Label Treatment Extension (Week 28 to Week 52) 
Procedure 
Open-Label Treatment Extension 
Safety Follow-Up 
Notes 
Wk 28 
(± 7 d) 
Wk 40 
(± 7 d) 
Wk 52 
(EOT2a) 
(± 7 d) 
30 Days After 
EOT1/EOT2b 
(EOS) 
(+ 7 d) 
Administrative procedures 
 
Contact IRT 
X 
X 
X 
X 
 
Prior/concomitant medications  
X 
X 
X 
X 
 
Application of study drug at site 
X 
X 
 
 
At each study visit, the participant should apply the study drug under direct 
supervision of the site staff. 
Dispense (D) and return (R) study 
drug and reminder/diary cards 
R/D 
R/D 
R 
 
All tubes of study drug will be weighed before being dispensed.  All 
returned tubes of study drug will be weighed. 
Collect study drug and collect/ 
review study drug diary cards 
X 
X 
X 
 
 
Assess compliance 
X 
X 
X 
 
 
Safety assessments 
 
AE assessment 
X 
X 
X 
X 
 
Comprehensive physical 
examination 
 
 
X 
 
 
Targeted physical examination 
X 
X 
 
X 
See Section 8.3.2. 
Vital signs 
X 
X 
X 
X 
 
 
Laboratory assessments 
 
Hematology and chemistry 
assessments 
X 
X 
X 
X 
 
Pregnancy testing 
X 
X 
X 
X* 
*Female participants of childbearing potential will have a serum test at the 
screening and safety follow-up visits.  A urine test will be conducted at all 
other visits.  A positive urine test must be confirmed by a serum test. 
 translational assessments 


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Table 4: 
Schedule of Activities:  Open-Label Treatment Extension (Week 28 to Week 52) (Continued) 
Procedure 
Open-Label Treatment Extension 
Safety Follow-Up 
Notes 
Wk 28 
(± 7 d) 
Wk 40 
(± 7 d) 
Wk 52 
(EOT2a) 
(± 7 d) 
30 Days After 
EOT1/EOT2b 
(EOS) 
(+ 7 d) 
 translational assessments (continued) 
Serum biomarker sampling 
 
X 
X* 
 
*Only for participants who stop treatment before Week 52 and do not 
complete the Week 40 visit. 
Skin biopsy:  lesional vitiligo 
skin (identified at baseline 
[Day 1]) 
 
X 
X* 
 
For lesional skin, 
 per timepoint will be taken from the inside 
edge of an active vitiligo lesion, and the sampling area should be entirely 
contained within lesional skin. 
See Section 8.5.1. 
*Only for participants who stop treatment before Week 52 and do not 
complete the Week 40 visit.  
Note:  Unscheduled visits may occur at any time at the investigator's discretion, and appropriate clinical and laboratory tests may be performed, as clinically indicated. 
a EOT2 assessments should be performed in the event a participant's treatment is stopped before Week 52 at any relevant study visit before that time. 
b After last application of study drug or last visit. 
 
 


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2. 
INTRODUCTION 
2.1. 
Background 
Ruxolitinib cream is a topical formulation of ruxolitinib phosphate under development for the 
treatment of patients with atopic dermatitis, alopecia areata, plaque psoriasis, and vitiligo.  
Ruxolitinib phosphate is an inhibitor of the JAK family of protein tyrosine kinases.  
Inflammatory cytokines are strongly implicated in the pathogenesis of several dermatologic 
diseases.  Because JAKs serve to translate extracellular signals from a number of relevant 
cytokines and growth factors upregulated in inflammatory diseases such as atopic dermatitis, 
alopecia areata, plaque psoriasis, and vitiligo, JAK inhibitors represent potential therapeutic 
agents for these disease states (Howell et al 2019). 
Nonclinical pharmacology, PK, pharmacodynamic, and toxicology data for ruxolitinib cream 
from in vitro and in vivo model systems support the use of topically applied ruxolitinib cream in 
the treatment of patients with atopic dermatitis, psoriasis, vitiligo, and other inflammatory 
diseases of the skin.  Refer to the ruxolitinib cream IB for a summary of findings from the 
nonclinical studies. 
Vitiligo is an autoimmune disease that is characterized by areas of depigmented skin; it affects 
up to 2% of the global population and is associated with a significantly reduced quality of life 
(Krüger and Schallreuter 2012).  Currently, there are no US FDA-approved treatments for 
vitiligo, and most treatment paradigms rely on the use of corticosteroids, narrowband UV light, 
off-label treatments, or combination therapy; these treatments produce unpredictable and 
inconsistent results and are frequently cosmetically unacceptable to the patient.  A treatment that 
produces predictable results and that can be applied by the patient is an area of high unmet need 
for patients with vitiligo. 
The skin of patients with vitiligo is characterized by depigmented patches that result from the 
infiltration of affected areas with activated antigen-specific CD8+ T cells that drive melanocyte 
death and disease pathogenesis (Taïeb and Picardo 2009, van den Boorn et al 2009).  
Recruitment of autoreactive CD8+ T cells to melanocytes is mediated by IFN-γ through the 
IFN-γ–induced chemokines CXCL9 and CXCL10, a signaling pathway regulated by JAK1 and 
JAK2 (Harris et al 2012, Rashighi et al 2014, Rashighi and Harris 2015).  The interruption of 
IFN-γ signaling via the JAK pathway represents an important therapeutic strategy to evaluate in 
the treatment of vitiligo (Dina et al 2019).  In a recent randomized, double-blind, placebo-
controlled Phase 2 study (INCB 18424-211; NCT03099304), ruxolitinib cream, a topical JAK1/2 
inhibitor, demonstrated efficacy in patients with vitiligo (Rosmarin et al 2020; see also 
Section 2.2.2 for a brief summary of findings from this study).  The specific impacts of 
ruxolitinib cream on the biology of melanocytes were not evaluated in this study, but the findings 
warrant an evaluation of the effects of ruxolitinib cream on melanocytes and support continued 
clinical development of ruxolitinib cream for the treatment of patients with vitiligo. 
Safety findings from this Phase 2 study and 2 ongoing Phase 3 studies (INCB 18424-306 and 
INCB 18424-307) in participants with vitiligo also support continued development of ruxolitinib 
cream for the treatment of patients with this condition.  As of the cutoff date for the ruxolitinib 
cream IB (Edition 9), a total of 203 participants with vitiligo have received ruxolitinib cream.  


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Safety findings across the 3 vitiligo studies showed that the majority of participants had good 
local tolerability with use of ruxolitinib cream, there were few application site reactions (all 
Grade 1 or 2), and all SAEs were reported in 1 participant each (ie, there were no patterns of 
SAEs). 
Refer to the ruxolitinib cream IB for a summary of available clinical efficacy and safety data 
from the vitiligo studies as well as safety data from ruxolitinib cream clinical studies conducted 
in other disease states. 
2.2. 
Study Rationale 
Three studies have been previously initiated to evaluate the safety and efficacy of ruxolitinib 
cream in patients with vitiligo:  Phase 2 study INCB 18424-211, ongoing Phase 3 study 
INCB 18424-306 (TRuE-V1), and ongoing Phase 3 study INCB 18424-307 (TRuE-V2); 
 
.  The purpose of the present study is to provide a more comprehensive evaluation 
than has been undertaken in the previously initiated studies of the MOA of ruxolitinib cream in 
vitiligo. 
2.2.1. 
Scientific Rationale for Study Design 
Janus kinases are intracellular signaling enzymes that act downstream of key proinflammatory 
cytokines implicated in the pathogenesis of vitiligo.  The safety and efficacy of topical cream 
containing ruxolitinib, a JAK inhibitor, was evaluated in a randomized, double-blind, 
vehicle-controlled Phase 2 study conducted in adults with vitiligo; the study has completed.  
Findings from the Phase 2 study demonstrated that treatment with ruxolitinib cream was 
associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all 
doses were well-tolerated (Rosmarin et al 2020).  The Phase 2 data suggest that JAK inhibition is 
an effective therapeutic strategy to treat patients with vitiligo.  Two identical Phase 3 studies 
were initiated to confirm the Phase 2 findings in a larger patient population and are ongoing. 
The objectives of the current Phase 2 MOA study are to collect data that will contribute to the 
understanding of immune biomarkers of vitiligo and to further confirm the safety and efficacy of 
ruxolitinib cream in patients with vitiligo.  Skin biopsies, serum, and PBMCs will be collected 
over time to further understand the effect of ruxolitinib cream 
 
 and to assess various biomarkers of inflammation. 
The population to be studied comprises adults (≥ 18 years of age) with nonsegmental vitiligo 
who have depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on 
nonfacial areas, and ≥ 3 T-VASI.  Total body involved vitiligo area (facial and nonfacial) should 
not exceed 50% BSA.   
Participants enrolled in this study will be randomized 2:1 to receive ruxolitinib cream 1.5% BID 
or vehicle BID and treated for 24 weeks in a double-blinded fashion.  After 24 weeks, 
participants originally randomized to vehicle will switch to active treatment with ruxolitinib 
cream.  
 
  Additionally, it is deemed unethical and impractical to deprive patients of 


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effective management of their skin disease for periods extending beyond a maximum of 
6 months.  In the Phase 2 study, up to 56.7% of the population was classified as having 
progressive disease, and long vehicle-controlled periods may have resulted in extension of their 
disease.  The vast majority of clinical studies in chronic nonfatal skin diseases do not use a 
placebo/vehicle arm for longer than 16 weeks.  The proposed 24 weeks is thus a compromise 
between the longest acceptable duration of no active treatment (vehicle) and the minimum time 
required to observe a meaningful clinical response to treatment (repigmentation).  Additionally, 
the 2:1 (versus a 1:1) randomization allows more of the study population to receive active 
treatment for the full duration of the study. 
The 28-week open-label period is designed to allow participants initially randomized to vehicle 
treatment to receive active drug and to further evaluate the 
 safety of ruxolitinib 
cream 1.5% BID treatment. 
 
 
 
 
 
 
 
 
 
  
 
 
 
2.2.2. 
Justification for Dose 
The dose that will be investigated in the current study is ruxolitinib cream 1.5% BID.  This is the 
dose that was selected for evaluation in the Phase 3 vitiligo studies based on findings from the 
completed Phase 2 study (INCB 18424-211) conducted in adults with vitiligo, which evaluated 
4 dose strengths of ruxolitinib cream (1.5% BID, 1.5% QD, 0.5% QD, and 0.15% QD).  The 
safety and efficacy outcomes from the Phase 2 study can be summarized as follows: 
• All ruxolitinib cream treatment arms (1.5% BID, 1.5% QD, 0.5% QD, and 
0.15% QD) demonstrated efficacy and superiority over vehicle in F-VASI50 and 
F-VASI75 at Week 24, with a clear separation from vehicle emerging by Week 12. 
• At Week 24, 1.5% QD and BID treatment regimens further separated from the 0.15% 
and 0.5% treatment regimens, with the highest response at Week 24 in F-VASI50 
(50.0%) in the 1.5% QD regimen. 


