Clinical trial NCT05456529
Conditions: Atopic Dermatitis (AD)
Keywords: atopic dermatitis (AD) adolescents pruritus eczema topical therapy JAK inhibitor
Sponsor: Incyte Corporation
Start date: 2022-09-01; Completion date: 2024-05-17
Enrollment: 103 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the long-term safety and tolerability of ruxolitinib cream in adolescents with Atopic Dermatitis (AD).

Detailed description:
The study comprises of a 8 week continuous treatment period followed by 44 week Long Term Safety (LTS) period and 30 days safety follow up period. During Continuous treatment period all lesions identified at baseline will be treated and during LTS period only active lesions will be treated.

Arms: arm 1: Ruxolitinib cream 1.5% twice daily (BID) during the continuous and LTS treatment period.
Interventions: intervention 1: Ruxolitinib Cream
Intervention descriptions: intervention 1: Ruxolitinib cream 1.5% twice daily (BID) during the continuous and LTS treatment period.

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Phase 3, Open-Label, One-Year Safety Study of Ruxolitinib Cream in 
Adolescents (Ages ≥ 12 Years to < 18 Years) With Atopic Dermatitis 
NCT Number: 
NCT05456529 
Document Date: 
Protocol INCB 18424-315 Am 1 Version 2 30 NOV 2022 
 
 
 


Incyte Corporation 
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Protocol INCB 18424-315 Am 1 
Version 2 
30 NOV 2022 
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CONFIDENTIAL 
 
Clinical Study Protocol 
 
 
 
INCB 18424-315 
A Phase 3, Open-Label, One-Year Safety Study of Ruxolitinib Cream in 
Adolescents (Ages ≥ 12 Years to < 18 Years) With Atopic Dermatitis  
 
Product: 
Ruxolitinib cream 
IND Number: 
77,101 
EudraCT Number: 
2021-006626-44 
Phase of Study: 
3 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
04 MAR 2022 
Amendment 1: 
30 NOV 2022 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki (Brazil 2013) and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and 
applicable laws and country-specific regulations, including WMO (Medical Research Involving Human Participants 
Act) and Clinical Trials Regulation (EU) No. 536/2014, 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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Protocol INCB 18424-315 Am 1 
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INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-315 Protocol Amendment 1 (dated 30 NOV 2022) and agree to 
conduct the study as outlined. I agree to maintain the confidentiality of all information received 
or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
2. 
INTRODUCTION ......................................................................................................17 
2.1. 
Background .................................................................................................................17 
2.2. 
Study Rationale ...........................................................................................................17 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Treatment Regimen ..........................................................................18 
2.3. 
Benefit/Risk Assessment ............................................................................................18 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................20 
4. 
STUDY DESIGN .......................................................................................................21 
4.1. 
Overall Design ............................................................................................................21 
4.2. 
Overall Study Duration ...............................................................................................22 
4.3. 
Study Termination ......................................................................................................22 
5. 
STUDY POPULATION .............................................................................................23 
5.1. 
Inclusion Criteria ........................................................................................................23 
5.2. 
Exclusion Criteria .......................................................................................................24 
5.3. 
Lifestyle Considerations .............................................................................................26 
5.4. 
Screen Failures ............................................................................................................26 
5.5. 
Replacement of Participants .......................................................................................26 
6. 
STUDY TREATMENT ..............................................................................................27 
6.1. 
Study Treatment Administered ...................................................................................27 
6.1.1. 
Study Treatment Application Guidance .....................................................................28 
6.2. 
Preparation, Handling, and Accountability ................................................................29 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................30 
6.4. 
Study Treatment Compliance .....................................................................................30 
6.5. 
Dose Modifications .....................................................................................................30 
6.5.1. 
Criteria and Procedures for Interruptions of Study Cream .........................................30 
6.5.2. 
Criteria for Permanent Discontinuation of Study Cream ...........................................32 


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6.6. 
Concomitant Medications and Procedures .................................................................32 
6.6.1. 
Permitted Medications and Procedures ......................................................................32 
6.6.2. 
Restricted Medications and Procedures ......................................................................33 
6.6.3. 
Prohibited Medications and Procedures .....................................................................34 
6.7. 
Treatment After the End of the Study .........................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Reasons for Discontinuation .......................................................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................36 
7.2. 
Participant Withdrawal From the Study .....................................................................36 
7.3. 
Lost to Follow-Up.......................................................................................................36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................37 
8.1. 
Administrative and General Procedures .....................................................................37 
8.1.1. 
Informed Consent Process ..........................................................................................37 
8.1.2. 
Screening Procedures ..................................................................................................38 
8.1.3. 
Interactive Response Technology Procedure ..............................................................38 
8.1.4. 
Distribution of Reminders and eDiaries .....................................................................39 
8.1.5. 
Demography and Medical History ..............................................................................39 
8.1.5.1. 
Demographics and General Medical History .............................................................39 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................39 
8.2. 
Efficacy Assessments .................................................................................................40 
8.2.1. 
Health Economics .......................................................................................................40 
8.2.2. 
Percent Body Surface Area Affected by Atopic Dermatitis .......................................40 
8.2.3. 
Investigator's Global Assessment ...............................................................................40 
8.2.4. 
Itch Numerical Rating Scale .......................................................................................41 
8.2.5. 
Eczema Area and Severity Index ................................................................................41 
8.3. 
Safety Assessments .....................................................................................................41 
8.3.1. 
Adverse Events ...........................................................................................................41 
8.3.2. 
Physical Examinations ................................................................................................42 
8.3.2.1. 
Comprehensive Physical Examination .......................................................................42 
8.3.2.2. 
Targeted Physical Examination ..................................................................................42 
8.3.3. 
Vital Signs, Height, and Weight .................................................................................43 


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8.3.4. 
Electrocardiograms .....................................................................................................43 
8.3.5. 
Laboratory Assessments .............................................................................................43 
8.3.5.1. 
Pregnancy Testing ......................................................................................................44 
8.3.5.2. 
Serology ......................................................................................................................44 
8.4. 
Pharmacokinetic Assessments ....................................................................................45 
8.5. 
Pharmacodynamic and Translational Assessments ....................................................45 
8.6. 
Unscheduled Visits .....................................................................................................46 
8.7. 
End of Treatment and/or Early Termination ..............................................................46 
8.8. 
Follow-Up ...................................................................................................................46 
8.8.1. 
Safety Follow-Up ........................................................................................................46 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................47 
9.1. 
Definition of Adverse Event .......................................................................................47 
9.2. 
Definition of Serious Adverse Event ..........................................................................48 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........49 
9.4. 
Reporting of Serious Adverse Events .........................................................................51 
9.5. 
Events of Clinical Interest ..........................................................................................52 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................52 
9.7. 
Pregnancy ...................................................................................................................52 
9.8. 
Warnings and Precautions ..........................................................................................53 
9.9. 
Product Complaints ....................................................................................................53 
9.10. 
Treatment of Excessive Use .......................................................................................53 
10. 
STATISTICS ..............................................................................................................54 
10.1. 
Sample Size Determination ........................................................................................54 
10.2. 
Populations for Analyses ............................................................................................54 
10.3. 
Level of Significance ..................................................................................................54 
10.4. 
Statistical Analyses .....................................................................................................54 
10.4.1. 
Primary Analysis ........................................................................................................54 
10.4.2. 
Secondary Analyses ....................................................................................................55 
10.4.2.1. 
Clinical Laboratory Tests ...........................................................................................55 
10.4.2.2. 
Vital Signs ..................................................................................................................55 
10.4.3. 
Pharmacokinetic Analyses ..........................................................................................55 
10.4.4. 
Exploratory Efficacy Analyses ...................................................................................56 


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10.4.5. 
Exploratory Analysis of Relationship Between Hematology Laboratory 
Results and Trough Ruxolitinib Concentrations .........................................................56 
10.5. 
Interim Analysis ..........................................................................................................57 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................58 
11.1. 
Investigator Responsibilities .......................................................................................58 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................59 
11.2. 
Data Management .......................................................................................................59 
11.3. 
Data Quality Assurance ..............................................................................................61 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................61 
11.5. 
'Financial Disclosure ...................................................................................................62 
11.6. 
Publication Policy .......................................................................................................62 
11.7. 
Study and Site Closure................................................................................................63 
12. 
REFERENCES ...........................................................................................................64 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................66 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................68 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................71 
 


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LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................10 
Table 2: 
Key Study Design Elements .......................................................................................10 
Table 3: 
Schedule of Activities: Continuous Treatment Period ...............................................12 
Table 4: 
Schedule of Activities: Long-Term Safety Period ......................................................15 
Table 5: 
Objectives and Endpoints ...........................................................................................20 
Table 6: 
Study Treatment Information .....................................................................................27 
Table 7: 
Guidelines for Interruption and Restarting of Study Cream Due to 
Laboratory Abnormalities ...........................................................................................31 
Table 8: 
Investigator's Global Assessment ...............................................................................40 
Table 9: 
Required Laboratory Analytes ....................................................................................44 
Table 10: Pharmacokinetic Blood and Saliva Sample Timing ...................................................45 
Table 11: Populations for Analysis .............................................................................................54 
Table 12: Summary of Primary Endpoint Analyses ...................................................................55 
Table 13: Summary of Secondary Endpoint Analyses ...............................................................56 
Table 14: Summary of Exploratory Endpoint Analyses .............................................................57 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................11 
Figure 2: 
Study Cream Application Using a Fingertip ..............................................................28 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
COVID-19 
coronavirus disease 2019 
CRO 
contract research organization 
CSR 
Clinical Study Report 
CT 
continuous treatment 
CTCAE 
Common Terminology Criteria for Adverse Events 
DVT 
deep vein thrombosis 
EASI 
Eczema Area and Severity Index 
EASI75 
≥75% improvement in EASI score 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
EOT 
end of treatment 
ET 
early termination 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator's Brochure 


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Abbreviations and 
Special Terms 
Definition 
ICF 
informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification 
IEC 
independent ethics committee 
IGA 
Investigator's Global Assessment 
IGA-TS 
Investigator's Global Assessment Treatment Success (IGA score of 0 or 1 with 
≥ 2 grade improvement from baseline) 
IRB 
institutional review board 
IRT 
interactive response technology 
Itch NRS 
Itch Numerical Rating Scale 
JAK 
Janus kinase 
LTS 
long-term safety 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPV 
mean platelet volume 
PD 
pharmacodynamic(s) 
PDE4 
phosphodiesterase 4 
PE 
pulmonary embolism 
PK 
pharmacokinetic(s) 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SPF 
sun protection factor 
STD 
standard deviation 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
UV 
ultraviolet 
WOCBP 
woman of childbearing potential 


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1. 
PROTOCOL SUMMARY 
Protocol Title: A Phase 3, Open-Label, One-Year Safety Study of Ruxolitinib Cream in 
Adolescents (Ages ≥ 12 Years to < 18 Years) With Atopic Dermatitis 
Protocol Number: INCB 18424-315  
Objectives and Endpoints: 
Table 1 presents the primary and secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the long-term safety and tolerability of 
ruxolitinib cream in adolescents with AD. 
Incidence of TEAEs, assessed by monitoring the type, 
frequency, and severity of AEs. 
Secondary 
To further evaluate the long-term safety and tolerability 
of ruxolitinib cream in adolescents with AD. 
Changes in vital signs, height, weight, and laboratory 
data for hematology and serum chemistry. 
To characterize the PK of ruxolitinib cream in 
adolescents with AD. 
Trough concentrations of ruxolitinib at each 
postbaseline visit. 
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 
Topical short-term and noncontinuous chronic treatment of mild to moderate AD 
in nonimmunocompromised patients 12 to 17 years of age whose disease is not 
adequately controlled with topical prescription therapies or when those therapies 
are not advisable. 
Population 
Male and female participants 12 to 17 years of age with a diagnosis of AD for at 
least 2 years, a total IGA score of 2 or 3, and BSA involvement of 3% to 20% 
(excluding the scalp). 
Number of Participants 
Approximately 100 participants will be enrolled. 
Study Design 
Open-label, single-group, LTS study. 
Estimated Duration of 
Study Participation 
Participants will take part in the study for up to approximately 60 weeks: 28 days 
in the screening period, 8 weeks in the CT period, 44 weeks in the LTS period, 
and 30 days in the safety follow-up period. 
Data Safety Monitoring 
Board/Data Monitoring 
Committee 
No 
Coordinating Principal 
Investigator 
To be determined 


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Treatment Groups and Duration: 
This is a Phase 3, open-label, 1-year safety study of ruxolitinib cream in approximately 
100 adolescents (ages ≥ 12 years to < 18 years) with AD whose disease is not adequately 
controlled with topical prescription therapies or when those therapies are not advisable (see study 
design schema in Figure 1). 
All participants will apply ruxolitinib cream at the FDA-approved strength (1.5%) BID, starting 
with an 8-week CT period during which participants will treat all baseline AD lesions BID, 
regardless of whether or not the lesion(s) improve, followed by a 44-week LTS period during 
which participants will only treat active AD lesions. 
All participants will have a safety follow-up visit 30 to 37 days following the end of treatment 
(Week 52/EOT2 or ET) to evaluate safety and duration of response except for participants who 
have been in an observation/no treatment cycle with a total IGA score of 0 from Week 48 or 
earlier until Week 52, for whom the Week 52/EOT2 visit will also count as the safety follow-up 
visit. 
Figure 1 presents the study design schema, and Table 3 (CT period) and Table 4 (LTS period) 
present the SoA. 
Figure 1: 
Study Design Schema 
 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 


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Table 3: 
Schedule of Activities: Continuous Treatment Period 
Visit Day (Range) 
Screening 
CT 
Notes 
Days −28 
to -1 
Day 1 
(Baseline) 
Week 2  
(± 3 d) 
Week 4  
(± 3 d) 
Week 8/EOT1a 
or ET  
(± 3 d) 
Administrative procedures 
Informed consent (including assent) 
X 
 
 
 
 
Section 8.1.1  
Contact IRT 
X 
X 
X 
X 
X 
Section 8.1.3  
Inclusion/exclusion criteria review 
X 
X 
 
