Clinical trial NCT04530344
Conditions: Vitiligo
Keywords: INCB018424
Sponsor: Incyte Corporation
Start date: 2020-09-24; Completion date: 2022-11-14
Enrollment: 458 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the duration of response following withdrawal of ruxolitinib cream (Cohort A vehicle group), safety and maintenance of response with continued use of ruxolitinib cream in participants who have completed either Study NCT04052425 or NCT04057573 (parent studies) in which the participants will have been using ruxolitinib cream BID for the previous 28 to 52 weeks depending on their initial randomization in the parent study.

Detailed description:

Arms: arm 1: Participants who achieve complete or almost complete facial repigmentation (achieve ≥ F VASI90) at Week 52 in the parent study will be assigned to Cohort A and will be randomized 1:1 to ruxolitinib cream. arm 2: Participants who achieve complete or almost complete facial repigmentation (ie, achieve ≥ F VASI90) at Week 52 in the parent study will be assigned to Cohort A and will be randomized 1:1 to vehicle cream. arm 3: Participants who did not achieve ≥ F-VASI90 at Week 52 of the parent studies will be assigned to Cohort B and will continue ruxolitinib cream.
Interventions: intervention 1: ruxolitinib intervention 2: Vehicle
Intervention descriptions: intervention 1: ruxolitinib cream is a topical formulation applied as a thin film to affected areas BID. intervention 2: Vehicle cream is a topical formulation applied as a thin film to affected areas.

Protocol documents:
Prot_000.pdf: 


Incyte Corporation 
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Protocol INCB 18424-308 Am 2 
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CONFIDENTIAL 
Clinical Study Protocol 
INCB 18424-308 
A Double-Blind, Vehicle-Controlled, Randomized Withdrawal and 
Treatment Extension Study to Assess the Long-Term Efficacy and 
Safety of Ruxolitinib Cream in Participants With Vitiligo 
(TRuE-V LTE) 
Product: 
Ruxolitinib Cream 
IND Number: 
 
EudraCT Number: 
2020-000987-53 
Phase of Study: 
3 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol: 
19 MAR 2020 
Protocol Amendment 1: 
28 SEP 2020 
Protocol Amendment 2: 
10 NOV 2020 
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 18424-308 Protocol (Amendment 2 dated 10 NOV 2020) 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 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
PROTOCOL SUMMARY ............................................................................................9 
2. 
INTRODUCTION ......................................................................................................15 
2.1. 
Background .................................................................................................................15 
2.1.1. 
Preclinical Safety ........................................................................................................16 
2.1.2. 
Clinical Pharmacokinetics ..........................................................................................16 
2.1.3. 
Clinical Efficacy and Safety of Ruxolitinib Cream in Vitiligo ..................................17 
2.2. 
Study Rationale ...........................................................................................................18 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Dose ..................................................................................................20 
2.3. 
Benefit/Risk Assessment ............................................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................22 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.2. 
Overall Study Duration ...............................................................................................25 
4.3. 
Study Termination ......................................................................................................25 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................27 
5.4. 
Screen Failures ............................................................................................................27 
5.5. 
Replacement of Participants .......................................................................................27 
6. 
STUDY TREATMENT ..............................................................................................28 
6.1. 
Study Treatments Administered .................................................................................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 .....................................................................................................31 
6.5.1. 
Criteria and Procedures for Application Interruptions and Modifications of 
Study Drug ..................................................................................................................31 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................32 
6.6. 
Concomitant Medications and Procedures .................................................................32 


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6.6.1. 
Permitted Medications and Procedures ......................................................................32 
6.6.2. 
Restricted Medications and Procedures ......................................................................33 
6.6.3. 
Prohibited Medications and Procedures .....................................................................33 
6.7. 
Rescue Treatment .......................................................................................................34 
6.8. 
Treatment After the End of the Study .........................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................34 
7.1. 
Discontinuation of Study Treatment ...........................................................................34 
7.1.1. 
Reasons for Discontinuation .......................................................................................34 
7.1.2. 
Discontinuation Procedures ........................................................................................35 
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. 
Eligibility Procedures .................................................................................................37 
8.1.3. 
Interactive Response Technology Procedure ..............................................................37 
8.1.4. 
Distribution of Reminder Cards and Diaries ..............................................................37 
8.2. 
Efficacy Assessments .................................................................................................38 
8.2.1. 
Body Surface Area ......................................................................................................38 
8.2.2. 
Vitiligo Area Scoring Index ........................................................................................38 
 
39 
 
39 
8.2.5. 
Photography ................................................................................................................39 
8.2.6. 
Patient-Reported Outcomes ........................................................................................40 
8.2.6.1. 
Vitiligo Noticeability Scale ........................................................................................40 
41 
41 
41 
8.2.6.5. 
Dermatology Life Quality Index ................................................................................41 
42 
42 
8.3. 
Safety Assessments .....................................................................................................42 


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8.3.1. 
Adverse Events ...........................................................................................................43 
8.3.2. 
Physical Examinations ................................................................................................43 
8.3.3. 
Vital Signs ..................................................................................................................43 
8.3.4. 
Laboratory Assessments .............................................................................................44 
8.3.4.1. 
Pregnancy Testing ......................................................................................................44 
8.4. 
Pharmacokinetic Assessments ....................................................................................45 
8.5. 
Pharmacodynamic and Translational Assessments ....................................................45 
8.6. 
Unscheduled Visits .....................................................................................................45 
8.7. 
End of Treatment and/or Early Termination ..............................................................45 
8.8. 
Safety Follow-Up ........................................................................................................46 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................46 
9.1. 
Definition of Adverse Event .......................................................................................46 
9.2. 
Definition of Serious Adverse Event ..........................................................................47 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........48 
9.4. 
Reporting of Serious Adverse Events .........................................................................50 
9.5. 
Emergency Unblinding of Treatment Assignment .....................................................51 
9.6. 
Pregnancy ...................................................................................................................52 
9.7. 
Warnings and Precautions ..........................................................................................52 
9.8. 
Product Complaints ....................................................................................................52 
9.9. 
Treatment of Overdose ...............................................................................................53 
10. 
STATISTICS ..............................................................................................................53 
10.1. 
Sample Size Determination ........................................................................................53 
10.2. 
Populations for Analysis .............................................................................................53 
10.3. 
Level of Significance ..................................................................................................54 
10.4. 
Statistical Analyses .....................................................................................................54 
10.4.1. 
Efficacy Analysis ........................................................................................................54 
10.4.2. 
Safety Analyses ..........................................................................................................55 
10.4.2.1. 
Adverse Events ...........................................................................................................55 
10.4.2.2. 
Clinical Laboratory Tests ...........................................................................................55 
10.4.2.3. 
Vital Signs ..................................................................................................................55 
10.4.3. 
Other Analyses ............................................................................................................55 
10.5. 
Interim Analysis ..........................................................................................................55 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................56 
11.1. 
Investigator Responsibilities .......................................................................................56 
11.2. 
Data Management .......................................................................................................57 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................58 
11.4. 
Financial Disclosure ...................................................................................................59 
11.5. 
Publication Policy .......................................................................................................59 
11.6. 
Study and Site Closure................................................................................................59 
12. 
REFERENCES ...........................................................................................................61 
APPENDIX A. ELIGIBILITY CRITERIA FROM STUDIES INCB 18424-306 AND 
INCB 18424-307 ........................................................................................................63 
APPENDIX B. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................66 
APPENDIX C. WHO CLASSIFICATION OF TOPICAL CORTICOSTEROIDS ...................67 
APPENDIX D. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................68 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................70 
 
LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .......................................................9 
Table 2: 
Key Study Design Elements .......................................................................................10 
Table 3: 
Schedule of Activities .................................................................................................12 
Table 4: 
Objectives and Endpoints ...........................................................................................22 
Table 5: 
Study Treatment Information .....................................................................................28 
Table 6: 
Guidelines for Interruption and Restarting of Study Drug .........................................31 
 
......................................39 
 
39 
Table 9: 
Required Laboratory Analytes ....................................................................................44 
Table 10: Populations for Analysis .............................................................................................53 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................11 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
2D 
2-dimensional 
3D 
3-dimensional 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BID 
twice daily 
BSA 
body surface area 
CDC 
Centers for Disease Control and Prevention 
CDLQI 
Children’s Dermatology Life Quality Index 
CFR 
Code of Federal Regulations 
CO2 
carbon dioxide 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLQI 
Dermatology Life Quality Index 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EOS 
end of study 
EOT 
end of treatment 
FAS 
Full Analysis Set 
F-BSA 
facial body surface area 
F-VASI 
Face Vitiligo Area Scoring Index 
F-VASI50/75/90 
≥ 50%/ 75%/ 90% improvement from baseline in Face Vitiligo Area Scoring 
Index score 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
IC50 
50% inhibitory concentration 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ID 
identification 


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Abbreviations and 
Special Terms 
Definition 
IEC 
independent ethics committee 
INFO 
International Initiative for Outcomes for Vitiligo 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT-Ext 
intent to treat long-term extension 
JAK 
Janus kinase 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
NB-UVB 
narrowband ultraviolet B 
 
 
PASI 
Psoriasis Area and Severity Index 
PD 
pharmacodynamic 
PDCO 
Paediatric Committee 
 
 
PhV 
pharmacovigilance 
PK 
pharmacokinetic 
PUVA 
psoralen and ultraviolet A 
QD 
once daily 
Rux 
ruxolitinib 
SAE 
serious adverse event 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SPF 
sun protection factor 
SUSAR 
suspected unexpected adverse reaction 
T-BSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
T-VASI 
total body Vitiligo Area Scoring Index 
T-VASI50/75/90 
≥ 50%/ 75%/ 90% improvement in total body Vitiligo Area Scoring Index 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
US 
United States (of America) 
UV 
ultraviolet 
VASI 
Vitiligo Area Scoring Index 
VNS 
Vitiligo Noticeability Scale 
WHO 
World Health Organization 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  A Double-Blind, Vehicle-Controlled, Randomized Withdrawal and Treatment 
Extension Study to Assess the Long-Term Efficacy and Safety of Ruxolitinib Cream in 
Participants With Vitiligo (TRuE-V LTE) 
Protocol Number:  INCB 18424-308 
Objectives and Endpoints: 
Table 1 presents the primary and secondary endpoints and objectives. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the duration of clinical response of 
ruxolitinib cream in participants with vitiligo. 
For participants who are randomized in Cohort A: 
• Time to relapse (defined as < F-VASI75). 
Key Secondary 
To evaluate the duration of clinical response of 
ruxolitinib cream in participants with vitiligo. 
For participants who are randomized in Cohort A: 
• Time to maintain ≥ F-VASI90 response. 
Secondary 
To further evaluate the efficacy of ruxolitinib 
cream. 
• Proportion of participants who achieve 
F-VASI50/75/90 during the extension treatment 
period. 
• Actual measurements, change, and percentage 
change from baseline in F-VASI. 
• Proportion of participants who achieve 
T-VASI50/75/90 during the extension treatment 
period. 
• Actual measurements, change, and percentage 
change from baseline in T-VASI. 
• Actual measurements, change, and percentage 
change from baseline in F-BSA. 
• Actual measurements, change, and percentage 
change from baseline in T-BSA. 
• Proportion of participants achieving a VNS of 
“4 – A lot less noticeable” or “5 – No longer 
noticeable” during the extension treatment 
period. 
To determine the participants' quality of life. 
• Change from Week 52 in DLQI (or CDLQI) 
during the extension treatment period. 
To evaluate the safety and tolerability of 
ruxolitinib cream. 
• The frequency and severity of AEs; includes 
performing physical examinations and 
collecting vital signs and laboratory data for 
hematology and serum chemistry. 
To evaluate the ruxolitinib PK in plasma after 
treatment with ruxolitinib cream. 
• Trough plasma concentrations of ruxolitinib at 
Week 80 and Week 104. 


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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 3 
Clinical Indication 
Vitiligo 
Population 
Male and female participants from Study INCB 18424-306 or Study 
INCB 18424-307 (parent studies) conducted in adults and adolescents with 
vitiligo who adequately completed the visits and assessments required for the 
treatment periods, as defined in the parent study protocol, and tolerated 
ruxolitinib cream treatment without safety concern for continuation. 
Number of 
Participants 
Approximately 500 
Study Design 
Double-blind, vehicle-controlled, randomized withdrawal (Cohort A) and 
treatment extension (Cohort A and Cohort B) 
Estimated Duration 
of Study 
Participation 
Extension treatment period:  52 weeks 
Safety follow-up:  4 weeks (30 days) after last application of study treatment 
or last study visit 
Total:  Up to approximately 56 weeks 
DSMB 
No 
Treatment Groups and Duration: 
This is a Phase 3, double-blind, vehicle-controlled, randomized withdrawal and treatment 
extension study that will enroll eligible participants who have completed either 
Study INCB 18424-306 or Study INCB 18424-307 (parent studies) in which the participants will 
have been using ruxolitinib cream 1.5% BID for the previous 28 to 52 weeks (depending on their 
initial randomization in the parent study; see Figure 1).  Participants who successfully complete 
either of the parent studies and tolerated ruxolitinib treatment without safety concern and with 
good compliance for continuation may be eligible to participate in this treatment extension study. 
The parent study population comprised adolescent and adult participants (age ≥ 12 years) with 
non-segmental vitiligo who had depigmented area including ≥ 0.5% BSA on the face, 
≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, and ≥ 3 T-VASI, with total body involved vitiligo 
area (facial and nonfacial) that was not to exceed 10% BSA. 
Eligible participants in this treatment extension study will be assigned to one of 2 cohorts, 
Cohort A or Cohort B, based on their F-VASI responses at the time of enrollment in this 
extension study (ie, at Week 52).  Participants who achieve complete or almost complete facial 
repigmentation (ie, achieve ≥ F-VASI90) at Week 52 in the parent study will be assigned to 
Cohort A, stratified by the original treatment received on study Day 1 of the parent study, and 
randomized 1:1 to treatment with vehicle cream BID or ruxolitinib cream 1.5% BID for an 
additional 52 weeks (ie, until EOT at Week 104).  However, any participants in Cohort A who 
experience relapse (defined as < F-VASI75) will receive ruxolitinib cream 1.5% BID as an 
open-label rescue treatment until they complete treatment (Week 104 or EOT).  Participants who 
did not achieve ≥ F-VASI90 at Week 52 of the parent studies will be assigned to Cohort B and 


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will continue ruxolitinib cream 1.5% BID for 52 weeks (ie, until EOT at Week 104).  For 
Cohort A, the participant, investigator, and sponsor will remain blinded to treatment assignment; 
the treatment for Cohort B will be open-label. 
See Section 4.1 for full details of the study design. 
Figure 1 presents the study design schema, and Table 3 presents the SoA.  Adherence to the 
study design requirements, including those specified in the SoA, is essential and required for 
study conduct. 
Figure 1: 
Study Design Schema 
 
1. All participants in Cohort A will use their randomly assigned treatment (either vehicle or ruxolitinib cream) on both the face 
and total body. 
2. Rescue treatment:  If, at any time, a participant in Cohort A loses a clinically meaningful response on the face (< F-VASI75), 
the participant will receive open-label 1.5% BID ruxolitinib cream until Week 104 or EOT. 


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Table 3: 
Schedule of Activities 
Evaluation 
Parent 
Study 
Extension Treatment Period 
Safety 
Follow-Up 
Notes 
Week 52 
(Parent 
Study) 
± 7 d 
Enrollment 
(Week 52) 
± 7 da 
Weeks 56, 
60, and 64 
± 7 d 
Week 68b 
± 7 d 
Week 80b 
± 7 d 
Week 92b 
± 7 d 
Week 104b 
(EOT) 
± 7 d 
30 Days 
After EOT 
(EOS) 
+ 7 d 
Administrative procedures 
Informed consent 
 
X 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
 
X 
 
 
 
 
 
 
 
Contact IRT 
 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medications 
X 
 
X 
X 
X 
X 
X 
X 
 
Apply study drug 
 
X 
X 
X 
X 
X 
 
 
 
Dispense (D) and return (R) 
study drug and diary cards 
R 
D 
R/D 
R/D 
R/D 
R/D 
R 
 
 
Safety assessments 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
 
Comprehensive physical 
examination 
X 
 
 
 
 
 
X 
 
 
Targeted physical 
examination 
 
 
 
X 
X 
X 
 
X 
A targeted physical examination 
should be conducted as indicated by 
symptoms reported by the 
participant, AEs, or other findings.  
Abnormalities that are considered 
clinically significant in the 
judgment of the investigator are to 
be reported as AEs.  See 
Section 8.3.2. 
Vital signs 
X 
 
X 
X 
X 
X 
X 
X 
 
Efficacy assessments 
F-BSA 
X 
 
X 
X 
X 
X 
X 
X 
 
T-BSA 
X 
 
X 
X 
X 
X 
X 
X 
Includes facial and nonfacial areas. 
F-VASI 
X 
 
X 
X 
X 
X 
X 
X 
 
T-VASI 
X 
 
X 
X 
X 
X 
X 
X 
Includes facial and nonfacial areas. 


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Table 3: 
Schedule of Activities (Continued) 
Evaluation 
Parent 
Study 
Extension Treatment Period 
Safety 
Follow-Up 
Notes 
Week 52 
(Parent 
Study) 
± 7 d 
Enrollment 
(Week 52) 
± 7 da 
Weeks 56, 
60, and 64 
± 7 d 
Week 68b 
± 7 d 
Week 80b 
± 7 d 
Week 92b 
± 7 d 
Week 104b 
(EOT) 
± 7 d 
30 Days 
After EOT 
(EOS) 
+ 7 d 
Efficacy assessments (continued) 
Photography of face 
X 
 
 
X 
X 
X 
X 
X 
2D photograph at all sites; 3D 
photography at selected sites. 
Photography of nonfacial 
target area 
X 
 
 
X 
X 
X 
X 
X 
2D photography at all sites.  The 
genitalia area should not be 
photographed. 
Patient-reported outcomes 
To be evaluated prior to any other 
study procedures/assessments. 
VNS 
X 
 
X 
X 
X 
X 
X 
X 
The participant will be provided 
their baseline photo and a mirror to 
perform this assessment. 
DLQI 
X 
 
X 
X 
X 
X 
X 
X 
For participants who are age 
< 16 years at baseline (Day 1) of the 
parent study, the CDLQI will be 
completed instead. 


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Table 3: 
Schedule of Activities (Continued) 
Evaluation 
Parent 
Study 
Extension Treatment Period 
Safety 
Follow-Up 
Notes 
Week 52 
(Parent 
Study) 
± 7 d 
Enrollment 
(Week 52) 
± 7 da 
Weeks 56, 
60, and 64 
± 7 d 
Week 68b 
± 7 d 
Week 80b 
± 7 d 
Week 92b 
± 7 d 
Week 104b 
(EOT) 
± 7 d 
30 Days 
After EOT 
(EOS) 
+ 7 d 
Laboratory assessments 
Hematology and chemistry 
assessments 
X 
 
X 
X 
X 
X 
X 
X 
 
Pregnancy testing 
X* 
 
X 
X 
X 
X 
X 
X* 
*Female participants of 
childbearing potential will have a 
serum pregnancy test at Week 52 
and at the safety follow-up visit.  A 
urine pregnancy test will be 
conducted at all other visits.  A 
positive urine test must be 
confirmed by a serum test. 
PK 
 assessments 
PK plasma sampling 
(trough) 
 
 
 
 
X* 
 
X 
 
Time of last study drug application 
to be recorded in eCRF.  Blood 
samples must not be drawn from the 
area that has been treated with study 
drug. 
*Samples will be drawn at predose.  
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 All scheduled assessments for the Week 52 visit must be performed before participants who meet eligibility criteria may enter the extension treatment period of this study. 
b Starting from Week 68, participants will be contacted by site personnel via telephone call every 4 weeks until Week 104 to follow-up on disease status.  If there is any disease 
progression or any concerns, unscheduled visits may occur. 