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• The 1.5% BID treatment regimen demonstrated the highest response for F-VASI75 at 
both Week 24 (30.3%) and Week 52 (51.5%).  The T-VASI50 response in the 1.5% 
BID regimen was modest at Week 24 (12.1%); however, this regimen also 
demonstrated the highest response for T-VASI50 (36.4%) at Week 52, and it is 
recognized that repigmentation on nonfacial areas proceeds slower than on facial 
areas. 
• All ruxolitinib treatment arms were generally safe and well-tolerated with no 
significant TEAEs or application site events and no clinically relevant hematologic 
changes through Week 52. 
Based on the above data, the treatment regimen of ruxolitinib cream 1.5% BID was chosen for 
the current Phase 2 MOA study. 
2.3. 
Benefit/Risk Assessment 
In nonclinical studies, ruxolitinib cream did not act as a contact sensitizer and did not produce 
significant dermal irritation or demonstrate phototoxicity or photoallergic potential.  The lack of 
adverse cutaneous effects has been supported by clinical studies to date, where cutaneous AEs 
have been infrequent and of similar frequency and severity as with vehicle control treatment.  
Long-term immune suppression may occur with JAK inhibition, which could potentially increase 
the risk of cutaneous viral skin infections and nonmelanoma skin cancers.  Participants should be 
monitored accordingly. 
The primary clinical risks noted with orally administered ruxolitinib for the treatment of 
polycythemia vera or myelofibrosis are the potential sequelae of decreased hematopoietic 
proliferation secondary to the inhibition of growth factor pathways by JAK2 antagonism.  
Dose-dependent, reversible thrombocytopenia has been observed in participants with 
myelofibrosis, as well as anemia and less frequently neutropenia.  An increased rate of infection 
is an additional potential risk of immunomodulation.  In healthy participants and participants 
with rheumatoid arthritis with greater bone marrow reserve, the effects on hematopoietic 
proliferation appear to be less pronounced.  Owing to its low systemic bioavailability, topical 
ruxolitinib cream is not expected to bring about clinically significant changes in hematology 
laboratory investigations. 
Results from the Phase 2 study (INCB 18424-211) conducted in adults with vitiligo have been 
reported (Rosmarin et al 2020), and key findings from this study are summarized in 
Section 2.2.1.  Based on the Week 24 and Week 52 results, all active treatment groups were 
found to have no clinically relevant AEs related to the treatment regimens and were 
well-tolerated on application sites.  Safety findings from this study were also unremarkable for 
laboratory values, vital signs, or physical examinations.  While minor changes in select 
hematology parameters (red blood cells and platelet counts) were noted in the laboratory 
assessments, they were mostly within the limits of the normal range of values, transient, 
asymptomatic, and clinically insignificant and did not necessitate any remedial action. 
Currently, there are no approved therapies for vitiligo, and treatments are empirical and directed 
by the available clinical guidelines.  Current therapies often do not lead to satisfactory response, 
and there are limitations and safety concerns with long-term use of some therapies, including 


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topical or oral corticosteroids and calcineurin inhibitors.  Given the psychosocial burden and 
stigma that has been reported in this disease, patients with vitiligo warrant access to new studies. 
In summary, ruxolitinib cream 1.5% BID can be safely used as a topical medication for vitiligo 
and represents the treatment regimen with the best benefit-to-risk ratio from among those 
investigated. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ruxolitinib cream may be found in the IB. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 5 presents the objectives and endpoints. 
Table 5: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the change in immune biomarkers 
in participants with vitiligo. 
• Percentage change from baseline in immune 
biomarkers, including CXCL10, at Week 4, 
Week 12, and Week 24.  
Secondary 
• To correlate the change in key serum and skin 
biomarkers of vitiligo to efficacy. 
• Correlation of key skin inflammatory biomarkers 
of vitiligo in target lesions to efficacy readouts at 
Week 12 and Week 24. 
• To assess the safety and local tolerability of 
ruxolitinib cream. 
• The frequency and severity of AEs. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a randomized, double-blind, vehicle-controlled study with an open-label treatment 
extension period in adult participants (age ≥ 18 years) with nonsegmental vitiligo who have 
depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial 
areas, and ≥ 3 T-VASI.  Total body involved vitiligo area (facial and nonfacial) should not 
exceed 50% BSA.  Approximately 60 participants will be randomized 2:1 to receive initial 
double-blind study treatment (ruxolitinib cream 1.5%:vehicle BID) administered BID for 
24 weeks (see Figure 1).  Participants will be stratified by age (≤ 40 years old and > 40 years 
old).   
During the double-blind treatment period, participants will receive ruxolitinib cream 1.5% BID 
or vehicle BID for 24 weeks to be applied to depigmented areas on the face and body up to 20% 
T-BSA.  For participants with depigmentation on > 20% BSA, the investigator will discuss with 
the participant which areas of vitiligo to treat and will document the areas to be treated in the 
eCRF.  Only those areas identified for treatment at baseline should be treated during the 
double-blind period; participants should continue to treat depigmented areas identified for 
treatment at baseline even if the area begins to improve or fully repigment.  Refer to Section 6.1 
for full information on study drug administration and to Section 6.5 for information on dose 
modification and additional application guidance. 
After completion of the Week 24 assessments from the double-blind treatment period, eligible 
participants will be offered the opportunity to continue the study in the 28-week open-label 
treatment extension period.  Participants initially randomized to vehicle will be crossed over to 
active drug (ruxolitinib cream 1.5% BID), and participants initially randomized to ruxolitinib 
cream will continue to receive treatment with ruxolitinib cream 1.5% BID.  To be eligible for the 
open-label treatment extension period, participants must have completed the baseline and 
Week 24 visit assessments, be compliant with study procedures, and not have any safety issues.  
During the open-label treatment extension period, participants should continue to treat 
depigmented areas identified for treatment at baseline even if the area begins to improve or fully 
repigment; additionally, if any new areas of vitiligo have appeared since baseline, the new areas 
can be treated during the open-label treatment extension period.  The total treated area in the 
open-label treatment extension period should not exceed 20% BSA (facial and nonfacial). 
Safety endpoints, such as nature of AEs (type, frequency, and severity), vital signs, targeted 
physical examination, and routine laboratory investigations, will be monitored and recorded 
throughout the course of this study.  
 
  Samples for translational assessments (serum, PBMCs, and skin biopsies) will be 
collected from participants during the study.  Following the last application of ruxolitinib cream 
at Week 52, there will be a 30-day safety follow-up period. 
4.2. 
Overall Study Duration 
Screening is up to 42 days (~6 weeks); the double-blind, vehicle-controlled treatment period is 
24 weeks; the open-label treatment extension period is 28 weeks; and safety follow-up is 
30 days.  Total duration is up to approximately 63 weeks (see Figure 1). 


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The study will begin when the first participant (or legally authorized representative) 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 date that the last participant discontinued study drug and completed applicable safety 
follow-up assessments or is lost to follow-up. 
A participant is considered to have completed the study if he/she has completed all study visits, 
including the safety follow-up visit.  A study is considered completed when the last participant 
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 or if required by regulatory agency.  In the event 
of significant safety findings, the study will be terminated.  If the study is terminated 
prematurely, the sponsor or designee will notify the investigators, the IRBs/IECs, and 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. Age ≥ 18 years. 
2. A clinical diagnosis of nonsegmental vitiligo with depigmented areas including ≥ 0.5% 
BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, and ≥ 3 T-VASI; total 
body vitiligo area (facial and nonfacial) should not exceed 50% BSA. 
3. At least 1 active vitiligo lesion (eg, such as confetti lesion, trichrome appearance, pinkish 
rim, or other evidence of inflammatory activity) at the site for skin biopsy.  
4. Agree to discontinue all agents used to treat vitiligo from screening through the final 
safety follow-up visit.  Over-the-counter preparations deemed acceptable by the 
investigator and camouflage makeups are permitted. 


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5. Willingness to take appropriate contraceptive measures to avoid pregnancy or fathering a 
child for the duration of study participation with the exception of the following: 
a. Female participants of nonchildbearing potential (ie, surgically sterile with a 
hysterectomy and/or bilateral oophorectomy OR postmenopausal [≥ 12 months of 
amenorrhea without an alternative medical cause]). 
Note:  Information about specific types of acceptable contraceptive measures and 
duration of contraceptive use are provided in Appendix A. 
6. Ability to comprehend and willingness to sign an ICF. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. No pigmented hair within any of the vitiligo areas on the face. 
2. Other forms of vitiligo (eg, segmental) or other differential diagnosis of vitiligo or other 
skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory 
hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical 
leukoderma, and tinea versicolor). 
3. Used depigmentation treatments (eg, monobenzone) for past treatment of vitiligo or other 
pigmented areas. 
Note:  Prior use of hydroquinone is not prohibited (because it is a bleaching agent, not a 
depigmentation treatment). 
4. Concurrent conditions and history of other diseases: 
a. Any other skin disease that, in the opinion of the investigator, would interfere with 
the study medication application or study assessments. 
b. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chickenpox) within 1 week before baseline. 
c. Conditions at baseline that would interfere with evaluation of vitiligo. 
d. Any serious illness or medical, physical, or psychiatric condition(s) that, in the 
investigator's opinion, would 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.  Examples include 
but are not limited to the following: 
− Clinically significant or uncontrolled cardiac disease, including unstable angina, 
acute myocardial infarction within 6 months from Day 1 of study drug 
administration, New York Heart Association Class III or IV congestive heart 
failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood 
pressure > 150/90 mmHg) unless approved by the medical monitor/sponsor. 
− History of thrombosis, including deep venous thrombosis and pulmonary 
embolism. 
− Concurrent malignant disease or a history of that in the 5 years preceding the 
baseline visit except for adequately treated nonmetastatic malignancies. 