 
 
Section 5 
Demography and general medical history 
X 
 
 
 
 
Section 8.1.5.1  
Relevant AD medical and treatment history 
X 
 
 
 
 
Section 8.1.5.2  
Prior/concomitant medications and procedures 
X* 
X 
X 
X 
X 
Section 6.6  
*For prior medications that require a 4-week washout 
period (Section 5.2, Exclusion Criterion 5b), a 35-day 
screening period is allowed. 
Apply study cream at site 
 
X 
X 
X 
X* 
Section 6.1.1; at the Day 1 visit, the participant should 
apply the first (morning) application at the site under 
direct site staff supervision. At all other visits, the 
participant may apply either of the 2 daily doses at the 
site, as long as it is at least 4 hours since the previous 
dose was applied (see Section 8.4). 
*Not applicable to the Week 8 visit if IGA score = 0 or 
to the ET visit. 
Weigh/dispense study cream and distribute 
reminder  
 
X 
X 
X 
X* 
Section 6.1.1 and Section 8.1.4 
*Not applicable to the ET visit. 
Collect/weigh returned study cream and 
review study cream eDiary compliance 
 
 
X 
X 
X 
Section 6.1.1 and Section 8.1.4 
Assess study cream application compliance 
 
 
X 
X 
X 
Section 6.4  
Assess Itch NRS eDiary compliance 
eDiary compliance should be assessed routinely 
Section 8.2.4 


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Table 3: 
Schedule of Activities: Continuous Treatment Period (Continued) 
Visit Day (Range) 
Screening 
CT 
Notes 
Days −28 
to -1 
Day 1 
(Baseline) 
Week 2  
(± 3 d) 
Week 4  
(± 3 d) 
Week 8/EOT1a 
or ET  
(± 3 d) 
Safety assessments 
AE assessments and targeted physical 
examination 
X 
X 
X 
X 
X* 
Section 8.3.1 and Section 8.3.2.2; body systems with 
symptoms should be physically examined. 
*Targeted physical examination not performed at ET 
visit. 
Comprehensive physical examination 
X 
 
 
 
X* 
Section 8.3.2.1  
*For the ET visit only. 
Body height and weight 
 
X 
 
 
X 
Section 8.3.3; height should be measured with a 
stadiometer and recorded. 
Vital signs 
X 
X 
X 
X 
X 
Section 8.3.3; vital signs should be taken before blood 
sampling and other procedures. 
12-lead ECG 
X 
 
 
 
 
Section 8.3.4; 12-lead ECG performed within 2 months 
before baseline is acceptable. 
Efficacy assessments 
%BSA affected by AD 
X 
X 
X 
X 
X* 
Section 8.2.2 
*At Week 8, to qualify for the LTS period, the %BSA 
range must be 0% to ≤ 20%. 
Total IGA and facial IGA 
X 
X 
X 
X 
X* 
Section 8.2.3  
*At Week 8, there are no restrictions on IGA score to 
qualify for the LTS period. 
EASI 
X 
X 
X 
X 
X 
Section 8.2.5  
Itch NRS 
eDiary is completed each evening from screening through the last 
application of study cream during the CT period (night before Week 
8 visit). 
Section 8.2.4  


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Table 3: 
Schedule of Activities: Continuous Treatment Period (Continued) 
Visit Day (Range) 
Screening 
CT 
Notes 
Days −28 
to -1 
Day 1 
(Baseline) 
Week 2  
(± 3 d) 
Week 4  
(± 3 d) 
Week 8/EOT1a 
or ET  
(± 3 d) 
Laboratory assessments 
Serum chemistries 
X 
X* 
X 
X 
X 
Section 8.3.5  
*Perform Day 1 testing only if the interval between 
Day 1 and the date of the screening laboratory test is > 
2 weeks. 
Hematology 
X 
X* 
X 
X 
X 
Section 8.3.5 
*Perform Day 1 testing only if the interval between 
Day 1 and the date of the screening laboratory test is 
> 2 weeks. 
Serology 
X 
 
 
 
 
Section 8.3.5.2; HIV antibody. 
Pregnancy testing 
X* 
X 
 
X 
X 
Section 8.3.5.1  
*WOCBP will have a serum pregnancy test at 
screening and a urine test at all other visits. A positive 
urine test must be confirmed with a serum test. 
PK blood and saliva sampling (trough) 
 
 
Blood 
and 
saliva 
Blood 
and 
saliva 
Saliva only 
Section 8.4; collected prior to study cream application 
at the clinic; the time of prior study cream application 
is to be recorded in the eCRF. 
Blood samples must not be drawn from an area that has 
been treated with study cream (or participants must not 
apply study cream from the previous application of 
study cream on the immediate body area where blood 
is to be drawn). 
a All assessments for the Week 8/EOT1 visit must be performed before participants may enter the LTS period. 


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Table 4: 
Schedule of Activities: Long-Term Safety Period 
Visit Day (Range) 
LTS 
Safety Follow-Up 
Notes 
Weeks 12, 20, 
28, 36, and 44 
(± 7 d) 
Week 52/EOT2 
or ET  
(± 7 d) 
Unscheduled 
Visits 
30-37 d After 
Week 52/EOT2 
or ET Visita 
Administrative procedures 
Contact IRT 
X 
X 
X 
X 
Section 8.1.3 
Prior/concomitant medications and procedures 
X 
X 
X 
X 
Section 6.6 
Apply study cream at site 
X 
 
 
 
Section 6.1.1; only for participants with 
active AD lesions at time of visit. 
Weigh/dispense study cream and distribute 
reminder  
X 
 
 
 
Section 6.1.1 and Section 8.1.4 
Collect/weigh returned study cream and review 
study cream eDiary compliance 
X 
X 
 
 
Section 6.1.1 and Section 6.4 
Record start and end dates of treatment cycle(s) 
X 
X 
 
 
Section 6.1; the start/end date will have been 
recorded by the participant. The end date 
should be 3 days after lesions clear; however, 
if this 3-day window is during a study visit 
and total IGA score = 0, stop treatment and 
record the date of the study visit as the 
treatment cycle end date. 
Assess study cream application compliance 
X 
X 
 
 
Section 6.4 
Assess Itch NRS eDiary compliance 
eDiary compliance should be assessed routinely 
 
Section 8.2.4 
Safety assessments 
AE assessments and targeted physical examination 
X 
X* 
X 
X 
Section 8.3.1 and Section 8.3.2.2; body 
systems with symptoms should be physically 
examined.  
*Targeted physical examination not 
performed at the Week 52/EOT2 or ET visit. 
Comprehensive physical examination 
 
X 
 
 
Section 8.3.2.1  
Body height and weight 
X* 
X 
 
 
Section 8.3.3; height should be measured 
with a stadiometer and recorded 
*Week 28 only.  
Vital signs 
X 
X 
X 
X 
Section 8.3.3; vital signs should be taken 
before blood/saliva sampling and other 
procedures. 


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Table 4: 
Schedule of Activities: Long-Term Safety Period (Continued) 
Visit Day (Range) 
LTS 
Safety Follow-Up 
Notes 
Weeks 12, 20, 
28, 36, and 44 
(± 7 d) 
Week 52/EOT2 
or ET  
(± 7 d) 
Unscheduled 
Visits 
30-37 d After 
Week 52/EOT2 
or ET Visita 
Disease severity assessments 
%BSA affected by AD 
X 
X 
X 
X 
Section 8.2.2  
Total IGA and facial IGA 
X 
X 
X 
X 
Section 8.2.3  
EASI 
X 
X 
X 
X 
Section 8.2.5 
Itch NRS 
eDiary is completed each evening through the last 
application of study cream during the LTS period. 
 
Section 8.2.4 
Laboratory assessments 
Serum chemistries 
X 
X 
X 
X 
Section 8.3.5 
Hematology 
X 
X 
X 
X 
Section 8.3.5 
Pregnancy testing 
X 
X 
X 
X 
Section 8.3.5.1; WOCBP will have a urine 
test at all visits. A positive urine test must be 
confirmed by a serum test. 
PK saliva sampling (trough) 
X*/† 
X†/‡ 
 
 
Section 8.4 
*Collected prior to study cream application 
at the clinic. 
†The time of prior study cream application is 
to be recorded in the eCRF. 
‡Not to be collected at the ET visit. 
a Except for participants who have been in an observation/no treatment cycle with a total IGA score of 0 (clear) from Week 48 or earlier until Week 52; such participants should 
complete the Week 52/EOT2 visit and this will also count as the safety follow-up visit. 
 


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2. 
INTRODUCTION 
2.1. 
Background 
Atopic dermatitis is a chronic, recurring, inflammatory, and highly pruritic skin condition that 
affects up to 25% of children and up to 12% of adults worldwide (Eichenfield et al 2014, Hanifin 
et al 2007, Harrop et al 2007, Rönmark et al 2012, Vinding et al 2014) and is one of the most 
common dermatoses encountered by pediatric health care providers. Although not 
life-threatening, patients with AD are at higher risk for the development of other potentially 
life-threatening disorders such as asthma and/or food allergy (Spergel 2010). According to the 
recent Global Burden of Disease project, AD is one of the 50 most prevalent diseases worldwide 
and has the second highest disability ranking of all nonmalignant skin diseases (Hay et al 2014). 
Despite the availability of a number of treatment options, there is still a significant medical need 
for safe topical therapies that provide rapid and effective control of the signs and symptoms of 
AD and that are also both effective and safe. Moderate to potent topical corticosteroids and 
calcineurin inhibitors have well-known safety restrictions limiting their use to 4 and 8 weeks, 
respectively. In addition, a PDE4 inhibitor, 2% crisaborole (Eucrisa®) ointment, is approved in 
the US for patients aged 3 months and older with mild to moderate AD and has no such safety 
limitations but was shown to have modest efficacy (Eucrisa 2020).  
Janus kinases are intracellular signaling enzymes that act downstream of key proinflammatory 
cytokines known to promote the pathogenesis of AD. Ruxolitinib (INCB018424) is a potent and 
selective JAK1 and JAK2 inhibitor that is currently approved for use in tablet form for the 
treatment of patients with myelofibrosis and polycythemia vera in multiple countries and acute 
and chronic graft-versus-host disease in the US. Recent studies suggest that JAK inhibition may 
have antipruritic effects by acting directly on sensory nerve fibers and may offer a novel 
therapeutic approach with dual anti-inflammatory and antipruritic properties. 
Ruxolitinib cream is a topical formulation of ruxolitinib phosphate that was recently approved in 
the US for the topical short-term and noncontinuous chronic treatment of mild to moderate AD 
in nonimmunocompromised patients 12 years of age and older whose disease is not adequately 
controlled with topical prescription therapies or when those therapies are not advisable 
(Opzelura™ 2022). This approval was based on data from 2 Phase 3 studies in adolescents and 
adults with AD (INCB 18424-303 and -304; Papp et al 2021) and supported by the results of a 
Phase 2 study in adults with AD (INCB 18424-206; Kim et al 2020a, Kim et al 2020b). Refer to 
the IB for additional details. 
2.2. 
Study Rationale 
The primary purpose of this study is to collect additional long-term safety data regarding the 
types and frequencies of TEAEs occurring in adolescents with AD who are treated with 
ruxolitinib 1.5% cream BID. In the Phase 3 studies, 114 adolescents were treated with ruxolitinib 
1.5% cream BID, and the safety profile was similar to that in adults. This is a Post-Marketing 
Requirement study for the FDA. 


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2.2.1. 
Scientific Rationale for Study Design 
As the intent of this study is to further assess the safety of ruxolitinib 1.5% cream BID in 
adolescents with AD in addition to what was studied in the Phase 3 studies, INCB 18424-303 
and INCB 18424-304, the study population has been based on that in the Phase 3 studies, namely 
adolescents aged ≥ 12 to < 18 years of age with AD for at least 2 years and affecting 3% to 20% 
BSA (excluding the scalp) plus a total IGA score of 2 or 3. 
In addition, given the recent concerns about the potential thromboembolic and cancer risks of 
oral JAK inhibitors that are currently approved as treatments for rheumatoid arthritis (Olumiant 
2021, Xeljanz 2021), the exclusion criteria have been augmented where necessary to exclude 
anyone with current or a history of venous thromboembolism (DVT or PE), major adverse 
cardiovascular events, or malignancies. 
The primary and secondary objectives and endpoints focus on further assessing the safety and 
tolerability of ruxolitinib 1.5% cream BID in adolescents through assessment of TEAEs, vital 
signs (in particular height and weight), laboratory data for hematology and serum chemistry, and 
PK (trough concentrations of ruxolitinib). 
2.2.2. 
Justification for Treatment Regimen 
All participants will apply ruxolitinib cream at the FDA-approved strength (1.5%) and 
application frequency (BID) using the same treatment paradigm as the Phase 3 AD studies, 
namely starting with an 8-week CT period during which participants will treat all baseline AD 
lesions, regardless of whether or not the lesion(s) improve, followed by a 44-week LTS period 
during which participants will only treat active AD lesions. Modifications to the treatment 
regimen will not be allowed, as in the Phase 3 AD studies (refer to Section 6.5, Dose 
Modifications, for more details). 
2.3. 
Benefit/Risk Assessment 
In the Phase 3 AD studies, ruxolitinib 1.5% cream BID rapidly and effectively improved both the 
signs and symptoms of AD in adults and adolescents, being statistically significantly superior to 
vehicle cream BID at the end of the vehicle-controlled period (Week 8) for IGA-TS, EASI75, 
and ≥ 4-point improvement in Itch NRS score. The antipruritic effect of ruxolitinib 1.5% cream 
BID showed a rapid onset with evidence of a treatment effect on daily Itch NRS scores as early 
as Day 1 (ie, within 12 hours after the first application of study cream). The disease course 
(assessed by IGA scores and %BSA affected by AD at study visits during Weeks 8 through 52) 
was well-controlled throughout the entirety of the LTS period of the study. The treatment effects 
of ruxolitinib 1.5% cream BID on IGA-TS, EASI75, and Itch NRS score were consistently 
observed across both adult and adolescent subgroups. 
Safety data from the Phase 3 AD studies demonstrated that use of ruxolitinib 1.5% cream BID 
continuously for 8 weeks followed by prolonged (44 weeks) intermittent use was safe and 
well-tolerated. The TEAEs were generally Grade 1 or 2 in severity and were most often events of 
nasopharyngitis and upper respiratory tract infection. Frequencies of these events were within the 
expected range for the general AD population. There were no meaningful differences in the 
TEAE profile of ruxolitinib 1.5% cream BID between the adult and adolescent subgroups. 