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2. 
INTRODUCTION 
Ruxolitinib cream is in Phase 3 development for the treatment of vitiligo and is a topical 
formulation of ruxolitinib phosphate, an inhibitor of the JAK family of protein TYKs.  Because 
JAKs serve to translate extracellular signals from a number of relevant cytokines and growth 
factors upregulated in inflammatory diseases such as vitiligo, JAK inhibitors represent potential 
therapeutic agents for this condition. 
2.1. 
Background 
Vitiligo is an autoimmune pigmentary disease that is estimated to affect 0.5% to 2% of the 
population worldwide (Krüger and Schallreuter 2012) and is characterized by depigmented 
patches of skin with a selective loss of melanocytes.  The natural course of the disease is 
generally unpredictable, but it is often progressive.  Some degree of spontaneous repigmentation 
may occur in 10% to 20% of patients; however, it is typically not cosmetically acceptable 
(Castanet and Ortonne 1997). 
Vitiligo is considered a serious disease owing to its substantial psychological burden on patients 
and its progressive course if left untreated.  Involvement of exposed skin (eg, face and hands) 
can have a major negative impact on self-esteem and quality of life (Silverberg and 
Silverberg 2013).  Studies also suggest that the onset of vitiligo beginning in childhood can be 
associated with significant psychological trauma that may have long lasting effects on 
self-esteem (Linthorst Homan et al 2008).  A majority of vitiligo sufferers feel their appearance 
is moderately to severely intolerable, are distressed about their disease, experience 
stigmatization, and have feelings of anxiety and embarrassment when meeting strangers or 
beginning a new sexual relationship (Porter et al 1990, Salzer and Schallreuter 1995, Krüger 
et al 2014).  Additionally, based on various meta-analyses, patients with vitiligo are 
approximately 5 times more likely to suffer from depression than healthy controls (Lai 
et al 2017, Wang et al 2018, Osinubi et al 2018). 
Currently, there is no approved drug treatment for vitiligo.  The management of vitiligo is 
empirical and based on the most recent consensus guidelines (American Academy of 
Dermatology, Gawkrodger et al 2008, Taieb et al 2013, Vitiligo Research Foundation).  In 
general, first-line treatments consist of topical steroids and calcineurin inhibitors, which may be 
most useful for treating disease that is localized.  However, this use is off-label, there are 
inconclusive (or insufficient) data supporting their efficacy, many have restrictions on duration 
of chronic use, and AEs can limit their tolerability.  Second-line treatments consist of 
phototherapy (NB-UVB and PUVA) and systemic steroid treatment.  However, phototherapy 
regimens typically require 2 to 3 treatments per week, and 12 to 24 months of continuous 
phototherapy may be necessary to acquire maximal repigmentation (Taieb et al 2013); relapses 
are common.  Third-line treatments consist of surgical grafting techniques and depigmenting 
treatments.  Surgery is best indicated for stable and localized forms of vitiligo, and only a small 
number of patients with vitiligo are considered suitable candidates.  All of these treatments can 
have adverse effects that limit their use. 
No available product or therapy is able to modify the course of vitiligo disease and produce a 
long-lasting effect.  Given the lack of approved therapies and safety concerns and modest 


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effectiveness of current off-label drug treatments, there is a need to identify a safe and effective 
new treatment for vitiligo. 
Janus kinases are intracellular signaling enzymes that act downstream of key proinflammatory 
cytokines implicated in vitiligo pathogenesis.  Ruxolitinib is a novel, potent, and selective 
inhibitor of the JAKs, specifically JAK1 and JAK2 with modest to marked selectivity against 
TYK2 and JAK3.  Ruxolitinib potently (IC50 < 5 nM) inhibits JAKs, yet it does not significantly 
inhibit (< 30% inhibition) a broad panel of 26 kinases when tested at 200 nM (approximately 
100 times the average IC50 value for JAK enzyme inhibition).  Ruxolitinib-mediated inhibition of 
JAK signaling may be an effective strategy for vitiligo treatment. 
2.1.1. 
Preclinical Safety 
In preclinical studies, ruxolitinib cream did not act as a contact sensitizer nor did it produce 
significant dermal irritation or demonstrate phototoxicity or photoallergenic potential.  Topical 
application of ruxolitinib cream 1.5% QD for 9 months to Gottingen minipigs did not result in 
any adverse systemic effects. 
The toxicity of ruxolitinib has been evaluated following oral administration to mice, rats, and 
dogs.  Findings in these studies were primarily those associated with the mechanism of action of 
ruxolitinib, including decreases in red blood cells, reticulocytes, eosinophils, and lymphocytes, 
which have been observed along with lymphoid depletion in bone marrow and lymphoid organs.  
Systemic exposures in these studies exceeded those anticipated with topical application.  
Ruxolitinib was not teratogenic when administered to pregnant rats or rabbits; there were no 
adverse developmental effects at doses below those associated with maternal toxicity.  In vitro 
testing also showed that ruxolitinib was not mutagenic or clastogenic. 
In a toxicity study of orally-administered ruxolitinib in juvenile rats beginning on Days 7, 14, or 
21 postpartum, dose-related effects on body weight gain and decrements in various bone 
measures were observed in all cohorts.  Hematology and other microscopic findings were similar 
to those previously observed in general toxicology studies.  Other than the bone findings, there 
were no other novel toxicities in juvenile animals.  In animals administered ruxolitinib orally 
beginning on Day 21 postpartum (considered approximately equivalent to a 2-year-old human), 
bone findings occurred at exposures higher than those anticipated with topical application.  The 
clinical relevance of these findings to humans is not clear. 
Further information on preclinical toxicology and safety is summarized in ruxolitinib cream 
IB Sections 4.3 and 4.4. 
2.1.2. 
Clinical Pharmacokinetics 
Clinical PK studies have demonstrated that exposures of ruxolitinib were generally 
strength-dependent with a moderate interparticipant variability.  The systemic PK following 
topical application in treatment of plaque psoriasis (Study INCB 18424-202) and AD (Study 
INCB 18424-206) is characterized by apparent first-order release, modest peak-to-trough 
excursion (ratio ~2), estimated relative bioavailability of 3% to 5%, and an apparent terminal 
elimination half-life of approximately 3 days.  The plasma metabolite profile following topical 
application is generally similar to that observed following oral administration. 


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Preliminary PK data are available from topical application in treatment of vitiligo (Study 
INCB 18424-211).  Plasma ruxolitinib concentrations reached steady-state at or before Week 4 
and were similar at Week 24/Week 28 after treatment of ruxolitinib cream.  Plasma 
concentrations of ruxolitinib for predose and 2.0-hour postdose were similar, indicating a slow 
rate of absorption.  Application of ruxolitinib cream 0.15% QD, 0.5% QD, 1.5% QD, and 
1.5% BID resulted in mean (range) plasma concentrations of 5.75 nM (0-28.8 nM), 
12.6 nM (0-82.1 nM), 59.1 nM (0-245 nM), and 113 nM (0-662 nM), respectively, after 
24 weeks of treatment.  Plasma concentrations increased as dose strength and frequency of 
dosing were increased. 
The ruxolitinib terminal half-life following oral administration is approximately 3 hours with no 
appreciable accumulation of either parent or metabolites with BID oral dosing.  However, the 
long apparent half-life (~4 days) observed in topical treatment is due to the slow absorption from 
the skin, which acts as a depot (Study INCB 18424-202).  Therefore, the plasma concentration of 
ruxolitinib (following its topical application) reaches steady-state in 2 to 4 weeks and remains 
relatively unchanged after steady-state is reached, and this was confirmed in Study 
INCB 18424-203 and Study INCB 18424-211. 
Preliminary PK data are available for adolescents (aged ≥ 12 to 17 years) with AD (Study 
INCB 18424-102).  Plasma concentrations of ruxolitinib were time-dependent with higher 
concentrations on Day 1 and decreasing concentrations on Day 15 and Day 29.  The observed 
decrease in ruxolitinib blood levels at Week 4 probably relates to a changing proportion of 
diseased to healthy skin treated at that timepoint and immediately before it.  Steady-state plasma 
concentrations (based on geometric mean) following 1.5% BID in adolescent participants is 
similar to that in adults, suggesting similar skin flux in the 2 age groups. 
Further information on clinical PK is summarized within ruxolitinib cream IB Section 5.2. 
2.1.3. 
Clinical Efficacy and Safety of Ruxolitinib Cream in Vitiligo 
The clinical efficacy and safety in vitiligo of ruxolitinib cream was evaluated in Study 
INCB 18424-211, a Phase 2, randomized, double-blind, vehicle-controlled study conducted in 
adults with vitiligo who have depigmented areas including at least 0.5% BSA on the face and at 
least 3% BSA on nonfacial areas.  In the first part of the study, a total of 157 participants were 
equally randomized to receive ruxolitinib cream 1.5% BID, 1.5% QD, 0.5% QD, 0.15% QD, or 
vehicle BID for 24 weeks.  In the second part of the study, all participants initially randomized to 
vehicle BID and participants initially randomized to 0.15% QD who did not achieve ≥ 25% 
improvement from baseline in F-VASI were re-randomized to 1 of the 3 higher dosing groups 
for an additional 28 weeks.  All other participants maintained the same treatment until Week 52.  
After Week 52, participants could receive open-label 1.5% BID for an additional 52 weeks.  The 
primary endpoint was the proportion of participants who achieved a ≥ 50% improvement from 
baseline in F-VASI50 at Week 24. 
All ruxolitinib treatment arms demonstrated clinically meaningful efficacy and superiority over 
vehicle.  The proportion of participants who achieved an F-VASI50 at Week 24 was statistically 
significantly greater for ruxolitinib cream versus vehicle with response rates of 32.3%, 25.8%, 
50.0%, and 45.5% for ruxolitinib cream 0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID, 
respectively, and 3.1% for vehicle.  The proportion of participants who achieved an F-VASI75 at 
Week 24 was also statistically significantly greater for ruxolitinib cream versus vehicle with 


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response rates of 9.7%, 16.1%, 16.7%, and 30.3% for ruxolitinib cream 0.15% QD, 0.5% QD, 
1.5% QD, and 1.5% BID, respectively, and 0% for vehicle.  For the participants who were 
initially randomized to ruxolitinib cream 0.5% QD, 1.5% QD, and 1.5% BID and continued on 
these treatments until Week 52, continued improvement in F-VASI response was observed with 
the proportion of participants who achieved an F-VASI75 at Week 52, demonstrating response 
rates of 29.0%, 30.0%, and 51.5% for ruxolitinib cream, respectively. 
Improvements in T-VASI were observed for both Week 24 and Week 52.  The proportion of 
participants who achieved a T-VASI50 at Week 24 was also statistically significantly greater for 
ruxolitinib cream 0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID compared with vehicle with 
response rates of 16.1%, 6.5%%, 23.3%, and 12.1%, respectively, compared with 0% in 
vehicle-treated participants.  Continued improvement in participants treated with 0.5% QD, 
1.5% QD, and 1.5% BID through Week 52 was observed with response rates in T-VASI50 
of 25.8%, 30.0%, and 36.4%, respectively. 
All ruxolitinib treatment arms were generally safe and well-tolerated with no significant TEAEs 
or application site events and no clinically relevant hematological changes.  The TEAE rate 
overall was low and similar between active treatment and vehicle.  There were 4 SAEs through 
52 weeks, none of which were treatment-related.  Discontinuations from treatment through 
52 weeks was low.  Safety and tolerability were similar between the Week 24 and Week 52 
period. 
Efficacy and safety data from the ongoing Phase 3 studies in vitiligo (INCB 18424-306 or 
INCB 18424-307) are not yet available. 
Further information on clinical efficacy and safety in vitiligo patients as well as other indications 
(psoriasis and AD) is summarized in ruxolitinib cream IB Section 5.3. 
2.2. 
Study Rationale 
This study is designed to evaluate the duration of response following withdrawal of ruxolitinib 
cream (Cohort A vehicle group) and maintenance of response with continued use of ruxolitinib 
cream in individuals with vitiligo who have experienced repigmentation with ruxolitinib cream 
treatment.  This study is also designed to characterize the long-term efficacy and safety profile of 
ruxolitinib cream in individuals with vitiligo treated for up to a total of 104 weeks. 
2.2.1. 
Scientific Rationale for Study Design 
Findings from the Phase 2 study, INCB 18424-211, suggest that JAK inhibition is an effective 
therapeutic strategy to treat patients with vitiligo (see Section 2.1.3).  The objective of this 
extension study and its parent studies is to confirm and extend the Phase 2 study efficacy and 
safety findings for ruxolitinib cream in a larger patient population. 
The current Phase 3 extension study is designed to evaluate the long-term efficacy, safety, and 
tolerability of ruxolitinib cream.  Combined with data from its Phase 3 parent studies, this study 
will provide efficacy and safety data in patients with vitiligo treated for up to 104 weeks with 
ruxolitinib cream 1.5% BID. 
This extension study will enroll interested and eligible participants from the study population of 
the parent studies.  The eligibility criteria used in the parent studies were generally designed to 
enroll a representative segment of the vitiligo patient population.  The parent studies enrolled 


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both male and female participants (the prevalence of vitiligo is similar between men and women) 
with non-segmental (generalized) vitiligo, which is the most common type of vitiligo, accounting 
for up to 90% of cases (Taieb et al 2009).  While the Phase 2 study enrolled participants 18 years 
or older, in the parent Phase 3 studies, participants ≥ 12 years of age were enrolled; this is 
important because almost 50% of vitiligo patients present before 20 years of age (Rodrigues 
et al 2017).  The emerging safety profile supports enrolling this population of adolescents as 
ruxolitinib cream has been well-tolerated in the Phase 2 vitiligo study and the AD studies, 
including Study INCB 18424-102, which enrolled participants with AD aged 12 to 18 years.  
Additionally, enrollment in the parent studies targeted participants who were amenable to topical 
therapy of their vitiligo with depigmented areas including ≥ 0.5% BSA on the face, 
≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, ≥ 3 T-VASI, and total body vitiligo area 
≤ 10% BSA (facial and nonfacial).  This extension study will thus be composed of participants 
meeting these same criteria. 
This study includes a 52-week vehicle group; however, participants randomized to vehicle will 
have already received at least 28 weeks of treatment with ruxolitinib cream 1.5% BID in the 
parent study, and only participants who have already achieved complete or near-complete 
response (ie, achieve ≥ F-VASI90) at the time of randomization in this extension study treatment 
will be subject to randomization to vehicle.  Additionally, if participants randomized to vehicle 
experience relapse (< F-VASI75), they will receive open-label rescue treatment of ruxolitinib 
cream 1.5% BID until they treatment.  Thus, under the design of this study, no participants will 
go untreated if they experience a clinically meaningful recurrence after withdrawal of active 
treatment.  Including this vehicle group for participants with ≥ F-VASI90 allows for a robust 
examination of the duration of response following ruxolitinib cream withdrawal. 
Inclusion of participants who have achieved ≥ F-VASI90 and are randomized to ruxolitinib 
cream 1.5% BID allows for an assessment of the maintenance of response with continued use of 
ruxolitinib cream.  Additionally, inclusion of participants who did not achieve ≥ F-VASI90 and 
are assigned to ruxolitinib cream 1.5% BID allows for an assessment of the maintenance of 
response and an evaluation of the time course of response with continued use of ruxolitinib 
cream in individuals who may be exhibiting slower response times.  For both of these groups, the 
additional 52 weeks of treatment in this extension study is designed to further evaluate the 
long-term efficacy and safety of ruxolitinib cream 1.5% BID treatment. 
The primary and key secondary endpoints in this study evaluate the duration of clinical response 
and the maintenance of response as measured by F-VASI.  VASI is recognized as a validated 
quantitative scale developed by Hamzavi et al (2004).  Areas affected by depigmentation due to 
vitiligo will be assessed using the VASI, which is a quantitative clinical tool that is analogous to 
the PASI used in psoriasis and is based on a composite estimate of the overall area of vitiligo 
patches at baseline and the degree of macular repigmentation within these patches over time.  In 
this extension study, both F-VASI and T-VASI will be evaluated.  F-VASI was the primary 
endpoint in the Phase 2 study and was found to accurately reflect the repigmentation response 
and discern clinically relevant differences in efficacy levels of individual treatment regimens.  In 
addition, from the patient’s perspective, facial disease involvement has the strongest relevance 
on appearance and correlation to the patient’s psychological burden.  Prior to the earlier parent 
Phase 3 studies, the sponsor performed additional analyses to evaluate the reliability, validity, 
ability to detect change, and score interpretability of the VASI instrument based on clinical data 
from the Phase 2 study.  The results indicate that the instrument met or exceeded the standards 


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for reliability, validity, and ability to detect change.  These analyses of treatment efficacy support 
the clinical relevance of the F-VASI and T-VASI endpoints for vitiligo. 
Considering findings from the INFO study (International Initiative for Outcomes [INFO] for 
Vitiligo; Eleftheriadou et al 2012), INCB 18424-211 results, and the methods used in the parent 
studies, a number of measures are incorporated into this extension study.  In contrast to the 
Phase 2 study, the primary outcome measure is the F-VASI75 as this represents a higher degree 
of response for the face.  The VNS has been included as a secondary measure.  This is a recently 
validated measure to address the question of satisfactory repigmentation from the patient 
perspective as the INFO study identified cosmetic acceptability of repigmentation to be of high 
importance to patients.  Other measures included in this study are the 
, 
, 
, DLQI (CDLQI), 
.  Relationships between improvement and 
VASI score improvements in these parameters will be examined. 
2.2.2. 
Justification for Dose 
The safety and efficacy outcomes from the Phase 2 study, INCB 18424-211, can be summarized 
as follows: 
• All ruxolitinib cream treatment arms 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 separate 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. 
• The 1.5% BID treatment regimen demonstrated the highest response for F-VASI75 at 
both Week 24 (30.3%) and Week 52 (51.5%).  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 hematological 
changes through Week 52. 
Based on the above data, the proposed treatment regimen of ruxolitinib cream for the Phase 3 
studies is 1.5% BID.  Limiting treatment to up to 10% BSA will limit exposure and potentially 
improve the benefit-risk. 
2.3. 
Benefit/Risk Assessment 
In nonclinical studies, ruxolitinib cream did not act as a contact sensitizer, nor did it produce 
significant dermal irritation or demonstrate phototoxicity or photoallergenic 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. 


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The primary clinical risks noted with orally administered ruxolitinib treatment for 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 rheumatoid arthritis participants with 
greater bone marrow reserve, the effects on hematopoietic proliferation appear to be less 
pronounced.  Owing to its low systemic bioavailability, ruxolitinib cream is not expected to bring 
about clinically significant changes in hematology laboratory investigations. 
Based on Week 24 and Week 52 results of the Phase 2 study, INCB 18424-211, all active 
treatment groups were found to have no clinically relevant AEs related to the treatment regimens 
and were well-tolerated on application sites.  They 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 
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 ruxolitinib cream IB. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 4 presents the objectives and endpoints. 
Table 4: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the duration of clinical response of 
ruxolitinib cream in participants with vitiligo. 
For participants who are randomized in Cohort A: 
• Time to relapse (defined as < F-VASI75). 
Key Secondary 
To evaluate the duration of clinical response of 
ruxolitinib cream in participants with vitiligo. 
For participants who are randomized in Cohort A: 
• Time to maintain ≥ F-VASI90 response. 
Secondary 
To further evaluate the efficacy of ruxolitinib 
cream. 
• Proportion of participants who achieve 
F-VASI50/75/90 during the extension treatment 
period. 
• Actual measurements, change, and percentage 
change from baseline in F-VASI. 
• Proportion of participants who achieve 
T-VASI50/75/90 during the extension treatment 
period. 
• Actual measurements, change, and percentage 
change from baseline in T-VASI. 
• Actual measurements, change, and percentage 
change from baseline in F-BSA. 
• Actual measurements, change, and percentage 
change from baseline in T-BSA. 
• Proportion of participants achieving a VNS of 
“4 – A lot less noticeable” or “5 – No longer 
noticeable” during the extension treatment 
period. 
To determine the participants' quality of life 
• Change from Week 52 in DLQI (or CDLQI) 
during the extension treatment period. 
To evaluate the safety and tolerability of 
ruxolitinib cream. 
• The frequency and severity of AEs; includes 
performing physical examinations and 
collecting vital signs and laboratory data for 
hematology and serum chemistry. 
To evaluate the ruxolitinib PK in plasma after 
treatment with ruxolitinib cream. 
• Trough plasma concentrations of ruxolitinib at 
Week 80 and Week 104. 


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Table 4: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 3, double-blind, vehicle-controlled, randomized withdrawal and treatment 
extension study that will enroll eligible participants who have completed either Study 
INCB 18424-306 or Study INCB 18424-307 (parent studies) in which the participants will have 
been using ruxolitinib cream 1.5% BID for the previous 28 to 52 weeks (depending on their 
initial randomization in the parent study; see Figure 1). 
The parent studies are randomized, vehicle-controlled studies in adolescent and adult participants 
(age ≥ 12 years) with non-segmental vitiligo who have depigmented area 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) was not to exceed 10% BSA.  Approximately 300 participants 
per each parent study were to be randomized 2:1 to receive an initial, double-blind study 
treatment of ruxolitinib cream 1.5% BID or vehicle (applied to depigmented vitiligo areas on the 
face and body up to 10% total BSA) for 24 weeks.  After completion of the Week 24 
assessments, participants in these studies were offered the opportunity to receive an additional 
28 weeks of open-label treatment extension with ruxolitinib cream 1.5% BID under the parent 
study protocol. 
Participants who successfully complete the 52-week treatment in either of the parent studies 
(ie, 52 weeks ruxolitinib cream or 24 weeks vehicle plus 28 weeks ruxolitinib cream) and 
tolerated ruxolitinib treatment without safety concern and with good compliance for continuation 
may be eligible to participate in this treatment extension study. 
Visits in this treatment extension study are named to reflect continuation from the parent studies, 
with the first visit of this treatment extension study occurring at Week 52.  The eligibility 
assessment for this extension study occurs at Week 52.  The treatment extension period of this 
study comprises the period from the Week 52 visit to the Week 104 visit (inclusive).  Following 
the last application of study treatment at Week 104, there will be a 30-day safety follow-up 
period to evaluate safety and duration of response.  Figure 1 presents the study design schema, 
and Table 3 presents the SoA. 
The purpose of this extension study is to evaluate the duration of response under randomized 
withdrawal of ruxolitinib cream and maintenance of response with continued use of ruxolitinib 
cream, in vitiligo patients who have experienced repigmentation with ruxolitinib cream 
treatment, as well as to provide long-term efficacy and safety data in vitiligo patients, regardless 
of how quickly or completely they responded to treatment initially.  Eligible participants in this 
study will be assigned to 1 of 2 cohorts, Cohort A or Cohort B, based on their F-VASI responses 
at the time of enrollment in this study (ie, at Week 52). 
Treatment in Cohort A is a randomized withdrawal design and will provide data on the duration 
of response following withdrawal of ruxolitinib cream and maintenance of response with its 
continued use.  Participants who achieve complete or almost complete facial repigmentation 
(ie, achieve ≥ F-VASI90) at Week 52 in the parent study will be assigned to Cohort A and will 
be stratified by the original treatment received on study Day 1 of the parent study and 
randomized 1:1 to treatment with vehicle cream BID or ruxolitinib cream 1.5% BID for an 
additional 52 weeks (ie, until EOT at Week 104).  However, any participants in Cohort A who 


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experience relapse (defined as < F-VASI75) will receive ruxolitinib cream 1.5% BID as an 
open-label rescue treatment until they complete treatment (Week 104 or EOT). 
Treatment in Cohort B will provide long-term efficacy and safety data for ruxolitinib cream in 
vitiligo patients.  Participants who did not achieve ≥ F-VASI90 at Week 52 of the parent studies 
will be assigned to Cohort B and will continue ruxolitinib cream 1.5% BID for 52 weeks 
(ie, until EOT Week 104). 
For Cohort A, the participant, investigator, and sponsor will remain blinded to treatment 
assignment; the treatment for Cohort B will be open-label. 
During this extension study, participants will receive study treatment (ruxolitinib cream 1.5% 
BID or vehicle) for 52 weeks to be applied to depigmented areas on the face and body; the total 
treated areas (facial plus nonfacial areas) should not exceed 10% BSA.  Participants should 
continue to treat depigmented areas identified for treatment at baseline of the parent study even if 
the area begins to improve or fully repigment. 
Thus, depending on their initial randomized treatment in the parent study and the treatment to 
which they are randomized at Week 52 in this extension study, participants will have received 
ruxolitinib cream 1.5% BID for a minimum of 28 weeks and a maximum of 104 weeks. 
Safety endpoints, such as nature of AEs (type, frequency, and severity includes performing 
targeted physical examination and collecting vital signs and routine laboratory investigations) 
will be monitored and recorded throughout the course of this study. 
4.2. 
Overall Study Duration 
Eligibility will be evaluated on the first day of this extension study, which occurs on the same 
day as the parent study Week 52 visit; the treatment extension period is 52 weeks; and safety 
follow-up is 30 days.  Total duration of this study is approximately 56 weeks (see Figure 1). 
The study will begin when the first participant (or parent or guardian) signs the 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. 
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 in writing of the 
study's completion or early termination, 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. 