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− Current and/or history of liver disease, including known hepatitis B or C, with 
hepatic or biliary abnormalities. 
− Current and/or history of tuberculosis. 
− History of alcohol use disorder or drug addiction within 1 year before screening 
or current alcohol or drug use that, in the opinion of the investigator, will interfere 
with the participant's ability to comply with the administration schedule and study 
assessments. 
− Committed to an institution by virtue of an order issued either by the judicial or 
the administrative authorities. 
5. Use of any of the following treatments within the indicated washout period before 
baseline: 
a. 1 week:  Topical drugs when used on the vitiligo areas, for example, corticosteroids, 
calcineurin, and phosphodiesterase type 4 inhibitors or retinoids. 
b. 4 weeks: 
− Melanocyte-stimulating agents (eg, afamelanotide). 
− Immunomodulating systemic medications (eg, corticosteroids, methotrexate, 
cyclosporine). 
− Any other systemic therapies that could increase the skin sensitivity to UV/visible 
light or impact skin pigmentation, for example, tetracyclines, methoxypsoralens. 
− Received live vaccine. 
Note:  Live vaccine is prohibited during the course of the study and within 
4 weeks after the EOT visit. 
c. 8 weeks:  Laser or any kind of phototherapy, including tanning beds or intentional 
UV exposure. 
d. 5 half-lives or 12 weeks, whichever is longer:  biologic agents, investigational or 
experimental therapy, or procedures for vitiligo.  Investigational biologics should be 
discussed with the sponsor to determine whether a longer period of discontinuation is 
required. 
6. Previously received JAK inhibitors, systemic or topical. 
7. Investigator-determined clinically significant abnormal laboratory values at screening:  
a. Hemoglobin (< 10 g/dL).  
b. Liver function tests:  
− AST or ALT ≥ 2 × ULN. 
− Alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin 
> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%). 
c. Severe renal disease (with creatinine clearance < 30 mL/min) or renal disease 
requiring dialysis. 


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d. Clinically significant abnormal TSH or free T4 at screening as determined by the 
investigator. 
e. Positive serology test results at screening for HIV antibody. 
f. Hepatitis B virus or HCV infection:  Participants who are positive for hepatitis B 
surface antigen or hepatitis B core antibody will be eligible if they are negative for 
HBV DNA; these participants should be considered for prophylactic antiviral therapy.  
Participants who are positive for anti-HCV antibody will be eligible if they are 
negative for HCV-RNA. 
8. Body mass index < 17 or > 40 kg/m2. 
9. Pregnant or lactating, or considering pregnancy during the period of their study 
participation. 
10. In the opinion of the investigator are unable or unlikely to comply with the administration 
schedule and study evaluations.  
11. Employees of the sponsor or investigator or are otherwise dependents of them. 
12. Known allergy or reaction to any component of the study formulation. 
13. Live with anyone participating in any current Incyte-sponsored ruxolitinib cream study. 
5.3. 
Lifestyle Considerations 
Participants should be cautioned to avoid excessive exposure to artificial sunlight (including 
tanning beds, sun lamps, etc). 
If sunscreen, makeup, or other cosmetics have been applied to the areas to be treated, participants 
should follow the application guidance (see Section 6.6.1). 
It is recommended that swimming should not take place within 2 hours before and after the 
planned study drug application. 
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 treatment.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes that the 
participant would be eligible if retested.  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 or any laboratory abnormality is inconsistent with the participant's medical 
history.  Participants who rescreen must reconsent and be assigned a new screening number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 


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6. 
STUDY TREATMENT 
See Appendix C for COVID-19–related guidance. 
6.1. 
Study Treatments Administered 
Table 6 presents the study treatment information. 
Table 6: 
Study Treatment Information 
 
Ruxolitinib 
Vehicle 
Study treatment name: 
 
 
MOA: 
Inhibitor of the JAK family of 
protein tyrosine kinases 
Not applicable 
Dosage formulation: 
Cream 
Unit dose strength(s)/dosage 
level(s): 
1.5% 
Not applicable 
Route of administration: 
Topical 
Administration 
instructions: 
A thin film is applied BID to depigmented vitiligo areas on the face 
and body up to 20% T-BSA. 
Packaging and labeling: 
Ruxolitinib cream and vehicle cream will be provided in 60 g tubes.  
Each tube will be labeled as required per country requirement. 
Storage: 
Ambient (15°C-30°C/59°F-86°F) 
Status of treatment in 
participating countries: 
Investigational 
Not applicable 
The application of study drug will be limited to ≤ 20% of the participant's T-BSA, regardless of 
whether the participant has depigmentation on > 20% BSA.  For participants with 
depigmentation on > 20% BSA, the investigator will discuss with the participant at baseline 
(Day 1) which areas of vitiligo to treat, and the areas selected for treatment must include all areas 
in which skin biopsies will be performed.  The site should document the area to be treated in the 
eCRF. 
All tubes of study drug will be weighed before being dispensed.  All returned tubes of study drug 
will also be weighed. 
Study drug will be applied as a thin film BID, with applications at least 8 hours apart.  
Participants should remove study drug from the tube in fingertip units until all of the areas to be 
treated are covered by a thin film. 
Participants will be instructed to document treated areas and advised to limit use to no more than 
1 tube (60 g) per 3-4 days.  Application instructions will be provided by the site study staff, and 
the participants will record their daily applications via a diary card given to the participants 
during each study visit.  Refer to the Study Pharmacy Manual for participant instructions for 
handling of study drug. 


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On the day of a visit, the participant should not apply their morning dose of study drug at home; 
instead, study drug will be applied from a new kit in the clinic during the visit, under direct 
supervision of the site staff.  The tube will be weighed before and after application to determine 
the participant's dosage. 
At any time during the study, if vitiligo areas become significantly more extensive than from the 
previous visit, the participant should contact the study site to discuss with the investigator 
whether additional evaluation at the clinic is required.  If any other skin products that are 
permitted under the study Protocol are used, participants should continue these unchanged during 
the study. 
6.1.1. 
Application During the Double-Blind, Vehicle-Controlled Treatment Period 
During the double-blind, vehicle-controlled treatment period (up to Week 24), participants 
should follow the study drug application guidance below: 
• Participants should apply study drug only to depigmented vitiligo areas identified by 
the investigators at baseline (Day 1) up to a T-BSA (facial and nonfacial) of ≤ 20%. 
• Participants should continue to treat all depigmented vitiligo areas identified for 
treatment at baseline even if the area begins to improve or fully repigment. 
• Participants who have an expansion of existing areas of vitiligo during the course of 
the double-blind period may treat these areas after a visit to document the VASI and 
other measures of vitiligo (may be an unscheduled visit), as long as the new treated 
T-BSA (facial and nonfacial) does not exceed 20% BSA. 
• Participants who develop new vitiligo lesions during the course of the double-blind 
period should not treat these areas during the double-blind period.  Newly developing 
vitiligo lesions should be documented in the eCRF, and the VASI for these new 
lesions should not be calculated and combined together with the area(s) to be treated 
identified at baseline. 
6.1.2. 
Application During the Open-Label Treatment Extension Period 
During the open-label treatment extension period (after Week 24), participants should follow the 
study drug application guidance below: 
• Participants should apply study drug to depigmented vitiligo areas identified by the 
investigators at baseline (Day 1) up to a T-BSA (facial and nonfacial) of ≤ 20%. 
• Participants should continue to treat all depigmented vitiligo areas identified for 
treatment at baseline even if the area begins to improve or fully repigment. 
• Participants who have an expansion of existing areas of vitiligo during the course of 
the open-label period may treat these areas after a visit to document the VASI and 
other measures of vitiligo (may be an unscheduled visit), as long as the new treated 
T-BSA (facial and nonfacial) does not exceed 20% BSA. 


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• Participants who develop new vitiligo lesions during the course of study may treat 
these areas during the open-label period after a visit to document the VASI and other 
measures of vitiligo (may be an unscheduled visit), as long as the new treated T-BSA 
(facial and nonfacial) does not exceed 20% BSA.  Newly developing vitiligo lesions 
should be documented in the eCRF and the VASI for these new lesions should not be 
calculated and combined together with the area(s) to be treated identified at baseline.  
6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm and document that appropriate temperature conditions 
(both ruxolitinib cream and vehicle cream are to be stored between 15°C and 30°C [59°F-86°F]) 
have been maintained during transit for all study drugs received and any discrepancies are 
reported and resolved before use of the study drug. 
Only participants enrolled in the study may receive study drug, and only authorized site staff 
may supply study drug.  Immediately after application of study drug, participants are to wash 
their hands thoroughly with soap and warm water (unless the area to be treated includes the 
hands).  Refer to the Study Pharmacy Manual for participant instructions for handling of study 
drug. 
All study drug 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.  Participants should store study drug at ambient 
temperature conditions. 
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 drugs to the study site. 
• Inventory of study drugs at the site. 
• Participant use of the study drugs, including tube counts from each supply dispensed. 
• Return of study drugs to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  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 


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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 drugs is included in 
the study materials provided to sites. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT system.  The system 
will assign study treatment in a 2:1 ratio (ruxolitinib cream 1.5% BID:vehicle BID), stratified by 
age (≤ 40 years old and > 40 years old).  The IRT will assign participant ID numbers, track 
participant visits, randomize participants according to the defined parameters, maintain the 
blinding, and manage study drug inventory.  Full details will be provided in the IRT Manual.  
Study treatment will be dispensed at the study visits summarized in the SoA (see Table 3 and 
Table 4). 
After the database lock for the primary analysis, the sponsor will be unblinded, but investigators 
and participants will still be blinded to individual treatment assignments.  This is implemented to 
minimize bias for the Week 52 analyses.  After Week 52, investigators and participants will be 
unblinded. 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments must be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with ruxolitinib cream or vehicle will be evaluated by participants' adherence to the 
application regimen and drug accountability documented by the site staff and monitored by the 
sponsor/designee (tube counts). 
In general, the application compliance will be determined by the number of actual versus 
anticipated number of applications, which should be at least 70% but no more than 130% of the 
prescribed number of applications.  Participants will be instructed to bring all study drug with 
them to the study visits in order for site personnel to conduct tube counts to assess study drug 
accountability.  The drug accountability documentation will be used by the sponsor to calculate 
treatment compliance. 
6.5. 
Dose Modifications 
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment. 
In some circumstances, it may be necessary to temporarily interrupt treatment with study drug.  
Except in cases of emergency, it is recommended that any findings of concern (eg, AE) be 
confirmed and that the investigator consult with the sponsor's medical monitor (or other 
representative of the sponsor) before interrupting study drug.  Additionally, the investigator must 
obtain approval from the sponsor before restarting study drug.  Participants who experience a 


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recurrence of the initial AEs upon restarting the study drug may need the study drug to be 
permanently discontinued. 
Instructions for application interruptions of study drug are outlined in Table 7.  Individual 
decisions regarding interruptions should be made using clinical judgment in consultation with the 
medical monitor (whenever possible), taking into account relatedness of the AE to the study 
treatment and the participant's underlying condition. 
Table 7: 
Guidelines for Interruption and Restarting of Study Drug 
Adverse Event 
Action Taken 
Chemistry 
ALT (> 3 × ULN) or AST (> 3 × ULN) 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results requested. 
• Study drug applications must be interrupted.  At the 
discretion of the investigator, after consultation with 
the sponsor, study drug application may be restored 
once these have resolved. 
Other laboratory abnormalities 
Any other Grade 3 laboratory abnormality, 
with the exception of asymptomatic 
elevations in triglyceride, cholesterol, or 
amylase 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results requested. 
• Study drug applications must be interrupted.  At the 
discretion of the investigator, after consultation with 
the sponsor, study drug application may be restored 
once these have resolved.  
Any Grade 4 laboratory abnormality or 
AST or ALT (> 5 × ULN) 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results requested.  
• Discontinue study drug if laboratory abnormalities are 
confirmed.  
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable severity of an AE not caused by the underlying disease will be 
presumed to be related to study drug and will require that the study drug be permanently 
discontinued.  Unacceptable severity is defined as follows: 
• Occurrence of an AE that is related to treatment with the 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 continuing treatment is 
considered to not be in the participant's best interest. 
• Worsening of vitiligo that requires treatment with a prohibited concomitant 
medication. 
See Section 7 for discontinuation procedures. 