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Results from dermal safety studies in healthy adult participants (INCB 18424-104, -105, -106, 
-107, and -108) to evaluate local tolerability demonstrated that ruxolitinib 1.5% cream did not 
cause sensitization and was only slightly irritating under exaggerated testing conditions 
(occlusive application). In addition, ruxolitinib 1.5% cream was not phototoxic and did not 
induce photosensitization. This was further confirmed by the Phase 3 (INCB 18424-303 and 
-304) safety data where ruxolitinib 1.5% cream BID was well-tolerated at the application sites 
with infrequently reported application site reactions. The most frequently reported application 
site reaction events were application site pain (lowest level terms were primarily application site 
burning or application site stinging) and application site pruritus; each of these events occurred 
in a lower proportion of participants in the ruxolitinib 1.5% cream BID treatment group 
(application site pain, 0.7%; application site pruritus, 0.6%) compared with the vehicle cream 
treatment group (application site pain, 4.8%; application site pruritus, 2.8%) during the 8-week, 
vehicle-controlled period, which may be attributable to worsening of the underlying disease in 
the absence of active drug treatment. 
The overall benefit/risk assessment of ruxolitinib 1.5% cream BID favors its use in both 
adolescent and adult patients with AD affecting areas up to and including 20% BSA. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ruxolitinib cream may be found in the IB. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 5 presents the objectives and endpoints. 
Table 5: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the long-term safety and tolerability 
of ruxolitinib cream in adolescents with AD. 
Incidence of TEAEs, assessed by monitoring the 
type, frequency, and severity of AEs. 
Secondary 
To further evaluate the long-term safety and 
tolerability of ruxolitinib cream in adolescents 
with AD. 
Changes in vital signs, height, weight, and 
laboratory data for hematology and serum 
chemistry. 
To characterize the PK of ruxolitinib cream in 
adolescents with AD. 
Trough concentrations of ruxolitinib at each 
postbaseline visit. 
Exploratory 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 3, open-label, 1-year safety study of ruxolitinib cream in adolescents (ages 
≥ 12 years to < 18 years) with AD whose disease is not adequately controlled with topical 
prescription therapies or when those therapies are not advisable (see study design schema in 
Figure 1). The study will be conducted at approximately 40 sites in North America and Europe. 
Approximately 100 participants with a diagnosis of AD (as defined by the Hanifin and Rajka 
[1980] criteria) with a duration of disease of at least 2 years, a total IGA score of 2 or 3, and 
%BSA affected by AD of 3% to 20% (excluding the scalp) will be enrolled.  
All participants will apply ruxolitinib cream at the FDA-approved strength (1.5%) BID using the 
same treatment paradigm as the INCB 18424-303 and -304 Phase 3 AD studies, namely starting 
with an 8-week CT period during which participants will treat all baseline AD lesions, regardless 
of whether or not the lesion(s) improve, followed by a 44-week LTS period during which 
participants will only treat active AD lesions. 
Participants who complete the Week 8 assessments with no safety concerns and with %BSA 
affected by AD no greater than 20% will continue into the LTS period.  
During the LTS period (ie, starting at the Week 8 visit), the treatment regimen will continue to 
be ruxolitinib 1.5% cream BID; however, participants will only treat active AD lesions. 
Participants will have the next study visit at Week 12, and then subsequent study visits will occur 
every 8 weeks until the end of the study (44 weeks total in the LTS period and 52 weeks total in 
the study). At those study visits, AD lesions will be evaluated by the investigator to confirm if 
the participant still requires continuation of therapy (total IGA score ≥ 1) or can otherwise 
(re)enter the observation/no treatment cycle (total IGA score = 0). Refer to Section 6.1 for 
further details. 
Participants will be assessed for the safety and tolerability of ruxolitinib cream throughout the 
study by monitoring the type, frequency, and severity of AEs; performing physical examinations; 
measuring vital signs, including height and weight; and conducting clinical laboratory 
assessments, as outlined in the SoA (see Table 3 [CT period] and Table 4 [LTS period]). In 
addition, the trough ruxolitinib concentration will be measured at various timepoints throughout 
the study (see Table 3 [CT period] and Table 4 [LTS period]), and its relationship with select 
hematology parameters such as platelet count, MPV, hemoglobin level, and neutrophil count will 
be assessed. 
Several exploratory disease severity assessments will be conducted throughout the study (see 
Table 3 [CT period] and Table 4 [LTS period]) to evaluate the long-term efficacy of ruxolitinib 
cream, namely 
 
 
All participants will have a safety follow-up visit 30 to 37 days following the end of treatment 
(Week 52/EOT2 or ET) to evaluate safety and duration of response except for participants who 
have been in an observation/no treatment cycle with a total IGA score of 0 from Week 48 or 
earlier until Week 52, for whom the Week 52/EOT2 visit will also count as the safety follow-up 
visit. See Section 8.8.1 for further details. 


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Figure 1 presents the study design schema, and Table 3 (CT period) and Table 4 (LTS period) 
present the SoA. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF. The end of the study is defined 
as the date of the last visit of the last participant in the study or the date that the last participant 
has discontinued study cream and has completed applicable safety follow-up assessments or is 
lost to follow-up. 
Participants will participate in the study for a duration of up to approximately 60 weeks: 28 days 
in the screening period, 8 weeks in the CT period, 44 weeks in the LTS period, and 30 days in 
the safety follow-up period (see Figure 1). 
A participant is considered to have completed the study if they have 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 of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively or if required by a regulatory agency. In the 
event of significant safety findings, the study will be terminated. If the study is terminated 
prematurely, the sponsor will notify the investigators, the IRBs and IECs, and the regulatory 
bodies of the decision and reason for termination of the study. 


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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. Adolescents aged ≥ 12 years to < 18 years (at the screening visit). 
2. A diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria. 
3. Duration of AD of at least 2 years. 
4. Total IGA score of 2 to 3 at the screening and baseline visits. 
5. Percent BSA (excluding the scalp) with AD involvement of 3% to 20% at the screening 
and baseline visits. 
6. Atopic dermatitis not adequately controlled with other topical prescription therapies or 
when those therapies are not advisable. See Section 8.1.5.2 for further details. 
7. Agree to discontinue all agents used to treat AD from screening through the final 
follow-up visit. 
8. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 90 days (a 
spermatogenesis cycle) after the last application of ruxolitinib cream and must refrain 
from donating sperm during this period. Permitted methods in preventing pregnancy 
(see Appendix A) should be communicated to the participants and their understanding 
confirmed. 
b. Female participants who are WOCBP must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test before the first application of 
ruxolitinib cream on Day 1 and must agree to take appropriate precautions to avoid 
pregnancy from screening through 30 days (1 menstrual cycle) after the last 
application of ruxolitinib cream and must refrain from donating oocytes during this 
period. Permitted methods in preventing pregnancy (see Appendix A) should be 
communicated to the participants and their understanding confirmed.  
c. A female participant not considered to be of childbearing potential as defined in 
Appendix A is eligible. 
9. Ability to comprehend and willingness to sign an ICF or written informed consent of the 
parent(s) or legal guardian(s) and written assent from the participant when possible. 
Note: 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. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. An unstable course of AD (spontaneously improving or rapidly deteriorating) as 
determined by the investigator in the 4 weeks prior to baseline. 
2. Concurrent conditions and history of other diseases: 
a. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, 
Wiskott-Aldrich syndrome). 
b. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline. 
c. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chickenpox) within 1 week before baseline. 
d. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton 
syndrome), pigmentation, or extensive scarring that, in the opinion of the investigator, 
may interfere with the evaluation of AD lesions or compromise participant safety. 
e. Presence of AD lesions only on the hands or feet without prior history of involvement 
of other classic areas of involvement such as the face or the flexural folds. 
f. Other types of eczema. 
g. Current or history of hepatitis B or C virus infection. 
3. Any current and/or history of serious illness or medical, physical, or psychiatric 
condition(s) that, in the investigator's opinion, would interfere with full participation in 
the study, including application of study cream and attending required study visits; pose a 
significant risk to the participant; or interfere with interpretation of study data. For 
example: 
a. Clinically significant or uncontrolled cardiovascular disease, including unstable 
angina, acute myocardial infarction or stroke within 6 months from Day 1 of study 
cream application, New York Heart Association Class III or IV congestive heart 
failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood 
pressure > 150/90 mm Hg) unless approved by the medical monitor/sponsor. 
b. Current and/or history of malignancy in the 5 years preceding the baseline visit, 
except for adequately treated, nonmetastatic nonmelanoma skin cancer. 
c. Current and/or history of arterial or venous thrombosis, including DVT and PE. 
d. Current and/or history of active tuberculosis or current and/or history of latent 
tuberculosis unless adequately treated. 
4. Any of the following clinical laboratory test results at screening: 
a. Hemoglobin < 100 g/L (< 10 g/dL) 
b. Liver function tests: 
− AST or ALT ≥ 2.5 × ULN 
− Total bilirubin > 1.5 × ULN with the exception of Gilbert disease.  
c. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (using the CKD 
Epidemiology Collaboration equation). 
d. Positive serology test results for HIV antibody. 
e. Any other clinically significant laboratory result that, in the opinion of the 
investigator, poses a significant risk to the participant. 


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5. Use of any of the following treatments within the indicated washout period before 
baseline: 
a. 5 half-lives or 12 weeks, whichever is longer – biologic agents (eg, dupilumab). For 
biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult 
the medical monitor. 
b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogues, 
cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or 
immunomodulating agents (eg, mycophenolate or tacrolimus). 
c. 2 weeks – immunizations with live-attenuated vaccines; sedating antihistamines, 
unless on long-term stable regimen (nonsedating antihistamines are permitted). 
Note: Live-attenuated vaccines are not recommended during the CT period.  
Note: COVID-19 vaccination is allowed.  
d. 1 week – use of other topical treatments for AD (other than bland emollients, eg, 
Aveeno® creams, ointments, sprays, soap substitutes), such as topical antipruritics 
(eg, doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar 
(shampoo), antibiotics, or antibacterial cleansing body wash/soap.  
Note: Diluted sodium hypochlorite "bleach" baths are allowed as long as they do not 
exceed 2 baths per week and their frequency remains the same throughout the study. 
6. Previously received systemic or topical JAK inhibitors (eg, ruxolitinib, tofacitinib, 
baricitinib, filgotinib, lestaurtinib, pacritinib).  
7. Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV 
radiation (eg, sunlight or tanning booth) within 2 weeks prior to the baseline visit and/or 
intention to have such exposure during the study, which is thought by the investigator to 
potentially impact the participant's AD. 
8. Pregnant or lactating, or considering pregnancy during the period of their study 
participation. 
9. 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. 
10. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
baseline with another investigational medication or current enrollment in another 
investigational drug protocol. 
11. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
baseline with a strong CYP3A4 inhibitor. 
12. Removed during Protocol Amendment 1. 
13. Known allergy or reaction to any component of the study cream formulation. 
14. In the opinion of the investigator unable or unlikely to comply with the administration 
schedule and study evaluations. 
15. Committed to a mental health institution by virtue of an order issued either by the judicial 
or the administrative authorities. 
16. Employees of the sponsor or investigator or are otherwise dependents of them. 


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5.3. 
Lifestyle Considerations 
Prolonged exposure to natural or artificial sources of UV radiation (including sun lamps, tanning 
booths, etc) is prohibited from 2 weeks prior to the baseline visit through the last study visit. 
When outdoors, participants will be advised to wear loose-fitting clothing that protects the 
treated areas from the sun. 
If sunscreen, makeup, or other cosmetics have been applied to the areas to be treated, participants 
should wash the treatment areas with mild soap and water and pat dry before application of study 
cream. See Section 6.6.1 for additional guidance. 
Participants should abstain from physical activity that can cause significant sweating for 
approximately 2 hours following study cream application. 
Swimming during the CT period of the study is not recommended. If unavoidable, it is 
recommended that swimming should not take place within 2 hours before and after study cream 
application. 
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. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error. Additionally, a participant who fails screening may 
repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status. Participants who rescreen must reconsent (if rescreened ≥ 28 days after the 
initial screening or ≥ 35 days after the initial screening for those participants on prior 
medications requiring a 4-week washout period, as described in Section 5.2, Exclusion Criterion 
5b) and be assigned a new participant number. 
5.5. 
Replacement of Participants 
Participants are not anticipated to be replaced during the study. However, as noted in 
Appendix B, due to the evolving situation of the COVID-19 pandemic, the sponsor may decide 
to recruit additional participants in the study beyond the expected number (eg, if a substantial 
number of participants withdraw early from the study).  