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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. Currently enrolled and receiving treatment in INCB 18424-306 or INCB 18424-307 
studies evaluating ruxolitinib cream in participants with vitiligo. 
Note:  Eligibility criteria for INCB 18424-306 or INCB 18424-307 are provided in 
Appendix A. 
2. Currently tolerating ruxolitinib cream in the parent study and no safety concerns per 
investigators judgment. 
3. Has demonstrated compliance, as assessed by the investigator, with the parent study 
protocol requirements. 
4. Willingness and ability to comply with scheduled visits, treatment plans, and any other 
study procedures indicated in this protocol. 
5. Male and female participants must be willing 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. Females of non-childbearing potential (ie, or surgically sterile with a hysterectomy 
and/or bilateral oophorectomy OR postmenopausal, ≥ 12 months of amenorrhea 
without an alternative medical cause). 
b. Prepubescent adolescents (age 12-18 years old at the time enrolled in parent studies). 
Note:  Information about specific types of acceptable contraceptive measures and 
duration of contraceptive use are provided in Appendix B. 
6. For adult participant, ability to comprehend and willingness to sign an ICF; for 
adolescent participant,  written informed consent of the parent(s) or legal guardian and 
written assent from the adolescent participant when possible. 
Note:  Adolescents, who during the course of the study become legal adults, will be asked 
for their consent to continue the study, and in the event of lack thereof, will be 
discontinued from further participation. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Has been permanently discontinued from study treatment in the parent study for any 
reason. 
2. Participants with an uncontrolled intercurrent illness or any concurrent condition that, in 
the investigator's opinion, would jeopardize the safety of the participant or compliance 
with the Protocol.  
Note:  See information provided in Exclusion Criterion 4 of the INCB 18424-306/ 
INCB 18424-307 parent study protocol (Appendix A); the investigator should consult 
with the sponsor medical monitor if there are any questions regarding uncontrolled 
intercurrent illness or any concurrent condition that may be exclusionary. 
3. Pregnant or breastfeeding woman. 
4. Participants who live with anyone participating in any current Incyte-sponsored 
ruxolitinib cream study. 
5.3. 
Lifestyle Considerations 
Participants should continue to avoid excessive exposure to artificial sunlight (including tanning 
booths, 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. 
Study drug should be applied at least 2 hours after shaving. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. 
5.5. 
Replacement of Participants 
Participants will not be replaced during the study. 


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6. 
STUDY TREATMENT 
See Appendix D for COVID-19–related guidance. 
6.1. 
Study Treatments Administered 
Table 5 presents the study treatment information. 
Table 5: 
Study Treatment Information 
Study treatment name: 
Ruxolitinib 
Vehicle 
Dosage formulation: 
Cream 
Unit dose strength(s)/dosage 
level(s): 
1.5% 
Not applicable 
Route of administration: 
Topical 
Administration 
instructions: 
BID.  A thin film is applied to 
depigmented vitiligo areas. 
BID.  A thin film is applied to the 
depigmented vitiligo areas. 
Packaging and labeling: 
Ruxolitinib cream and vehicle cream will be provided in 60 g tube.  
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 
On visit days, study drug will be applied in the clinic during the visit.  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; the tube will be weighed before and after application to determine the 
participant’s dosage.  On the day of a visit, the participant should not apply the study drug at 
home and will apply study drug from the new kit in the clinic.  Participants will be instructed to 
document treated areas and be advised to limit use to no more than one 60 g tube per week.  
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. 
At any time, 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. 
During the treatment extension period, participants should follow the below study drug 
application guidance: 
• All participants in Cohort A will use their randomly assigned treatment (either vehicle 
or ruxolitinib cream) on both the face and total body. 
• Participants should apply study drug to depigmented vitiligo areas up to a T-BSA 
(facial and nonfacial) of ≤ 10% BSA. 


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• Participants should continue to treat all depigmented vitiligo areas identified for 
treatment at baseline (Day 1 of the parent study) even if the area begins to improve or 
fully repigment. 
• Participants who have an expansion of existing areas of vitiligo or develop new 
vitiligo lesions during the course of the treatment extension period may treat these 
areas after a visit to document the VASI score and other measures of vitiligo (may be 
unscheduled visit), as long as the new treated T-BSA (facial and nonfacial) does not 
exceed 10% BSA.  Newly developing vitiligo lesions should be documented in the 
eCRF.  The VASI scores for these new lesions should not be calculated with or 
combined together with treated areas identified at baseline (Day1 of parent study). 
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 treatments received and that any discrepancies 
are reported and resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply study treatment.  Immediately after application of ruxolitinib cream, 
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 treatment must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions, with access 
limited to the investigator and authorized site staff.  Participants should store study treatment 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 drug(s) to the study site. 
• Inventory of study drug(s) at the site. 
• Participant use of the study drug(s) including tube counts from each supply 
dispensed. 
• Return of study drug(s) 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. 


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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 investigational supply, the site should (where 
local procedures allow) maintain the investigational supply until the study monitor inspects the 
accountability records in order to evaluate compliance and accuracy of accountability by the 
investigative site.  At sites where the study drug is destroyed before monitor inspection, the 
monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the 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.  For Cohort A, 
the system will assign in a 1:1 ratio (ruxolitinib cream 1.5% BID:vehicle).  For Cohort B, the 
system will assign all participants to ruxolitinib cream 1.5% BID. 
The IRT will track participant visits, randomize participants according to the defined parameters, 
maintain the blinding (Cohort A only), 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). 
For Cohort A, the participant, investigator, and sponsor will remain blinded to treatment 
assignment; the treatment for Cohort B will be open-label.  After the database lock for the 
primary analysis (Week 104), the participant, the investigator, and the sponsor 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 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 within 70% to 130% of the prescribed 
number of applications.  Participants will be instructed to bring all study drugs 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. 


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6.5. 
Dose Modifications 
6.5.1. 
Criteria and Procedures for Application Interruptions and Modifications of 
Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine whether the participant should continue or discontinue study treatment. 
In some circumstances, it may be necessary to temporarily interrupt treatment with study drug 
(ruxolitinib cream or vehicle cream).  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 
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 recurrence of the initial AEs upon restarting the study drug 
and the AE is confirmed related to the study drug may need the study drug to be permanently 
discontinued. 
Instructions for application interruptions of study treatment are outlined in Table 6.  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 drug 
and the participant's underlying condition. 
Table 6: 
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 lab abnormalities are 
confirmed. 


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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 treatment 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. 
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 reviewed at each study visit.  
Any concomitant medication/treatment received from the first dose of study treatment in this 
extension study through 30 days after the last dose of study treatment will be recorded in the 
eCRF.  Any addition, deletion, or change in the dose of these medications will also be recorded.  
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 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 judgement with these recommendations and adhere to 
the guidelines as closely as possible.  The sponsor should be consulted if there are specific 
questions. 
• Participants may use bland emollients or camouflage makeup. 
Note:  Emollients or camouflage makeup should not be used within 2 hours after 
study drug application.  The study drug may not be applied over sunscreen 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. 


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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) from the time 
of the Week 52 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) from the time of the Week 52 visit through the 
safety follow-up visit, unless deemed acceptable by the investigator. 
• Participants should not take baths or showers within 2 hours after study drug 
application. 
• Treatment for dermatologic disease besides vitiligo (eg, AD or psoriasis) is allowed 
for areas not being treated for vitiligo: 
− 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 C) are at a stable dose. 
− Topical corticosteroids Class 1 through 5 (see Appendix C) 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 drugs. 
• 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) use 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). 
• Biological therapies or other immunosuppressant agents. 
• Any phototherapy, including tanning beds. 
• Live or live-attenuated vaccination. 


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6.7. 
Rescue Treatment 
For participants in Cohort A, if there is a loss of clinically meaningful response on the face 
(ie, < F-VASI75) at any time, the participants will receive open-label ruxolitinib cream 1.5% 
BID until completing the study (ie, Week 104 or EOT). 
6.8. 
Treatment After the End of the Study 
No treatment will be provided to participants after the end of the study. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinuation from study treatment for the following reasons: 
• A participant is found not to have met eligibility criteria (any exclusion criterion or 
any inclusion criteria 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 they 
do not want to be followed any longer; in this case no further data, except data in 
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 one 60 g tube per 
week. 
• 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. 


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7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
safety follow-up visit.  These visits are described in Table 3.  The last date of the last dose of 
study treatment and the reason for discontinuation of study treatment 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 withdrawal must be documented in the participant's medical record 
and the primary reason for withdrawal must be included in the eCRF. 
• The EOT visit should be performed. 
• 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/efficacy 
assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
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. 
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. 
See Table 3 for data to be collected at the time of study discontinuation and safety 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/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 


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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 participant will be counseled regarding the importance of 
maintaining the assigned visit schedule, and the site 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. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
See Appendix D 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/assent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the protocol. 
Note:  Adolescent participants who become legal adults during the study will be 
asked for their signed consent to continue the study, and in the event of lack 
thereof, will be discontinued from further participation. 
− Informed consent/assent 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/assent template.  The 
ICF/assent must include a statement that the sponsor or its designee and 
regulatory authorities have direct access to participant records. 
− The ICF/assent 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 


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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(s) 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. 
8.1.2. 
Eligibility Procedures 
All information associated with eligibility requirements must be entered into the appropriate 
eCRF pages. 
Results from the eligibility assessments will be reviewed by the investigators to confirm 
eligibility before administration of study treatment in this extension study. 
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; this will be the same participant ID number as 
assigned in the parent study.  Upon determining that the participant is eligible for study entry, the 
IRT system will be contacted to obtain the study medication 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 Week 52 visit and each visit thereafter, 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. 


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Participants will be provided with a reminder card starting on Week 52 and at all visits (through 
Week 92).  The reminder card will indicate the date/time of the next visit and will also remind 
the participant that they should have their application at the clinic during the visit under site 
supervision after their blood draws for PK and safety evaluations have been completed. 
8.2. 
Efficacy Assessments 
8.2.1. 
Body Surface Area 
Facial % BSA and total % BSA (includes facial and nonfacial areas) depigmented by vitiligo 
will be estimated at each visit.  Body surface area assessment will be performed by the Palmar 
Method.  BSA should be estimated to the nearest 0.1%.  The approximate size of the 
participant’s entire palmar surface (ie, the palm plus 5 digits) should be considered as 1% BSA, 
and the approximate size of the participant’s thumb should be considered as 0.1% BSA. 
8.2.2. 
Vitiligo Area Scoring Index 
Areas affected by depigmentation due to vitiligo will be assessed using the VASI.  It is based on 
a composite estimate of the overall area of vitiligo patches at baseline and the degree of macular 
repigmentation within these patches over time. 
Facial VASI is measured by percentage of vitiligo involvement (% of BSA) and the degree of 
depigmentation.  The percentage of BSA (hand unit) vitiligo involvement is estimated by the 
investigator using the Palmar Method (see Section 8.2.1).  Hand unit is based on participant’s 
hand size.  Investigator uses his/her hand to mimic the participant’s hand size to evaluate 
percentage of BSA vitiligo involvement.  The degree of depigmentation for each vitiligo 
involvement site is determined and estimated to the nearest of the following percentages:  0, 
10%, 25%, 50%, 75%, 90%, or 100%.  At 100% depigmentation, no pigment is present; at 90%, 
specks of pigment are present; at 75%, the depigmented area exceeds the pigmented area; at 
50%, the depigmented and pigmented area are equal; at 25%, the pigmented area exceeds the 
depigmented area; at 10%, only specks of depigmentation are present.  The F-VASI is then 
derived by multiplying the values assessed for the vitiligo involvement by the percentage of 
affected skin for each site on the face and summing the values of all sites together (possible 
range 0-3). 
The area "Face" is defined as including the area on the forehead to the original hairline, on 
the cheek vertically to the jawline and laterally from the corner of the mouth to the tragus.  
The area "Face" will not include surface area of the lips, scalp, ears, or neck but will 
include the nose and eyelids. 
Total body VASI is calculated using a formula that includes contributions from all body regions 
(possible range, 0-100). 
VASI = Σ [hand units] × [Residual Depigmentation] all body sites 
The body is divided into the following 6 separate and mutually exclusive sites:  (1) head/neck, 
(2) hands, (3) upper extremities (excluding hands), (4) trunk, (5) lower extremities (excluding 
feet), and (6) feet.  The percentage of vitiligo involvement is estimated in hand units (% of BSA) 
by the same investigator during the entire course of the study.  Hand unit is based on 
participant’s hand size.  The investigator uses his/her hand to mimic the participant’s hand size to 


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evaluate % BSA vitiligo involvement.  The degree of depigmentation for each body site is 
determined and estimated to the nearest of the following percentages:  0, 10%, 25%, 50%, 75%, 
90%, or 100%.  The T-VASI is then derived by multiplying the values assessed for the vitiligo 
involvement by the percentage of affected skin for each body site and summing the values of all 
body sites together (Hamzavi et al 2004). 
Full details will be provided in the Study Manual. 
8.2.5. 
Photography 
Photography of the face and/or body areas affected with vitiligo will be obtained at visits listed 
in Table 3. 


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All sites will use 2D photography, and selected sites will also use 3D photography, to 
photograph areas of the participant’s face affected with vitiligo.  2D photography will be used at 
all sites for the target nonfacial depigmented area. 
Target nonfacial vitiligo depigmented area definition:  At the baseline visit (Day 1) of the 
parent study (INCB 18424-306 or INCB 18424-307), depigmented nonfacial areas that are 
representative of the participant's overall disease and that are to be treated with study drug will 
have been selected as targeted nonfacial vitiligo depigmented areas.  These same areas will be 
assessed, measured, and documented in the participant's medical record at each visit of this 
treatment extension study (see Table 3).  The genitalia area should not be photographed. 
Ad hoc photography of skin-related AEs is recommended. 
Photographic procedures will be standardized, and a full description of the methodology will be 
provided in a photography manual to be provided to the sites. 
8.2.6. 
Patient-Reported Outcomes 
Quality of life will be assessed (see Table 3) using the following tools: 
• VNS (Section 8.2.6.1); 
 
 
 
 
 
 
• DLQI/CDLQI (Section 8.2.6.5); 
 
 
 
 
In order to avoid bias in the participants' responses to the questionnaires, all these assessments 
should be completed before any other evaluations or study procedures on the day of the study 
visit and before discussions with the investigator or study site staff. 
8.2.6.1. 
Vitiligo Noticeability Scale 
The VNS is a patient‐reported measure of vitiligo treatment success, which has a 5-point scale 
(Batchelor et al 2016).  The baseline facial photograph from the parent study (INCB 18424-306 
or INCB 18424-307) will be shown to the participants for reference and a mirror will be 
provided for the participants to assess the vitiligo on their face.  The participant will be asked to 
respond to the following query: 
Compared with before treatment, how noticeable is the vitiligo now?  Responses:  (1) More 
noticeable, (2) As noticeable, (3) Slightly less noticeable, (4) A lot less noticeable, and 
(5) No longer noticeable. 
VNS scores of 4 or 5 can be interpreted as representing treatment success. 


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8.2.6.5. 
Dermatology Life Quality Index 
The DLQI is a simple, 10-question validated questionnaire to measure how much the skin 
problem has affected the participant over the previous 7 days (Finlay and Khan 1994).  
Participants age ≥ 16 years will answer the questionnaire with (1) very much, (2) a lot, (3) a 
little, or (4) not at all. 
The questionnaire is analyzed under 6 headings as follows: 
• Symptoms and feelings (Questions 1 and 2); 
• Daily activities (Questions 3 and 4); 
• Leisure (Questions 5 and 6); 
• Work and school (Question 7); 


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• Personal relations (Questions 8 and 9); 
• Treatment (Question 10). 
CDLQI is the youth/children’s version of the DLQI.  For participants who are age < 16 years at 
baseline (Day 1) of the parent study (INCB 18424-306 or INCB 18424-307), the CDLQI will be 
completed instead of the DLQI throughout their participation in this extension study.  This 
questionnaire is self-explanatory and can be simply given to the participant who is asked to fill it 
in and who may ask the help of the parent or guardian.  The questionnaire is analyzed under 
6 headings as follows:  
• Symptoms and feelings (Questions 1 and 2); 
• Leisure (Questions 4, 5, and 6); 
• School or holidays (Question 7); 
• Personal relationships (Questions 3 and 8); 
• Sleep (Question 9); 
• Treatment (Question 10). 
Full details will be provided in the Study Manual. 
Full details will be provided in the Study Manual. 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Table 3). 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 


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8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study treatment.  Adverse events 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.  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 treatment, or that caused the participant to discontinue the study 
treatment.  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 between visits or through physical 
examinations, laboratory tests, or other assessments.  The definition, reporting, and recording 
requirements for AEs are described in Section 9. 
The investigator will submit any updated SAE data to the sponsor 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). 
8.3.2. 
Physical Examinations 
Physical examinations will be conducted at the timepoints listed in Table 3. 
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 
neurological examination will also be performed. 
A targeted physical examination should be conducted as indicated by symptoms reported by the 
participant, AEs, or other findings.  Abnormalities that are considered clinically significant in the 
judgment of the investigator are to be reported as AEs. 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits. 
8.3.3. 
Vital Signs 
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, semi-recumbent, 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. 


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8.3.4. 
Laboratory Assessments 
Required laboratory tests are listed in Table 9, which include serum chemistry, hematology, and 
pregnancy testing (see Table 3 for timing of laboratory assessments).  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 
treatment, 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 9: 
Required Laboratory Analytes 
Serum Chemistriesa 
Hematology 
Pregnancy Testing 
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 
• MCV 
• Platelet count 
• Mean platelet volume 
• Red blood cell count 
• Reticulocyte count 
• White blood cell count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Female participants of childbearing 
potential have a serum test at 
Week 52 and at the safety 
follow-up visit.  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. 
a All serum chemistries will be performed on samples collected without respect to food intake (ie, nonfasting). 
8.3.4.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during the 
Week 52 visit and at the safety follow-up visit (30 [+ 7] days after EOT).  Urine pregnancy tests 
will be conducted as outlined in Table 3, as medically indicated, or per country-specific 
requirement.  Urine pregnancy tests will be performed locally.  If a urine pregnancy test is 
positive, the results should be confirmed with a serum pregnancy test, which may be performed 
locally. 


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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 9.6 for reporting 
requirements. 
8.4. 
Pharmacokinetic Assessments 
Venous blood samples will be collected to assess the PK of ruxolitinib cream in participants at 
each study visit indicated in Table 3. 
The exact date and time of the PK blood draws and the date and time of the last application of 
study drug preceding the blood draw (if applicable) will be recorded in the eCRF. 
Instructions for sample preparation and shipping will be provided in the Laboratory Manual.  
Participants will receive reminder cards in advance of the study visit providing instruction to 
hold the application of study drug on the day of the visit and a place to record the time of the 
prior dose of study drug. 
Pharmacokinetic blood samples can be collected at any time prior to study drug application at the 
site at the Week 80 visit and at any time at the W104 (EOT) visit.  Blood samples must not be 
drawn from the area that has been treated with study drug.  If it is not possible to access an area 
that is not treated with study drug, the site must adequately document this in the eCRF and not 
take the PK blood sample for that visit.  After the PK sample is drawn, participants will apply 
ruxolitinib cream 1.5% or vehicle cream at the site. 
All analyses will be conducted by Incyte Corporation (Wilmington, DE) or Incyte's designee. 
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, whether the 
participant is terminating the study early or the participant has completed the study, the EOT 
visit should be conducted.  If the EOT visit coincides with a regular study visit, 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. 


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8.8. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit 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 at least 30 days after the last dose of study 
drug, the date of the safety follow-up visit, or 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. 
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 considered drug-related. 
• An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
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). 
• Abnormal laboratory test results constitute 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 lab result (eg, low hemoglobin, platelet count decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication.  Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent.  Such overdoses should be 
reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an 
AE or SAE.  Such instances will be captured in the efficacy assessments.  However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if 
they fulfill the definition of an AE or SAE.   


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Events NOT Meeting the Adverse Event Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety assessments that are 
associated with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant's condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant's condition or 
considered to be treatment-related by the investigator. 
• Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that leads to the 
procedure is the AE if it occurred after signing the ICF. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
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 occurred.  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 (usually 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 of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
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 


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f. Other situations (Important Medical Event) 
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 invasive or malignant cancers (excluding the 
disease[s] under study in oncology protocols), intensive treatment in an emergency department or at 
home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse. 
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. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics 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 AE eCRF page. 
• There may be 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 on the copies 
of the medical records before submission. 
• 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 severity grade (CTCAE 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 final safety follow-up. 
• 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 Adverse Event Form, and the treatment should 
be specified on the appropriate eCRF (eg, Concomitant Medications, Procedures and Non-Drug 
Therapy). 


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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories:  
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate 
activities of daily living. 
• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment and each occurrence 
of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are 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 relationship. 
• The investigator will also consult the RSI in the ruxolitinib cream IB in his/her assessment. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study treatment 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 to the sponsor or designee.  However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor or designee. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
send a follow-up SAE report with 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 or designee to elucidate the 
nature and/or causality of the AE/SAE as fully as possible.  This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other healthcare 
professionals. 
• If a participant dies during participation in the study or during a recognized safety follow-up period, 
the investigator will provide the sponsor or designee with a copy of any postmortem findings, 
including histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 


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• Any updated SAE data will be submitted to the sponsor or designee immediately, without undue 
delay, under no circumstances later than 24 hours following knowledge of the event. 
• Once an AE is detected, it should be followed 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 until the event resolves. 
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 treatment, 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 treatment 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 towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
If the SAE is not documented in the ruxolitinib cream IB for the study drug (new occurrence) 
and is thought to be related to the sponsor's 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 treatment 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 SUSARs 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 a 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.  
Refer to the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Facsimile or email transmission of the Serious Adverse Event Report Form is the preferred method 
to transmit this information to the PhV/designee.  The contact information of the sponsor's 
study-specific representatives is listed in the Study Manual provided to each site.  The original copy 
of the Serious Adverse Event Report Form and the confirmation sheet must be kept at the study site. 
• Follow-up information is recorded 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. 
• In rare circumstances and in the absence of facsimile or computer equipment, notification by 
telephone is acceptable with a copy of the Incyte Serious Adverse Event Report Form sent by 
overnight mail or courier service.  Initial notification via telephone does not replace the need for the 
investigator to complete and sign the Serious Adverse Event Report Form within the designated 
reporting time frames. 
• Contacts for SAE reporting can be found in the Study Manual. 
9.5. 
Emergency Unblinding of Treatment Assignment 
In a medical emergency, 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 be withdrawn from the study treatment, unless there are ethical reasons to have 
the participant remain on the study treatment.  In these cases, the investigator must obtain 
specific approval from the sponsor's (or its designee's) medical monitor for the participant to 
continue in the study. 