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6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
prior medication received up to 42 days before the first dose of study drug through 30 days after 
the last dose of study drug will be recorded in the eCRF.  Any addition, deletion, or change in the 
dose of these medications will also be recorded.  Concomitant medications administered after 
30 days after the last dose of study drug should be recorded in the eCRF only if the medication 
was administered due to an SAE (as defined in Section 9.2).  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 there are any questions 
regarding concomitant or prior therapy. 
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 judgment 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 or camouflage makeups. 
Note:  Emollients or camouflage makeups should not be used within 2 hours after 
study drug application.  The study drug may not be applied over sunscreens and 
camouflage makeup.  These must be carefully removed from the skin before 
application of the study drug.  Any makeup remover must then be washed off and the 
skin dried before application of the study drug. 
• If sunscreen is needed, a mineral-based sunscreen (such as zinc oxide– or titanium 
oxide–based) with SPF of at least 30 may be used at least 2 hours after study drug 
application. 
Note:  Sunscreen must be carefully removed from the skin before study drug 
application if it has been applied to the areas to be treated. 
• Study drug should be applied at least 2 hours after shaving.  
• Concomitant oral vitamins 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 any over-the-counter, nonprescription preparations (including vitamins, 
minerals, and phytotherapeutic, herbal, or plant-derived preparations) within 7 days 
before the baseline visit through the safety follow-up visit, unless deemed acceptable 
by the investigator. 
• Use of any prescription medication (including immunizations, phytotherapeutic, 
herbal, or plant-derived preparations) within 7 days before the baseline visit through 
the safety follow-up visit, unless deemed acceptable by the investigator. 


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• Baths or showers within 2 hours after study drug application. 
• Treatment for dermatologic disease besides vitiligo (eg, atopic dermatitis or psoriasis) 
is allowed for areas not being treated for vitiligo, if: 
− It involves < 10% of the BSA outside of the areas treated for vitiligo. 
− Topical tacrolimus, pimecrolimus, or corticosteroids Class 6 or 7 (or low potency 
per WHO classification; see Appendix B) are at a stable dose. 
− Topical corticosteroids Class 1 through 5 (see Appendix B) are used for no longer 
than 7 sequential days and no more than 14 days in total. 
• Use of oral corticosteroids for no longer than 7 days if deemed acceptable by the 
investigator and the sponsor for nondermatologic conditions (eg, asthma 
exacerbation, bronchitis). 
6.6.3. 
Prohibited Medications and Procedures 
Participants should not use any other treatments for vitiligo at any time during the study.  The 
following medications are not permitted during the study: 
• Any investigational medication other than the study drug 
• Treatment known to affect the course of vitiligo, such as skin bleaching treatments 
(eg, hydroquinone) or depigmenting agents (eg, monobenzone) 
Note:  Skin bleaching (eg, hydroquinone) is prohibited during the study but is allowed 
as prior therapy. 
• Other topical agents (except those in Section 6.6.1) or treatments for vitiligo 
(including corticosteroids [topical, systemic, or oral], vitamin D derivatives, 
calcineurin inhibitors, laser or surgical treatments, phototherapy, or other procedures) 
• Biologic therapies or other immunosuppressant agents 
• Any phototherapy, including tanning beds 
• Live or live-attenuated vaccination 
6.7. 
Treatment After the End of the Study 
No treatment will be provided after the end of the 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: 
• A participant is found not to have met eligibility criteria (any exclusion criterion or 
any inclusion criterion related to participant safety) or if legal requirements have been 
violated. 
• 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 for 
safety monitoring. 
• 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 6.5.2. 
• 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, at 2 consecutive study visits, a participant's drug usage exceeds 1 tube (60 g) per 
3-4 days. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's opinion, the medical monitor 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, an EOT 
visit should be conducted (EOT1 or EOT2, depending on the period during with the participant 
discontinues treatment).  Reasonable efforts should be made to have the participant return for a 
safety follow-up visit.  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. 
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. 


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• An EOT visit should be performed (EOT1 or EOT2, depending on the period during 
with the participant discontinues treatment). 
• The date of the EOT visit should be recorded in the eCRF. 
• Participants must be followed for safety until the time of the safety follow-up visit or 
until study treatment–related AEs 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 safety follow-up period of the study for safety
 
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. 
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. 
See Table 3 and Table 4 for data to be collected at the time of study withdrawal and follow-up 
and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or 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.  The site will counsel the participant on the importance of 
maintaining the assigned visit schedule and will 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. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
See Appendix C for COVID-19–related guidance. 
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 country 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. 
• 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. 


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day that the participant is assigned to 
the study drug (Day 1).  Screening assessments for determination of eligibility may be performed 
over a period lasting up to 42 days. 
Procedures conducted as part of the participant's routine clinical management (eg, clinical 
laboratory tests) and collected before informed consent is obtained may be used for screening or 
baseline purposes, provided the procedure meets the Protocol-defined criteria and has been 
performed within 42 days before Day 1.  All information associated with eligibility 
requirements, including demography and medical history, must be entered into the appropriate 
eCRF pages. 
Results from the screening assessments will be reviewed by the investigators to confirm 
eligibility before Day 1 and administration of study drug.  Test results that fail eligibility 
requirements may be repeated once during screening if the investigator believes that the 
participant would be eligible if retested.  For screening assessments that are repeated, the most 
recently available result before administration of study drug will be used to determine eligibility.  
See Section 5.4 regarding screen failures. 
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 personnel should contact the IRT system 
to obtain the participant ID number during screening.  Upon determining that the participant is 
eligible for study entry, the IRT system will be contacted to obtain the study treatment kit 
assignment.  Additionally, the IRT system will be contacted at each regular study visit to update 
the study drug supply.  Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and Diaries 
Starting at the baseline (Day 1) visit and each visit thereafter (except for the Week 24 [EOT1], 
Week 52 [EOT2], and EOS visits), a study drug–specific diary will be given to each participant 
in order to record use of the study drug.  The completed diary will be collected during each of the 
participant's visits. 
Qualified clinical site staff will review the participants' entries for compliance.  Participants who 
are noncompliant with their study drug schedule (defined as < 70% or > 130% of the expected 
number of applications between study visits) will have their administration instructions 
reinforced by the investigator or a qualified designee.  Participants will be considered compliant 
with the treatment regimen if they apply at least 70% but no more than 130% of the expected 
applications during participation in the treatment period of the study. 
Participants will be provided with a reminder card starting on Day 1 and at all visits (through 
Week 52).  The reminder card will indicate the date/time of the next visit and will also remind 
the participant that on visit days, they will perform their morning study drug application at the 
clinic during the visit under site supervision after their blood draws for 
 safety evaluations 
have been completed. 


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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, medical and surgical 
history, and current illnesses.  Medical history will include relevant medical or surgical treatment 
within the past 2 years that are 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 recorded.  A medical history of other conditions related to vitiligo will also 
be collected at screening. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 


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8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in Table 3 and Table 4. 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study drug.  Adverse events for randomized participants that begin 
or worsen after informed consent should be recorded on the Adverse Event 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, or that 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. 


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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). 
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 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. 
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.  Abnormalities identified after the first dose of study drug constitute an AE if they are 
considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study treatment. 
8.3.3. 
Vital Signs 
Vital sign measurements will be taken at all visits. 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the participant in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest.  Any abnormalities that are considered clinically 
significant in the judgment of the investigator are to be reported as AEs. 
8.3.4. 
Electrocardiograms 
Electrocardiograms will be performed as indicated in Table 3. 
All 12-lead ECGs will be performed with the participant in a recumbent or semirecumbent 
position after 5 minutes of rest.  Additional 12-lead ECGs may be performed at other visits as 
deemed clinically necessary.  Findings from a 12-lead ECG performed within 2 months before 
baseline are acceptable to use as the participant's screening value. 
ECGs 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.  There is no central reader of ECGs for this 
study.  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. 


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8.3.5. 
Laboratory Assessments 
Required clinical laboratory tests are listed in Table 8, which include hematology, chemistry, 
urinalysis, serology, free T4, TSH, FSH, and pregnancy testing, and will be performed as 
indicated in Table 3 and Table 4.  Clinical laboratory tests will be performed at a central 
laboratory (refer to the Laboratory Manual for sample handling and shipping instructions). 
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, or within 30 days after the last dose of study drug, 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 
Table 8: 
Required Laboratory Analytes 
Serum Chemistriesa 
Hematology 
Urinalysis With 
Microscopic 
Examination 
Serology 
Other 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Bicarbonate or CO2 
Blood urea nitrogen or 
urea 
Calcium 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is elevated 
above ULN) 
Total protein 
Complete blood 
count, including: 
• Hemoglobin 
• Hematocrit 
• Mean 
corpuscular 
volume (MCV) 
• Platelet count 
• Mean platelet 
volume 
• Red blood cell 
count 
• Reticulocyte 
count 
• White blood cell 
count 
 
Differential count, 
including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Color and 
appearance 
pH and specific 
gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Hepatitis B surface 
antigen 
Hepatitis B core 
antibody 
Hepatitis B core 
immunoglobulin M 
antibody 
HCV antibody 
HCV-RNA (only 
performed if 
antibody positive) 
HIV antibody 
FSHb 
Free T4 
TSH 
Pregnancy Testing 
Female participants of childbearing potential will undergo a 
serum test at the screening and safety follow-up visits.  A urine 
test will be conducted at all other visits.  A positive urine test 
will be confirmed by a serum test. 
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. 
a All serum chemistries will be performed on samples collected without respect to food intake (ie, nonfasting). 
b FSH is only measured for postmenopausal women (defined by amenorrhea for ≥ 12 months without an alternative medical 
cause before screening); FSH should be in the postmenopausal range to consider the participant of nonchildbearing potential. 


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8.3.5.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during screening 
and at the safety follow-up visit (30 [+ 7] days after EOT; EOT1 or EOT2 as applicable).  Urine 
pregnancy tests will be conducted as outlined in Table 3 and Table 4, as medically indicated, or 
per country-specific requirement.  Urine pregnancy tests will be performed locally.  If a urine 
pregnancy test is positive, the result should be confirmed with a serum pregnancy test, which 
may be performed locally. 
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, see Section 9.7 for reporting 
requirements. 
8.3.5.2. 
Serology 
Hepatitis and HIV screening assessments will be performed during the screening period to rule 
out infection; required analytes are shown in Table 8. 
Serology 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. 
8.5. 
Pharmacodynamic and Translational Assessments 
All participants will have serum, 
 and 2.5-mm skin biopsies collected at the visits 
outlined in Table 3.  Serum 
 will be used for changes in immune parameters, 
including but not limited to soluble proteins, such as cytokines and chemokines, 
 
.  
 