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
Table 6 presents the study treatment information. 
Table 6: 
Study Treatment Information 
Study Treatment Name: 
Ruxolitinib 
Dosage Formulation: 
Cream 
Unit Strength: 
1.5% 
Route of Administration: 
Topical 
Administration 
Instructions: 
BID. A thin film is applied to areas affected by AD in the morning and 
in the evening at least 1 hour before bedtime. 
Packaging and Labeling: 
Ruxolitinib cream will be provided in 60-g tubes. Each tube will be 
labeled as required per country requirements. 
Storage: 
Ambient (15°C-30°C/59°F-86°F) 
Status of Treatment in 
Participating Countries: 
Approved in the USa; investigational in all other countries 
a Opzelura (ruxolitinib) cream. 
Ruxolitinib cream study drug will be supplied in 60-g tubes and applied topically as a thin film 
BID (optimally at equal intervals, eg, ideally 12 hours apart but with at least 8 hours between 
applications) to the affected areas in the morning and in the evening, with the evening 
application at least 1 hour before bedtime. 
At the baseline visit, an estimate of the %BSA to be treated will be used by the IRT system to 
calculate the number of tubes of study cream to be dispensed. All AD areas identified at the 
baseline visit should continue to be treated through the end of the CT period (at Week 8), even if 
the area begins to improve or the AD resolves completely, unless the participant meets any 
criteria for stopping study cream. 
If there are new areas to be treated, including expansion of existing areas or development of new 
areas, after consultation with the investigator, and if there are no safety concerns, study cream 
should be applied to these areas in addition to the areas identified at the baseline visit (up to a 
maximum total of 20% BSA) for the remainder of the CT period, and the percentage of BSA to 
be treated will be recalculated and increased accordingly. This new estimate will be entered into 
the IRT system to calculate the number of tubes of study cream to be dispensed. Approval to 
treat these additional areas may occur via telephone, although the investigator, at their discretion, 
may ask the participant to return for an unscheduled visit. This is a close reflection of the clinical 
practice of managing AD in the outpatient setting. During the CT period, participants whose 
additional new areas to be treated in addition to the areas identified at the baseline visit exceed 
20% BSA should be discontinued from study cream and complete the ET assessments. 
During the LTS period (ie, starting at the Week 8 visit), participants will have study visits at 
Week 12 and then every 8 weeks until the end of the study (44 weeks total), with the final 
possible application being the evening application on the day before the Week 52 visit. At each 




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BID and should limit use to no more than one 60-g tube per week. Refer to the Study Manual for 
participant instructions for handling study cream. 
6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions (ruxolitinib cream 
is to be stored between 15°C and 30°C [59°F-86°F]) have been maintained during transit for all 
study cream received and any discrepancies are reported and resolved before use of the study 
cream. 
Only participants enrolled in the study may receive study cream, and only authorized site staff 
may distribute study cream. The cream will be applied by the participant or her/his parent/legal 
guardian. Immediately after application of study cream, the hands should be thoroughly washed 
with soap and water, except where there are AD lesions on the hands. Note that the study cream 
is for exclusive use on the skin. In case of accidental exposure to the eyes or mucous membranes, 
the cream should be immediately removed from that area and necessary supportive measures 
taken. Refer to the Study Manual for participant instructions for handling of study cream.  
All study cream 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 cream at ambient 
temperature conditions. 
The investigator or designee is responsible for study cream 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 the following: 
• Delivery of study cream to the study site. 
• Inventory of study cream at the site. 
• Participant use of the study cream, including tube counts from each supply dispensed. 
• Return of study cream 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 cream. These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the investigational product and study 
participants. 
Completed accountability records will be archived by the site. The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study cream 
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 destruction of any remaining study cream 
according to institutional SOPs. If however, local procedures do not allow on-site destruction, 
shipment of the study cream back to the sponsor is allowed. In this case, the site should (where 
local procedures allow) maintain the study cream supply until the study monitor inspects the 
accountability records in order to evaluate compliance and accuracy of accountability by the 


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investigative site. At sites where the study cream 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 cream are included in 
the study materials provided to sites. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable.  
6.4. 
Study Treatment Compliance 
Compliance will be assessed for frequency of application of study cream by reviewing the 
participants' eDiaries. Participants will also be questioned regarding study cream application 
technique, missed applications, and use of any additional topical or systemic prescriptions of 
other products or over-the-counter products. Compliance with study cream will be evaluated by 
the participant's adherence to the BID application regimen (evaluation of actual number vs 
prescribed number of applications) and documented by the site staff and monitored by the 
sponsor/designee. 
Qualified clinical staff will review the eDiary entries for compliance. Participants will be 
considered compliant with the treatment regimen if they apply at least 80% but no more than 
120% of the prescribed number of applications during participation in the CT period of the study. 
Participants who are noncompliant during the CT period and LTS period (if on a treatment cycle) 
will be reinstructed by the investigator (or designee), and the sponsor should be consulted by the 
investigator for instruction on the proper handling of the participant. 
Drug accountability will be assessed by documenting the quantities of drug used between study 
visits (tube counts and weighing). At the first clinic visit and subsequent study visits, the amount 
of study cream to be applied is to be determined by weighing a tube before and after the 
participant applies a thin film of study cream to the affected areas. Participants will be instructed 
to bring all study cream with them to the study visits in order for site personnel to assess study 
cream accountability.  
6.5. 
Dose Modifications 
There are no application adjustments/modifications allowed (decrease or increase in study cream 
strength or frequency of application) except for drug interruption or permanent discontinuation if 
needed (eg, for management of an AE). 
Temporary interruption could be due to an AE during the CT or LTS periods or due to clearance 
of the AD lesions during the LTS period, as described in Section 6.1. 
6.5.1. 
Criteria and Procedures for Interruptions of Study Cream 
Safety concerns should be discussed with the medical monitor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study cream. 
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or laboratory abnormalities that may have an unclear relationship to study cream. In the event 
that an AE is present only at a specific site of study cream application, treatment may be 


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temporarily withheld only at that lesional site and continued elsewhere. This should be recorded 
as a dose interruption on the AE eCRF page. Except in cases of emergency, it is recommended 
that any findings of concern (eg, AE) be confirmed and that the investigator consult with the 
medical monitor before interrupting study cream applications. Additionally, the investigator must 
obtain approval from the medical monitor before restarting study cream. Participants who 
experience a recurrence of the initial AEs upon restarting the study cream may need to 
permanently discontinue treatment with the study cream. 
Participants should be closely monitored for the development of signs and symptoms of infection 
during treatment with the study cream and up to the safety follow-up visit. Study cream should 
be interrupted if a participant develops a serious infection, an opportunistic infection, or sepsis. 
Study cream application should not be resumed until the infection is controlled. 
Instructions for interruption of study cream–related laboratory abnormalities are outlined in 
Table 7. 
Table 7: 
Guidelines for Interruption and Restarting of Study Cream Due to 
Laboratory Abnormalities 
AE Related to Study Cream 
Action Taken 
Any Grade 3 laboratory abnormality 
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results requested. 
• Interrupt study cream, based on clinical judgment in 
consultation with the medical monitor (whenever 
possible), taking into account the relatedness of the AE 
to the study cream and the participant's underlying 
condition.  
• Interruption may occur after the initial test result or may 
be delayed until or unless the repeat test confirms the 
laboratory abnormality; however, if the repeat test does 
confirm the laboratory abnormality, the study cream 
must be interrupted unless the medical monitor approves 
continuation. 
• At the discretion of the investigator, after consultation 
with the medical monitor, study cream application may 
be restarted once the AE has resolved. 
Any Grade 4 laboratory abnormality  
• Laboratory abnormalities should be confirmed with 
repeat testing within 48 hours whenever possible and 
immediate delivery of the laboratory results requested. 
• Permanently discontinue study cream if laboratory 
abnormalities are confirmed. Study cream may also be 
discontinued after the initial laboratory abnormality, 
with approval from the medical monitor. 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Cream 
Participants must permanently discontinue study cream if they meet any of the following criteria: 
• Occurrence of an AE that is related to treatment with the study cream that, in the 
judgment of the investigator or the medical monitor, compromised the participant's 
ability to continue study-specific procedures or is considered to not be in the 
participant's best interest.  
• Worsening of AD that requires treatment with a prohibited concomitant medication. 
• Any Grade 4 laboratory abnormality related to the study cream (see Table 7). 
• Persistent AE requiring an interruption of study cream for more than 2 weeks without 
resolution of the AE. 
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 recorded in the eCRF as 
follows: 
• Non-AD medications and treatments that are taken between 35 days before the first 
application of study cream and 30 days after the last application of study cream. 
• AD medications and treatments that are taken between 12 months before the start of 
Screening and 30 days after the last application of study cream. 
Any addition, deletion, or change in the dose of these medications will also be recorded. 
Concomitant medications administered more than 30 days after the last application of study 
cream should be recorded for SAEs as defined in Section 9.2. Concomitant 
treatments/procedures that are required to manage a participant's medical condition during the 
study will also be recorded in the eCRF. The medical monitor should be contacted if there are 
any questions regarding concomitant or prior therapy. 
6.6.1. 
Permitted Medications and Procedures 
The following are permitted during the study: 
• Participants may use bland emollients (except those containing urea, salicylic acid, or 
lactic acid) such as Eucerin cream. Participants should continue to use the bland 
emollient/moisturizer in the same manner they did before entering the study and 
throughout the course of the study. 
Note: Emollients should not be used within 4 hours before and 2 hours after 
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• Bathing during the study should be limited to once daily for no longer than 
15 minutes and not within 2 hours following study cream application. During baths, 
tepid (not hot) water and mild cleansing agents (eg, Basis® bar or Dove®) should be 
used. (See Section 5.3 for swimming guidance.) Showers should be limited in time 
with warm water and mild cleansing agents used.  
• 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 not less than 4 hours before and at 
least 2 hours after study cream application. 
• Participants may use nonsedating, over-the-counter antihistamines. 
6.6.2. 
Restricted Medications and Procedures 
The following are permitted during the study under specified conditions: 
• Short-term use of systemic corticosteroids may be permitted to treat acute AEs 
(eg, asthma) during the LTS period, and the decision to keep the participant in the 
study (or to permanently discontinue study cream) will be made in consultation with 
the medical monitor. 
• Participants may continue using sedating antihistaminic drugs as long as their use is 
part of a preexisting and well-established regimen. There are no restrictions for use of 
nonsedating antihistamines. 
• Use of any over-the-counter, nonprescription preparations deemed acceptable by the 
investigator is permitted under an established and stable treatment regimen. 
• Use of any prescription medication (including phytotherapeutic, herbal, or 
plant-derived preparations) is not permitted within 7 days before the baseline visit 
through the safety follow-up visit, unless deemed acceptable by the investigator. 
• Immunizations with a live-attenuated vaccine are not recommended during the CT 
period (first 8 weeks) unless deemed necessary by the investigator. 
• Allergen immunotherapy (desensitization) that is ongoing at a stable dose at the time 
of study entry may be continued while on study but only at the same dose. 
• Bleach baths are allowed as long as they do not exceed 2 baths per week and their 
frequency remains the same throughout the study. 
• Participants should not take baths or showers within 2 hours after study cream 
application. 
• Topical anti-infectives or other topical treatments applied to active AD lesions should 
not be used for at least 4 hours before and 2 hours after application of study cream. 


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6.6.3. 
Prohibited Medications and Procedures 
The following are not permitted during the study:  
• Any investigational medication other than the study cream. 
• Topical corticosteroids, tacrolimus, pimecrolimus, and PDE4 inhibitors (eg, Eucrisa). 
• Other topical agents for AD (except bland emollients as noted in Section 6.6.1). 
• Treatment known to affect the course of AD. 
• Systemic corticosteroids (except the example stated in Section 6.6.2), methotrexate, 
cyclosporin A, azathioprine and biologic therapies, or other immunosuppressant 
agents. 
• Phototherapy or tanning beds. 
6.7. 
Treatment After the End of the Study 
There will be no treatment provided after the end of the study. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• Lack of efficacy response during the LTS period (defined as no change/improvement 
in either %BSA or IGA score when treated continuously for any 8-week interval 
during the LTS period). 
• Worsening of AD during either the CT period or the LTS period, to the point where 
the extent of AD to be treated (ie, all areas excluding the scalp) exceeds 20% BSA. 
• 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 the 
public domain, may be solicited from or collected on the participant. Participants may 
choose to discontinue study treatment and remain in the study to be followed 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, after 2 consecutive study visits and reinforcement of study cream application 
guidance by site staff, a participant's drug usage exceeds one 60-g tube per week, a 
participant who again fails to meet compliance benchmarks at a subsequent visit may 
be considered for withdrawal from the study. The medical monitor should be 
consulted for instruction on handling the participant. 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study cream application 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 prior to the 
Week 52/EOT2 study visit, the ET visit should be conducted. Reasonable efforts should be made 
to have the participant return for the safety follow-up visit. The date of the last application of 
study cream and the reason for discontinuation of study cream will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The ET visit should be performed and date recorded in the eCRF. 
• Participants must be followed for safety until the time of the 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), then no additional data collection should occur; however, 
participants will have the option of withdrawing consent for study treatment but continuing in the 
follow-up period of the study for safety assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at their 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, they may request destruction of any samples taken and not tested, and 
the investigator must document this in the site study records. 
Data to be collected at the time of study withdrawal and follow-up and for any further 
evaluations should conform to the requirements of the ET/EOT visit (see Table 3 [CT period] 
and Table 4 [LTS period]). 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 


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• 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, they will be considered to have 
withdrawn from the study. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
See Appendix B for COVID-19 pandemic–related guidance. 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or their representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant. A template will be 
provided by the sponsor or its designee. The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template. The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent/assent that meets the applicable requirements and regulations for the 
countries in which the study is being conducted as well as the IRB/IEC or study 
center. 
• The participant must be informed that their 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 their 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. 


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• The medical record must include a statement that written informed consent was 
obtained before the participant underwent any study-related procedures and the date 
the written consent was obtained. The authorized person obtaining the informed 
consent must also sign the ICF/assent. 
• Participants must provide consent to the most current version of the ICF/assent during 
their participation in the study. 
• A copy of the ICF(s)/assent(s) must be provided to the participant or the participant's 
legally authorized representative. 
8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF/assent and the day the participant is enrolled in 
the study (Day 1). Informed consent (or assent) must be obtained before performing any 
study-specific procedures. Screening assessments for determination of eligibility may be 
performed over a period of up to 28 days, or up to 35 days for participants on prior medications 
requiring a 4-week washout period, as described in Section 5.2 (Exclusion Criterion 5b). 
Assessments that are required to demonstrate eligibility may be performed over the course of 
1 or more days during the screening process. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment or the application of study cream. Tests with results that fail eligibility requirements 
may be repeated once during screening if the investigator believes the results to be in error. For 
screening assessments that are repeated, the most recent available laboratory results before 
enrollment will be used to determine eligibility. Additionally, a participant who fails screening 
may repeat the screening process 1 time if the investigator believes that there has been a change 
in eligibility status (eg, after recovery from an infection). The participant is not required to sign 
another ICF if the rescreening occurs within 35 days (screening period) of the previous ICF 
signature date. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number. Site staff should contact the IRT system to 
obtain the participant ID number during screening. Upon determining that the participant is 
eligible for study entry, the IRT system will be contacted to obtain the study medication kit 
assignment. Additionally, the IRT system will be contacted at each regular study visit during 
both the CT period and the LTS period as indicated in Table 3 and Table 4, respectively, to 
update the study cream supply. The IRT system will also be used during the study visits to 
recalculate the amount of study cream to be dispensed if the participant's %BSA of AD lesions to 
be treated has increased (during the CT period) or has either increased or decreased (during the 
LTS period). Additional details are provided in the IRT Manual. 