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9.6. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that 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. 
• 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 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. 
9.7. 
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 ruxolitinib cream 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. 
9.8. 
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. 
9.9. 
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 
Any eligible participants will be enrolled from the 2 parent Phase 3 studies, INCB 18424-306 
and INCB 18424-307.  The sample size is not based on any statistical power calculations. 
10.2. 
Populations for Analysis 
Table 10 presents the populations for analysis. 
Table 10: 
Populations for Analysis 
Population 
Description 
Full analysis set 
(FAS) 
All participants enrolled in the study who receive at least 1 dose of study drug 
(ruxolitinib cream or vehicle) at or after Week 52.a 
Intent-to-treat in 
long-term 
extension 
(ITT-Ext) 
All participants who achieve ≥ F-VASI90 at Week 52a and are randomized.  
Treatment groups for this population will be defined according to the treatment 
assignment at the time of randomization regardless of the actual study medication 
the participant might take the study. 
PK evaluable 
The PK evaluable population includes participants who received at least 1 dose of 
ruxolitinib cream and provided at least 1 measurable postdose PK 
sample/assessment.  The study pharmacokineticist will review data listings of 
participant administration and sample records to identify participants to be 
excluded from the analysis. 
PK/PD evaluable 
The PK/PD evaluable population includes participants who received at least 
1 dose of study drug (ruxolitinib cream or vehicle) and provided at least 
1 measurable/evaluable postdose PK/PD sample/assessment.  The study 
pharmacokineticist will review data listings of participant administration and 
sample records to identify participants to be excluded from the analysis. 
a Week 52 is the first visit of the treatment extension study (visits are named to reflect continuation from the parent 
study). 


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10.3. 
Level of Significance 
The primary and key secondary endpoints will be tested in a fixed sequence at 2-sided α = 0.05 
level, that is, the key secondary endpoint will be tested only if the primary is rejected.  No formal 
statistical tests will be performed for other endpoints.  All confidence intervals will be 95%. 
10.4. 
Statistical Analyses 
10.4.1. 
Efficacy Analysis 
Efficacy endpoints are listed in Section 3. 
For all complete or near-complete responders in the ITT-Ext population (defined as achieving 
F-VASI90 at Week 52) in the treatment extension period, the events can be defined as follows: 
• Relapse is defined as a loss of F-VASI75 response assessed as percentage change 
from the baseline (Day 1 of the parent study) on F-VASI < 75%. 
• Loss of complete or near-complete response is defined as participants who do not 
maintain an F-VASI90. 
For relapse, a binary variable event is defined to be equal to 1 (Yes) when the value is greater or 
equal to 75% and 0 (No) for less than 50%. 
For loss of F-VASI90 response, a categorical variable event is defined to be equal to 1 (Yes) 
when the value is greater or equal to 90% and 0 (No) for less than 90%. 
The time to relapse or loss of adequate response is defined as the number of days from the 
Week 52 randomization to the first evaluation date at which the participant has met the criteria.  
For participants who discontinue early or who complete without meeting criteria for the event, 
the time-to-event will be censored and defined as the number of days from the Week 52 
randomization to the participant’s last evaluation date. 
The time to event data will be assessed using the Kaplan-Meier product limit method.  Treatment 
comparisons between ruxolitinib cream 1.5% BID to vehicle will be performed using the 
log-rank test.  Hazard ratios and the corresponding 95% confidence intervals will be estimated 
using the Cox proportional hazards model. 
The incidence of relapse or loss of adequate response following the Week 52 randomization will 
be summarized by ruxolitinib cream 1.5% BID and vehicle at each timepoint. 
Other efficacy endpoints will be summarized in FAS.  Descriptive summaries for continuous 
variables will include, but not be limited to, the number of observations, mean, standard 
deviation, median, minimum, and maximum.  Descriptive summaries for categorical variables 
will include the number and percentage of participants in each category. 
For all relapse participants, the time to regaining F-VASI75/90 response is defined as the number 
of days from the start of the retreatment of ruxolitinib cream 1.5% BID to the first visit at which 
the participant has regained the F-VASI75/90 response.  For participants who discontinue or 
complete treatment before regaining F-VASI75/90, the time to regaining F-VASI75/90 is 
censored.  The time to event data will be assessed using the Kaplan-Meier product limit method. 




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


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− 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, or 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. 
• 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. 
• 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 at the 
investigator's site. 


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− 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.  Also, current applicable medical records must be 
available. 
• May have responsibility for sending participants’ data, either as unique samples, or 
copies, or photographs, to be evaluated centrally or analyzed centrally, or both, by a 
qualified vendor designated by the sponsor. 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other study 
related documents.  The investigator must immediately notify the sponsor when 
contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number and the participant's initials (participant's initials will only be recorded if allowable by 
local regulations) will be recorded in the eCRF, where permitted; 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 local data protection laws. 


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11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to 
21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered studies") are 
required to submit a completed Clinical Investigator Financial Disclosure Form that sufficiently 
details any financial interests and arrangements that apply.  For the purpose of this regulation, 
"clinical investigator" is defined as any investigator or subinvestigator who is directly involved 
in the treatment or evaluation of research participants, including the spouse and each dependent 
child of the clinical investigator or subinvestigator.  These requirements apply to both US and 
foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his or 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.  The sponsor commits to also adhere to supranational/international rules regarding 
publishing research results, as set by the Helsinki Declaration.  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. 


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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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APPENDIX A. ELIGIBILITY CRITERIA FROM STUDIES 
INCB 18424-306 AND INCB 18424-307 
INCB 18424-306 and -307 Inclusion Criteria: 
Participants were eligible to be included in study INCB 18424-306 or study INCB 18424-307 
only if all of the following criteria applied: 
1. Adolescents and adults aged ≥ 12 years. 
2. Participants with a clinical diagnosis of non-segmental vitiligo with depigmented area 
including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, 
≥ 3 T-VASI, and total body vitiligo area (facial and nonfacial) not exceeding 10% BSA. 
3. Participants who 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. 
4. Male and female participants must be willing 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. Females of non-childbearing potential (ie, or surgically sterile with a hysterectomy 
and/or bilateral oophorectomy OR postmenopausal, ≥ 12 months of amenorrhea 
without an alternative medical cause). 
b. Prepubescent adolescents. 
Note:  Information about specific types of acceptable contraceptive measures and 
duration of contraceptive use are provided in Appendix B. 
5. For adult participant, ability to comprehend and willingness to sign an ICF; for 
adolescent participant, written informed consent of the parent(s) or legal guardian and 
written assent from the adolescent participant. 
Note:  Adolescents, who during the course of the study become legal adults, will be asked 
for their consent to continue the study, and in the event of lack thereof, will be 
discontinued from further participation. 
INCB 18424-306 and -307 Exclusion Criteria: 
Participants were excluded from study INCB 18424-306 and study INCB 18424-307 if any of 
the following criteria applied: 
1. Participants who have 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. Participants who have used depigmentation treatments (eg, monobenzone) for past 
treatment of vitiligo or other pigmented areas. 
Note:  Prior use of hydroquinone is not prohibited (as it is a bleaching agent, not a 
depigmentation treatment). 


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4. Participants with 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, chicken pox) 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. 
− Participants with concurrent malignant disease or a history of that in the 5 years 
preceding the baseline visit except for adequately treated nonmetastatic 
malignancies. 
− 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 alcoholism 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. 
− Participants who are committed to an institution by virtue of an order issued either 
by the judicial or the administrative authorities. 
5. Participants using 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, metoxypsoralens. 


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− 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 bed 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. Participants who have previously received JAK inhibitors, systemic or topical. 
7. Participants with 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. 
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. 
8. Body mass index < 17 or > 40 kg/m2 for adult participants (age ≥ 18 years).  BMI-for-age 
in the < 5th percentile or ≥ 85th percentile range for adolescent participants (age ≥ 12 to 
< 18 years) according to the CDC BMI Percentile Calculator for Child and Teen (2019). 
Note:  Adolescent BMI criterion added based on INCB 18424-306 and INCB 18424-307 
Protocol Amendment 3-US-CA (dated 13 MAR 2020). 
9. Pregnant or lactating participants, or those considering pregnancy during the period of 
their study participation. 
10. Participants who, 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. Participants with known allergy or reaction to any component of the study formulation. 
13. Participants who live with anyone participating in any current Incyte-sponsored 
ruxolitinib cream study. 


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APPENDIX B. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
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 child-bearing 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.  Males 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 less than 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 partnera,b 
• 
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 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 less than 1% failure rate methods. 
e A combination 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 Trial Facilitation and Coordination Group 2014. 


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APPENDIX C. 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. 


Incyte Corporation 
Page 68 of 71 
Protocol INCB 18424-308 Am 2 
Version 3 
  
 10 NOV 2020 
CONFIDENTIAL 
APPENDIX D. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic presents numerous challenges to the ongoing conduct of 
clinical trials.  In line with the European Medicines Agency Guidelines on the Management of 
Clinical Trials During the COVID-19 (Coronavirus) Pandemic (2020), the sponsor has issued the 
following Protocol considerations to ensure participant safety is maintained and adequate 
benefit/risk analyses are applied relative to the completion of study procedures and maintaining 
the investigational product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added to respective study manuals and project plan documents and 
communicated to the investigative sites as needed. 
Study Site Visits 
If local travel restrictions, isolation requirements, or the investigator's benefit/risk assessment 
determines it to be unsafe for participants to attend study visits at the investigational site, the site 
staff may elect to pursue the following: 
• In order to minimize participant risk, study visits (except Week 52 and Week 104 
visits) may be conducted via telemedicine modalities (phone or video).  At a 
minimum, a review of AEs, concomitant medications, and study drug compliance 
must be completed.  Periodic on-site visits should be conducted whenever feasible.  
The physician efficacy assessments must not be conducted by phone or video. 
• Week 52 and Week 104 Visits must be conducted in person in their entirety because 
VASI assessments must be completed by the qualified raters face to face.  These 
visits cannot be missed or conducted remotely.  The investigator should document the 
visit window deviation in the eCRF if necessary.  
Investigational Medicinal Product Dispensation and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug to 
participants.  Adequate supplies of study drug as determined by the investigator to cover 
12 weeks can be shipped to the participants by the investigator or appropriately delegated staff 
(eg, the study pharmacy staff) using a third-party service if duly authorized by the participant.  
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment) or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed; however, the site monitor will continue to employ 
off-site monitoring practices such as routine communication methods (eg, phone calls, emails, 
video visits) with the sites to get information on trial progress, participant status, and information 
on issue resolution.  The study monitor may remotely review data entered into the EDC for 
accuracy and completeness.  Remote source data verification may be implemented with 
agreement of the principal investigator and institution, as applicable. 


Incyte Corporation 
Page 69 of 71 
Protocol INCB 18424-308 Am 2 
Version 3 
  
 10 NOV 2020 
CONFIDENTIAL 
If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes, and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training.  The study drug can be returned to the sponsor by the hospital pharmacy directly, or it 
can be destroyed in accordance with local practices, if applicable, and with sponsor approval. 
 


Incyte Corporation 
Page 70 of 71 
Protocol INCB 18424-308 Am 2 
Version 3 
  
 10 NOV 2020 
CONFIDENTIAL 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1: 
28 SEP 2020 
Amendment 2:  
10 NOV 2020 
Amendment 2 (10 NOV 2020) 
Overall Rationale for the Amendment: 
The main purpose of this amendment is to add language to the Protocol to inform sites of 
alternative strategies to guarantee continuity of the clinical trial conduct and oversight in 
response to the COVID-19 pandemic. 
1. Appendix D, COVID-19 Pandemic Mitigation Strategies and Instructions 
Description of change:  Added Appendix D to the Protocol and added 
cross-references to the appendix to relevant sections. 
Rationale for change:  To provide sites with Protocol-related guidance in response 
to the COVID-19 pandemic. 
2. Incorporation of administrative changes.  Other minor, administrative changes and 
clarifications have been incorporated throughout the Protocol and are noted in the 
redline version of the amendment. 


Incyte Corporation 
Page 71 of 71 
Protocol INCB 18424-308 Am 2 
Version 3 
  
 10 NOV 2020 
CONFIDENTIAL 
Amendment 1 (28 SEP 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to 
accommodate the EMA PDCO recommendation regarding the DLQI/CDLQI endpoint and to 
align the PK endpoints with those of parent studies INCB 18424-306 and INCB 18424 307. 
1. Title Page; Section 1, Protocol Summary 
Description of change:  Added TRuE-V LTE to the Protocol title. 
Rationale for change:  To include the short name in the title. 
2. Section 1, Protocol Summary (Table 1:  Primary and secondary Objectives and 
Endpoints); Section 3, Objectives and Endpoints (Table 8:  Objectives and 
Endpoints) 
Description of change:  Moved endpoint for DLQI/CDLQI from exploratory to 
secondary. 
Rationale for changes:  To address EMA PDCO recommendation. 
2. Section 1, Protocol Summary (Table 1:  Primary and Secondary Objectives and 
Endpoints); Section 3, Objectives and Endpoints (Table 8:  Objectives and 
Endpoints) 
Description of change:  Moved endpoint for PK from exploratory to secondary. 
Rationale for change:  To align with INCB 18424-306 and INCB 18424-307 parent 
studies. 
3. Section 1, Protocol Summary (Table 3:  Schedule of Activities); Section 8.4, 
Pharmacokinetic Assessments 
Description of change:  Added clarifications that PK samples should be collected at 
predose and the time of the last study drug application is to be recorded in the eCRF. 
Rationale for change:  To align PK sample collection procedures with INCB 18424-306 
and INCB 18424-307 parent studies. 
4. Section 5.1, Inclusion Criteria (Inclusion Criteria 5a and 6) 
Description of change:  Clarified wording of inclusion criteria. 
Rationale for change:  To align with INCB 18424-306 and INCB 18424-307 parent 
studies. 
5. Section 10.4.3, Other Analyses 
Description of change:  Corrected PK data analysis method. 
Rationale for change:  Ruxolitinib plasma concentration data analysis is not based on a 
population PK modeling approach. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-010468 v3.0
Signature Page for VV-CLIN-010468 v3.0
Approval
Approver
10-Nov-2020 14:33:43 GMT+0000
Approval
Approver
10-Nov-2020 14:35:05 GMT+0000
Approval
Approver
10-Nov-2020 15:18:06 GMT+0000
Approval
Approver
11-Nov-2020 14:35:04 GMT+0000
Approval
Approver
11-Nov-2020 20:52:23 GMT+0000

SAP_001.pdf: 




I nc yte C or p orati o n 
Pa ge 2 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7
C O N FI D E N TI A L 
T A B L E O F C O N T E N T S 
TI T L E P A G E ................................................................................................................................... 1  
T A B L E O F C O N T E N T S ................................................................................................................. 2  
LI S T O F A B B R E VI A TI O N S ......................................... ................................................................. 6 
1. 
I N T R O D U C TI O N ........................................................................................................ 8  
2.
S T U D Y I N F O R M A TI O N, O BJ E C TI V E S, A N D E N D P OI N T S .................. ............... 9 
2. 1.  
Pr ot oc ol a n d Case Re p ort F or m Versi o n ......................... ............................................. 9 
2. 2.  
St u d y O bjecti ves a n d E n d p oi nts ................................ ................................................... 9 
3. 
S T U D Y D E SI G N ....................................................................................................... 1 1  
3. 1.  
Ra n d o mizati o n ................................................. ........................................................... 1 2 
3. 2.  
C o ntr ol of T y pe I Err or ....................................... ........................................................ 1 2 
3. 3.  
Sa m ple Size C o nsi derati o ns ....................................................................................... 1 2  
3. 4.  
Sc he d ule of Assess me nts ....................................... ..................................................... 1 2 
4.
D A T A H A N D LI N G D E FI NI TI O N S A N D C O N V E N TI O N S ..................... ............. 1 3 
4. 1.  
Sc he d ule d St u d y E val uati o ns a n d St u d y Peri o ds ....................................................... 1 3  
4. 1. 1.  
Da y 1 ........................................................................................................................... 1 3  
4. 1. 2.  
St u d y Da y ................................................................................................................... 1 3  
4. 1. 3.  
Baseli ne Val ue ................................................ ............................................................ 1 3 
4. 1. 4.  
Ha n dli n g of Missi n g a n d I nc o m plete Data ....................... .......................................... 1 4 
4. 2.  
Varia ble Defi niti o ns .......................................... .......................................................... 1 4 
4. 2. 1.  
B o d y Mass I n de x ........................................................................................................ 1 4  
4. 2. 2.  
C o nc o mita nt Me dicati o n ........................................ .................................................... 1 4 
5.
S T A TI S TI C A L M E T H O D O L O G Y ....................................... .................................... 1 5 
5. 1.  
Ge neral Met h o d ol o g y ................................................................................................. 1 5  
5. 2.  
Treat me nt Gr o u ps .............................................. ......................................................... 1 5 
5. 3.  
A nal ysis P o p ulati o ns .................................................................................................. 1 5  
5. 3. 1.  
F ull A nal ysis Set ............................................. ............................................................ 1 5 
5. 3. 2.  
I nte nt-t o- Treat i n L o n g-ter m E xte nsi o n ...................................................................... 1 5 
5. 3. 3.  
Rela pse E val ua ble Set ......................................... ........................................................ 1 6 
5. 3. 4.  
P har mac o ki netic/
 E val ua ble P o p ulati o n ....................................... 1 6 
6.
B A S E LI N E, E X P O S U R E, A N D DI S P O SI TI O N ........................... ........................... 1 6 
6. 1.  
Baseli ne, De m o gra p hics, a n d Disease Hist or y ................... ........................................ 1 6 


I nc yte C or p orati o n 
Pa ge 3 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7
C O N FI D E N TI A L 
6. 1. 1.  
De m o gra p hics ............................................................................................................. 1 6  
6. 1. 2.  
Baseli ne Disease C haracteristics .............................. .................................................. 1 6 
6. 2.  
Dis p ositi o n of P artici pa nts .......................................................................................... 1 7  
6. 3.  
Pr ot oc ol De viati o ns .................................................................................................... 1 7  
6. 4.  
E x p os ure ...................................................... ...............................................................1 7  
6. 5.  
St u d y Dr u g C o m plia nce ......................................... .................................................... 1 7 
6. 6.  
C o nc o mita nt Me dicati o ns ....................................... .................................................... 1 7 
7. 
E F FI C A C Y ................................................................................................................. 1 8  
7. 1.  
Ge neral C o nsi derati o ns ........................................ ....................................................... 1 8 
7. 2.  
Efficac y Meas ures ...................................................................................................... 1 8  
7. 2. 1.  
B o d y S urface Area ............................................. ......................................................... 1 8 
7. 2. 2.  
Vitili g o Area Sc ori n g I n de x ................................... ..................................................... 1 8 
 
1 9  
 
1 9  
7. 2. 5.  
Patie nt- Re p orte d O utc o mes ........................................................................................ 2 0  
7. 2. 5. 1.  
Vitili g o N oticea bilit y Scale .................................. ...................................................... 2 0 
 
2 1  
 
2 1  
 
2 1  
7. 2. 5. 5.  
Der mat ol o g y Life Q ualit y I n de x ................................................................................ 2 1  
 
. 2 3 
 
. 2 4 
7. 3.  
A nal ysis of t he Pri mar y Efficac y Para meter .................... .......................................... 2 4 
7. 3. 1.  
Pri mar y Efficac y A nal ysis ..................................... ..................................................... 2 4 
7. 4.  
A nal ysis of t he Ke y Sec o n dar y Efficac y Para meters ............. .................................... 2 4 
7. 5.  
A nal ysis of Ot her Sec o n dar y Efficac y Para meters ............... ...................................... 2 5 
7. 5. 1.  
Ot her Sec o n dar y Efficac y A nal ysis ............................................................................ 2 5  
7. 5. 1. 1.  
C o nti n u o us Efficac y E n d p oi nts .................................................................................. 2 5  
7. 5. 1. 2.  
Cate g orical Efficac y E n d p oi nts ................................ .................................................. 2 5 
 
2 5  
 
2 5  
 
2 6  
7. 7.  
P har mac o ki netic A nal yses ...................................... .................................................... 2 6 


I nc yte C or p orati o n 
Pa ge 4 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
 
. 2 6 
 
. 2 7 
8.  
S A F E T Y A N D T O L E R A BI LI T Y .............................................................................. 2 7  
8. 1.  
Ge neral C o nsi derati o ns ........................................ ....................................................... 2 7 
8. 2.  
A d verse E ve nts ........................................................................................................... 2 7  
8. 2. 1.  
A d verse E ve nt Defi niti o ns .......................................................................................... 2 7  
8. 2. 2.  
A d verse E ve nts of I nterest .......................................................................................... 2 8  
8. 2. 3.  
A d verse E ve nt S u m maries ....................................... ................................................... 2 8 
8. 3.  
Cli nical La b orat or y Tests ..................................... ...................................................... 2 9 
8. 3. 1.  
La b orat or y Val ue Defi niti o ns ..................................................................................... 2 9  
8. 3. 2.  
La b orat or y Val ue S u m maries ..................................................................................... 2 9  
8. 4.  
Vital Si g ns ................................................... ...............................................................3 0  
9.  
P L A N N E D A N A L Y S E S .............................................. .............................................. 3 1 
1 0.  
C H A N G E S A N D M O DI FI C A TI O N S T O T H E A N A L Y SI S P L A N ................ ........ 3 1 
1 0. 1.  
C ha n ges t o Pr ot oc ol- Defi ne d A nal yses .......................... ............................................ 3 1 
1 0. 2.  
C ha n ges t o t he Statistical A nal ysis Pla n ...................... ............................................... 3 1 
1 1.  
R E F E R E N C E S .................................................... ....................................................... 3 2 
A P P E N DI X A.   P L A N N E D T A B L E S A N D FI G U R E S .................................... ......................... 3 3 
 
 
LI S T O F T A B L E S 
Ta ble 1:  
O bjecti ves a n d E n d p oi nts ............................................................................................. 9  
Ta ble 2:  
Al g orit h m f or Ce ns ori n g ....................................... ...................................................... 1 4 
 
1 9  
 
2 0  
Ta ble 5:  
Criteria f or Cli nicall y N ota ble Vital Si g n A b n or malities f or Pa rtici pa nts 
1 2 t o 1 5 Years Ol d ............................................ .......................................................... 3 0 
Ta ble 6:  
Criteria f or Cli nicall y N ota ble Vital Si g n A b n or malities f or Pa rtici pa nts 
1 6 t o 1 7 Years Ol d ............................................ .......................................................... 3 0 
Ta ble 7:  
Criteria f or Cli nicall y N ota ble Vital Si g n A b n or malities f or Pa rtici pa nts 
≥ 1 8 Years Ol d ............................................................................................................ 3 1  
Ta ble 8:  
Statistical A nal ysis Pla n Versi o ns ............................ .................................................. 3 1 
 


I nc yte C or p orati o n 
Pa ge 5 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7
C O N FI D E N TI A L 
LI S T O F FI G U R E S 
Fi g ure 1:  
St u d y Desi g n Sc he ma ................................................................................................. 1 2  