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All analyses will be conducted by Incyte Corporation (Wilmington, DE) or Incyte's designee.  
Refer to the procedure-specific Study Manuals for detailed instructions. 
8.5.1. 
Skin Biopsy 
Skin biopsies (2.5 mm punch biopsy) will be collected from a target lesion at the timepoints 
outlined in Table 3.  Skin biopsies cannot be taken from the hands, feet, head/neck, face, and 
genital area.  The target lesion for skin biopsy should be defined at baseline (Day 1) as an active 
vitiligo lesion, such as confetti lesion, trichrome appearance, pinkish rim, or other evidence of 
inflammatory activity and/or active changes to the lesion.  
 small (2.5 mm, which does not require stitches) biopsies will be collected from lesional skin 
at each timepoint (Baseline/Day 1, Week 12, Week 24, and Week 40) 
 
.  At baseline (Day 1), an additional  small (2.5 mm) skin biopsies will also be collected 
from nonlesional skin adjacent to the target lesion, 
.  
 
small biopsies will be taken at each timepoint to accommodate different analyses, each requiring 
profoundly different processing.  At each timepoint, 1 biopsy will be processed for 
immunohistochemistry and other imaging technologies to enable protein and gene expression 
analyses by imaging, 
 
    
The skin biopsies at Week 12, Week 24, and Week 40 will be collected in the vicinity but at least 
1 cm distant from where the biopsies were collected at baseline (Day 1), even if the target lesion 
area has cleared.  The baseline (Day 1) lesional skin biopsy sampling area should be from the 
inside edge of an active vitiligo lesion, and the sampling area should be entirely contained within 
lesional skin.  
Details about the collection, processing, handling, storage, and shipping of samples will be 
provided in the Study Manuals. 
 
 
 
 
 
 
 
 
 


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8.5.3. 
Immunohistology and Other Imaging Techniques 
Analyses will be performed 
 to evaluate skin 
 
 biomarkers.  This will enable, but not limit, the evaluation of changes in leukocyte 
infiltration to vitiligo lesions and the correlation with biological response relating to vitiligo or 
the MOA of ruxolitinib 1.5% cream. 
8.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time at the investigator's discretion, and appropriate clinical 
and laboratory tests may be performed, as clinically indicated. 
8.7. 
End of Treatment and/or Early Termination 
If a decision is made that the participant will permanently discontinue study drug, then an EOT 
visit should be conducted (EOT1 or EOT2, depending on the study period when the participant 
discontinues).  If the EOT visit coincides with a regular study visit, then the EOT evaluations 
will supersede those of that scheduled visit, and the data should be entered in the EOT page in 
the eCRF.  If this decision does not coincide with a regular visit, reasonable efforts should be 
made to have the participant return to the site to have the EOT procedures completed. 
8.8. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit (EOT1 or EOT2, depending on 
the study period when the participant discontinues) and the scheduled safety follow-up visit, 
which should occur 30 (+ 7) days after the EOT visit (or after the last dose of study drug if an 
EOT visit was not performed). 
Adverse events and SAEs must be reported up until 1) at least 30 days after the last dose of study 
drug or the date of the safety follow-up visit or 2) 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 safety follow-up visit and report any AEs that may occur during this 
period. 


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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. 
• 
 "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  
. 
• 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) are not considered SAEs. 
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, 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. 
 


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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.  AEs/SAEs should be reported for randomized participants, but 
only SAEs need to be reported for screen failure participants.  For randomized participants, 
conditions that were present at the time informed consent was given should be recorded on the 
Medical History Form in the eCRF.  For detailed information, refer to the eCRF guidelines. 
• 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 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, Procedures and 
Non-Drug Therapy). 
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 
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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 for study drug 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. 
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. 


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• 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. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedure[s]), all SAEs 
occurring after the participant has signed the ICF through the last study visit (or 30 days after the 
last dose of study drug, whichever occurs later) must be reported to the sponsor (or designee) 
immediately, without undue delay, under no circumstances later than 24 hours following 
knowledge of the event. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation.  However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers it is at least 
reasonably possible that the event is related to the study drug or study participation, then the 
investigator must notify the sponsor (or designee) immediately, without undue delay, under no 
circumstances later than 24 hours following knowledge 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 of a 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 
information from the investigator for 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. 


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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 also complete the Incyte Serious Adverse Event Report Form in English.   
• Follow-up information is also recorded and transmitted to Incyte Pharmacovigilance on an 
amended or new Serious Adverse Event Report Form, with an indication that it is follow-up to the 
previously reported SAE and the date of the original report.  The follow-up report should include 
information that was not provided on the previous Serious Adverse Event Report Form, such as the 
outcome of the event (eg, resolved or ongoing), 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. 
• Contacts for SAE reporting can be found in the Study Manual. 
9.5. 
Events of Clinical Interest 
Not applicable. 
9.5.1. 
Adverse Events of Special Interest 
Not applicable. 
9.6. 
Emergency Unblinding of Treatment Assignment 
In a medical emergency during the double-blind, vehicle-controlled period, if the investigator 
deems it necessary to determine optimal medical management of the participant, emergency 
unblinding will be performed exclusively by the principal investigator and subinvestigator as 
described in the IRT Study Manual.  The IRT system has an option to select for "Emergency 
Code Break" action for a given participant.  After entering the 6-digit study drug tube number 
and verification of the unmasking information, the investigator/subinvestigator will proceed to 
either final confirmation or cancellation of the code break procedure. 
If a participant's treatment assignment is unblinded, the sponsor or its designee must be notified 
immediately by telephone, followed up with an email.  
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant must discontinue study drug unless there are ethical reasons to have the participant 
remain on the study drug.  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. 


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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. 
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. 
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. 


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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 ruxolitinib cream.  Treatment of 
overdose should consist of general supportive measures. 
10. 
STATISTICS 
10.1. 
Sample Size Determination 
Due to the exploratory nature of the study, the sample size is not only based on calculation of 
statistical power.  The sample size is considered to be sufficient to obtain adequate 
 
safety, tolerability, 
 data to achieve the objectives of the study. 
Approximately 60 participants will be randomized 2:1 to ruxolitinib cream 1.5% BID or vehicle 
BID to ensure approximately 45 participants will have multiple biomarker data (eg, CXCL10) 
available at Week 24. 
On the basis of the results of a Phase 2 study (INCB 18424-211), the anticipated difference in 
percentage of change from baseline in CXCL10 between ruxolitinib cream 1.5% BID and 
vehicle is 22% (standard deviation = 0.25%).  Using a 2-sample t-test, the sample size of 45 will 
provide great power (≥ 80%) to detect such difference with a 2-sided alpha of 0.10. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 9. 
Table 9: 
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 applied 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. 


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10.3. 
Level of Significance 
Not applicable. 
10.4. 
Data Handling Definitions and Conventions 
10.4.1. 
Day 1 
Day 1 is the date that the first application of ruxolitinib cream or vehicle cream is administered 
to the participants. 
For randomized participants not treated with any study drug, Day 1 is defined as the day of 
randomization.  
10.4.2. 
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. 
10.4.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before or on the day of first application of 
ruxolitinib cream or vehicle cream. 
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. 
10.4.4. 
Handling of Missing and Incomplete Data 
In general, missing data will not be imputed. 
10.5. 
Statistical Analyses 
10.5.1. 
Baseline, Demographics, Disease History, and Prior and Concomitant 
Medication 
The following demographics will be summarized for the ITT population: age, age group, sex, 
race, ethnicity, region, weight, height, and body mass index. 
Baseline disease characteristics, prior medications for vitiligo, medical history, and prior and 
concomitant medications will be summarized by treatment group.  
10.5.2. 
Disposition of Participants  
The number and percentage of participants who were enrolled, randomized, treated, and 
completed for each period will be summarized for the ITT population. 


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10.5.3. 
Exposure and Study Drug Compliance   
For participants in the ITT population, descriptive statistics will be provided for duration of 
treatment, average daily dose, total dose, and study drug compliance.  
 
 
 
 
 
 
10.5.5. 
Safety Analysis 
Safety is being evaluated as a secondary objective in this study.  Safety analyses will be 
conducted using the safety population and are summarized in Table 10. 
Table 10: 
Safety Analyses 
Objective 
Statistical Analysis Methods 
To assess the safety 
and local tolerability 
of ruxolitinib cream. 
Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event 
after first dose of study drug.  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 coded using MedDRA and tabulated by preferred term and 
system organ class.  Severity of AEs will be based on the 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. 
Clinical Laboratory Tests 
Actual values and changes from baseline in clinical laboratory test results will be 
summarized using descriptive statistics.  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 will be tabulated. 
Laboratory data will be classified into Grades 1 through 5 using CTCAE v5.0.  The 
following summaries will be produced for the laboratory data: 
• 
Number and percentage of participants with worst postbaseline CTCAE grade 
(regardless of baseline value).  Each participant will be counted only for the worst 
grade observed postbaseline. 
• 
Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• 
For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 
Vital Signs 
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. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG 
parameter at each assessment time. 


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10.5.6. 
Translational Analyses 
Translational endpoints are listed in Section 3.  These are being evaluated as primary, secondary, 
 objectives.  Details of translational analyses will be provided in the Statistical 
Analysis Plan. 
10.6. 
Interim Analysis 
No formal interim analysis is planned in this study.  The primary analysis will occur after the 
primary database lock, when all participants have completed the vehicle-controlled, double-blind 
treatment period.  The sponsor will be unblinded, while investigators and participants will still be 
blinded, to the study treatment after the primary database lock.  After Week 52, investigators and 
participants will be unblinded. 
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. 


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− 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. 
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, or biomarker plans, 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. 


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• 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, biomarker 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 (e.g., 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).  
• 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 (e.g., 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.  


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• 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. 
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. 
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. 


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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 
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 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2014. 
Dina Y, McKesey J, Pandya AG. Disorders of hypopigmentation. J Drugs Dermatol 
2019;18:s115-s116. 
European Medicines Agency. Guidance on the Management of Clinical Trials During the 
COVID-19 (Coronavirus) Pandemic. 2020. 
González U, Whitton M, Eleftheriadou V, Pinart M, Batchelor J, Leonardi-Bee J. Guidelines for 
designing and reporting clinical trials in vitiligo. Arch Dermatol 2011;147:1428-1436. 
 