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8.1.4. 
Distribution of Reminders and eDiaries 
Starting at the Day 1 visit, each participant will use a study cream–specific eDiary in order to 
record use of the study cream. The completed eDiary will be reviewed during each of the 
participant's study visits and data will be confirmed by the study staff.  
Qualified clinical study staff will review the participants' entries for compliance, as outlined in 
Section 6.4. 
Participants will be provided with a reminder starting on Day 1 and at all CT and all LTS visits 
through Week 48. The reminder will indicate the date and time of the next visit and will also 
remind the participant that their morning application of study cream will be take place at the 
clinic under site supervision after blood or saliva collection for PK and safety evaluations have 
been completed. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses. General medical history will include relevant medical or surgical 
treatment within the past 2 years that are considered to be clinically significant by the 
investigator. Treatment history for AD is covered in Section 8.1.5.2. 
8.1.5.2. 
Disease Characteristics and Treatment History 
An AD-targeted medical and treatment history will be collected at screening. Details regarding 
the participant's AD, including date of diagnosis and relevant disease characteristics, will be 
recorded. A medical history of other conditions related to AD will also be collected at this time. 
In addition, information about topical, prescription AD treatments (eg, name, start/end dates, 
regimen) used within 12 months prior to screening, and the reason for discontinuation 
(eg, inadequate response, intolerance) will be collected. 
Also, information about when the use of topical, prescription AD treatments within 12 months 
prior to screening was not advisable will be collected. An example of when other topical 
prescription therapies were not advisable is when the participant had previously experienced 
clinically relevant side effects/safety risks and/or skin tolerability issues that outweigh the 
potential treatment benefits and are the reason why a topical treatment cannot be initiated.  
Acceptable documentation for the use of topical prescription treatments or when those treatments 
were not advisable (within 12 months prior to screening) include: 
• Medical records, and/or 
• Communication with the participant's treating physician, and/or 
• Investigator documentation based on: 
o An interview with the participant or legal representative; and/or 
o Review of participant- or legal representative-reported medication history. 


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8.2. 
Efficacy Assessments 
8.2.1. 
Health Economics 
Not applicable. 
8.2.2. 
Percent Body Surface Area Affected by Atopic Dermatitis 
Total %BSA affected by AD will be estimated at each visit as outlined in the SoA (see Table 3 
[CT period] and Table 4 [LTS period]). Body surface area assessment will be approximated to 
the nearest 0.1% using the handprint (palmar) method as a guide. The approximate size of the 
participant's entire palmar surface (ie, the palm plus 5 digits, with fingers tucked together and 
thumb tucked to the side) should be considered as 1% BSA, and the approximate size of the 
participant's thumb should be considered as 0.1% BSA.  
Participants must have BSA involvement (excluding the scalp) of 3% to 20% at the screening 
and baseline visits to enroll in the study; they must have 0% to 20% BSA involvement at Week 8 
(baseline for the LTS period) to enter the LTS period. 
During the LTS period, including Week 8 (baseline for the LTS period), %BSA will be 
evaluated by the investigator to determine whether the participant requires continuation of 
treatment or should (re)enter an observation/no treatment cycle. 
8.2.3. 
Investigator's Global Assessment 
Investigator's Global Assessment is an overall eczema severity rating on a 0 to 4 scale that will 
be assessed for the whole body (total IGA) and for the face only (facial IGA) during site visits as 
outlined in the SoA (see Table 3 [CT period] and Table 4 [LTS period]). The area "Face" is 
defined as including the area on the forehead to the original hairline, on the cheek to the jawline 
vertically to the jawline and laterally from the corner of the mouth to the tragus. The area "Face" 
will not include the surface area of the lips, scalp, ears, or neck but will include the nose and 
eyelids. The severity strata for the IGA are shown in Table 8. 
Table 8: 
Investigator's Global Assessment 
Grade 
Severity 
Status 
0 
Clear 
No erythema or induration/papulation, no oozing/crusting; there may be 
minor residual discoloration 
1 
Almost clear There may be trace faint pink erythema, with almost no 
induration/papulation, and no oozing/crusting 
2 
Mild 
There may be faint pink erythema, with mild induration/papulation and no 
oozing/crusting 
3 
Moderate 
There may be pink-red erythema with moderate induration/papulation and 
there may be some oozing/crusting 
4 
Severe 
There may be deep or bright red erythema with severe induration/papulation 
and with oozing/crusting 
Source: FDA 2012.  


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Participants must have a total IGA score of 2 or 3 at the screening and baseline visits to enroll in 
the study; there is no limitation for total or facial IGA score at Week 8 (baseline for the LTS 
period) to enter the LTS period. 
During the LTS period, including Week 8 (baseline for the LTS period), total IGA will be 
evaluated by the investigator to determine whether the participant requires continuation of 
treatment or should (re)enter an observation/no treatment cycle. If the total IGA score is ≥ 1, the 
participant will start or continue active treatment with ruxolitinib cream 1.5% BID. If the total 
IGA score is 0 (clear), the participant will (re)enter an observation/no treatment cycle. 
 
 
 
8.2.4. 
Itch Numerical Rating Scale 
The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch 
intensity (Pruritus Resources). Participants will be asked to rate the itch severity of their AD by 
selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst 
level of itching in the past 24 hours as outlined in the SoA (see Table 3 [CT period] and Table 4 
[LTS period]). Participants will be issued an eDiary in which to record itch severity. The 
participants will be instructed to complete the eDiary each night beginning on the day of 
screening through the last day of the LTS period. Detailed directions for the administration of an 
eDiary will be provided in the Study Manual. 
8.2.5. 
Eczema Area and Severity Index 
Atopic dermatitis will be assessed as outlined in the SoA (see Table 3 [CT period] and Table 4 
[LTS period]) using the EASI scoring system (refer to the Study Manual), which is a validated 
scoring system that grades the physical signs of AD to provide a measure of AD severity 
(ranging from 0 to 72; Hanifin et al 2001). The EASI scoring system examines 4 regions of the 
body (head/neck, upper limbs, trunk, and lower limbs) and weights them. Each of the 4 body 
regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations 
(Ex), and lichenification (L) for an average degree of severity of each sign in each region. 
The severity strata for the EASI are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 
7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; and 50.1 to 72.0 = very severe 
(Leshem et al 2015). 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see Table 3 [CT period] 
and Table 4 [LTS period]). 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last application of study drug. Adverse events for enrolled participants that 


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begin or worsen after informed consent/assent should be recorded on the Adverse Events Form 
in the eCRF regardless of the assumption of a causal relationship with the study cream. 
Conditions that were already present at the time of informed consent/assent should be recorded 
on the Medical History Form in the eCRF. Adverse events (including laboratory abnormalities 
that constitute AEs) should be described using a diagnosis whenever possible rather than by 
individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
considered related to the study cream/procedures, or caused the participant to discontinue the 
study cream. Care will be taken not to introduce bias when detecting AEs and/or SAEs. 
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences. Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments. The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and AEs 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 
During the study, participants will be assessed by the investigator or medically qualified 
designee per institutional standard of care. Physical examinations will be conducted at the 
timepoints listed in the SoA (see Table 3 [CT period] and Table 4 [LTS period]). 
8.3.2.1. 
Comprehensive Physical Examination 
At the screening visit and Week 52/EOT2 or ET visit, a comprehensive physical examination 
should be conducted. The comprehensive physical examination will include assessment(s) 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; as well as a brief 
neurological examination. 
8.3.2.2. 
Targeted Physical Examination 
At the visits indicated in the SoA (see Table 3 [CT period] and Table 4 [LTS period]), a targeted 
physical examination will be a symptom-directed evaluation (ie, conducted only if indicated by 
symptoms, AEs, or other findings); clinically significant abnormalities (in the investigator's 
judgment) are to be reported as AEs and documented on the Adverse Events Form in the eCRF. 


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8.3.3. 
Vital Signs, Height, and Weight 
Vital signs, height, and weight will be measured as outlined in the SoA (see Table 3 [CT period] 
and Table 4 [LTS period]). 
Vital sign measurements (to be taken before blood/saliva collection for laboratory tests) include 
blood pressure, pulse, respiratory rate, and body temperature. Blood pressure and pulse will be 
taken with the participant in the sitting position after 5 minutes of rest. Abnormal vital sign 
results identified after the first application of study cream constitute an AE if they are considered 
clinically meaningful, induce clinical signs or symptoms, or require concomitant therapy. 
Height and weight will be assessed at the baseline, Week 8/EOT1/ET, Week 28, and 
Week 52/EOT2/ET visits. Height will be measured using a stadiometer. The stadiometer should 
be calibrated, and a wall-mounted one is recommended. Participants should be measured without 
socks and 3 measurements taken to the nearest 0.1 cm. The average of the 3 height 
measurements of individual participants should be recorded in the eCRF. 
8.3.4. 
Electrocardiograms 
A single 12-lead ECG will be obtained at screening (12-lead ECG performed within 2 months 
before baseline is acceptable) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTc intervals. All 12-lead ECGs will be performed with the 
participant in a recumbent or semirecumbent position after 5 minutes of rest.  
The decision to include or exclude a participant or withdraw a participant from the study cream 
based on an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of the 
investigator, in consultation with the sponsor's medical monitor, as appropriate. Clinically 
notable abnormalities that are considered clinically significant in the judgment of the investigator 
are to be reported as AEs. 
8.3.5. 
Laboratory Assessments 
See Table 9 for the list of clinical laboratory tests to be performed and the SoA (see Table 3 [CT 
period] and Table 4 [LTS period]) for the timing and frequency. A central laboratory will 
perform all clinical laboratory assessments for safety (ie, blood chemistries and hematology 
assessments) and will store the samples for PK analysis. Additional testing may be required by 
the sponsor based on emerging safety data. All Protocol-required laboratory assessments must be 
conducted in accordance with the Laboratory Manual and the SoA (see Table 3 [CT period] and 
Table 4 [LTS period]). Information regarding collection, processing, and shipping of samples for 
laboratory assessment is provided in the Laboratory Manual. 
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 application of study 
cream should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor. 
If screening laboratory assessments are performed less than or equal to 2 weeks before Day 1, 
then the Day 1 serum chemistry and hematology assessments do not need to be performed. 


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See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 
Table 9: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology 
Serology 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Blood urea nitrogen or urea 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin is 
elevated above ULN) 
Complete blood count, including: 
• Hemoglobin 
• Hematocrit 
• Mean corpuscular volume 
• MPV 
• Platelet count 
• Red blood cell count 
• White blood cell count 
 
Differential count (absolute and %), 
including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
HIV antibody 
 
 
 
 
 
 
Pregnancy Testing 
WOCBP will have a serum test at 
screening and a urine test at all 
other visits. 
A positive urine test must be 
confirmed by a serum test. 
Note: Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data or to rule 
out a diagnosis.  
8.3.5.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during 
screening. Urine pregnancy tests will be performed locally as outlined in the SoA (see Table 3 
[CT period] and Table 4 [LTS period]), as medically indicated (eg, in case of loss of menstrual 
cycle, when pregnancy is suspected), or per country-specific requirement (note that 
country-required urine pregnancy testing will be outlined and communicated to investigational 
sites under separate cover). If a urine pregnancy test is positive, the results must be confirmed 
with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study cream and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 
8.3.5.2. 
Serology 
An HIV antibody assessment will be performed at the screening visit to rule out HIV infection. 
Generally, HIV tests should be performed early in the screening process due to the length of time 
needed to obtain the results. Additional tests may be performed if clinically indicated. 


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8.4. 
Pharmacokinetic Assessments 
Pharmacokinetic blood and saliva samples will be collected from all participants at the visits and 
collection times shown in the SoA (see Table 3 [CT period] and Table 4 [LTS period]) and as 
noted in Table 10. 
The exact date and time of the PK blood and saliva sampling and the date and time of the last 
application of study cream preceding the blood or saliva sample (if applicable) will be recorded 
in the eCRF. 
Instructions for sample preparation and shipping will be provided in the Laboratory Manual. 
Participants will receive reminders in advance of the study visit providing instructions to hold the 
application of study cream on the day of the visit and to record the time of the prior application 
of study cream. 
Blood samples for PK must be drawn from an area that has not been treated with study cream, or 
if that is not possible, the participant must not apply study cream from the previous application 
of study cream on the immediate body area where blood is to be drawn (ie, for site visits in the 
morning, this means the application on the evening before [second dose of that day]; for site 
visits in the afternoon this means the application on the morning of the same day [first dose of 
that day]).  
If blood is drawn from an area that has been treated with study cream, the site personnel must 
document the missed application at the location of the blood draw in the eCRF. After the PK 
blood or saliva sample is collected, participants will apply ruxolitinib 1.5% cream. 
All analyses will be conducted by Incyte Corporation (Wilmington, DE) or Incyte's designee. 
Table 10: 
Pharmacokinetic Blood and Saliva Sample Timing 
Study Visit 
Timing of Sample 
CT period 
 
 
 
• 
Week 2 
• 
Week 4 
• 
Week 8/EOT1 or ET 
Samples will be collected at any time prior to study cream application during study 
visits, but must be at least 4 hours after the previous application of study cream 
and after assessment of vital signs during the visit: 
• Blood and saliva samples 
• Blood and saliva samples 
• Saliva sample only 
LTS period: Weeks 12, 20, 
28, 36, 44, and 52/EOT2  
Saliva samples will be collected at any time prior to study cream application 
during study visits, but must be at least 4 hours after the previous application of 
study cream and after assessment of vital signs during the visit. No blood samples 
will be collected during the LTS period. 
8.5. 
Pharmacodynamic and Translational Assessments 
Not applicable. 