I nc yte C or p orati o n 
Pa ge 6 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7
C O N FI D E N TI A L 
LI S T O F A B B R E VI A TI O N S 
A b bre vi ati o n  
Ter m 
A E 
a d verse e ve nt 
A S R 
a p plicati o n site reacti o n 
BI D 
t wice dail y 
B MI 
b o d y mass i n de x 
B S A 
b o d y s urface area 
C D L QI 
C hil dre n's Der mat ol o g y Life Q ualit y I n de x 
CI 
c o nfi de nce i nter val 
C mi n,ss  
mi ni m u m c o nce ntrati o n d uri n g a d osi n g i nter val at stea d y state  
C R F 
case re p ort f or m 
C S R 
Cli nical St u d y Re p ort 
C T C A E 
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts 
D L QI 
Der mat ol o g y L ife Q ualit y I n de x 
E O T 
e n d of treat me nt 
F A S 
f ull a nal ysis set 
F- B S A
facial b o d y s urface area 
 
 
F- V A SI
Face Vitili g o Area Sc ori n g I n de x 
F- V A SI 5 0/ 7 5/ 9 0 
≥ 5 0 %/ 7 5 %/ 9 0 % i m pr o ve me nt fr o m baseli ne i n Face Vitili g o Area Sc ori n g 
I n de x sc ore 
I F N 
i nterfer o n 
I L 
i nterle u ki n 
I T T- E xt 
i nte nt-t o-treat i n l o n g-ter m e xte nsi o n 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
 
 
 
 
P K 
p har mac o ki netic 
P T 
preferre d ter m 
R E S 
rela pse e val u a ble set 
S A P 
Statistical A n al ysis Pla n 
S O C 
s yste m or ga n class 
T- B S A
t otal b o d y s urface area 
T E A E 
treat me nt-e mer ge nt a d verse e ve nt 


I nc yte C or p orati o n 
Pa ge 7 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
A b bre vi ati o n  
Ter m 
T- V A SI 
t otal b o d y Vitili g o Area Sc ori n g I n de x 
T- V A SI 5 0/ 7 5/ 9 0  
≥ 5 0 %/ 7 5 %/ 9 0 % i m p r o ve me nt i n t otal b o d y Vitili g o Area Sc ori n g I n de x 
V A SI 
Vitili g o Area Sc ori n g I n de x 
 
 
V N S 
Vitili g o N oticea bilit y Scale 
W H O 
W orl d Healt h Or ga nizati o n 
 
 


I nc yte C or p orati o n 
Pa ge 8 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
1.  
I N T R O D U C TI O N 
T his is a P hase 3, d o u ble- bli n d, ve hicle-c o ntr olle d, ra n d o mize d wit h dra wal a n d treat me nt 
e xte nsi o n st u d y t hat will e nr oll eli gi ble partici pa nts w h o ha ve  c o m plete d eit her St u d y I N C B 
1 8 4 2 4- 3 0 6 or St u d y I N C B 1 8 4 2 4- 3 0 7 ( pare nt st u dies) i n w hic h t he partici pa nts will ha ve bee n 
usi n g r u x oliti ni b crea m 1. 5 % B I D f or t he pre vi o us 2 8 t o 5 2 wee ks ( de pe n di n g o n t heir i nitial 
ra n d o mizati o n i n t he pare nt st u d y). Partici pa nts w h o s uccessf ull y c o m plete d eit her of t he pare nt 
st u dies a n d t olerate d r u x oliti nib crea m treat me nt wit h o ut a saf et y c o ncer n a n d wit h g o o d 
c o m plia nce f or c o nti n uati o n ma y be  eli gi ble t o partici pate i n this treat me nt e xte nsi o n st u d y. 
Eli gi ble partici pa nts i n t his treat me nt e xte nsi o n st u d y will be  assi g ne d t o 1 of 2 c o h orts, 
C o h ort A or C o h ort B, base d o n t heir F- V A SI res p o nses at t he ti me of e nr oll me nt i n t his 
e xte nsi o n st u d y (ie, at Wee k 5 2). Partici pa nts w h o ac hie ve d c o m plete or al m ost c o m plete facial 
re pi g me ntati o n (ie, ac hie ve d ≥ F- V A SI 9 0) at Wee k 5 2 i n t he parent st u d y will be assi g ne d t o 
C o h ort A, stratifie d b y t he ori gi nal treat me nt recei ve d o n st u d y Da y 1 of t he pare nt st u d y, a n d 
ra n d o mize d 1: 1 t o treat me nt wit h ve hicle crea m BI D or r u x oliti ni b crea m 1. 5 % BI D f or a n 
a d diti o nal 5 2 wee ks (ie, u ntil E O T or at Wee k 1 0 4). H o we ver, a n y partici pa nt i n C o h ort A w h o 
e x perie nces rela pse ( defi ne d as < F- V A SI 7 5) will recei ve r u x oli ti ni b crea m 1. 5 % BI D as a n 
o pe n-la bel resc ue treat me nt u ntil t he y c o m plete treat me nt ( Wee k 1 0 4 or E O T). Partici pa nts w h o 
di d n ot ac hie ve ≥ F- V A SI 9 0 at Wee k 5 2 of t he pare nt st u dies will be assi g ne d t o C o h ort B a n d 
will c o nti n ue r u x oliti ni b crea m  1. 5 % BI D f or u p t o 5 2 wee ks (ie, E O T or Wee k 1 0 4).   
T he p ur p ose of t his S A P is t o pr o vi de details of t he statistica l a nal yses t hat ha ve bee n o utli ne d i n 
t he st u d y Pr ot oc ol. T he sc o pe of this pla n will be e xec ute d b y t he De part me nt of Bi ostatistics or 
desi g nee, a n d t he a nal yses of P K will be e xec ute d b y t he De part me nt of Cli nical 
P har mac o ki netics or desi g nee. 


I nc yte C or p orati o n 
Pa ge 9 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
2.  
S T U D Y I N F O R M A TI O N, O B J E C TI V E S, A N D E N D P OI N T S 
2. 1.  
Pr ot oc ol a n d C ase Re p ort F or m Versi o n 
T his S A P is base d o n I N C B 1 8 4 2 4- 3 0 8  Pr ot oc ol ( A me n d me nt 2 date d 1 0 N O V 2 0 2 0) a n d I N C B 
1 8 4 2 4- 3 0 8 C R F a p pr o ve d 0 1 D E C 2 0 2 0. U nless s u perse de d b y a n a me n d me nt, t his S A P will be 
effecti ve f or all s u bse q ue nt Pr ot oc ol a me n d me nts a n d C R F versi o ns. 
2. 2.  
St u d y O bjecti ves a n d E n d p oi nts 
Ta ble 1  prese nts t he e n d p oi nts a n d o bjecti ves. 
T a ble 1:  
O bjecti ves a n d E n d p oi nts 
 
O bjecti ves 
E n d p oi nts 
Pri m ar y 
T o e val uate t he d urati o n of cli nical res p o nse of 
r u x oliti ni b crea m i n partici pa nts wit h vitili g o. 
F or partici pa nts w h o are  ra n d o mize d i n C o h ort A: 
 Ti me t o rela pse ( defi ne d as < F- V A SI 7 5). 
Ke y Sec o n d ar y 
T o e val uate t he d urati o n of cli nical res p o nse of 
r u x oliti ni b crea m i n partici pa nts wit h vitili g o. 
F or partici pa nts w h o are  ra n d o mize d i n C o h ort A: 
 Ti me t o mai ntai n ≥ F- V A SI 9 0 res p o nse. 
Sec o n d ar y 
T o f urt her e val uate t he ef ficac y of r u x oliti ni b crea m. 
 Pr o p orti o n of partici p a nts w h o ac hie ve 
F- V A SI 5 0/ 7 5/ 9 0 d uri n g t he e xte nsi o n treat me nt 
peri o d. 
 Act ual meas ure me nts, c ha n ge, a n d perce nta ge 
c ha n ge fr o m base li ne i n F- V A SI. 
 Pr o p orti o n of partici p a nts w h o ac hie ve 
T- V A SI 5 0/ 7 5/ 9 0 d uri n g t he e xte nsi o n treat me nt 
peri o d. 
 Act ual meas ure me nts, c ha n ge, a n d perce nta ge 
c ha n ge fr o m base li ne i n T- V A SI. 
 Act ual meas ure me nts, c ha n ge, a n d perce nta ge 
c ha n ge fr o m base li ne i n F- B S A. 
 Act ual meas ure me nts, c ha n ge, a n d perce nta ge 
c ha n ge fr o m baseli ne i n T- B S A. 
 Pr o p orti o n of partici pa nts a c hie vi n g a V N S of " 4 – 
A l ot less n oticea ble" or " 5 – N o l o n ge r n oticea ble" 
d uri n g t he e xte nsi o n treat me nt peri o d. 
T o deter mi ne t he partici p a nts' q ualit y of life. 
 C ha n ge fr o m Wee k 5 2 i n D L QI ( or C D L QI) d uri n g 
t he e xte nsi o n treat me nt peri o d. 
T o e val uate t he safet y a n d t olera bilit y of r u x oliti ni b 
crea m. 
 T he fre q ue nc y a n d se ver it y of A Es; i ncl u des 
perf or mi n g p h ysical e xa mi nati o ns a n d c ollecti n g 
vital si g ns a n d la b orat or y data f or he mat ol o g y a n d 
ser u m c he mistr y. 
T o e val uate t he r u x oliti ni b P K i n plas ma after 
treat me nt wit h r u x oliti ni b crea m. 
 Tr o u g h plas ma c o nce ntrati o ns of r u x oliti ni b at 
Wee k 8 0 a n d Wee k 1 0 4. 


I nc yte C or p orati o n 
Pa ge 1 0 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T a ble 1:  
O bjecti ves a n d E n d p oi nts ( C o nti n ue d) 
O bjecti ves 
E n d p oi nts 


I nc yte C or p orati o n 
Pa ge 1 1 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
3.  
S T U D Y D E SI G N 
T his is a P hase 3, d o u ble- bli n d, ve hicle-c o ntr olle d, ra n d o mize d wit h dra wal a n d treat me nt 
e xte nsi o n st u d y t hat will e nr oll eli gi ble partici pa nts w h o ha ve  c o m plete d eit her St u d y I N C B 
1 8 4 2 4- 3 0 6 or St u d y I N C B 1 8 4 2 4- 3 0 7 ( pare nt st u dies) i n w hic h t he partici pa nts will ha ve bee n 
usi n g r u x oliti ni b crea m 1. 5 % B I D f or t he pre vi o us 2 8 t o 5 2 wee ks ( de pe n di n g o n t heir i nitial 
ra n d o mizati o n i n t he pare nt st u d y; see Fi g ure 1 ). 
T he pare nt st u dies are ra n d o mi ze d, ve hicle-c o ntr olle d st u dies i n a d olesce nt a n d a d ult partici pa nts 
(a ge ≥ 1 2 years) wit h n o nse g me ntal vitili g o w h o ha ve de pi g me nte d areas i ncl u di n g ≥ 0. 5 % B S A 
o n t he face, ≥ 0. 5 F- V A SI, ≥ 3 % B S A o n n o nfacial areas, a n d ≥ 3 T- V A SI. T otal b o d y i n v ol ve d 
vitili g o area (facial  a n d n o nfacial) was n ot t o e xcee d 1 0 % B S A. I n eac h pare nt st u d y, 
a p pr o xi matel y 3 0 0 partici pa nts wer e t o be ra n d o mize d 2: 1 t o recei ve a n i nitial, d o u ble- bli n d 
st u d y treat me nt of r u x oliti ni b crea m 1. 5 % BI D or ve hicle crea m BI D (a p plie d t o de pi g me nte d 
vitili g o areas o n t he face a n d b o d y u p t o 1 0 % t otal B S A) f or 2 4  wee ks. After c o m pleti o n of t he 
Wee k 2 4 assess me nts, partici pa nts i n t hese st u dies were offere d  t he o p p ort u nit y t o recei ve a n 
a d diti o nal 2 8 wee ks of o pe n-la be l treat me nt e xte nsi o n wit h r u x oliti ni b crea m 1. 5 % BI D u n der 
t he pare nt st u d y pr ot oc ol. 
Partici pa nts w h o s uccessf ull y c o m plete d t he 5 2- wee k treat me nt i n eit her of t he pare nt st u dies (ie, 
5 2 wee ks of r u x oliti ni b crea m or  2 4 wee ks of ve hicle crea m pl us 2 8 wee ks of r u x oliti ni b crea m) 
a n d t olerate d r u x oliti ni b crea m  treat me nt wit h o ut safet y c o ncern a n d wit h g o o d c o m plia nce f or 
c o nti n uati o n ma y be eli gi ble t o partici pate i n t his treat me nt e xte nsi o n st u d y.  
Visits i n t his treat me nt e xte nsi o n st u d y are na me d t o reflect c o nti n uati o n fr o m t he pare nt st u dies, 
wit h t he first visit of t his tr eat me nt e xte nsi o n st u d y occ urri n g at Wee k 5 2. T he eli gi bilit y 
assess me nt f or t his e xte nsi o n st u d y occ urs at Wee k 5 2. T he treat me nt e xte nsi o n peri o d of t his 
st u d y c o m prises t he peri o d fr o m t he Wee k 5 2 visit t o t he Wee k 10 4 visit (i ncl usi ve). F oll o wi n g 
t he last a p plicati o n of st u d y treat me nt at Wee k 1 0 4, t here will be a 3 0- da y safet y f oll o w- u p 
peri o d t o e val uate safe t y a n d d urati o n of res p o nse.  
Eli gi ble partici pa nts i n t his st u d y will be assi g ne d t o 1 of 2 c o h orts, C o h ort A or C o h ort B, base d 
o n t heir F- V A SI res p o nses at t he ti me of e nr oll me nt i n t his st u d y (ie, at Wee k 5 2).  
Treat me nt i n C o h ort A is a ra n d o mize d wit h dra wal desi g n a n d wil l pr o vi de data o n t he d urati o n 
of res p o nse f oll o wi n g wit h dra wal of  r u x oliti ni b crea m a n d mai nte na nce of res p o nse wit h its 
c o nti n ue d use. Partici pa nts w h o ac hie ve c o m plete or al m ost c o m plete facial re pi g me ntati o n (ie, 
ac hie ve ≥ F- V A SI 9 0) at Wee k 5 2 i n t he pare nt st u d y will be assi g ne d t o C o h ort A a n d will be 
stratifie d b y t he ori gi nal treat me nt recei ve d o n st u d y Da y 1 of t he pare nt st u d y a n d ra n d o mize d 
1: 1 t o treat me nt wit h ve hicle cr ea m BI D or r u x oliti ni b crea m 1.5 % BI D f or a n a d diti o nal 
5 2 wee ks (ie, u ntil E O T at Wee k 1 0 4 ).  H o we ver, a n y partici pa nts i n C o h ort A w h o e x perie nce 
rela pse ( defi ne d as < F- V A SI 7 5) will recei ve r u x oliti ni b crea m 1. 5 % BI D as a n o pe n-la bel 
resc ue treat me nt u ntil t he y c o m plete treat me nt ( Wee k 1 0 4 or E O T). 
Treat me nt i n C o h ort B will pr o vi de l o n g-ter m efficac y a n d safet y data f or r u x oliti ni b crea m i n 
partici pa nts wit h vitili g o. Par tici pa nts w h o di d n ot ac hie ve ≥ F- V A SI 9 0 at Wee k 5 2 of t he pare nt 
st u dies will be assi g ne d t o C o h ort B a n d will c o nti n ue r u x oliti ni b crea m 1. 5 % BI D f or 5 2 wee ks 
(ie, u ntil E O T Wee k 1 0 4). 




I nc yte C or p orati o n 
Pa ge 1 3 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
4.  
D A T A H A N D LI N G D E FI NI TI O N S A N D C O N V E N TI O N S 
4. 1.  
Sc he d ule d St u d y E v al u ati o ns a n d St u d y Peri o ds 
4. 1. 1.  
D a y 1 
Da y 1 is t he date t hat t he first a p plicati o n of r u x oliti ni b cre a m or ve hicle crea m is a d mi nistere d 
t o t he partici pa nts i n t he e xtensi o n treat me nt peri o d (ie, St u d y I N C B 1 8 4 2 4- 3 0 8).  
F or ra n d o mize d partici pa nts n ot  treate d wit h a n y st u d y dr u g, Day 1 is defi ne d as t he da y of 
ra n d o mizati o n. 
4. 1. 2.  
St u d y D a y 
If a visit/re p orti n g date is o n or after Da y 1, t he n t he st u d y da y at t he visit/re p orti n g date will be 
calc ulate d as 
Da y # = ( visit/re p orti n g da te – Da y 1 date + 1). 
If t he visit/re p orti n g date is bef ore Da y 1, t he n t he st u d y da y at t he visit/re p orti n g date will be 
calc ulate d as 
Da y # = ( visit/re p orti n g date – Da y 1 date). 
A st u d y da y of −1 i n dicates 1 da y bef ore Da y 1. 
4. 1. 3.  
B aseli ne V al ue 
F or ra n d o mize d partici pa nts n ot  treate d wit h a n y st u d y dr u g, baseli ne is defi ne d as t he last 
n o n missi n g assess me nt bef ore or  o n t he da y of ra n d o mizati o n f or all para meters. 
F or partici pa nts w h o c o nti n ue i n t he e xte nsi o n treat me nt peri o d , baseli ne is defi ne d as f oll o ws: 
 F or efficac y e val uati o n, baseli ne is t he last n o n missi n g meas ur e me nt o btai ne d bef ore 
t he first a p plicati o n of st u d y dr u g i n t he pare nt st u d y. 
 F or C o h ort B safet y e val uati o n, baseli ne is t he last n o n missi n g  meas ure me nt o btai ne d 
bef ore or o n t he da y of first a p p licati o n of r u x oliti ni b crea m i n t he pare nt st u d y. 
 F or C o h ort A safet y e val uati o n,  
 F or partici pa nts w h o are i nitiall y ra n d o mize d t o recei ve r u x oli ti ni b crea m i n t he 
e xte nsi o n treat me nt peri o d (ie, St u d y I N C B 1 8 4 2 4- 3 0 8), baseli ne is t he last 
n o n missi n g meas ure me nt o btai ne d bef ore t he first a p plicati o n of  r u x oliti ni b crea m 
i n t he pare nt st u d y. 
 F or partici pa nts w h o are i nitial l y ra n d o mize d t o recei ve ve hicle crea m i n t he 
e xte nsi o n treat me nt peri o d (ie, St u d y I N C B 1 8 4 2 4- 3 0 8), baseli ne is t he last 
n o n missi n g meas ure me nt o btai ne d bef ore t he first a p plicati o n of  ve hicle crea m i n 
t he e xte nsi o n peri o d. 


I nc yte C or p orati o n 
Pa ge 1 4 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
W he n sc he d ule d assess me nts a n d u nsc he d ule d assess me nts occ ur o n  t he sa me da y a n d ti me of 
t he assess me nt or ti me of first a p plicati o n is n ot a vaila ble, use t he f oll o wi n g c o n ve nti o n t o 
deter mi ne baseli ne: 
 If b ot h a sc he d ule d a n d a n u nsc he d ule d visit are a vaila ble o n the da y of t he first 
a p plicati o n a n d t he ti me is m issi n g, use t he sc he d ule d assess ment as baseli ne. 
 If all sc he d ule d assess me nts are missi n g o n t he da y of t he first a p plicati o n a n d a n 
u nsc he d ule d assess me nt is a vaila bl e, use t he u nsc he d ule d assess me nt as baseli ne. 
4. 1. 4.  
H a n dli n g of Missi n g a n d I nc o m plete D at a 
F or t he pri mar y a n d ke y sec o n dar y e n d p oi nts, w hic h are d urati o ns of res p o nses, t he al g orit h m i n 
Ta ble 2  will be a p plie d t o deter mi ne ce ns ori n g or e ve nt.  
T a ble 2:  
Al g orit h m f or Ce ns ori n g 
Sit u ati o n 
D ate of Rel a pse/ L ost Res p o nse or 
Ce ns ori n g 
O utc o me 
Rela pse/l ost res p o nse d oc u me nte d o n 
or bet wee n sc he d ule d visits  
Date of rela pse/l ost res p o nse 
 
Rela pse d/l ost res p o nse 
N o rela pse/ mai ntai n res p o nse  
Dat e of last assess me nt  
Ce ns ore d 
Treat me nt disc o nti n uati o n  
Date of last assess me nt  
Ce ns ore d 
A p pl yi n g resc ue treat me nt ( 1. 5 % 
BI D) i n e xte nsi o n treat me nt peri o d 
wit h o ut rela pse/l ost res p o nse stat us 
Date of  resc ue treat me nt 
 
Ce ns ore d 
F or all ot her e n d p oi nts, n o i m p utati o n will be perf or me d f or mi ssi n g val ues u nless ot her wise 
s pecifie d. 
4. 2.  
V ari a ble Defi niti o ns 
4. 2. 1.  
B o d y M ass I n de x 
B o d y mass i n de x will be calc ulate d as f oll o ws: 
B MI ( k g/ m 2) = ( wei g ht ([ k g])/( hei g ht [ m])2. 
4. 2. 2.  
C o nc o mit a nt Me dic ati o n 
C o nc o mita nt me dicati o n is defi ne d as a n y n o nst u d y me dicati o n t h at is starte d acc or di n gl y: 
 Bef ore t he date of first a p plicati o n of st u d y dr u g i n St u d y I N C B 1 8 4 2 4- 3 0 8 a n d is 
o n g oi n g t hr o u g h o ut t he st u d y or e n ds  o n/after t he date of first a p plicati o n of st u d y 
treat me nt. 
 O n/after t he date of first a p plicati o n of st u d y dr u g i n St u d y I N C B 1 8 4 2 4- 3 0 8 a n d is 
o n g oi n g or e n ds d uri n g t he c o urse of st u d y treat me nt. 
A c o nc o mita nt me dicati o n c o ul d a ls o be classifie d as " b ot h pri or a n d c o nc o mita nt me dicati o n" if 
t he e n d date is o n or after t he first a p plicati o n of st u d y dr u g. I n t he listi n g, it will be i n dicate d 
w het her a me dicati o n is pri o r o nl y, c o nc o mita nt o nl y, or b ot h pri or a n d c o nc o mita nt. 