 
 
 
 
 
Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. 
Front Immunol 2019;10:2342.  
Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in 
children/adolescents and adults. Int J Dermatol 2012;51:1206-1212. 
Rashighi M, Agarwal P, Richmond JM, et al. CXCL10 is critical for the progression and 
maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 2014;6:223ra23. 
Rashighi M, Harris JE. Interfering with the IFN-γ/CXCL10 pathway to develop new targeted 
treatments for vitiligo. Ann Transl Med 2015;3:343. 
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. 
Ruxolitinib Cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Taïeb A, Picardo M. Clinical practice. Vitiligo. N Engl J Med 2009;360:160-169. 
van den Boorn JG, Konijnenberg D, Dellemijn TA, et al. Autoimmune destruction of skin 
melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 
2009;129:2220-2232. 
World Health Organization. WHO Model Prescribing Information: Drugs Used in Skin Diseases. 
1997. 
 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS 
For male participants in the study: 
Male participants should use a condom during treatment through 90 days after the end of systemic 
exposure.  If the male participant has a partner that is of childbearing potential, the partner should also 
use contraception through 90 days after the end of relevant systemic exposure.  In addition, male 
participants must refrain from donating sperm during the study through 90 days after the end of 
relevant systemic exposure.  Male participants who have had a vasectomy qualify as having met the 
requirement for a highly effective birth control method. 
For female participants in the study: 
The following methods that can achieve a failure rate of < 1% per year when used consistently and 
correctly are considered as highly effective birth control methods: 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation 
− 
oral 
− 
intravaginal 
− 
transdermal 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
− 
oral 
− 
injectable 
− 
implantablea 
• 
Intrauterine devicea 
• 
Intrauterine hormone-releasing systema 
• 
Bilateral tubal occlusiona 
• 
Vasectomized partnerab 
• 
Sexual abstinencec 
Acceptable birth control methods that result in a failure rate of more than 1% per year include:d 
• 
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary 
mode of action 
• 
Male or female condom with or without spermicidee 
• 
Cap, diaphragm, or sponge with spermicidee 
• 
Tubal ligation 
a Contraception methods that in the context of this guidance are considered to have low user dependency. 
b Vasectomized partner is a highly effective method of avoiding pregnancy provided that the 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. 
c 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. 
d Choices are for US and Canada participants only and include above < 1% failure rate methods. 
e Combinations of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) are 
also considered acceptable, but not highly effective, birth control methods. 
Source:  Clinical Trials Facilitation and Coordination Group 2014. 


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APPENDIX B. WHO CLASSIFICATION OF TOPICAL 
CORTICOSTEROIDS 
Hydrocortisone and betamethasone are examples of low- and high-potency topical 
corticosteroids.  Topical corticosteroids have been ranked in terms of potency into 4 groups 
consisting of 7 classes.  Class I topical corticosteroids are the most potent, and Class VII are the 
least potent.  Efficacy and side effects are greatest with the Class I ultra-high–potency 
preparations, which should only be used for limited time periods (2-3 weeks).  Representative 
preparations by group are listed in the table below.  These groups may vary depending on the 
formulation and concentration and should be considered approximate.  In general, ointments are 
more potent than creams or lotions.  Potency is also increased when topical corticosteroids are 
used under occlusive dressings or in intertriginous areas. 
Potency 
Class 
Topical Corticosteroid 
Formulation 
Ultra high 
I 
Clobetasol propionate 
Cream, 0.05% 
Diflorasone diacetate 
Ointment, 0.05% 
High 
II 
Amcinonide 
Ointment, 0.1% 
Betamethasone dipropionate 
Ointment, 0.05% 
Desoximetasone 
Cream or ointment, 0.025% 
Fluocinonide 
Cream, ointment or gel, 0.05% 
Halcinonide 
Cream, 0.1% 
III 
Betamethasone dipropionate 
Cream, 0.05% 
Betamethasone valerate 
Ointment, 0.1% 
Diflorasone diacetate 
Cream, 0.05% 
Triamcinolone acetonide 
Ointment, 0.1% 
Moderate 
IV 
Desoximetasone 
Cream, 0.05% 
Fluocinolone acetonide 
Ointment, 0.025% 
Fludroxycortide 
Ointment, 0.05% 
Hydrocortisone valerate 
Ointment, 0.2% 
Triamcinolone acetonide 
Cream, 0.1% 
V 
Betamethasone dipropionate 
Lotion, 0.02% 
Betamethasone valerate 
Cream, 0.1% 
Fluocinolone acetonide 
Cream, 0.025% 
Fludroxycortide 
Cream, 0.05% 
Hydrocortisone butyrate 
Cream, 0.1% 
Hydrocortisone valerate 
Cream, 0.2% 
Triamcinolone acetonide 
Lotion, 0.1% 
Low 
VI 
Betamethasone valerate 
Lotion, 0.05% 
Desonide 
Cream, 0.05% 
Fluocinolone acetonide 
Solution, 0.01% 
VII 
Dexamethasone sodium phosphate 
Cream, 0.1% 
Hydrocortisone acetate 
Cream, 1% 
Methylprednisolone acetate 
Cream, 0.25% 
Source:  WHO 1997. 
 


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APPENDIX D. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Not applicable. 


Signature Page for VV-CLIN-011898 v3.0
Signature Page for VV-CLIN-011898 v3.0
Approval
Approver
03-Mar-2021 17:02:15 GMT+0000
Approval
Approver
03-Mar-2021 17:08:12 GMT+0000
Approval
Approver
03-Mar-2021 17:14:13 GMT+0000
Approval
Approver
03-Mar-2021 17:19:42 GMT+0000
Approval
Approver
03-Mar-2021 19:00:43 GMT+0000

SAP_001.pdf: 
Official Title: 
A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the 
Mechanism of Action of Ruxolitinib Cream for Vitiligo (TRuE-V MOA)
NCT Number:         NCT04896385 
Document Date: 
Statistical Analysis Plan Original: 14-October-2022 


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INCB 18424-214 Statistical Analysis Plan 
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Statistical Analysis Plan 
TITLE PAGE 
INCB 18424-214 
A Randomized, Double-Blind, Vehicle-Controlled Study to Evaluate the 
Mechanism of Action of Ruxolitinib Cream for Vitiligo 
(TRuE-V MOA) 
IND Number: 
 
EudraCT Number: 
2021-000361-32 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol dated 03 MAR 2021 
CRF Approval Date: 
24 MAR 2022 
SAP Version: 
Original 
SAP Author: 
 
 
Date of Plan: 
14 OCT 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 ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................6 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................7 
2.1. 
Protocol and Case Report Form Version ......................................................................7 
2.2. 
Study Objectives and Endpoints ...................................................................................7 
3. 
STUDY DESIGN .........................................................................................................8 
3.1. 
Randomization ..............................................................................................................8 
3.2. 
Control of Type I Error .................................................................................................8 
3.3. 
Sample Size Considerations .........................................................................................8 
3.4. 
Schedule of Assessments ..............................................................................................9 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ....................................9 
4.1. 
Scheduled Study Evaluations and Study Periods .........................................................9 
4.1.1. 
Day 1 .............................................................................................................................9 
4.1.2. 
Study Day .....................................................................................................................9 
4.1.3. 
Baseline Value ..............................................................................................................9 
4.1.4. 
Handling of Missing and Incomplete Data ...................................................................9 
4.1.5. 
Handling of Missing and Incomplete Dates ...............................................................10 
4.2. 
Variable Definitions ....................................................................................................10 
4.2.1. 
Body Mass Index ........................................................................................................10 
4.2.2. 
Prior and Concomitant Medication .............................................................................10 
5. 
STATISTICAL METHODOLOGY ...........................................................................11 
5.1. 
General Methodology .................................................................................................11 
5.2. 
Treatment Groups .......................................................................................................11 
5.3. 
Analysis Populations ..................................................................................................11 
5.3.1. 
All-Screened Population .............................................................................................11 
5.3.2. 
Intent-to-Treat Population ..........................................................................................11 
5.3.3. 
Safety Population ........................................................................................................11 
5.3.4. 
Treatment-Extension Evaluable Population ...............................................................11 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................12 


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6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................12 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................12 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................12 
6.1.3. 
Prior Therapy for Vitiligo ...........................................................................................12 
6.1.4. 
Medical History ..........................................................................................................12 
6.2. 
Disposition of Participants ..........................................................................................13 
6.3. 
Protocol Deviations ....................................................................................................13 
6.4. 
Exposure .....................................................................................................................13 
6.5. 
Study Drug Compliance .............................................................................................13 
6.6. 
Prior and Concomitant Medication .............................................................................13 
 
14 
 
14 
 
14 
 
14 
 
14 
 
15 
8. 
PHARMACODYNAMICS ........................................................................................15 
9. 
SAFETY AND TOLERABILITY ..............................................................................16 
9.1. 
General Considerations ...............................................................................................16 
9.2. 
Adverse Events ...........................................................................................................16 
9.2.1. 
Adverse Event Definitions ..........................................................................................16 
 
17 
9.2.3. 
Adverse Event Summaries ..........................................................................................17 
9.3. 
Clinical Laboratory Tests ...........................................................................................18 
9.3.1. 
Laboratory Value Definitions .....................................................................................18 
9.3.2. 
Laboratory Value Summaries .....................................................................................18 
10. 
VITAL SIGNS ............................................................................................................19 
11. 
PLANNED ANALYSES ............................................................................................19 
12. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................20 
12.1. 
Changes to Protocol-Defined Analyses ......................................................................20 
12.2. 
Changes to the Statistical Analysis Plan .....................................................................20 
13. 
REFERENCES ...........................................................................................................21 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................22 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................7 
Table 2: 
Normal Ranges for Vital Sign Values ........................................................................19 
Table 3: 
Statistical Analysis Plan Versions ..............................................................................20 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema ...................................................................................................8 
 


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LIST OF ABBREVIATIONS 
Abbreviations 
Definition 
AE 
adverse event 
ASR 
application site reaction 
BID 
twice daily 
BMI 
body mass index 
BSA 
body surface area 
CI 
confidence interval 
 
 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
electronic case report form 
F-BSA 
facial body surface area 
F-VASI 
facial Vitiligo Area Scoring Index 
F-VASI25/50/75/90 
≥ 25%/50%/75%/90% improvement from baseline in facial Vitiligo Area 
Scoring Index 
IFN-γ 
interferon gamma 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
 
 
PT 
preferred term 
SAP 
Statistical Analysis Plan 
SOC 
system organ class 
STD 
standard deviation 
T-BSA 
total body surface area 
TEE 
treatment-extension evaluable 
TEAE 
treatment-emergent adverse event 
T-VASI 
total body Vitiligo Area Scoring Index 
T-VASI25/50/75/90 
≥ 25%/50%/75%/90% improvement in total body Vitiligo Area Scoring Index 
VASI 
Vitiligo Area Scoring Index 