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8.6. 
Unscheduled Visits 
Unscheduled study visits may occur at any time medically warranted, including when 
participants develop new areas of AD (see Section 6.1). Any assessments performed at those 
visits should be recorded in the eCRF. 
8.7. 
End of Treatment and/or Early Termination 
The end of treatment for the CT period (EOT1) coincides with the Week 8 visit. At that time, if 
the participant continues into the LTS period, then the Week 8/EOT1 visit should be conducted. 
However, if the participant does not continue into the LTS period, the ET evaluations should be 
conducted instead. For participants who permanently discontinue study cream prior to the 
Week 8/EOT1 visit, the ET visit and evaluations should be conducted. If the ET visit coincides 
with a regular study visit, then the respective ET evaluations will supersede those of that 
scheduled visit, and the data should be entered in the ET page in the eCRF. If the decision to 
permanently discontinue study cream does not coincide with a regular visit, reasonable efforts 
should be made to have the participant return to the site to have the ET procedures completed. 
The end of treatment for the LTS period, and hence also the whole study (EOT2), coincides with 
the Week 52 visit. A participant who completes the Week 52/EOT2 visit will have reached the 
end of treatment with study cream. For participants who permanently discontinue study cream 
during the LTS period and prior to the Week 52/EOT2 visit, the ET visit and evaluations should 
be conducted. If the ET visit coincides with a regular study visit, then the respective ET 
evaluations will supersede those of that scheduled visit, and the data should be entered in the ET 
page in the eCRF. If the decision to permanently discontinue study cream does not coincide with 
a regular visit, reasonable efforts should be made to have the participant return to the site to have 
the ET procedures completed. 
8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
All participants will have a safety follow-up visit 30-37 days following the end of treatment 
(Week 52/EOT2 or ET) to evaluate safety and disease control parameters. One exception to this 
would be for participants in the LTS period who have been in an observation/no treatment cycle 
with a total IGA score of 0 (clear) from Week 48 or earlier until Week 52; for such participants, 
the Week 52/EOT2 visit will also count as the safety follow-up visit. 
Adverse events and SAEs must be followed up until 1) at least 30 days after the last application 
of study cream or 2) until toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. Reasonable efforts should be made to have the participant return for the 
follow-up visit and report any AEs that may occur during this period. 


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


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


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


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The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2: Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4: Life-threatening consequences; urgent treatment indicated. 
• Grade 5: Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study cream and each occurrence of 
each AE/SAE.  
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB in making their assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study cream application, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that they have reviewed the 
AE/SAE and have provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report. However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements. Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change their opinion of causality in light of follow-up information and 
submit the updated causality assessment. 
Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the Adverse Events Form in the eCRF 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 cream, the 
interventions required to treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 


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• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology.  
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study cream or study procedure[s]), all 
SAEs occurring after the participant has signed the ICF/assent through the last safety visit or at 
least 30 days after the last application of study cream, whichever occurs later, must be reported 
to the sponsor (or designee) immediately, without undue delay but not later than within 24 hours 
of obtaining knowledge of its occurrence unless otherwise specified by the Protocol. The 
investigator will submit any updated SAE data to the sponsor (or designee) immediately, without 
undue delay but not later than within 24 hours of it being available.  
Investigators are not obligated to actively seek SAE information after conclusion of study 
participation (ie, after the safety follow-up visit or 30 days after the last application of study 
cream, whichever occurs later). If the investigator learns of any SAE, including death, at any 
time after a participant has been discharged from the study, and they consider the event to be 
reasonably related to the study cream or study participation, then the investigator must notify the 
sponsor (or designee) within 24 hours of becoming aware of the event.  
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
cream under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB for the study cream (new occurrence) and is 
thought to be related to the study cream, the sponsor or its designee may urgently require further 
information from the investigator for expedited reporting to health authorities. The sponsor or its 
designee may need to issue an Investigator Notification to inform all investigators involved in 
any study with the same drug that this SAE has been reported. Suspected unexpected serious 
adverse reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC or as per national regulatory requirements 
in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study cream under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 


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Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Events Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available). The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual or as per the Incyte Reference Guide for 
Completing the Serious Adverse Event Report Form. 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Event Report Form. Once the EDC system is functional, 
the SAE report should be retrospectively added to the EDC system and follow-up should be 
completed through the EDC. The original copy of the Serious Adverse Event Report Form and the 
email or facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference 
Guide for Completing the Serious Adverse Event Report Form or Study Reference Manual for details 
and for the email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system. The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study cream because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation). Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs. 
9.5. 
Events of Clinical Interest 
Not applicable. 
9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study 
cream 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 
cream, the following procedures should be followed in order to ensure safety: 
• The study cream must be discontinued immediately (female participants only).  
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 


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Data on fetal outcome are collected for regulatory reporting and drug safety evaluations. 
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 cream 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 the pregnancy of a study participant must be recorded and 
reported as described in Section 9.4. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4. If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.8. 
Warnings and Precautions 
Special warnings or precautions for the study cream, derived from safety information collected 
by the sponsor or its designee, are presented in the IB. Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications. Any 
important new safety information should be discussed with the participant during the study as 
necessary. If new significant risks are identified, they will be added to the ICF/assent. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor. All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or their 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, they will return a copy of the 
product complaint communication with the product. 
9.10. 
Treatment of Excessive Use 
There has been no clinical experience with overdose resulting from excessive use of ruxolitinib 
cream. Treatment of excessive use should consist of general supportive measures. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
Approximately 100 participants will be enrolled. The study is not powered for statistical 
comparison but instead is based on the evaluation of safety. This sample size will provide > 99% 
chance of detecting at least 1 AE of interest if the underlying AE rate is 5%, and therefore it is 
anticipated that sufficient data for safety investigation will be permitted. As this is an open-label 
study, all participants will be treated with ruxolitinib 1.5% cream. 
10.2. 
Populations for Analyses 
The populations for analysis are provided in Table 11. 
Table 11: 
Populations for Analysis 
Population 
Description 
FAS 
The FAS will include all participants enrolled in the study who applied study 
cream at least once. The FAS will be used for the summary of demographics, 
baseline characteristics, participant disposition, and all analyses of efficacy and 
safety data. 
PK/hematology 
lab evaluable 
The PK evaluable population will include all participants who applied study cream 
at least once and provided at least 1 postbaseline PK sample (1 PK measurement). 
The hematology lab evaluable population will include all participants who applied 
study cream at least once, provided the baseline hematology blood sample, and at 
least 1 postbaseline hematology blood sample (1 hematology measurement). 
The PK/hematology lab evaluable population will include all participants who are 
both PK evaluable and hematology lab evaluable. 
10.3. 
Level of Significance 
This is a safety study. No formal hypotheses will be tested; all efficacy analyses are exploratory. 
10.4. 
Statistical Analyses 
10.4.1. 
Primary Analysis 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first application of study cream and up to 30 days after the last application of study cream. 
Analysis of AEs will be limited to TEAEs, but data listings will include all AEs regardless of 
their timing in relation to study cream application. Treatment-emergent AEs will be tabulated by 
the MedDRA preferred term and system organ class. Severity of AEs will be based on CTCAE 
v5.0 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a relationship to study cream will be 
considered to be treatment-related AEs. If the investigator does not specify the relationship of the 
AE to study cream, then the AE will be considered treatment-related. The incidence of TEAEs, 
treatment-related TEAEs, serious TEAEs, Grade 3 or higher TEAEs, and TEAEs leading to 


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study cream interruption or study discontinuation will also be tabulated. A summary of primary 
endpoint analyses is provided in Table 12.  
Table 12: 
Summary of Primary Endpoint Analyses 
Endpoint 
Population 
Treatment 
Population-Level 
Summary Metric 
Incidence of TEAEs, 
treatment-related TEAEs, 
serious TEAEs, Grade 3 or 
higher TEAEs 
FAS 
Ruxolitinib 1.5% BID cream 
Rate of TEAEs 
Incidence of TEAEs leading to 
study cream interruption or 
study discontinuation 
FAS 
Ruxolitinib 1.5% BID cream 
Rate of TEAEs 
Incidence of TEAEs 
summarized by Grades of AE 
FAS 
Ruxolitinib 1.5% BID cream 
Rates of TEAEs 
10.4.2. 
Secondary Analyses 
10.4.2.1. Clinical Laboratory Tests 
The clinical laboratory data will be analyzed using summary statistics.  
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory. The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. In addition, distributions of key laboratory 
parameters may be plotted over time; these values will also be classified into CTCAE toxicity 
grades and tabulated.  
10.4.2.2. Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature), height, and weight at each assessment 
time. Vital sign results will be reviewed for clinically notable abnormalities. 
10.4.3. 
Pharmacokinetic Analyses 
Descriptive analysis of PK concentration data will be performed by matrix (plasma and saliva), 
study period, and/or visit, using summary statistics such as, but not limited to, number of 
observations, mean, STD, minimum, median, maximum, geometric mean, geometric coefficient 
of variation, and/or empirical percentiles as deemed appropriate.  
Additional summaries may also be generated by subgroups such as geographical region, age, 
%BSA treated, and/or disease severity indices at baseline, as deemed appropriate. 
Table 13 summarizes all secondary endpoint analyses. 


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Table 13: 
Summary of Secondary Endpoint Analyses 
Endpoint 
Population 
Treatment 
Population-Level 
Summary Metric 
Change from baseline 
in vital signs 
FAS 
Ruxolitinib 1.5% BID cream 
Descriptive statistics and 
mean change from baseline 
Change from baseline 
in laboratory values 
FAS 
Ruxolitinib 1.5% BID cream 
Descriptive statistics and 
mean change from baseline 
Height 
FAS 
Ruxolitinib 1.5% BID cream 
Descriptive statistics 
Weight 
FAS 
Ruxolitinib 1.5% BID cream 
Descriptive statistics 
PK concentration 
PK evaluable 
Ruxolitinib 1.5% BID cream 
Descriptive statistics 
10.4.4. 
Exploratory Efficacy Analyses 
 
 
 
  
10.4.5. 
Exploratory Analysis of Relationship Between Hematology Laboratory Results 
and Trough Ruxolitinib Concentrations 
Exploratory descriptive and/or graphical analyses, as deemed appropriate, will be performed on 
the relationships between clinical laboratory test results of select hematology parameters such as 
platelet count, MPV, hemoglobin, and neutrophil count and the trough ruxolitinib concentration 
by visit. 
Graphical analyses will include line plots of the mean ± STD values of the laboratory test results 
(the measured value, the change from the baseline, and/or the percent change from the baseline) 
by visit grouped by the trough ruxolitinib concentration quartiles (or other ways of 
discretization) as deemed appropriate.  
The distribution of ruxolitinib concentrations versus the incidences and/or grade of severity of 
clinical laboratory CTCAE abnormalities in these hematology endpoints will be explored by the 
means of box-whisker plots or other types of visualization, as deemed appropriate. 
Additional grouping methods based on participant-level characteristics such as age, %BSA, 
and/or IGA, may also be attempted in these analyses, as deemed appropriate.  
A summary of all exploratory endpoint analyses is provided in Table 14. 


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Table 14: 
Summary of Exploratory Endpoint Analyses 
10.5. 
Interim Analysis 
No formal interim analysis is planned in this study. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol Amendments, ICF/assent, 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 and health authorities before the study is 
initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both health authorities 
and the IRB/IEC before implementation of changes made to the study design, except 
for changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC. Each investigator is responsible for enrolling participants who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study during the 
retention period 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. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study. As part of their responsibilities, the coordinating principal investigator will review the 
final CSR. Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system. The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF. The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements. Other data outside the EDC system required in the study conduct of 
the Protocol, such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and as designated by the sponsor, will have their own data flow 
management plans, study charters, or biomarker plans, as applicable. 
The sponsor (or designee) will be responsible for the following: 
• 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 the following: 
• 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. 


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• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail). Source data are, in general, all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data are contained in source 
documents (original records or certified copies).  
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed and 
available at the investigator's site. Examples of source documents are original 
documents, data, and records (eg, hospital records; electronic hospital records; 
clinical and office charts; laboratory notes; memoranda; participants' diaries or 
evaluation checklists; pharmacy dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiches; photographic negatives; microfilm or 
magnetic media; x-rays, participants' files; and e-records/records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in 
the clinical trial).  
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, 
depending on the study. Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, or copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor. 
− As required by privacy and data protection regulations and Incyte's privacy 
policies, if any photographs of participants are to be taken, the photographs must 
be limited to the area of the face or the body that is strictly necessary and the 
photographs should be masked (ie, identifying features such as eyes, mouth, scars, 
tattoos, or unique markings or features should be either obscured with a black bar 
or digitally pixelated so as to not permit the reidentification of the participants and 
preserve their confidentiality) by a specially designated photography vendor prior 
to sending the photographs to Incyte or any other third-party vendors for analysis 
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• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring: Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan. The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing: Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct. The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection: Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product. The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents. The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Quality Assurance 
The sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations). The sponsor or designee is responsible for the data management of this 
study, including quality checking of the data. Further, monitoring details describing strategy, 
including definition of study -critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical risk-
based monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues, Protocol deviations, and monitoring techniques (eg, central, remote, or 
on-site monitoring) are provided in the Clinical Monitoring Plan. 
Quality tolerance limits will be predefined in the Integrated Quality Risk Management Plan to 
identify systematic issues that can impact participants' safety, efficacy results and analysis, 
and/or reliability of study results. These predefined parameters will be monitored during the 
study and can be adjusted during the study upon data review. Important deviations from the 
quality tolerance limits and remedial actions taken, including reporting to IRBs/IECs and health 
authorities if applicable, will be summarized in the CSR. 
11.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations. The investigator and the sponsor or its designee are responsible for ensuring that 
personal information is handled in accordance with local data protection laws (including but not 
limited to HIPAA and GDPR) as applicable, and the sponsor operates comprehensive data 
privacy and data security programs that are applicable to this study. Appropriate notice, or notice 
and consent (as may be required by each applicable jurisdiction), for collection, use, disclosure, 




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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. 
11.7. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study cream development. 