I nc yte C or p orati o n 
Pa ge 1 5 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
F or t he p ur p oses of a nal ysis, all me dicati o ns will be c o nsi dere d c o nc o mita nt me dicati o ns u nless 
t he me dicati o ns ca n u ne q ui v ocally be defi ne d as n ot c o nc o mita nt . 
5.  
S T A TI S TI C A L M E T H O D O L O G Y 
5. 1.  
Ge ner al Met h o d ol o g y 
U nless ot her wise n ote d, S A S ®  s oft ware ( S A S I nstit ute I nc, Car y, N C; v 9. 1 or later) will be use d 
f or t he ge nerati o n of all ta bles, gra p hs, a n d statistical a nal yses. Descri pti ve s u m maries f or 
c o nti n u o us varia bles will i ncl u de, b ut n ot be li mite d t o, t he n u m ber of o bser vati o ns, mea n, 
sta n dar d de viati o n, me dia n, mi ni m u m, ma xi m u m, first q uartile, thir d q uartile, a n d 9 5 % CI.  
Descri pti ve s u m maries f or cate g orical varia bles will i ncl u de t h e n u m ber a n d perce nta ge of 
partici pa nts i n eac h cate g or y.  
5. 2.  
Tre at me nt Gr o u ps 
T his is a d o u ble- bli n d, ve hicle -c o ntr olle d, ran d o mize d wit h dra wal a n d treat me nt e xte nsi o n st u d y 
t hat will e nr oll eli gi ble partici pa nts wh o ha ve c o m plete d eit he r St u d y I N C B 1 8 4 2 4- 3 0 6 or St u d y 
I N C B 1 8 4 2 4- 3 0 7 ( pare nt st u dies). Data will be s u m marize d base d o n t he treat me nt re gi me n t hat 
was assi g ne d at Wee k 5 2 (I T T- E xt)  or t hat t he partici pa nt act uall y a p plie d ( F A S). 
F or C o h ort A, treat me nt gr o u ps a re r u x oliti ni b crea m 1. 5 % BI D an d ve hicle crea m f or 
partici pa nts bef ore o pe n-la bel resc ue treat me nt. F or partici pa nts w h o cr oss o ver fr o m ve hicle 
crea m t o o pe n-la bel r u x oliti ni b crea m, t he treat me nt gr o u p will  be Ve hicle- 1. 5 % BI D. F or 
C o h ort B, t he treat me nt gr o u p will be base d o n t he treat me nt assi g n me nt at Da y 1 of t he pare nt 
st u d y ( ve hicle t o 1. 5 % BI D a n d 1. 5 % BI D t o 1. 5 % BI D). 
5. 3.  
A n al ysis P o p ul ati o ns 
T he data fr o m partici pa nts at Site 7 1 0 were re m o ve d fr o m all ef ficac y a nal yses perf or me d o n t he 
I T T- E xt p o p ulati o n a n d F A S o win g t o n o nc o m plia nce wit h t he Pr ot oc ol i n t he pare nt st u d y 
res ulti n g i n seri o us c o ncer ns wit h t he data q ualit y. 
5. 3. 1.  
F ull A n al ysis Set 
All partici pa nts e nr olle d i n t he st u d y w h o a p plie d st u d y dr u g ( r u x oliti ni b crea m or ve hicle) at 
least o nce at or after Wee k 5 2 for eac h c o h ort ( F A S C o h ort A a n d F A S C o h ort B) will c o nstit ute 
t he F A S. 
T he F A S will be use d f or t he s u m mar y of a nal yses of de m o gra p hic s, baseli ne c haracteristics, 
partici pa nt dis p ositi o n, efficac y, a n d safet y data. 
5. 3. 2.  
I nte nt-t o- Tre at i n L o n g-ter m E xte nsi o n 
All partici pa nts w h o ac hie ve d ≥ F- V A SI 9 0 at Wee k 5 2  will be ra n d o mize d i nt o C o h ort A a n d 
will c o nstit ute t he I T T- E xt p o p ulati o n. Treat me nt gr o u ps f or t h is p o p ulati o n will be defi ne d 
acc or di n g t o t he treat me nt assi g n me nt at t he ti me of ra n d o mizat i o n re gar dless of t he act ual st u d y 
me dicati o n t he partici pa nt mi g ht ta ke d uri n g t he st u d y. 


I nc yte C or p orati o n 
Pa ge 1 6 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
5. 3. 3.  
Rel a pse E v al u a ble Set 
All partici pa nts w h o are i n t he  I T T- E xt p o p ulati o n, e x perie nce rela pse ( defi ne d as < F- V A SI 7 5), 
a n d recei ve o pe n-la bel resc ue treat me nt will c o nstit ute t he R E S . 
5. 3. 4.  
P h ar m ac o ki netic
E v al u a ble P o p ul ati o n 
T he P K 
 e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o a p plie d r u x oliti ni b crea m at 
least o nce a n d pr o vi de d at least 1 bl o o d sa m ple ( 1 P K 
 meas ure me nt) t hat c o m plies wit h t he 
i nstr ucti o ns i n t he Pr ot oc ol. The st u d y p har mac o ki neticist will  re vie w data listi n gs of st u d y dr u g 
a p plicati o n a n d sa m ple rec or ds t o i de ntif y partici pa nts t o be excl u de d fr o m P K data a nal yses.  
T he st u d y researc h i n vesti gat or w ill re vie w data listi n gs of  
 data a n d sa m ple rec or ds t o 
i de ntif y partici pa nts t o be e xclu de d fr o m a nal yses of  
 data. 
6.  
B A S E LI N E, E X P O S U R E, A N D DI S P O SI TI O N  
A p pe n di x A  pr o vi des a list of pla n ne d ta bles, fi g ures, a n d listi n gs. Sa m ple data dis pla ys are 
i ncl u de d i n a se parate d oc u me nt. 
6. 1.  
B aseli ne, De m o gr a p hics, a n d Dise ase Hist or y 
6. 1. 1.  
De m o gr a p hics 
T he f oll o wi n g de m o gra p hics will  be s u m marize d f or t he F A S p o p ulati o n f or eac h c o h ort b y 
treat me nt gr o u p: a ge, a ge gr o u p ( < 1 8 years, 1 8 t o < 6 5 years, ≥ 6 5 years; < 1 8 years, 
≥ 1 8 years), se x, race, et h nicit y, re gi o n, wei g ht, hei g ht, a n d B MI. 
6. 1. 2.  
B aseli ne Dise ase C h ar acteristics 
Baseli ne disease c haracteristics s u m marize d f or t he F A S p o p ulat i o n i ncl u de b ut are n ot li mite d 
t o t he f oll o wi n g: 
 Ti me si nce i nitial di a g n osis of vitili g o 
 Vitili g o dia g n ose d i n c hil d h o o d ( N o/ Yes [a ge]: 0- 5 years, 6- 1 1 years, 1 2- 1 7 years) 
 Disease stat us (sta ble/ pr o gressi ve) 
 S ki n t y pe ( T y pe I/II/III/I V/ V/ VI) 
 Ot her a ut oi m m u ne dis or ders  
 Pri or t hera p y f or vitili g o ( pre de fi ne d s yste mic treat me nts, p h ot ot hera p y, a n d s ur gical 
pr oce d ures)  
 Hist or y of ac ne v ul garis ( N o/ Yes) 
 C urre ntl y ha ve ac ne v ul garis o n t he face ( N o/ Yes) 
 Vitili g o i n ge nital area ( N o/ Yes) 
 Baseli ne F- V A SI sc ore  
 Baseli ne T- V A SI sc ore 


I nc yte C or p orati o n 
Pa ge 1 7 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
 Baseli ne F- B S A i n v ol ve me nt  ( % of t he t otal b o d y) 
 Baseli ne T- B S A i n v ol ve me nt  ( % of t he t otal b o d y) 
6. 2.  
Dis p ositi o n of P artici p a nts 
T he n u m ber a n d perce nta ge of par tici pa nts w h o were ra n d o mize d, treate d, a n d c o m plete d t he 
e xte nsi o n treat me nt peri o d will be s u m marize d b y treat me nt gr o u ps f or eac h c o h ort. M ore o ver, 
partici pa nts w h o disc o nti n ue d t he treat me nt or wit h dre w fr o m t he st u d y d uri n g t he e xte nsi o n 
treat me nt peri o d wit h a pri mary reas o n f or disc o nti n uati o n will  als o be s u m marize d.  
6. 3.  
Pr ot oc ol De vi ati o ns 
Pr ot oc ol de viati o ns will be s u m mari ze d b y treat me nt gr o u ps f or eac h c o h ort.  
6. 4.  
E x p os ure 
A s u m mar y f or o verall  e x p os ure wit hi n t his st u d y will be pr o vi de d f or t he F A S f or eac h c o h ort. 
F or C o h ort A, a s u m mar y will be pr o vi de d base d o n t he act ual tr eat me nt recei ve d as defi ne d i n 
Secti o n 5. 2 . 
6. 5.  
St u d y Dr u g C o m pli a nce 
O verall c o m plia nce ( %) f or t he a p plicati o n of r u x oliti ni b crea m  or ve hicle crea m will be 
calc ulate d f or all partici pa nts base d o n t he act ual treat me nt recei ve d i n t he F A S p o p ulati o n as 
f oll o ws: 
O verall a p plicati o n c o m plia nce ( %) = 1 0 0  [t otal n u m ber of n o n missi n g a p plicati o ns]/[t otal 
n u m ber of i nte n de d a p plicati o ns] 
w here t he t otal n u m ber of n o n missi n g a p plicati o ns is t he t otal n u m ber of a p plicati o ns t hat t he 
partici pa nt act uall y a p plie d d ur i n g t he st u d y. T he t otal n u m ber of i nte n de d a p plicati o ns is t he 
n u m ber of pla n ne d a p plicati o ns mi n us t he n u m ber of i nterr u pte d a p plicati o ns. 
6. 6.  
C o nc o mit a nt Me dic ati o ns 
F or partici pa nts i n t he F A S p o p ulati o n,  c o nc o mita nt me dicati o ns will be c o de d usi n g t he W H O 
Dr u g Dicti o nar y a n d s u m marize d as  n u m ber a n d perce nta ge of partici pa nts wit h c o nc o mita nt 
me dicati o ns b y W H O dr u g class a n d W H O dr u g ter m.   
C o nc o mita nt me dicati o ns will be s u m marize d b y treat me nt gr o u ps f or eac h c o h ort. Als o, listi n gs 
will be pr o vi de d f or b ot h C o h orts A a n d B. 


I nc yte C or p orati o n 
Pa ge 1 8 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
7.  
E F FI C A C Y 
A p pe n di x A  pr o vi des a list of pla n ne d ta bles, fi g ures, a n d listi n gs. Sa m ple data dis pla ys are 
i ncl u de d i n a se parate d oc u me nt.  
7. 1.  
Ge ner al C o nsi der ati o ns 
F or all c o nti n u o us varia bles, b ot h t he act ual va l ue, c ha n ge, a nd perce nta ge fr o m baseli ne (if 
a vaila ble) will be a nal yze d. 
All b y- visit a nal yses will i ncl u de t he f oll o w- u p peri o d if t he data are a vaila ble. 
7. 2.  
Effic ac y Me as ures  
7. 2. 1.  
B o d y S urf ace Are a 
Facial a n d t otal % B S A (i ncl u de s facial a n d n o nfacial areas) de pi g me nte d b y vitili g o will be 
esti mate d at eac h visit.  B o d y s urface area assess me nt will be perf or me d b y t he pal mar met h o d.  
B o d y s urface area s h o ul d be esti mate d t o t he nearest 0. 1 %. T he a p pr o xi mate size of t he 
partici pa nt's e ntire pal mar s urface (ie, t he pal m pl us 5 di gits ) s h o ul d be c o nsi dere d as 1 % B S A, 
a n d t he a p pr o xi mate size of t he partici pa nt's t h u m b s h o ul d be c o nsi dere d as 0. 1 % B S A. 
7. 2. 2.  
Vitili g o Are a Sc ori n g I n de x  
Areas affecte d b y de pi g me ntati o n d ue t o vitili g o will be assess e d usi n g t he V A SI. It is base d o n a 
c o m p osite esti mate of t he o verall area of vitili g o patc hes at baseli ne a n d t he de gree of mac ular 
re pi g me ntati o n wit hi n t hese patc hes o ver ti me. 
Facial V A SI is meas ure d b y perce nta ge of vitili g o i n v ol ve me nt ( % B S A) a n d t he de gree of 
de pi g me ntati o n. T he perce nta ge of B S A ( ha n d u nit) vitili g o i n v o l ve me nt is esti mate d b y t he 
i n vesti gat or usi n g t he pal mar met h o d. Ha n d u nit is base d o n t he partici pa nt's ha n d size. T he 
i n vesti gat or uses t heir ha n d t o mi mic t he partici pa nt's ha n d size t o e val uate perce nta ge of B S A 
vitili g o i n v ol ve me nt. T he de gree of de pi g me ntati o n f or eac h vit ili g o i n v ol ve me nt site is 
deter mi ne d a n d esti mate d t o t he  nearest of t he f oll o wi n g perce nta ges: 0, 1 0 %, 2 5 %, 5 0 %, 7 5 %, 
9 0 %, or 1 0 0 %. At 1 0 0 % de pi g me ntati o n, n o pi g me nt is prese nt; at  9 0 %, s pec ks of pi g me nt are 
prese nt; at 7 5 %, t he de pi g me nte d area e xcee ds t he pi g me nte d are a; at 5 0 %, t he de pi g me nte d a n d 
pi g me nte d area are e q ual; at 2 5 %, t he pi g me nte d area e xcee ds t h e de pi g me nte d area; at 1 0 %, 
o nl y s pec ks of de pi g me ntati o n are  prese nt. T he F- V A SI is t he n deri ve d b y m ulti pl yi n g t he val ues 
assesse d f or t he vitili g o i n v ol ve me nt b y t he perce nta ge of affe cte d s ki n f or eac h site o n t he face 
a n d s u m mi n g t he val ues of all si tes t o get her ( p ossi ble ra n ge, 0- 3). 
T he are a " F ace " is defi ne d as i ncl u di n g t he are a o n t he f ore he a d t o t he ori gi n al h airli ne, o n 
t he c hee k t o t he j a wli ne verticall y t o t he j a wli ne a n d l ater all y fr o m t he c or ner of t he m o ut h 
t o t he tr a g us. T he are a " F ace " will n ot i ncl u de t he s urf ace area of t he li ps, sc al p, e ars, or 
nec k b ut will i ncl u de t he n ose a n d e yeli ds. 


I nc yte C or p orati o n 
Pa ge 1 9 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T otal b o d y V A SI is calc ulate d usi n g a f or m ula t hat i ncl u des c o n tri b uti o ns fr o m all b o d y re gi o ns 
( p ossi ble ra n ge, 0- 1 0 0). 
𝑉𝐴𝑆𝐼 
ℎ𝑎𝑛𝑑 𝑢𝑛𝑖𝑡𝑠 𝑥 𝑅𝑒𝑠𝑖𝑑𝑢𝑎𝑙 𝐷𝑒𝑝𝑖𝑔𝑚𝑒𝑛𝑡𝑎𝑡𝑖𝑜𝑛
 
 
 
T he b o d y is di vi de d i nt o t he f o ll o wi n g 6 se parate a n d m ut uall y e xcl usi ve sites: 1) hea d/ nec k, 
2) ha n ds, 3) u p per e xtre mities (e xcl u di n g ha n ds), 4) tr u n k, 5) l o wer e xtre mities (e xcl u di n g feet), 
a n d 6) feet. T he perce nta ge of v itili g o i n v ol ve me nt is esti mated i n ha n d u nits ( % B S A) b y t he 
sa me i n vesti gat or d uri n g t he e ntire c o urse of t he st u d y. Ha n d unit is base d o n t he partici pa nt's 
ha n d size.  T he i n vesti gat or uses  t heir ha n d t o mi mic t he partici pa nt's ha n d size t o e val uate 
% B S A vitili g o i n v ol ve me nt. T he de gree of de pi g me ntati o n f or eac h b o d y site is deter mi ne d a n d 
esti mate d t o t he nearest of t he f oll o wi n g perce nta ges: 0 %, 1 0 %,  2 5 %, 5 0 %, 7 5 %, 9 0 %, or 1 0 0 %. 
T he T- V A SI is t he n deri ve d b y m ulti pl yi n g t he val ues assesse d f or t he vitili g o i n v ol ve me nt b y 
t he perce nta ge of affecte d s kin f or eac h b o d y site a n d s u m mi n g t he val ues of all b o d y sites 
t o get her (Ha mza vi et al 2 0 0 4 ). 
T he cate g orical varia ble F- V A SI 5 0 will be e q ual t o 1 f or perce n ta ge i m pr o ve me nt fr o m baseli ne 
i n F- V A SI of ≥ 5 0 % a n d will be e q ual t o 0 f or perce nta ge i m pr o ve me nt of < 5 0 %. T he 
F- V A SI 7 5/ 9 0 a n d T- V A SI 7 5/ 9 0 will be defi ne d wit h t he sa me patte r n. 


I nc yte C or p orati o n 
Pa ge 2 0 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
7. 2. 5.  
P atie nt- Re p orte d O utc o mes  
Patie nt-re p orte d o utc o mes a n d q uali t y of life will be assesse d usi n g t he f oll o wi n g t o ols: 
 V N S (see Secti o n 7. 2. 5. 1 ) 
 D L QI or C D L QI (see Secti o n 7. 2. 5. 5 ) 
7. 2. 5. 1.  
Vitili g o N otice a bilit y Sc ale  
T he V N S is a patie nt‐re p orte d meas ure of vitili g o treat me nt s uc cess, w hic h has a 5- p oi nt scale 
(Batc hel or et al 2 0 1 6 ). T he baseli ne facial p h ot o gra p h fr o m t he pare nt st u d y (I N C B 18 4 2 4- 3 0 6 
or I N C B 1 8 4 2 4- 3 0 7) will be s h o w n t o t he partici pa nts f or refere nce a n d a mirr or will be 
pr o vi de d f or t he partici pa nts t o assess t he vitili g o o n t heir f ace. T he partici pa nt will be as ke d t o 
res p o n d t o t he f oll o wi n g q uer y: 
C o m pare d wit h bef ore treat me nt, h o w n oticea ble is t he vitili g o n o w? Res p o nses: ( 1) M ore 
n oticea ble, ( 2) As n oticea ble, ( 3) Sli g htl y less n oticea ble, ( 4 ) A l ot less n oticea ble, a n d ( 5) 
N o l o n ger n oticea ble 
V N S sc ores of 4 or 5 ca n be i nter pr ete d as re prese nti n g treat me nt s uccess. 


I nc yte C or p orati o n 
Pa ge 2 1 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
7. 2. 5. 5.  
Der m at ol o g y Life Q u alit y I n de x 
T he D L QI is a si m ple, 1 0- q uesti o n vali date d q uesti o n naire t o me as ure h o w m uc h t he s ki n 
pr o ble m  has affecte d t he partici pa nt o ver t he pre vi o us 7 da ys (Fi nla y a n d K ha n 1 9 9 4 ). 
Partici pa nts a ge d ≥ 1 6 years will  a ns wer t he q uesti o n naire wit h ( 1) ver y m uc h, ( 2) a l ot, ( 3) a 
little, or ( 4) n ot at all. 
T he q uesti o n naire is a nal yze d u n der 6 hea di n gs as f oll o ws: 
 S y m pt o ms a n d feeli n gs ( Q uesti o ns 1 a n d 2) 
 Dail y acti vities ( Q uesti o ns 3 a n d 4) 
 Leis ure ( Q uesti o ns 5 a n d 6) 
 W or k a n d sc h o ol ( Q uesti o n 7) 


I nc yte C or p orati o n 
Pa ge 2 2 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
 Pers o nal relati o ns ( Q uesti o ns 8 a n d 9) 
 Treat me nt ( Q uesti o n 1 0) 
T he sc ori n g of eac h q uesti o n is as  f oll o ws: Ver y m uc h = 3; A l ot = 2; A little = 1; N ot at all = 0; 
N ot rele va nt = 0; Q uesti o n 7, " Pre ve nte d w or k or st u d yi n g" = 3.  
T he f oll o wi n g i m p utati o ns will be a p plie d f or i nc orrectl y c o m pl ete d q uesti o n naires: 
 If 1 q uesti o n is left u na ns wered, t his is sc ore d 0 a n d t he sc or es are s u m me d a n d 
e x presse d as us ual o ut of a ma xi m u m of 3 0. 
 If 2 or m ore q uesti o ns are left u na ns were d, t he q uesti o n naire is n ot sc ore d. 
 If Q uesti o n 7 is a ns were d " yes," t his is sc ore d 3. If Q uesti o n 7 is a ns were d " n o," b ut 
t he n eit her "a l ot" or "a little" is tic ke d, t his is t he n sc ored 2 or 1. If " N ot rele va nt" is 
tic ke d, t he sc ore f or Q uesti o n 7 is 0. If it is a ns were d " n o," b ut t he sec o n d half is left 
i nc o m plete, t he sc ore will re mai n 0. 
 If 2 or m ore res p o nse o pti o ns are tic ke d, t he res p o nse o pti o n wit h t he hi g hest sc ore 
s h o ul d be rec or de d. 
 If t here is a res p o nse bet ween 2 tic k b o xes, t he l o wer of t he 2  sc ore o pti o ns s h o ul d be 
rec or de d. 
 F or t he 6 D L QI s u bscales, if t h e a ns wer t o 1 q uesti o n i n a s u bs cale is missi n g, t hat 
s u bscale s h o ul d n ot be sc ore d. 
T he D L QI is calc ulate d b y s u m mi n g t he sc ore of eac h q uesti o n, r es ulti n g i n a ma xi m u m of 
3 0 a n d a mi ni m u m of 0. T he hi g her t he sc ore, t he m ore q ualit y of life is i m paire d. 
T he mea ni n g of t otal D L QI sc ores  ca n be cate g orize d as f oll o ws: 
 0 t o 1 = N o effect 
 2 t o 5 = S mall effect 
 6 t o 1 0 = M o derate effect 
 1 1 t o 2 0 = Ver y lar ge effect 
 2 1 t o 3 0 = E xtre mel y lar ge effect 
A c ha n ge fr o m baseli ne i n D L QI a n d C D L QI sc ore of at least 4 p o i nts is c o nsi dere d cli nicall y 
i m p orta nt (Basra et al 2 0 1 5 , Waters et al 2 0 1 0 ). 
T he q uesti o n naire is als o a nal y ze d u n der 6 s u bscales as f oll o ws : 
 S y m pt o ms a n d feeli n gs ( Q uesti o ns 1 a n d 2) 
 Dail y acti vities ( Q uesti o ns 3 a n d 4) 
 Leis ure ( Q uesti o ns 5 a n d 6) 
 W or k a n d sc h o ol ( Q uesti o n 7) 
 Pers o nal relati o ns ( Q uesti o ns 8 a n d 9) 
 Treat me nt ( Q uesti o n 1 0) 


I nc yte C or p orati o n 
Pa ge 2 3 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T he C D L QI is t he y o ut h/c hil dre n's versi o n of t he D L QI. F or part ici pa nts w h o are a ge d 
< 1 6 years at baseli ne ( Da y 1) of  t he pare nt st u d y (I N C B 1 8 4 2 4-3 0 6 or I N C B 1 8 4 2 4- 3 0 7), t he 
C D L QI will be c o m plete d i nste a d of t he D L QI t hr o u g h o ut t heir pa rtici pati o n i n t his e xte nsi o n 
st u d y.  
T he sc ori n g of eac h q uesti o n is as  f oll o ws: Ver y m uc h = 3; Q uite a l ot = 2; O nl y a little = 1; 
N ot at all = 0; Q uesti o n u na ns were d = 0; Q uesti o n 7: " Pre ve nte d  sc h o ol" = 3. 
T he C D L QI is calc ulate d b y s u m mi n g t he sc ore of eac h q uesti o n, res ulti n g i n a ma xi m u m of 3 0 
a n d a mi ni m u m of 0. T he hi g her t he sc ore, t he m ore q ualit y of life is i m paire d. 
T he q uesti o n naire is als o a nal y ze d u n der 6 s u bscales as f oll o ws : 
 S y m pt o ms a n d feeli n gs ( Q uesti o ns 1 a n d 2) 
 Leis ure ( Q uesti o ns 4, 5, a n d 6) 
 Sc h o ol or h oli da ys ( Q uesti o n 7) 
 Pers o nal relati o ns hi ps ( Q uesti o ns 3 a n d 8) 
 Slee p ( Q uesti o n 9) 
 Treat me nt ( Q uesti o n 1 0) 
T he se verit y ba n di n g f or C D L QI sc ores is as f oll o ws: 
 0 t o 1 = N o effect o n c hil d's life 
 2 t o 6 = S mall effect 
 7 t o 1 2 = M o derate effect 
 1 3 t o 1 8 = Ver y lar ge effect 
 1 9 t o 3 0 = E xtre mel y lar ge effect 
T he f oll o wi n g i m p utati o ns will be a p plie d f or i nc orrectl y c o m pl ete d q uesti o n naires: 
 If 1 q uesti o n is left u na ns wered, t his is sc ore d 0, a n d t he sc o res are s u m me d a n d 
e x presse d as us ual o ut of a ma xi m u m of 3 0. 
 If 2 or m ore q uesti o ns are left u na ns were d, t he q uesti o n naire is n ot sc ore d. 
 If b ot h parts of Q uesti o n 7 are c o m plete d, t he hi g her of t he 2 sc ores s h o ul d be 
c o u nte d. 