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1. 
INTRODUCTION 
This is a multicenter, randomized, double-blind, vehicle-controlled study with an open-label 
treatment extension period in adult participants (age ≥ 18 years) with nonsegmental vitiligo who 
have depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on 
nonfacial areas, and ≥ 3 T-VASI. Total body involved vitiligo area (facial and nonfacial) should 
not exceed 50% BSA. Approximately 60 participants will be randomized 2:1 to receive initial 
double-blind study treatment (ruxolitinib 1.5% cream:vehicle cream) administered BID for 
24 weeks. Participants will be stratified by age (≤ 40 years old and > 40 years old). 
During the study, participants will apply study drug to depigmented areas on the face and body 
up to 20% T-BSA (facial and nonfacial). After completion of the Week 24 assessments from the 
double-blind treatment period, eligible participants will be offered the opportunity to continue 
the study in the 28-week, open-label, treatment extension period. Participants initially 
randomized to vehicle cream will be crossed over to active drug (ruxolitinib 1.5% cream BID), 
and participants initially randomized to ruxolitinib cream will continue to receive treatment with 
ruxolitinib 1.5% cream BID. Following the last application of ruxolitinib cream at Week 52, 
there will be a 30-day safety follow-up period. 
Section 2 of the Protocol provides a detailed description of the investigational product, target 
patient population, rationale for doses to be examined, and potential risks and benefits of 
treatment with ruxolitinib cream. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 18424-214 Protocol. The scope of this plan will be executed by the Department of 
Biostatistics or designee. The details of the analysis methodology of biomarkers and 
pharmacodynamics and results will appear in a separate report. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 18424-214 Protocol dated 03 MAR 2021 and CRFs approved 
09 APR 2021. Unless superseded by an amendment, this SAP will be effective for all subsequent 
Protocol amendments and CRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the change in immune biomarkers in 
participants with vitiligo. 
Percentage change from baseline in immune 
biomarkers, including CXCL10, at Week 4, 
Week 12, and Week 24.  
Secondary 
To correlate the change in key serum and skin 
biomarkers of vitiligo to efficacy. 
Correlation of key skin inflammatory biomarkers 
of vitiligo in target lesions to efficacy readouts at 
Week 12 and Week 24. 
To assess the safety and local tolerability of 
ruxolitinib cream. 
The frequency and severity of AEs. 


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3. 
STUDY DESIGN 
This is a multicenter, randomized, double-blind, vehicle-controlled study with an open-label 
treatment extension period in adult participants (age ≥ 18 years) with nonsegmental vitiligo who 
have depigmented areas including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on 
nonfacial areas, and ≥ 3 T-VASI. Total body involved vitiligo area (facial and nonfacial) should 
not exceed 50% BSA. Approximately 60 participants will be randomized 2:1 to receive initial 
double-blind study treatment (ruxolitinib 1.5% cream:vehicle cream) administered BID for 
24 weeks. Participants will be stratified by age (≤ 40 years old and > 40 years old). 
After completion of the Week 24 assessments from the double-blind treatment period, eligible 
participants will be offered the opportunity to continue the study in the 28-week, open-label, 
treatment extension period. Participants initially randomized to vehicle cream will be crossed 
over to active drug (ruxolitinib 1.5% cream BID), and participants initially randomized to 
ruxolitinib cream will continue to receive treatment with ruxolitinib 1.5% cream BID. 
The study schema is shown below in Figure 1. All participants will have follow-up assessments 
30 (+ 7) days after the last application of study drug. 
Figure 1: 
Study Design Schema 
 
3.1. 
Randomization 
Approximately 60 participants will be randomized 2:1 to receive initial double-blind study 
treatment (ruxolitinib 1.5% cream BID:vehicle cream BID) for 24 weeks. Participants will be 
stratified by age (≤ 40 years old and > 40 years old). 
3.2. 
Control of Type I Error 
 No alpha control will be 
implemented. Unless otherwise specified, all CIs provided will be at the 95% confidence level. 
3.3. 
Sample Size Considerations 
Due to the exploratory nature of the study, the sample size is not based on calculation of 
statistical power. The sample size is considered to be sufficient to obtain adequate 
 
safety, tolerability, 
 data to achieve the objectives of the study. 


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Approximately 60 participants will be randomized 2:1 to ruxolitinib 1.5% cream BID or vehicle 
cream BID to ensure approximately 45 participants will have multiple biomarker data 
(eg, CXCL10; Rashighi and Harris 2015) available at Week 24. 
On the basis of the results of a Phase 2 study (INCB 18424-211), the anticipated difference in 
percentage change from baseline in CXCL10 between ruxolitinib 1.5% cream BID and vehicle 
cream BID is 22% (STD = 0.25%). Using a 2-sample t-test, the sample size of 45 will provide 
great power (≥ 80%) to detect such difference with a 2-sided alpha of 0.10. 
3.4. 
Schedule of Assessments 
Refer to Protocol dated 03 MAR 2021 for a full description of all study procedures and 
assessment schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first application of ruxolitinib cream or vehicle cream is administered 
to the participants in the specific period. 
For randomized participants not treated with any study drug, Day 1 is defined as the date 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 application of ruxolitinib 
cream or vehicle cream in the double-blind period. 
For randomized participants not treated with any study drug, baseline is defined as the last 
nonmissing assessment before randomization for all parameters. 
4.1.4. 
Handling of Missing and Incomplete Data 
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections. 


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4.1.5. 
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 on 
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 vitiligo, a partial vitiligo 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 application is used in deriving variables such as duration of treatment 
or TEAE flag, a missing or partial date of the last application 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 earlier date of treatment discontinuation date, end of study date, last 
contact date, or the cutoff date will be used as the date of the last application. 
4.2. 
Variable Definitions 
The following variables will only be calculated if not reported on the eCRF. 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (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 application of 
study treatment. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first application of study treatment and is ongoing throughout the 
study or ends on/after the date of first application of study treatment. 
• On/after the date of first application of study treatment and is ongoing or ends during 
the course of study treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after the first application of study treatment. In the listing, it will be indicated 
whether a medication is prior-only, concomitant-only, 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, STD, 
median, minimum, maximum, first quartile, third quartile, and 95% CI. 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, vehicle-controlled study followed by an open-label treatment 
extension period. Data will be summarized based on the treatment regimen that was assigned at 
randomization (ITT population) or based on the treatment the participant actually applied on 
Day 1 (safety population). 
During the double-blind period, the treatment groups will be ruxolitinib 1.5% cream BID and 
vehicle cream. 
During the open-label treatment extension period, the treatment groups will be ruxolitinib 1.5% 
cream BID and vehicle cream to ruxolitinib 1.5% cream BID. 
5.3. 
Analysis Populations 
5.3.1. 
All-Screened Population 
The all-screened population will include all participants who signed the informed consent form. 
5.3.2. 
Intent-to-Treat Population 
All participants who were randomized to the study will 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 study. 
The ITT population will be used for the summary of demographics, baseline characteristics, 
participant disposition, 
. 
5.3.3. 
Safety Population 
All randomized participants who applied ruxolitinib cream or vehicle cream at least once will 
constitute the safety population. Treatment groups for this population will be determined 
according to the actual treatment the participant applied on Day 1 regardless of assigned study 
treatment. 
All safety analyses will be conducted using the safety population. 
5.3.4. 
Treatment-Extension Evaluable Population 
Participants who applied ruxolitinib cream at least once in the treatment extension period will 
constitute the TEE population. The TEE population will be used for summary of 
 
safety during the treatment extension period. 


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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 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics and baseline characteristics will be summarized for the ITT and 
TEE populations: age, age group, sex, race, ethnicity, region, weight, height, BMI, and skin type 
(Fitzpatrick scale Type I/II/III/IV/V/VI). 
6.1.2. 
Baseline Disease Characteristics and Disease History 
Baseline disease characteristics summarized for the ITT population include but are not limited to 
the following: 
• Time since initial diagnosis of vitiligo 
• Vitiligo diagnosed in childhood (No/Yes [age]: 0-5 years, 6-11 years, 12-17 years) 
• Other autoimmune disorders 
• Prior therapy given for vitiligo (predefined systemic treatments, phototherapy, and 
surgical procedures) 
• History of acne vulgaris (No/Yes) 
• Currently have acne vulgaris on the face (No/Yes) 
• Vitiligo in genital area (No/Yes) 
 
 
 
 
 
 
 
 
6.1.3. 
Prior Therapy for Vitiligo 
Prior medication information for vitiligo will be used to identify other, non-predefined 
medication received by participants before enrollment into the study. Prior medications for 
vitiligo will be summarized by treatment group. 
6.1.4. 
Medical History 
For participants in the ITT population, medical history will be summarized by treatment group. 
This summary will include the number and percentage of participants with medical history for 
each SOC/PT as documented in the eCRF. 


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6.2. 
Disposition of Participants 
The number and percentage of participants who were enrolled, who were randomized 
(double-blind period only), who were treated, and who completed treatment for each period will 
be summarized for the ITT and TEE populations. The number of participants enrolled by country 
and/or site will also be provided by treatment group. 
6.3. 
Protocol Deviations 
Protocol deviations will be summarized and listed. 
6.4. 
Exposure 
For participants in the safety population during the double-blind period and overall treatment 
period and for participants in the TEE population during the treatment extension period, 
descriptive statistics will be provided for duration of treatment, average daily dose, and total 
dose. 
6.5. 
Study Drug Compliance 
Overall compliance (%) for the application of ruxolitinib cream or vehicle cream during the 
double-blind period and overall treatment period (safety population) and ruxolitinib cream 
during the treatment extension period (TEE population) will be calculated for all participants as 
follows: 
Overall application compliance (%) = 100  [total number of nonmissing applications] / 
[total number of intended applications] 
The total number of nonmissing applications is the total number of applications that the 
participant actually applied in each period during the study. The total number of intended 
applications is the number of planned applications minus the number of interrupted applications. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary 
and summarized as the number and percentage of participants with prior and concomitant 
medications by WHO drug class and WHO drug term. 
For participants in the ITT population, prior and concomitant medications will be summarized by 
treatment group as well as listed. For participants in the TEE population, concomitant 
medications will be summarized by treatment group as well as listed. 


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. 
 
 
8. 
PHARMACODYNAMICS 
Serum CXCL10 levels and skin biomarkers will be evaluated for percentage change from 
baseline at Week 4, Week 12, and Week 24. Likewise, a change from baseline in CXCL10 gene 
expression and skin biomarkers will be evaluated in skin samples at Week 12 and Week 24. 
 
 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
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. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first application of study drug and within 30 days of the last application of study drug. For 
participants who cross over treatments, the first application date is period-specific, and the end 
date is 30 days after the last application date in the period, or the day before the first application 
date in the next period, whichever comes first. 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 application. 
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. Serious AEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution. Unresolved missing 
causality and severity will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 
Application site reactions are AEs that occur at the site of study drug application. A summary of 
ASRs will be provided. Exposure-adjusted summaries will be provided for the safety population 
including cumulative TEAEs. 