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12. 
REFERENCES 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic 
dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol 
2014;70:338-351. 
Eucrisa (crisaborole) [prescribing information]. Pfizer Inc; April 2020. 
Food and Drug Administration. Draft Guidance on Pimecrolimus. March 2012. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl 
(Stockh) 1980;92:44-47. 
Hanifin JM, Reed ML, Eczema Prevalence and Impact Working Group. A population-based 
survey of eczema prevalence in the United States. Dermatitis 2007;18:82-91. 
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and 
severity index (EASI): assessment of reliability in atopic dermatitis EASI Evaluator Group. Exp 
Dermatol 2001;10:11-18. 
Harrop J, Chinn S, Verlato G, et al. Eczema, atopy and allergen exposure in adults: a 
population-based study. Clin Exp Allergy 2007;37:526-535. 
Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of 
the prevalence and impact of skin conditions. J Invest Dermatol 2014;134:1527-1534. 
Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis 
with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol 
2020a;145:572-582. 
Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream 
on pruritus and quality of life in atopic dermatitis: results from a phase 2, randomized, 
dose-ranging, vehicle- and active-controlled study. J Am Acad Dermatol 2020b;82:1305-1313.  
Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score 
tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol 
2015;172:1353-1357. 
Olumiant (baricitinib) [prescribing information]. Eli Lilly and Company; December 2021. 
Opzelura (ruxolitinib) [prescribing information]. Incyte Corporation; July 2022. 
Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the 
treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am 
Acad Dermatol 2021:85;863-872. 
Pruritus Resources. Numerical Rating Scale (NRS). Accessed December 6, 2021. 
http://www.pruritussymposium.de/numericalratingscale.html  
Rönmark EP, Ekerljung L, Lötvall J, et al. Eczema among adults: prevalence, risk factors and 
relation to airway diseases. Results from a large-scale population survey in Sweden. Br J 
Dermatol 2012;166:1301-1308. 


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Ruxolitinib cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Spergel JM. Epidemiology of atopic dermatitis and atopic march in children. Immunol Allergy 
Clin North Am 2010;30:269-280. 
Vinding GR, Zarchi K, Ibler KS, Miller IM, Ellervik C, Jemec GB. Is adult atopic eczema more 
common than we think? – A population-based study in Danish adults. Acta 
Derm Venereol 2014;94:480-482.  
Xeljanz (tofacitinib) [prescribing information]. Pfizer Inc; December 2021. 


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


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 that can achieve a failure 
rate of less than 1% per year when used consistently and correctly are considered as highly effective 
birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationd 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulationd  
− oral 
− injectable 
− implantablee 
• Intrauterine devicee 
• Intrauterine hormone-releasing systeme 
• Bilateral tubal occlusione 
• Vasectomized partnere,f 
• Sexual abstinencec 
a Documentation can come from the site personnel's review of the participant's medical records, medical 
examination, or medical history interview. 
b If the male participant has a partner with childbearing potential, the partner should also use contraceptives. 
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 Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may 
reduce the efficacy of the contraception method. 
e Contraception methods that in the context of this guidance are considered to have low user dependency. 
f Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the 
surgical success. 
Source: Clinical Trials Facilitation and Coordination Group 2020. 


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APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical trials. The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the study cream supply 
chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the trial. Because of this risk and 
in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines: 
The evolving situation of the pandemic may lead to further travel restrictions and isolation 
requirements that could impact the participant. Also, the investigator's benefit/risk assessment 
may determine it to be unsafe for participants to attend study visits at the investigational site. In 
such cases, the site staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video calls). At a minimum, a review of AEs, concomitant 
medications, and study cream compliance must be completed. Periodic on-site visits 
should be conducted whenever feasible, in particular the critical on-site visits outlined 
below. 
• No investigator-assessed efficacy evaluations (ie, %BSA, IGA, or EASI) can be 
performed via telemedicine (video call or phone call). 
• Laboratory sampling: No off-site laboratory sampling will be allowed. 
Critical On-Site Visits: 
The visits outlined below must be performed in person in order for the investigator to assess 
the participant's eligibility for the CT (screening and baseline) and LTS (Week 8) periods, and 
the participant's continued eligibility throughout the LTS period, even if the date that the 
participant eventually comes into the clinic deviates from the visit window.  
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic. Further instructions 
will be provided if needed. 


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During the CT period, the following visits must be performed in person: 
• Screening 
• Day 1 (Baseline) 
• Week 8  
During the LTS period, the participant may not miss consecutive on-site visits. For example, if 
the pandemic necessitates the participant to have a remote visit for Week 20, they could not also 
have a remote visit for Week 28. In addition, if a scheduled site visit is missed, if possible, the 
participant is encouraged to return to the clinic for an unscheduled visit prior to the next 
regularly scheduled Protocol-defined visit. 
Investigational Medicinal Product Dispensing 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 cream via 
shipment to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study cream 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant.  
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the site monitor will continue to employ off-site monitoring practices such as routine 
communication methods (eg, phone calls, e-mails, video visits) with the sites to get information 
on trial progress, subject status, and information on issue resolution. The study monitor may 
remotely review data entered into electronic systems such as the EDC for accuracy and 
completeness. If allowed by local regulations, remote source data verification may be 
implemented with agreement of the principal investigator and institution, as applicable. 
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 video 
visit. Alternatively, it may be performed by a pharmacist from the hospital pharmacy or by the 
study coordinator/data manager with suitable training. The study cream can be destroyed in 
accordance with local practices, or returned to the sponsor by the hospital pharmacy directly, 
with sponsor approval. 
Other Considerations  
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight. In such situations, the investigator is required to provide the 
local physician with a delegation letter listing all delegated activities. The sponsor, through the 


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Protocol INCB 18424-315 Am 1 
Version 2 
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VV-CLIN-017192 
CONFIDENTIAL 
study investigator or institution, will reimburse the local physician for the tests/procedures 
conducted outside of the standard of care. 
• In case of need, participants may refer to the local health care provider. Participants will 
be requested to obtain certified copies of the source data at the local health facility with 
the outcome of the contact and provide those to the investigator for appropriate oversight. 
The investigator/delegate will be requested to enter any relevant information into the 
EDC. 
• Should COVID-19–related restrictions be localized and have an effect on a limited 
number of sites, the affected sites may utilize direct contracting of third parties to support 
continuous study conduct (eg, home nursing services, couriers, etc). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [nearby] laboratory tests).  


Incyte Corporation 
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Protocol INCB 18424-315 Am 1 
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CONFIDENTIAL 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
30 NOV 2022 
Amendment 1 (30 NOV 2022) 
Overall Rationale for the Amendment 
The primary purpose of this amendment is to clarify that Day 1 serum chemistry and hematology 
testing will be performed only if the screening laboratory test date is more than 2 weeks before 
Day 1. Additional changes and clarifications are summarized below. 
1. Section 1, Protocol Summary (Table 3: Schedule of Activities: Continuous Treatment 
Period; Table 4: Schedule of Activities: Long-Term Safety Period); Section 6.1.1, Study 
Treatment Application Guidance; Section 8.4, Pharmacokinetic Assessments (Table 10: 
Pharmacokinetic Blood and Saliva Sample Timing) 
Description of change: Removed the requirement for all morning study cream applications 
to be performed at the site, and revised to allow participants to apply either of the 2 daily 
doses at the site after Day 1. 
Rationale for change: To allow flexibility in appointment time and to ease the burden on the 
participant and/or legal guardian. 
2. Section 1, Protocol Summary (Table 3: Schedule of Activities: Continuous Treatment 
Period); Section 8.3.5, Laboratory Assessments 
Description of change: Updated to clarify that Day 1 testing for serum chemistries and 
hematology will only be performed if the interval between Day 1 and the date of the 
screening laboratory tests is great than 2 weeks. 
Rationale for change: To clarify when Day 1 testing is required. 
3. Section 1, Protocol Summary (Table 3: Schedule of Activities: Continuous Treatment 
Period; Table 4: Schedule of Activities: Long-Term Safety Period) 
Description of change: Added an assessment for Itch NRS eDiary compliance. 
Rationale for change: To improve compliance of Itch NRS eDiary assessments. 
4. Section 1, Protocol Summary (Table 3: Schedule of Activities: Continuous Treatment 
Period); Section 8.4, Pharmacokinetic Assessments (Table 10: Pharmacokinetic Blood 
and Saliva Sample Timing) 
Description of change: Revised the timing of the PK blood draw from morning to any time 
prior to study drug application but at least 4 hours after the previous application of study 
cream. Also, provided guidance on blood draws from treated areas if no other acceptable 
blood draw areas are available. 
Rationale for change: To decrease participant burden by allowing flexibility in the 
appointment time and minimize missed PK assessments. 


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CONFIDENTIAL 
5. Section 3, Objectives and Endpoints (Table 5: Objectives and Endpoints) 
Description of change: Revised the exploratory endpoints for the evaluation of efficacy of 
ruxolitinib cream in adolescents with AD. Removed the Itch NRS score at each postbaseline 
visit, and add measurement timing for EASI scores, itch scores, and ITCH4. 
Rationale for change: To include the analysis of EASI scores and also the daily itch and 
Itch NRS responses at each postbaseline visit. 
6. Section 5.2, Exclusion Criteria (Criterion 12) 
Description of change: Deleted the exclusion criterion regarding the inability to draw blood 
for PK from any nonlesional areas. 
Rationale for change: To allow for drawing blood from a treated area provided the study 
cream is not applied at that area during the previous application. 
7. Section 6.2, Preparation, Handling, and Accountability 
Description of change: Revised study cream accountability at the conclusion of the study to 
reflect the process for handling remaining study cream for destruction at the site, or if local 
procedures do not allow on-site destruction, then shipment back to the sponsor is allowed. 
Rationale for change: To reflect the current procedure for sample accountability following 
completion of the study. 
8. Section 6.6, Concomitant Medications and Procedures 
Description of change: Clarified the timeframes to be followed for recording in the eCRF 
for non-AD medications and treatments and for AD medications and treatments. 
Rationale for change: To allow collection of prior AD medications and treatments for a 
12-month period. 
9. Section 6.6.2, Restricted Medications and Procedures; Section 6.6.3, Prohibited 
Medications and Procedures 
Description of change: Updated to allow the short-term use of systemic corticosteroids to 
treat acute AEs (eg, asthma) during the LTS period. 
Rationale for change: To allow for short-term treatment of a concomitant illness which has 
no impact on safety or efficacy. 
10. Section 8.1.5.2, Disease Characteristics and Treatment History 
Description of change: Added acceptable forms of documentation that can be used to collect 
prior medical history for the use of topical prescription treatments or when those treatments 
were not advisable. 
Rationale for change: To provide guidance to the sites on the acceptable documentation for 
prior AD medical history. 
11. Incorporation of administrative changes. Other regulatory guidance and administrative 
changes have been incorporated throughout the Protocol and are noted in the redline version 
of the amendment. 


Signature Page for VV-CLIN-017192 v3.0
Signature Page for VV-CLIN-017192 v3.0
Approval Task
Approver
 Biostatistics
30-Nov-2022 22:58:30 GMT+0000
Approval Task
Approver
 Clinical Research Scientist
30-Nov-2022 23:06:47 GMT+0000
Approval Task
Approver
 Inflammation &
01-Dec-2022 23:39:42 GMT+0000

SAP_001.pdf: 
Offici al Title:  
A P hase 3, O pe n -La bel, O ne -Year Safet y St u d y of R u x oliti ni b Crea m i n  
A d olesce nts ( A ges ≥ 1 2 Years t o < 1 8 Years) Wit h At o pic Der matitis  
N C T N u m ber:  
N C T 0 5 4 5 6 5 2 9  
D oc u me nt D ate:  
I N C B 1 8 4 2 4-3 1 5 Statistical A nal ysis Pla n 1 0 M A Y 2 0 2 4  
 
 
 




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V V -C LI N -0 2 6 6 9 1  
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  ..........................................................................................................5  
1.  
I N T R OD U C TI O N  ........................................................................................................6  
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 .................................7  
2. 1.  
Pr ot oc ol a n d Case Re p ort F or m Versi o n  ......................................................................7  
2. 2.  
St u d y O bjecti ves a n d E n d p oi nts  ...................................................................................7  
3.  
S T U D Y D E SI G N  .........................................................................................................8  
3. 1.  
Ra n d o mizati o n  ..............................................................................................................8  
3. 2.  
C o ntr ol of T y pe I Err or  .................................................................................................8  
3. 3.  
Sa m ple Size C o nsi derati o ns  .........................................................................................9  
3. 4.  
Sc he d ule of Assess me nts  ..............................................................................................9  
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  ....................................9  
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  .........................................................9  
4. 1. 1.  
Da y 1  .............................................................................................................................9  
4. 1. 2.  
St u d y Da y  .....................................................................................................................9  
4. 1. 3.  
Baseli ne Val ue  ..............................................................................................................9  
4. 1. 4.  
Ha n dli n g of Missi n g a n d I n c o m plete Dat es  ...............................................................1 0  
4. 2.  
Varia ble Defi niti o ns  ....................................................................................................1 0  
4. 2. 1.  
B o d y Mass I n d e x  ........................................................................................................1 0  
4. 2. 2.  
Pri or a n d C o nc o mita nt Me dicati o n  .............................................................................1 0  
5.  
S T A TI S TI C A L M E T H O D O L O G Y  ...........................................................................1 1  
5. 1.  
Ge neral Met h o d ol o g y  .................................................................................................1 1  
5. 2.  
Treat me nt Gr o u ps  .......................................................................................................1 1  
5. 3.  
A nal ysis P o p ulati o ns  ..................................................................................................1 1  
5. 3. 1.  
F ull A nal ysis Set  .........................................................................................................1 1  
5. 3. 2.  
P har mac o ki netic/ He m at ol o g y La b E val ua ble P o p ulati o n  ..........................................1 1  
5. 3. 3.  
L o n g -Ter m Safet y E val u a ble P o p ulati o n  ...................................................................1 1  
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 2  
6. 1.  
De m o gra p hics, Bas eli ne C haracteristics, a n d Disease Hist or y  ..................................1 2  
6. 1. 1.  
De m o gra p hics a n d Baseli ne C haract eristics  ...............................................................1 2  