I nc yte C or p orati o n 
Pa ge 2 4 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
7. 3.  
A n al ysis of t he Pri m ar y Effic ac y P ar a meter  
T he pri mar y e n d p oi nt is ti me t o r ela pse ( defi ne d as < F- V A SI 7 5)  f or partici pa nts w h o are 
ra n d o mize d i n C o h ort A. 
7. 3. 1.  
Pri m ar y Effic ac y A n al ysis 
T he pri mar y a nal ysis will be ba se d o n t he I T T- E xt p o p ulati o n ( defi ne d as ac hie vi n g ≥ F- V A SI 9 0 
at Wee k 5 2). Rela pse, a bi nar y vari a ble e ve nt, is defi ne d as a l oss of F- V A SI 7 5 res p o nse 
assesse d as perce nta ge i m pr o ve me nt fr o m baseli ne ( Da y 1 of t he pare nt st u d y) t o F- V A SI 
< 7 5 %. T he ti me t o rela pse is de fi ne d as t he n u m ber of da ys fr om t he Wee k 5 2 ra n d o mizati o n 
date t o t he first e val uati o n date at w hic h t he partici pa nt meet s t he defi niti o n of rela pse. F or 
partici pa nts w h o disc o nti n ue ear l y, c o m plete t he st u d y wit h o ut meeti n g criteria f or t he e ve nt, or 
recei ve d o pe n-la bel resc ue treat me nt ( 1. 5 % BI D) wit h o ut meeti n g t he criteria f or t he e ve nt, t he 
ti me t o e ve nt will be ce ns ore d at t he last assess me nt date or the date of resc ue treat me nt. Details 
of t he ce ns ori n g a n d missi n g da ta ha n dli n g are pr o vi de d i n Ta ble 2 . T he ti me-t o-e ve nt data will 
be assesse d usi n g t he Ka pla n- Me ier pr o d uct li mit met h o d. Treat me nt c o m paris o ns bet wee n 
r u x oliti ni b 1. 5 % crea m BI D a n d vehicle crea m BI D will be perf or me d usi n g t he l o g-ra n k test. 
Hazar d rati os a n d t he c orres p o n di n g 9 5 % CIs will be esti mate d usi n g t he C o x pr o p orti o nal 
hazar ds m o del. T his m o del will  i ncl u de t he treat me nt gr o u p ( 1. 5% BI D a n d ve hicle) a n d 
stratificati o n fact ors (s ki n t y pe a n d re gi o n). 
T he i nci de nce of rela pse will  be s u m marize d b y r u x oliti ni b crea m 1. 5 % BI D a n d ve hicle at eac h 
ti me p oi nt. S wi m mer pl ots will be pr o vi de d f or t he ti me t o rela pse a n d s u b gr o u p s wi m mer pl ots 
b y baseli ne c haracteristics, s uc h as a ge gr o u p a n d d urati o n of disease, will be pr o vi de d.   
7. 4.  
A n al ysis of t he Ke y Sec o n d ar y Effic ac y P ar a meters 
T he ke y sec o n dar y e n d p oi nt will  be a nal yze d usi n g t he I T T- E xt po p ulati o n. 


I nc yte C or p orati o n 
Pa ge 2 5 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T he ke y sec o n dar y e n d p oi nt will be  t he ti me t o mai ntai n ≥ F- V A SI 9 0 res p o nse. F or F- V A SI 9 0 
res p o nse, a cate g orical varia ble e ve nt is defi ne d t o be e q ual to 1 ( Yes) w he n t he i m pr o ve me nt 
fr o m baseli ne i n F- V A SI is ≥ 9 0 % a n d 0 ( N o) if < 9 0 %. T he ti me t o mai ntai n ≥ F- V A SI 9 0 
res p o nse is defi ne d as t he n u m ber of da ys fr o m t he Wee k 5 2 ra n do mizati o n t o t he first e val uati o n 
date at w hic h t he partici pa nt ha s perce nta ge c ha n ge fr o m baseline i n F- V A SI < 9 0 %.  
T he statistical c o m paris o ns a n d ce ns ori n g a n d missi n g data ha n dli n g f or t he ke y sec o n dar y 
e n d p oi nt will be a nal yze d usi n g a  si milar met h o d as s pecifie d in t he pri mar y a nal ysis. 
7. 5.  
A n al ysis of Ot her Sec o n d ar y Effic ac y P ar a meters 
7. 5. 1.  
Ot her Sec o n d ar y Effic ac y A n al ysis 
All ot her sec o n dar y efficac y a nal yses will be c o n d ucte d base d o n t he F A S f or C o h orts A a n d B 
se paratel y. F or C o h ort A, o nl y assess me nts o n or bef ore t he first d ose date of o pe n-la bel resc ue 
treat me nt will be s u m marize d an d all assess me nts will be liste d . 
7. 5. 1. 1.  
C o nti n u o us Effic ac y E n d p oi nts 
B y- visit s u m mar y statistics f or t he f oll o wi n g c o nti n u o us meas ur e me nts, i ncl u di n g act ual 
meas ure me nt, c ha n ge fr o m baseli n e, a n d perce nta ge c ha n ge fr o m b aseli ne, will be prese nte d f or 
t he f oll o wi n g: 
 F- V A SI/ T- V A SI 
 F- B S A/ T- B S A 
 D L QI ( or C D L QI) t otal sc ore a n d s u bsc ores 
S u m mar y statistics, i ncl u di n g sa m ple size, mea n, me dia n, sta n da r d de viati o n, mi ni m u m, 
ma xi m u m, first q uartile, t hir d q uartile, a n d 9 5 % CI, will be pr ese nte d b y visits f or b ot h 
C o h orts A a n d B.    
7. 5. 1. 2.  
C ate g oric al Effic ac y E n d p oi nts 
F or t he f oll o wi n g cate g orical para meters, s u m mar y statistics, i ncl u di n g sa m ple size, fre q ue nc y, 
a n d perce nta ges, will be prese nte d b y visit f or b ot h c o h orts.   
 Pr o p orti o n of partici pa nts ac hie vi n g F- V A SI 5 0/ 7 5/ 9 0  
 Pr o p orti o n of partici pa nts ac hie vi n g T- V A SI 5 0/ 7 5/ 9 0  
 Pr o p orti o n of partici pa nts ac hie vi n g a V N S of " 4 – A l ot less n oticea ble" or " 5 – N o 
l o n ger n oticea ble" 


I nc yte C or p orati o n 
Pa ge 2 6 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
7. 7.  
P h ar m ac o ki netic A n al yses 
Plas ma c o nce ntrati o ns of r u x oliti n i b at all st u d y visits will be s u m marize d usi n g descri pti ve 
statistics b y c o h ort, treat me nt gr o u p, a n d/ or visit. 
Plas ma r u x oliti ni b stea d y-state e x p os ures ( C mi n,ss ) will be deri ve d as t he a vera ge of all 
prea p plicati o n c o nce ntrati o ns of r u x oliti ni b f or  eac h partici pant, a n d t he n descri pti ve s u m maries 
of C mi n,ss  will be ge nerate d b y c o h ort a n d treat me nt gr o u p. 


I nc yte C or p orati o n 
Pa ge 2 7 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
8.  
S A F E T Y A N D T O L E R A BI LI T Y 
A p pe n di x A  pr o vi des a list of pla n ne d ta bles, fi g ures, a n d listi n gs. Sa m ple data dis pla ys are 
i ncl u de d i n a se parate d oc u me nt. 
8. 1.  
Ge ner al C o nsi der ati o ns 
T he a nal yses i n t his secti o n w ill be pr o vi de d f or t he F A S p o p ulati o n f or eac h c o h ort. Safet y data 
f or eac h c o h ort will be s u m marize d i n se parate ta bles. 
F or A Es, s u m mar y ta bles will be  pr o vi de d base d o n t he act ual treat me nt recei ve d as defi ne d i n 
Secti o n 5. 2 .  
F or la b orat or y tests a n d vital si g ns, s u m mar y ta bles will be pr o vi de d base d o n t he act ual 
treat me nt recei ve d at Wee k 5 2. F or C o h ort A, o nl y assess me nts on or bef ore t he first d ose date 
of o pe n-la bel resc ue treat me nt will be s u m marize d. 
Als o, f or safet y e val uati o ns, base li ne will be defi ne d as stated i n Secti o n 4. 1. 3 . 
S u m mar y ta bles ma y be re place d w it h listi n gs w he n a p pr o priate. F or i nsta nce, a n A E fre q ue nc y 
ta ble ma y be re place d wit h a listi n g if it o nl y c o ntai ns a fe w u ni q ue P Ts re p orte d o n relati vel y 
fe w partici pa nts. 
8. 2.  
A d verse E ve nts 
8. 2. 1.  
A d verse E ve nt Defi niti o ns 
A T E A E is a n y A E eit her re p orte d f or t he first ti me or w orse ni n g of a pre-e xisti n g e ve nt after 
first a p plicati o n of st u d y dr u g in St u d y I N C B 1 8 4 2 4- 3 0 8 a n d wit hi n 3 0 da ys of t he last d ose of 
st u d y dr u g. F or partici pa nts w h o cr oss o ver treat me nts, t he first a p plicati o n date is 
treat me nt-s pecific, a n d t he en d date is 3 0 da ys after t he last a p plicati o n date of this treat me nt, or 
t he first a p plicati o n date i n t he ne xt treat me nt, w hic he ver c o mes first. A nal ysis of A Es (as 
disc usse d bel o w) will be li mite d t o T E A Es, b ut data listi n gs wi ll i ncl u de all A Es re gar dless of 
t heir ti mi n g i n relati o n to st u d y dr u g a p plicati o n. 
A d verse e ve nts will be ta b ulate d b y Me d D R A P T a n d S O C. Se verit y  of A Es will be gra de d 
usi n g t he Nati o nal Ca ncer I nstit ute C T C A E v 5. 0.  T he C T C A E re p orti n g g ui deli nes a n d gra di n g 
details are a vaila ble o n t he Ca ncer T hera p y E val uati o n Pr o gra m we bsite. 
T he s u bset of A Es c o nsi dere d b y t he i n vesti gat or t o be relate d t o st u d y dr u g will be c o nsi dere d t o 
be treat me nt-relate d A Es. If t he i n vesti gat or d oes n ot s pecif y t he relati o ns hi p of t he A E t o st u d y 
dr u g, t he A E will be c o nsi dere d t o be treat me nt-relate d. T he i n ci de nce of A Es a n d 
treat me nt-relate d A Es will be ta bulate d. Seri o us A Es will als o be ta b ulate d. 


I nc yte C or p orati o n 
Pa ge 2 8 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
A n y missi n g o nset date, ca usalit y, or se verit y m ust be q uerie d f or res ol uti o n. U nres ol ve d missi n g 
ca usalit y a n d se verit y will be ha n dle d acc or di n g t o t he f oll o wi n g r ules: 
 A n u nres ol ve d missi n g ca usalit y will be c o nsi dere d treat me nt-re late d. 
 A n u nres ol ve d missi n g se verit y w ill be i de ntifie d as a n u n k n o w n se verit y. 
F or p ur p oses of a nal ysis, all A Es will be c o nsi dere d T E A Es u nless t he A E ca n u ne q ui v ocall y be 
defi ne d as n ot treat me nt-e mer ge nt. 
A p plicati o n site reacti o ns are A Es t hat occ ur at t he site of dr u g a p plicati o n. A s u m mar y of A S Rs 
will be pr o vi de d.  
8. 2. 2.  
A d verse E ve nts of I nterest 
A d verse e ve nts of i nterest will be s u m marize d i n t he f oll o wi n g cate g ories: 
 C yt o pe nias 
 A ne mia 
 T hr o m b oc yt o pe nia 
 Ne utr o pe nia  
 Her pes z oster 
 Viral s ki n i nfecti o ns 
 S ki n ne o plas ms 
 Ve n o us a n d arterial t hr o m b oe m b olic e ve nts 
 T hr o m b oc yt osis a n d ele vate d mea n platelet v ol u me 
 Li ver f u ncti o n tes t ele vati o ns 
8. 2. 3.  
A d verse E ve nt S u m m aries 
A n o verall s u m mar y of A Es b y treat me nt gr o u ps (as defi ne d i n Se cti o n 4. 2 ) will be s u m marize d 
se paratel y f or eac h c o h ort a n d will i ncl u de t he f oll o wi n g: 
 N u m ber ( %) of partici pa nts re p orti n g a n y T E A Es 
 N u m ber ( %) of partici pa nts re p orti n g a n y A S Rs 
 N u m ber ( %) of partici pa nts r e p orti n g a n y seri o us T E A Es 
 N u m ber ( %) of partici pa nts re p orti n g a n y Gra de 3 or hi g her T E A E s 
 N u m ber ( %) of partici pa nts re p or ti n g a n y treat me nt-relate d T E A Es 
 N u m ber ( %) of partici pa nts w h o t e m p oraril y i nterr u pte d st u d y dr u g beca use of 
T E A Es 
 N u m ber ( %) of partici pa nts w h o per ma ne ntl y disc o nti n ue d st u d y d r u g beca use of 
T E A Es 
 N u m ber ( %) of partici pa nts w h o ha d a fatal T E A E 


I nc yte C or p orati o n 
Pa ge 2 9 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T he f oll o wi n g s u m maries will be pr o d uce d b y Me d D R A ter m (if 2 o r fe wer partici pa nts a p pear 
i n a ta ble, a listi n g ma y be a p pr o priate): 
 S u m mar y of T E A Es b y S O C a n d P T 
 S u m mar y of T E A Es b y P T i n decr easi n g or der of fre q ue nc y 
 S u m mar y of e x p os ure-a dj uste d i nc i de nce rates of T E A Es b y P T i n decreasi n g or der 
of fre q ue nc y ( C o h ort A o nl y) 
 S u m mar y of Gra de 3 or hi g her A Es b y S O C a n d P T 
 S u m mar y of Gra de 3 or hi g her A E s b y P T i n decreasi n g or der of fre q ue nc y 
 S u m mar y of seri o us T E A Es b y S O C a n d P T 
 S u m mar y of seri o us T E A Es b y P T i n decreasi n g or der of fre q ue nc y  
 S u m mar y of A S Rs b y S O C a n d P T 
 S u m mar y of A S Rs b y P T i n decr easi n g or der of fre q ue nc y 
 S u m mar y of e x p os ure-a dj uste d i nc i de nce rates of A S Rs b y P T i n decreasi n g or der of 
fre q ue nc y ( C o h ort A o nl y) 
 S u m mar y of treat me nt-rel ate d T E A Es b y S O C a n d P T 
 S u m mar y of treat me nt-relate d T E A Es b y P T i n decreasi n g or der of  fre q ue nc y 
 S u m mar y of Gra de 3 or hi g her trea t me nt-relate d T E A Es b y S O C a n d P T 
 S u m mar y of treat me nt-relate d seri o us T E A Es b y S O C a n d P T 
 S u m mar y of T E A Es wit h a fatal o utc o me b y S O C a n d P T 
 S u m mar y of T E A Es lea di n g t o d os e i nterr u pti o n of st u d y dr u g b y S O C a n d P T 
 S u m mar y of T E A Es lea di n g t o di sc o nti n uati o n of st u d y dr u g b y S OC a n d P T 
 S u m mar y of A Es of i nterest b y P T i n decreasi n g or der of fre q ue nc y 
8. 3.  
Cli nic al L a b or at or y Tests 
8. 3. 1.  
L a b or at or y V al ue Defi niti o ns 
La b orat or y val ues a n d c ha n ge fr o m baseli ne val ues will be s u m ma rize d descri pti vel y b y visit, 
a n d n o n- n u meric test val ues will be ta b ulate d w he n necessar y. 
8. 3. 2.  
L a b or at or y V al ue S u m m aries 
Cli nical la b orat or y tests, i ncl u di n g he mat ol o g y a n d ser u m c he mistr y, will be perf or me d at t he 
Pr ot oc ol-s pecifie d visits. 
All test res ults a n d ass ociate d n or mal ra n ges fr o m ce ntral la b o rat ories will be re p orte d i n 
SI u nits. All tests wit h n u meric val ues will ha ve a u ni q ue u nit  per test. A n y la b orator y test res ults 
a n d ass ociate d n or mal ra n ges fr o m l ocal la b orat ories will be c o n verte d t o SI u nits. 


I nc yte C or p orati o n 
Pa ge 3 0 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
F or test res ults t hat will be s u m mari ze d wit h a vaila ble n or mal ra n ges, t he n u m ber a n d perce nta ge 
of partici pa nts wit h t he la b orat or y val ues bei n g l o w ( b ut ne ver  hi g h), n or mal, hi g h ( b ut ne ver 
l o w), a n d b ot h l o w a n d hi g h will be calc ulate d f or eac h test.  
T hese s hift s u m maries will be pr o d uce d f or eac h test f or t he F A S p o p ulati o n acc or di n g t o t he 
treat me nt gr o u ps defi ne d f or t he 2 c o h orts i n Secti o n 5. 2 . S hift ta bles will als o be prese nte d 
s h o wi n g c ha n ge i n C T C A E gra de fro m baseli ne t o w orst gra de p ost baseli ne. T he de n o mi nat or 
f or t he perce nta ge calc ulati o n will use t he n u m ber of partici pants i n t he baseli ne cate g or y. 
8. 4.  
Vit al Si g ns 
Val ues at eac h sc he d ule d visit,  c ha n ge, a n d perce nta ge c ha n ge fr o m baseli ne f or vital si g ns, 
i ncl u di n g s yst olic bl o o d press ure, diast olic bl o o d press ure, p ulse, res pirat or y rate, a n d b o d y 
te m perat ure, will be s u m marized descri pti vel y b y treat me nt gr o u p.  
Criteria f or cli nicall y n ota bl e vital si g n a b n or malities are de fi ne d i n Ta ble 5 , Ta ble 6 , a n d 
Ta ble 7 . T he a b n or mal val ues f or partici pa nts e x hi biti n g cli nicall y n ota ble vital si g n 
a b n or malities will be liste d al o n g wit h t heir assi g ne d c o h ort an d treat me nt gr o u p. Alert vital 
si g ns are defi ne d as a n a bs ol ute val ue o utsi de t he defi ne d ra n g e a n d perce nta ge c ha n ge > 2 5 %.  
T he a b n or mal val ues f or partici p a nts e x hi biti n g alert vital si gn a b n or malities will be liste d. 
T a ble 5:  
Criteri a f or Cli nic all y N ot a ble Vit al Si g n A b n or m aliti es f or P artici p a nts 
1 2 t o 1 5 Ye ars Ol d 
P ar a meter 
Hi g h T hres h ol d 
L o w T hres h ol d 
S yst olic bl o o d press ure 
> 1 3 1 m m H g 
< 1 1 0 m m H g 
Diast olic bl o o d press ure 
> 8 3 m m H g 
< 6 4 m m H g 
P ulse 
> 1 0 0 b p m 
< 6 0 b p m 
Te m perat ure 
> 3 8. 0º C 
< 3 5. 5º C 
Res pirat or y rate 
> 2 0 breat hs/ mi n 
< 8 breat hs/ mi n 
T a ble 6:  
Criteri a f or Cli nic all y N ot a ble Vit al Si g n A b n or m aliti es f or P artici p a nts 
1 6 t o 1 7 Ye ars Ol d 
P ar a meter 
Hi g h T hres h ol d 
L o w T hres h ol d 
S yst olic bl o o d press ure 
> 1 2 0 m m H g 
< 9 0 m m H g 
Diast olic bl o o d press ure 
> 8 5 m m H g 
< 5 0 m m H g 
P ulse 
> 1 0 0 b p m 
< 4 5 b p m 
Te m perat ure 
> 3 8. 0º C 
< 3 5. 5º C 
Res pirat or y rate 
> 2 0 breat hs/ mi n 
< 8 breat hs/ mi n 


I nc yte C or p orati o n 
Pa ge 3 1 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T a ble 7:  
Criteri a f or Cli nic all y N ot a ble Vit al Si g n A b n or m aliti es f or P artici p a nts 
≥ 1 8 Ye ars Ol d 
P ar a meter 
Hi g h T hres h ol d 
L o w T hres h ol d 
S yst olic bl o o d press ure 
> 1 5 5 m m H g 
< 8 5 m m H g 
Diast olic bl o o d press ure 
> 1 0 0 m m H g 
< 4 0 m m H g 
P ulse 
> 1 0 0 b p m 
< 4 5 b p m 
Te m perat ure 
> 3 8º C 
< 3 5. 5º C 
Res pirat or y rate 
> 2 0 breat hs/ mi n 
< 8 breat hs/ mi n 
9.  
P L A N N E D A N A L Y S E S 
T he pri mar y a nal ysis will occ ur after t he pri mar y data base l oc k , w he n all partici pa nts ha ve 
c o m plete d t he ve hicle-c o ntr oll e d, d o u ble- bli n d treat me nt peri o d .   
1 0.  
C H A N G E S A N D M O DI F I C A TI O N S T O T H E A N A L Y SI S P L A N 
All versi o ns of t he S A P are liste d i n Ta ble 8.  
T a ble 8:  
St atistic al A n al ysis Pl a n Versi o ns 
S A P Versi o n 
D ate 
Ori gi nal 
0 6 O C T 2 0 2 2 
1 0. 1.  
C h a n ges t o Pr ot oc ol- Defi ne d A n al yses 
T he data fr o m partici pa nts at Site 7 1 0 were re m o ve d fr o m all ef ficac y a nal yses perf or me d o n t he 
I T T- E xt p o p ulati o n a n d F A S f or t he fi nal C S R o wi n g t o n o nc o m plia nce wit h t he Pr ot oc ol i n t he 
pare nt st u d y res ulti n g i n seri o us c o ncer ns wit h t he data q ualit y. Data fr o m partici pa nts at 
Site 7 1 0 were i ncl u de d i n all ot he r a nal yses beca use all partici pa nts at Site 7 1 0 a p plie d st u d y 
dr u g at least o nce. 
1 0. 2.  
C h a n ges t o t he St atistic al A n al ysis Pl a n 
N ot a p plica ble. 