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9.2.3. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include: 
• 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 drug because of 
TEAEs 
• Number (%) of participants who permanently discontinued study drug because of 
TEAEs 
• Number (%) of participants who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if 5 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of Grade 3 or higher TEAEs by SOC and PT 
• Summary of Grade 3 or higher TEAEs by PT in decreasing order of frequency 
• Summary of serious TEAEs by SOC and PT 
• Summary of serious TEAEs by PT in decreasing order of frequency 
• Summary of ASRs by SOC and PT 


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•  Summary of ASRs by PT in decreasing order of frequency 
• Summary of treatment-related TEAEs by SOC and PT 
• Summary of treatment-related TEAEs by PT in decreasing order of frequency 
• Summary of Grade 3 or higher treatment-related TEAEs by SOC and PT 
• Summary of treatment-related serious TEAEs by SOC and PT 
• Summary of TEAEs with a fatal outcome by SOC and PT 
• Summary of TEAEs leading to dose interruption of study drug by SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by SOC and PT 
 
 
9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
All laboratory assessments will be performed using a central laboratory except for urine 
pregnancy tests (as applicable). Laboratory values and change from baseline values will be 
summarized descriptively by visit, and non-numeric test values will be tabulated when necessary. 
The baseline value will be determined using the last nonmissing value collected before the first 
application, prioritizing scheduled assessments for baseline identification over unscheduled 
visits. The last record before application 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. 
9.3.2. 
Laboratory Value Summaries 
Actual values and changes from baseline in clinical laboratory test results will be summarized 
using descriptive statistics. 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 will be tabulated. 
Laboratory data will be classified into Grades 1 through 5 using CTCAE v5.0. The following 
summaries will be produced for the laboratory data: 
• Number and percentage of participants with worst postbaseline CTCAE grade 
(regardless of baseline value). Each participant will be counted only for the worst 
grade observed postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 


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10. 
VITAL SIGNS 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, temperature, and respiratory 
rate, will be summarized descriptively. 
Normal ranges for vital sign values are defined in Table 2. 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 normal range and percentage 
change > 25%. The abnormal values for participants exhibiting alert vital sign abnormalities will 
be listed. 
Table 2: 
Normal Ranges for Vital Sign Values 
Parameter 
Low Threshold 
High Threshold 
Systolic blood pressure 
≥ 85 mmHg 
≤ 155 mmHg 
Diastolic blood pressure 
≥ 40 mmHg 
≤ 100 mmHg 
Pulse 
≥ 45 bpm 
≤ 100 bpm 
Temperature 
≥ 35.5°C 
≤ 38°C 
Respiratory rate 
≥ 8 breaths/min 
≤ 24 breaths/min 
11. 
PLANNED ANALYSES 
No formal interim analysis is planned in this study. 
The primary analysis will occur after the primary database lock, when all participants have 
completed the vehicle-controlled, double-blind treatment period. After the primary database 
lock, the sponsor will be unblinded and investigators and participants will remain blinded to the 
study treatment. After Week 52, investigators and participants will be unblinded. 


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12. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 3. 
Table 3: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
14 OCT 2022 
12.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
12.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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13. 
REFERENCES 
 
 
 
 
Rashighi M, Harris JE. Interfering with the IFN γ/CXCL10 pathway to develop new targeted 
treatments for vitiligo. Ann Transl Med 2015;3:343. 


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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables and listings for the Clinical Study Report. All 
tables are standard and will follow the conventions in the Standard Safety Tables v1.12. 
The lists of tables and listings are to be used as guidelines. Modifications of the lists that do not 
otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Demographics and disposition 
1.1.1 
Analysis Populations 
All-screened 
1.1.2.1 
Summary of Participant Disposition in Double-Blind Period 
ITT 
1.1.2.2 
Summary of Participant Disposition in Treatment Extension Period 
TEE 
1.1.3 
Summary of Number of Participants Enrolled by Country and Site 
ITT 
1.1.4.1 
Summary of Protocol Deviations in Double-Blind Period 
ITT 
1.1.4.2 
Summary of Protocol Deviations in Treatment Extension Period 
TEE 
1.2.1 
Summary of Demographics and Baseline Characteristics 
ITT 
1.2.2 
Summary of Demographics and Baseline Characteristics in Treatment Extension 
Period 
TEE 
1.3 
Summary of Baseline Disease Characteristics 
ITT 
1.4.1 
Summary of Prior Therapy for Vitiligo 
ITT 
1.4.2 
Summary of Prior Medications 
ITT 
1.4.3.1 
Summary of Concomitant Medications in Double-Blind Period 
ITT 
1.4.3.2 
Summary of Concomitant Medications in Treatment Extension Period 
TEE 
1.5 
Summary of General Medical History 
ITT 
1.6 
Summary of Participants With Assessments Not Done Due to COVID-19 
Pandemic 
ITT 
Biomarkers 
2.1.1 
Summary and Analysis of CXCL10 During the Double-Blind Period 
ITT 
2.1.2 
Summary and Analysis of Skin Biomarkers During the Double-Blind Period 
ITT 
 


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Table No. 
Title 
Population 
Exposure and compliance 
3.1.1.1 
Summary of Exposure in Double-Blind Period 
Safety 
3.1.1.2 
Summary of Exposure in Treatment Extension Period 
TEE 
3.1.1.3 
Summary of Exposure During Treatment Period 
Safety 
3.1.2.1 
Summary of Study Drug Compliance in Double-Blind Period 
Safety 
3.1.2.2 
Summary of Study Drug Compliance in Treatment Extension Period 
TEE 
3.1.2.3 
Summary of Study Drug Compliance During Treatment Period 
Safety 
Adverse events 
3.2.1.1.X 
Overall Summary of Treatment-Emergent Adverse Events 
Safety/TEE 
3.2.1.1.Y 
Overall Summary of Exposure-Adjusted Treatment-Emergent Adverse Events 
Safety 
3.2.2.1.X 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term 
Safety/TEE 
3.2.3.1.X 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency 
Safety/TEE 
3.2.3.1.2.X 
Summary of Application Site Reactions by MedDRA System Organ Class and 
Preferred Term 
Safety/TEE 
3.2.3.1.3.X 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety/TEE 
3.2.3.1.Y 
Summary of Treatment-Emergent Adverse Events With Vehicle Group by 
MedDRA Preferred Term in Decreasing Order of Frequency During the 
Treatment Period  
Safety 
3.2.3.1.2.Y 
Summary of Application Site Reactions With Vehicle Group by MedDRA 
Preferred Term in Decreasing Order of Frequency During the Treatment Period 
Safety 
3.2.3.1.3.Y 
Summary of Exposure-Adjusted Incidence Rates of Treatment-Emergent Adverse 
Events With Vehicle Group by MedDRA Preferred Terms in Decreasing Order of 
Frequency During the Treatment Period 
Safety 
3.2.3.1.5.Y 
Summary of Exposure-Adjusted Incidence Rates of Application Site Reactions 
With Vehicle Group by MedDRA Preferred Term in Decreasing Order of 
Frequency During the Treatment Period 
Safety 
3.2.4.1.X 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term  
Safety/TEE 
3.2.4.2.X 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency  
Safety/TEE 
3.2.5.1.X 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term  
Safety/TEE 
3.2.5.2.X 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency  
Safety/TEE 
3.2.6.1.X 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term  
Safety/TEE 
3.2.6.2.X 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency  
Safety/TEE 
3.2.7.1.X 
Summary of Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term  
Safety/TEE 


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Table No. 
Title 
Population 
3.2.8.1.X 
Summary of Treatment-Related Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term  
Safety/TEE 
3.2.9.1.X 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term  
Safety/TEE 
3.2.10.1.X 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption 
of Study Drug by MedDRA System Organ Class and Preferred Term  
Safety/TEE 
3.2.11.1.X 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
Study Drug by MedDRA System Organ Class and Preferred Term  
Safety/TEE 
 
  
 
Laboratory values and vital signs 
3.3.1.X 
Summary of Laboratory Values – Hematology 
Safety/TEE 
3.3.3.X 
Shift Summary of Hematology Laboratory Values in CTCAE Grade – To the 
Worst Abnormal Value 
Safety/TEE 
3.3.4.X 
Summary of Laboratory Values – Chemistry 
Safety/TEE 
3.3.6.X 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade – To the Worst 
Abnormal Value  
Safety/TEE 
3.4.1.X 
Summary of Systolic Blood Pressure 
Safety/TEE 
3.4.2.X 
Summary of Diastolic Blood Pressure  
Safety/TEE 
3.4.3.X 
Summary of Pulse 
Safety/TEE 
3.4.4.X 
Summary of Respiration Rate 
Safety/TEE 
3.4.5.X 
Summary of Body Temperature 
Safety/TEE 
Note: For AE tables ending with X, separate tables will be provided for the double-blind period (safety population) and treatment 
extension period (TEE population). 
Note: For AE tables ending with Y, tables will be provided for the overall treatment period (double-blind and treatment extension 
periods). Participants who cross over should be included in both treatment groups. 
Note: For laboratory values/vital sign tables ending with X, separate tables will be provided for the double-blind period (safety 
population) and treatment extension period (TEE population). 


Incyte Corporation 
Page 25 of 25 
INCB 18424-214 Statistical Analysis Plan 
14 OCT 2022 
VV-CLIN-022090 
CONFIDENTIAL 
Listings 
Listing No. 
Title 
Demographic and baseline characteristics 
2.1.1 
Participant Enrollment and Disposition Status 
2.1.2 
Participants Who Discontinued Treatment or Discontinued From Study Due to COVID-19 
2.1.3 
Participants With Assessments Not Done Due to COVID-19 Pandemic 
2.2.1 
Protocol Deviations 
2.2.2 
Participant Inclusion and Exclusion Criteria Violations 
2.3 
Analysis Populations 
2.4.1 
Demographic Characteristics 
2.4.2 
Baseline Disease Characteristics 
2.4.3 
Medical History 
2.4.4 
Prior and Concomitant Medications 
2.4.5 
Prior Medications for Vitiligo 
2.5.1 
Study Drug Exposure and Compliance 
 
Adverse events 
2.7.1 
Adverse Events 
2.7.2 
Adverse Events Leading to Study Drug Discontinuation 
2.7.3 
Serious Adverse Events 
2.7.4 
Treatment-Related Adverse Events 
2.7.5 
Adverse Events With a Fatal Outcome 
2.7.6 
Adverse Events Leading to Interruption of Study Drug 
2.7.8 
Grade 3 or Higher Adverse Events 
2.7.9 
Application Site Reactions 
 
 
Laboratory data 
2.8.1.1 
Clinical Laboratory Values – Hematology 
2.8.1.2 
Clinical Laboratory Values – Chemistry 
2.8.1.3 
Abnormal Clinical Laboratory Values – Hematology 
2.8.1.4 
Abnormal Clinical Laboratory Values – Chemistry 
Vital signs 
2.8.2.1 
Vital Signs 
2.8.2.2 
Abnormal Vital Sign Values 
2.8.2.3 
Alert Vital Sign Values