I nc yte C or p orati o n 
Pa ge 3 2 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
1 1.  
R E F E R E N C E S 
Basra M K, Sale k M S, Ca milleri L, St ur ke y R, Fi nla y A Y. Deter mi n i n g t he mi ni mal cli nicall y 
i m p orta nt differe nce a n d res p o nsi ve ness of t he Der mat ol o g y Life  Q ualit y I n de x ( D L QI): f urt her 
data. Der mat ol o g y 2 0 1 5; 2 3 0: 2 7- 3 3. 
Batc hel or J M, Ta n W, T o ur S, Y o n g A, M o nt g o mer y A A, T h o mas K S. Vali dati o n of t he Vitili g o 
N oticea bilit y Scale: a patie nt-r e p orte d o utc o me meas ure of viti li g o treat me nt s uccess. Br J 
Der mat ol 2 0 1 6; 1 7 4: 3 8 6- 3 9 4. 
Fi nla y A Y, K ha n G K. Der mat ol o g y Life Q ualit y I n de x ( D L QI) — a si m ple practical meas ure f or 
r o uti ne cli nical use. Cli n E x p Der mat ol 1 9 9 4; 1 9: 2 1 0- 2 1 6. 
Ha mza vi I, Jai n H, Mc Lea n D, S ha pir o J, Ze n g H, L ui H. Para metric m o deli n g of narr o w ba n d 
U V- B p h ot ot hera p y f or vitili g o usi n g a n o vel q ua ntitati ve t o ol: t he Vitili g o Area Sc ori n g I n de x. 
Arc h Der mat ol 2 0 0 4; 1 4 0: 6 7 7- 6 8 3. 
Waters A, Sa n d h u D, Beattie P, Ez u g ha h F, Le wis-J o nes S. Se verit y stratificati o n of C hil dre n's 
Der mat ol o g y Life Q ualit y I n de x ( C D L QI) sc ores. Br J Der mat ol 2 0 1 0; 1 6 3(s u p pl 1): 1 2 1 [a bstr 
P A- 8]. 
W orl d Healt h Or ga nizati o n. W H O M o del Prescri bi n g I nf or mati o n: D r u gs Use d i n S ki n Diseases. 
1 9 9 7. htt ps://a p ps. w h o.i nt/ me d ici ne d ocs/e n/ d/J h 2 9 1 8e/ 
 


I nc yte C or p orati o n 
Pa ge 3 3 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
A P P E N DI X A.  P L A N N E D T A B L E S A N D FI G U R E S 
T his a p pe n di x pr o vi des a list of t he pla n ne d ta bles, fi g ures, a n d listi n gs f or t he C S R. S hells are 
pr o vi de d i n a se parate d oc u me nt  f or ta bles t hat are n ot i n t he Sta n dar d Safet y Ta bles v 1. 1 2. 
T he lists of ta bles, fi g ures, listi n gs are t o be use d as g ui deli nes. M o dificati o ns of t he lists t hat d o 
n ot ot her wise affect t he nat ure  of t he a nal ysis will n ot warra nt a n a me n d me nt t o t he S A P. 
F or ta bles a n d fi g ures usi n g t he F A S p o p ulati o n, se parate ta ble s a n d fi g ures will be pr o vi de d f or 
C o h ort A a n d C o h ort B. 
T a bles 
T a ble 
N o.  
Title  
P o p ul ati o n  St a n d ar d 
1. 1. 1  
A nal ysis P o p ulati o ns 
All  
X 
1. 1. 2. 1  
S u m mar y of Partici pa nt Dis p ositi o n  
F A S  
X 
1. 1. 3  
S u m mar y of N u m ber of Partici pa nts E nr olle d b y C o u ntr y a n d  Site  
F A S  
X 
1. 1. 4  
S u m mar y of Pr ot oc ol De viati o ns  
F A S  
X 
1. 2  
S u m mar y of De m o gra p hics a n d  Baseli ne C haracteristics 
F A S  
X 
1. 3  
S u m mar y of Baseli ne Di sease C haracteristics 
F A S  
X 
1. 4. 1  
S u m mar y of Pri or T hera p y f or Vitili g o 
F A S  
X 
1. 4. 2  
S u m mar y of Pri or Me dicati o ns 
F A S  
X 
1. 4. 3  
S u m mar y of C o nc o mita nt Me dicati o ns  
F A S  
X 
1. 5  
S u m mar y of Ge neral M e dical Hist or y  
F A S  
X 
1. 6  
S u m mar y of Partici pa nts Wit h Assess me nts N ot D o ne D ue t o C O VI D- 1 9 
Pa n de mic 
F A S  
 
2. 1. 1. 1  
S u m mar y a n d A nal ysis of Ti me t o Rela pse   
I T T- E xt  
X 
2. 1. 1. 2  
S u m mar y of Rela pse b y Visit 
I T T- E xt  
X 
2. 2. 1. 1  
S u m mar y a n d A nal ysis of Ti me t o Mai ntai n ≥ F- V A SI 9 0 
I T T- E xt  
 
2. 2. 1. 2  
S u m mar y of Ti me t o L oss of F- V A SI 9 0 Res p o nse 
I T T- E xt  
 
2. 3. 1. 1  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g F- V A SI 5 0  
FA S  
X 
2. 3. 1. 2  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g F- V A SI 7 5  
FA S  
X 
2. 3. 1. 3  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g F- V A SI 9 0  
FA S  
X 
2. 3. 1. 4  
S u m mar y a n d A nal ysis of F- V A SI 
F A S  
X 
2. 3. 1. 5  
S hift S u m mar y of F- V A SI 
F A S a 
 
2. 3. 2. 1  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g T- V A SI 5 0  
FA S  
X 
2. 3. 2. 2  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g T- V A SI 7 5  
FA S  
X 
2. 3. 2. 3  
S u m mar y a n d A nal ysis of Partici pa nts Ac hie vi n g T- V A SI 9 0  
FA S  
X 
2. 3. 2. 4  
S u m mar y a n d A nal ysis of T- V A SI 
F A S  
X 
2. 3. 2. 5  
S hift S u m mar y of  T- V A SI 
F A S a 
 
2. 4. 1  
S u m mar y a n d A nal ysis of F- B S A 
F A S  
X 
2. 4. 2  
S u m mar y a n d A nal ysis of T- B S A 
F A S  
X 
2. 4. 1  
S u m mar y a n d A nal ysis of Pa rtici pa nts Ac hievi n g V N S Sc ores  of 4 or 5  
F A S  
X 
2. 4. 2  
S u m mar y of Partici pa nts i n Eac h Cate g or y of V N S Sc ores 
F A S  
X 
2. 4. 3  
S hift S u m mar y of  V N S Sc ores 
F A S a 
 


I nc yte C or p orati o n 
Pa ge 3 4 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T a ble 
N o. 
Title 
P o p ul ati o n  St a n d ar d 
2. 9. 2  
S u m mar y of D L QI  
F A S  
X 
2. 9. 3  
S u m mar y of C D L QI  
F A S  
X 
3. 1. 1  
S u m mar y of E x p os ure  
F A S  
X 
3. 1. 2  
S u m mar y of St u d y Dr u g C o m plia nce  
F A S  
X 
3. 2. 1. 1   
O verall S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts  
F A S  
X 
3. 2. 2. 1   
S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts b y Me d D R A  S yste m 
Or ga n Class a n d Preferre d Ter m  
F A S  
X 
3. 2. 3. 1   
S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts b y Me d D R A  Preferre d 
Ter m i n Decreasi n g Or der of Fre q ue nc y  
F A S  
X 
3. 2. 3. 2  
S u m mar y of E x p os ure- A dj uste d I nci de nce Rates of T E A Es b y Me d D R A 
Preferre d Ter m i n Decreas i n g Or der of Fre q ue nc y 
F A S  
X 
3. 2. 4. 1   
S u m mar y of Gra de 3 or Hi g her A d verse E ve nts b y Me d D R A S yste m 
Or ga n Class a n d Preferre d Ter m  
F A S  
X 
3. 2. 5. 1   
S u m mar y of Gra de 3 or Hi g her A d verse E ve nts b y Me d D R A Preferre d 
Ter m i n Decreasi n g Or der of Fre q ue nc y   
F A S  
X 
3. 2. 6. 1   
S u m mar y of Seri o us Treat me nt- E mer ge nt A d verse E ve nts b y Me d D R A 
S yste m Or ga n Class a n d Preferre d Ter m    
F A S  
X 
3. 2. 7. 1   
S u m mar y of Seri o us Treat me nt- E mer ge nt A d verse E ve nts b y Me d D R A 
Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y   
F A S  
X 
3. 2. 8. 1   
S u m mar y of A p plicati o n Site Reacti o ns b y Me d D R A S yste m  Or ga n 
Class a n d Preferre d Ter m    
F A S  
X 
3. 2. 9. 1   
S u m mar y of A p plicati o n Site Reacti o ns b y Me d D R A Prefer re d Ter m i n 
Decreasi n g Or der of Fre q ue nc y   
F A S  
X 
3. 2. 9. 2  
S u m mar y of E x p os ure- A dj uste d I nci de nce Rates of A S Rs b y  Me d D R A 
Preferre d Ter m i n Decreas i n g Or der of Fre q ue nc y 
F A S  
X 
3. 2. 1 0. 1   
S u m mar y of Treat me nt- R elate d Treat me nt- E mer ge nt A d ver se E ve nts b y 
Me d D R A S yste m Or ga n Class a n d Preferre d Ter m   
F A S  
X 
3. 2. 1 1. 1   
S u m mar y of Treat me nt- R elate d Treat me nt- E mer ge nt A d ver se E ve nts b y 
Me d D R A Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y   
F A S  
X 


I nc yte C or p orati o n 
Pa ge 3 5 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
T a ble 
N o. 
Title 
P o p ul ati o n  St a n d ar d 
3. 2. 1 2. 1   
S u m mar y of Gra de 3 or Hi g her Treat me nt- Relate d Treat m e nt- E mer ge nt 
A d verse E ve nts b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m 
F A S  
X 
3. 2. 1 3. 1   
S u m mar y of Treat me nt- Relate d Seri o us Treat me nt- E mer ge nt A d verse 
E ve nts b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m 
F A S  
X 
3. 2. 1 4. 1   
S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts Wit h a F atal O utc o me 
b y Me d D R A S yste m Or ga n C lass a n d Preferre d Ter m 
F A S  
X 
3. 2. 1 5. 1   
S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts Lea di n g t o D ose 
I nterr u pti o n of St u d y Dr u g b y Me d D R A S yste m Or ga n Class a n d 
Preferre d Ter m 
F A S  
X 
3. 2. 1 6. 1   
S u m mar y of Treat me nt- E mer ge nt A d verse E ve nts Lea di n g t o 
Disc o nti n uati o n of St u d y Dr u g b y Me d D R A S yste m Or ga n Class a n d 
Preferre d Ter m 
F A S  
X 
3. 2. 1 7. 1  
S u m mar y of A d verse E ve nts of I nterest b y Me d D R A Prefer re d Ter m i n 
Decreasi n g Or der of Fre q ue nc y 
F A S  
X 
3. 3. 1   
S u m mar y of La b orat or y Val ues – He mat ol o g y 
F A S  
X 
3. 3. 2   
S hift S u m mar y of He mat ol o g y La b orat or y Val ues i n C T C A E G ra de – T o 
t he W orst A b n or mal Val ue 
F A S  
X 
3. 3. 3   
S u m mar y of La b orat or y Val ues – C he mistr y 
F A S  
X 
3. 3. 4   
S hift S u m mar y of C he mistr y La b orat or y Val ues i n C T C A E Gr a de – T o 
t he W orst A b n or mal Val ue 
F A S  
X 
3. 4. 1. 1  
S u m mar y of S yst olic Bl o o d Press ure 
F A S  
X 
3. 4. 2. 1  
S u m mar y of Diast olic Bl o o d Press ure 
F A S  
X 
3. 4. 3. 1  
S u m mar y of P ulse 
F A S  
X 
3. 4. 4. 1  
S u m mar y of Res pirat or y Rate 
F A S  
X 
3. 4. 5. 1  
S u m mar y of B o d y Te m perat ure 
F A S  
X 
a  F A S C o h ort B o nl y. 
Fi g ures 
Fi g ure N o. 
Title 
P o p ul ati o n 
4. 1. 1  
Ka pla n- Meier C ur ve of t he Ti me t o Rela pse  
I T T- E xt 
4. 1. 1. 1  
S wi m mer Pl ot of t he Ti me t o Rela pse  
I T T- E xt 
4. 1. 1. 2  
S wi m mer Pl ot of t he Ti me t o Rela pse b y S u b gr o u ps 
I T T- E xt 
4. 1. 2  
Ka pla n- Meier C ur ve f or Mai nte na nce of F- V A SI 9 0 Res p o nse  
I T T- E xt 
4. 1. 3  
Pr o p orti o n of Partici pa n ts Ac hie vi n g F- V A SI 5 0   
F A S 
4. 1. 4  
Pr o p orti o n of Partici pa n ts Ac hie vi n g F- V A SI 7 5   
F A S 
4. 1. 5  
Pr o p orti o n of Partici pa n ts Ac hie vi n g F- V A SI 9 0   
F A S 
4. 1. 6  
Mea n a n d Sta n dar d Err or Pl ot of F- V A SI  
F A S 
4. 1. 7  
Mea n a n d Sta n dar d Err or Pl ot of C ha n ge Fr o m Baseli ne i n F - V A SI 
F A S 
4. 1. 8  
Mea n a n d Sta n dar d Err or Pl ot of Perce nta ge C ha n ge Fr o m Ba seli ne i n F- V A SI    
F A S 
4. 2. 1  
Pr o p orti o n of Partici pa n ts Ac hie vi n g T- V A SI 5 0    
F A S 
4. 2. 2  
Pr o p orti o n of Partici pa n ts Ac hie vi n g T- V A SI 7 5    
F A S 
4. 2. 3  
Pr o p orti o n of Partici pa n ts Ac hie vi n g T- V A SI 9 0    
F A S 
4. 2. 4  
Mea n a n d Sta n dar d Err or Pl ot of T- V A SI   
F A S 
4. 2. 5  
Mea n a n d Sta n dar d Err or Pl ot of C ha n ge Fr o m Baseli ne i n T - V A SI    
F A S 
4. 2. 6  
Mea n a n d Sta n dar d Err or Pl ot of Perce nta ge C ha n ge Fr o m Ba seli ne i n T- V A SI    
F A S 


I nc yte C or p orati o n 
Pa ge 3 6 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
Fi g ure N o. 
Title 
P o p ul ati o n 
4. 3. 1  
Mea n a n d Sta n dar d Err or Pl ot of F- B S A   
F A S 
4. 3. 2  
Mea n a n d Sta n dar d Err or Pl ot of C ha n ge Fr o m Baseli ne i n F - B S A    
F A S 
4. 3. 3  
Mea n a n d Sta n dar d Err or Pl ot of Perce nta ge C ha n ge Fr o m Ba seli ne i n F- B S A    
F A S 
4. 4. 1  
Mea n a n d Sta n dar d Err or Pl ot of T- B S A   
F A S 
4. 4. 2  
Mea n a n d Sta n dar d Err or Pl ot of C ha n ge Fr o m Baseli ne i n T - B S A    
F A S 
4. 4. 3  
Mea n a n d Sta n dar d Err or Pl ot of Perce nta ge C ha n ge Fr o m Ba seli ne i n T- B S A    
F A S 
4. 5  
Pr o p orti o n of Partici pa nts Ac hie vi n g V N S Sc ores of 4 or 5   
F A S 
4. 1  
Ka pla n- Meier C ur ve of t he Ti me t o Re gai n F- V A SI 7 5 
R E S 
4. 1 1  
Ka pla n- Meier C ur ve of t he Ti me t o Re gai n F- V A SI 9 0 
R E S 
5. 1. 1  
B o x Pl ot of He m o gl o bi n ( g/ L) b y Visit  
F A S 
5. 1. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n He m o gl o bi n ( g/ L) b y V isit  
F A S 
5. 1. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n He m o gl o bi n  ( g/ L) b y Visit   
F A S 
5. 2. 1  
B o x Pl ot of Platelets ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 2. 2  
B o x Pl ot of C ha n ge Fr o m Ba seli ne i n Platelets ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 2. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n Platelets ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 3. 1  
B o x Pl ot of Ne utr o p hils ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 3. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n Ne utr o p hils ( 1 0 ^ 9/ L) b y Visit   
F A S 
5. 3. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n Ne utr o p hil s ( 1 0 ^ 9/ L) b y Visit   
F A S 
5. 4. 1  
B o x Pl ot of Le u k oc ytes ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 4. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n Le u k oc ytes ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 4. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n Le u k oc ytes  ( 1 0 ^ 9/ L) b y Visit   
F A S 
5. 5. 1  
B o x Pl ot of L y m p h oc ytes ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 5. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n L y m p h oc ytes ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 5. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n L y m p h oc yte s ( 1 0 ^ 9/ L) b y Visit   
F A S 
5. 6. 1  
B o x Pl ot of Er yt hr oc ytes ( 1 0 ^ 1 2/ L) b y Visit  
F A S 
5. 6. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n Er yt hr oc ytes ( 1 0 ^ 1 2/ L ) b y Visit  
F A S 
5. 6. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n Er yt hr oc yt es ( 1 0 ^ 1 2/ L) b y Visit   
F A S 
5. 7. 1  
B o x Pl ot of Retic ul oc ytes ( 1 0 ^ 9/ L) b y Visit  
F A S 
5. 7. 2  
B o x Pl ot of C ha n ge Fr o m Baseli ne i n Retic ul oc ytes ( 1 0 ^ 9/ L ) b y Visit   
F A S 
5. 7. 3  
B o x Pl ot of Perce nta ge C ha n ge Fr o m Baseli ne i n Retic ul oc y tes ( 1 0 ^ 9/ L) b y Visit   
F A S 


I nc yte C or p orati o n 
Pa ge 3 7 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
Listi n gs 
Listi n g N o.  
Title 
2. 1. 1 
Partici pa nt E nr oll me nt a n d Dis p ositi o n Stat us 
2. 1. 2 
Partici pa nts W h o Disc o nti n ue d Treat me nt or Disc o nti n ue d F r o m St u d y D ue t o C O VI D- 1 9 
2. 1. 3 
Partici pa nts Wit h Assess me nt s N ot D o ne D ue t o C O VI D- 1 9 Pan de mic 
2. 2. 1 
Partici pa nt I ncl usi o n a n d E xcl usi o n Criteria Vi olati o ns 
2. 2. 2 
Pr ot oc ol De viati o ns 
2. 3 
A nal ysis P o p ulati o ns 
2. 4. 1 
De m o gra p hic C haracteristics 
2. 4. 2 
Baseli ne Disease C haracteristics 
2. 4. 3 
Me dical Hist or y 
2. 4. 4 
Pri or a n d C o nc o mita nt Me dicati o ns 
2. 4. 5 
Pri or T hera p y f or Vitili g o 
2. 5. 1 
St u d y Dr u g E x p os ure a n d C o m plia nce 
2. 6. 1 
Ti me t o Rela pse  
2. 6. 2 
Ti me t o L oss of A de q uate Res p o nse 
2. 6. 5 
F- V A SI Sc ore 
2. 6. 6 
T- V A SI Sc ore 
2. 6. 7 
F- B S A 
2. 6. 8 
T- B S A 
2. 6. 9 
V N S Sc ore 
2. 6. 1 5 
D L QI Sc ore 
2. 6. 1 6 
C D L QI Sc ore 
2. 6. 1 9 
Partici pa nts Wit h F- V A SI Assess me nts N ot D o ne D ue t o C O V I D- 1 9 Pa n de mic 
2. 7. 1 
A d verse E ve nts 
2. 7. 2 
A d verse E ve nts Lea di n g t o St u d y Dr u g Disc o nti n uati o n 
2. 7. 3 
Seri o us A d verse E ve nts 
2. 7. 4 
Treat me nt- Relat e d A d verse E ve nts 
2. 7. 5 
A d verse E ve nts Wit h a Fatal O utc o me 
2. 7. 6 
A d verse E ve nts Lea di n g t o I nterr u pti o n of St u d y Dr u g 
2. 7. 8 
Gra de 3 or Hi g her A d verse E ve nts 
2. 7. 9 
A p plicati o n Site Reacti o ns 
2. 7. 1 0 
A d verse E ve nts of I nterest 
2. 7. 1 1 
Pri or A d verse E ve nts 
2. 8. 1. 1 
Cli nical La b orat or y Val ues – He mat ol o g y 
2. 8. 1. 2 
Cli nical La b orat or y Val ues – C he mistr y 


I nc yte C or p orati o n 
Pa ge 3 8 of 3 8 
I N C B 1 8 4 2 4- 3 0 8 Statistical A nal ysis Pla n  
0 6 O C T 2 0 2 2 
V V- C LI N- 0 2 1 8 9 7 
C O N FI D E N TI A L 
2. 8. 1. 3 
A b n or mal Cli nical La b orat or y Val ues – He mat ol o g y 
2. 8. 1. 4 
A b n or mal Cli nical La b orat or y Val ues – C he mistr y 
2. 8. 2. 1 
Vital Si g ns 
2. 8. 2. 2 
A b n or mal Vital Si g n Val ues 
2. 8. 2. 3 
Alert Vital Si g n Val ues