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V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
6. 1. 2.  
Baseli ne Disease C haracteristics  ................................................................................1 2  
6. 1. 3.  
Pri or T hera p y f or At o pic Der matitis  ...........................................................................1 2  
6. 1. 4.  
Me dical Hist or y  ..........................................................................................................1 2  
6. 2.  
Dis p ositi o n of Partici pa nt  ...........................................................................................1 3  
6. 3.  
Pr ot oc ol De viati o ns  ....................................................................................................1 3  
6. 4.  
E x p os ure  .....................................................................................................................1 3  
6. 5.  
St u d y Dr u g C o m plia nce  .............................................................................................1 3  
6. 6.  
Pri or a n d C o nc o mita nt Me dicati o n  .............................................................................1 3  
7.  
E F FI C A C Y  .................................................................................................................1 4  
7. 1.  
Ge neral C o nsi derati o ns  ...............................................................................................1 4  
7. 2.  
Efficac y H y p ot heses  ...................................................................................................1 4  
7. 3.  
A nal ysis of E x pl orat or y Efficac y Para m eters  .............................................................1 4  
7. 3. 1.  
E x pl orat or y Effi cac y M eas ures  ..................................................................................1 4  
8.  
P H A R M A C O KI N E TI C S A N D P H A R M A C O D Y N A MI C S  .....................................1 7  
8. 1.  
P har mac o ki netic A n al yses  ..........................................................................................1 7  
9.  
S A F E T Y A N D T O L E R A BI LI T Y  ..............................................................................1 7  
9. 1.  
Ge neral C o nsi derati o ns  ...............................................................................................1 7  
9. 2.  
A d verse E v e nts  ...........................................................................................................1 7  
9. 2. 1.  
A d verse E v e nt Defi niti o ns  ..........................................................................................1 7  
9. 2. 2.  
A d verse E v e nt S u m maries  ..........................................................................................1 8  
9. 3.  
Cli nical La b orat or y Tests  ...........................................................................................1 9  
9. 3. 1.  
La b orat or y Val ue Defi niti o ns  .....................................................................................1 9  
9. 3. 2.  
La b orat or y Val ue S u m maries  .....................................................................................1 9  
9. 4.  
Vital Si g ns  ..................................................................................................................2 0  
1 0.  
I N T E RI M A N A L Y S E S ..............................................................................................2 1  
1 1.  
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  ........................2 1  
1 1. 1.  
C ha n ges t o Pr ot oc ol -Defi ne d A nal yses  ......................................................................2 1  


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C O N FI D E N TI A L  
1 1. 2.  
C ha n ges t o t he Statistical A nal ysis Pla n  .....................................................................2 1  
1 2.  
R E F E R E N C E S  ...........................................................................................................2 2  
A P P E N DI X  A.  P L A N N E D T A B L E S, FI G U R E S, A N D LI S TI N G S  ........................................2 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  .............................................................................................7  
Ta ble  2:  
I n v esti gat or's Gl o bal Ass ess me nt ...............................................................................1 5  
Ta ble  3:  
Ecze ma Area a n d Se v erit y I n d e x Sc ore C alc ulati o n  ..................................................1 5  
Ta ble  4:  
Criteria f or Cli nicall y N ota ble Vital Si g n A b n or malities f or A ge ≥ 1 2 t o 
<  1 6  Years  ...................................................................................................................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 A ge ≥ 1 6 t o 
<  1 8  Years  ...................................................................................................................2 0  
Ta ble  6:  
Statistical A nal ysis Pla n Versi o ns  ..............................................................................2 1  
 
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  ...................................................................................................8  
 


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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 D  
at o pic der matitis  
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 S A  
b o d y s urface area  
CI  
c o nfi de nce i nter val  
C R F  
case re p ort f or m  
C T  
c o nti n u o us treat me nt  
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  
E A SI  
Ecze ma Area a n d Se verit y I n de x  
E A SI 7 5  
≥ 7 5 % i m pr o ve me nt i n E A SI sc ore  
e C R F 
electr o nic case re p ort f or m  
E O T  
e n d of treat me nt  
E T  
earl y ter mi nati o n 
F A S  
f ull a nal ysis set 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
I G A 
I n vesti gat or's Gl o bal Assess me nt 
I G A-T S  
I n vesti gat or's Gl o bal Assess me nt Treat me nt S uccess (I G A sc ore of 0 or 1 wit h 
≥ 2  gra de i m pr o ve me nt fr o m baseli ne)  
I T C H 4 
≥ 4 -p oi nt i m pr o ve me nt i n I T C H sc ore 
L T S  
lo n g -ter m safet y 
L T S -E V  
l o n g-ter m safet y e val ua ble 
Me d D R A  
Me d ical Dict i o nary  fo r Re g u lato ry  Acti v ities 
M P V  
mea n platelet v ol u me  
N CI  
Nati o nal Ca ncer I nstit ue  
N R S  
n u m erical  rati ng  scale 
P K  
p har mac o ki netic(s)  
P T  
preferre d ter m  
S A P  
Statistical A nal ysis Pla n  
S O C  
s yste m or ga n class 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
W H O  
W orl d Healt h Or ga nizati o n   


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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 an  o pe n -la bel, 1-year safet y  st u d y wit h a n L T S peri o d. A d olesce nts  a ge d ≥ 1 2 t o 
<  1 8  y ears wit h A D f or at least 2 years a n d affecti n g 3 % t o 2 0 % B S A (e xcl u di n g t he scal p) pl us 
a t otal I G A sc ore of 2 or 3.  T he pri mar y p ur p ose of t his st u d y is t o c ollect a d diti o nal l o n g -ter m 
safet y data re gar di n g t he t y pes, se verit y, a n d fre q u e ncies of T E A Es occ urri n g i n a d olesce nts wit h 
A D w h o are treate d wit h r u x oliti ni b 1. 5 % crea m BI D.  
T he p ur p ose of t his S A P is t o pr o vi de details of t he statistical a nal yses t hat ha ve bee n o utli ne d i n 
t he I N C B 1 8 4 2 4 -3 1 5 Pr ot oc ol. T he sc o pe of t his pla n i ncl u des t he fi nal a nal yses t hat are pla n ne d 
a n d 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 De part me nt of 
Cli nical P har mac o ki netics or desi g nee will e xec ut e t he a nal ysis of P K.  


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1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
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 1 5  Pr ot oc ol A me n d me nt 1 date d 3 0 N O V  2 0 2 2 a n d C R Fs 
a p pr o ve d 1 2 J U N 2 0 2 3 . U nless s u perse d e 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 e 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  pres e nts t he o bje cti ves a n d e n d p oi nts.  
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 v al uate t he l o n g -ter m safet y a n d t olera bilit y of 
r u x oliti ni b crea m i n a d olesce nts wit h A D. 
I nci de nce of T E A Es, assesse d b y m o nit ori n g t he t y pe, 
fre q ue nc y, a n d se verit y of A Es. 
Sec o n d ar y  
T o f urt her e v al uate t he l o n g -ter m safet y a n d t olera bilit y 
of r u x oliti ni b crea m i n a d olesce nts wit h A D.  
C ha n ges i n vital si g ns, hei g ht, wei g ht, 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 c h aracterize t he P K of r u x oliti ni b crea m i n 
a d olesce nts wit h A D.  
Tr o u g h c o nce ntrati o ns of r u x oliti ni b at eac h 
p ost baseli ne visit.  
E x pl or at or y  
 


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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, o pe n -la bel, 1-year safet y st u d y of r u x oliti ni b crea m i n a d olesce nts (a g es 
≥ 1 2  years t o < 1 8 years) wit h A D w h ose diseas e is n ot a de q uatel y c o ntr oll e d wit h t o pical 
prescri pti o n t hera pies or w he n t h ose t hera pies are n ot a d visa ble.  
All partici pa nts will a p pl y r u x oliti ni b crea m at t he F D A -a p pr o ve d stre n gt h ( 1. 5 %) BI D usi n g t he 
sa me treat me nt para di g m as t he I N C B 1 8 4 2 4-3 0 3 a n d -3 0 4 P hase 3 A D st u d ies, na mel y starti n g 
wit h a n 8 -wee k C T peri o d d uri n g w hic h partici pa nts will treat all baseli ne A D lesi o ns, re gar dless 
of w het her or n ot t he lesi o n(s) i m pr o ve, f oll o we d b y a 4 4 -wee k L T S peri o d d uri n g w hic h 
partici pa nts will o nl y treat acti ve A D l esi o ns wit h t he sa me treat me nt re gi me n. Partici pa nts w h o 
c o m plete t he Wee k 8 ass ess me nts wit h n o safet y c o ncer ns a n d wit h % B S A affecte d b y A D n o 
greater t ha n 2 0 % will c o nti n ue i nt o t he L T S peri o d.  
Partici pa nts will ha ve a s afet y f oll o w -u p visit 3 0 t o 3 7 da ys f oll o wi n g t he e n d of treat me nt 
( Wee k 5 2/ E O T 2 or E T) t o e val uate safet y a n d d urati o n of res p o nse e xce pt f or partici pa nts w h o 
ha ve bee n i n a n o bser vati o n/ n o treat me nt c ycle wit h a t otal I G A sc ore of 0 fr o m Wee k 4 8 or 
earlier u ntil Wee k 5 2, f or w h o m t he Wee k 5 2/ E O T 2  visit will als o c o u nt as t he safet y f oll o w -u p 
visit.  
T he st u d y sc he ma is pres e nte d bel o w i n  Fi g ur e  1 . 
Fi g ure  1 : 
St u d y Desi g n Sc he m a  
 
3. 1.  
R a n d o miz ati o n  
N ot a p plica ble.  
3. 2.  
C o ntr ol of T y pe I Err or  
All statistical a nal yses f or effic ac y are e x pl orat or y i n nat ure; t heref ore, n o al p ha c o ntr ol will be 
i m ple me nte d i n t his st u d y. U nless ot her wise s pecifie d, all CIs pr o vi de d will be at t he 9 5 % 
c o nfi de nce le vel . 


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I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
3. 3.  
S a m ple Size C o nsi der ati o ns  
T he sa m ple size is bas e d o n t he e val uati o n of safet y a n d is n ot base d o n statistical p o wer 
calc ulati o ns.  
3. 4.  
Sc he d ule of Assess me nts  
Refer t o Pr ot oc ol A me n d me nt 1  date d 3 0 N O V 2 0 2 2 f or a f ull des cri pti o n of all st u d y pr oce d ures 
a n d assess me nt sc h e d ules f or t his st u d y.  
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 d ose of st u d y dr u g (r u x oliti ni b) is a p plie d t o t he partici pa nts.  
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 d ate –  Da y 1 d ate + 1).  
If t he visit/re p orti n g date is bef ore D a y 1, t he n t he st u d y da y at t he visit/rep orti n g date will be 
calc ulate d as  
Da y # = ( visit/re p orti n g d ate –  Da y 1 d ate).  
A st u d y da y of – 1 i n dicat es 1  da y bef ore Da y 1.  
4. 1. 3.  
B aseli ne V al ue  
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 pli cati o n of r u x oliti ni b 
crea m, u nless ot her wise defi ne d.  
W he n sc he d ul e d assess m e nts a n d u nsc he d ule d ass ess me nts occ ur o n t he s a me da y a n d t he 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 bas eli 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 t he da y of t h e first 
a p plicati o n a n d t he ti me is missi n g, use t he sc he d ule d assess me nt as bas eli 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 ass ess me nt is a vaila ble, use t he u ns c h e d ule d assess me nt as b as eli ne.  


I nc yte C or p orati o n 
Pa ge 1 0  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
4. 1. 4.  
H a n dli n g of Missi n g a n d I nc o m plete D ates  
I n g e neral, val ues f or missi n g dates will n ot be ha n dle d u nless met h o ds f or ha n dli n g missi n g 
dates are s pecifi e d i n t his secti o n or rele va nt secti o ns.  T he f oll o wi n g r ules will be use d f or 
ha n dli n g partial dates f or a nal yses re q uiri n g dates : 
•  If o nl y t he da y is missi n g, t he n t he 1 5 t h of t he m o nt h will be use d.  
•  If b ot h t he m o nt h a n d da y are missi n g, t he n 0 1 J U L of t he year will be use d. 
•  If t he dia g n osis date is c o m pletel y missi n g, t he n t he ti me si nce dia g n osis will n ot be 
calc ulate d.  
4. 2.  
V ari a ble Defi niti o ns  
T he f oll o wi n g varia bles will o nl y be calc ulate d if n ot re p orte d o n t he e C R F.  
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 o d y mass i n de x ( k g/ m 2) = [ wei g ht ( k g)] / [ hei g ht ( m)]2. 
4. 2. 2.  
Pri or a n d C o nc o mit a nt Me dic ati o n  
Pri or me dicati o n is defi n e d as a n y n o nst u d y me di cati o n starte d bef ore t h e first a p plicati o n of 
r u x oliti ni b crea m. 
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 hat is starte d a cc or di n gl y:  
•  Bef ore t he d ate of first a p plicati o n of r u x oliti ni b crea m  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 st u d y dr u g a p plicati o n.  
•  O n/after t he d ate of first a p plicati o n of r u x oliti ni b  crea m 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.  
A pri or me dicati o n c o ul d als o be classifie d as " b ot h pri or a n d c o n c o mita nt me dicati o n" if t he e n d 
date is o n or after first a p plicati o n of r u x oliti ni b crea m. I n t he listi n g, it will be i n dicate d w h et her 
a me dicati o n is o nl y pri or, o nl y c o nc o mita nt, or b ot h pri or a n d c o nc o mita nt.  
F or t he p ur p os es of a n al 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 n e q ui v ocall y be defi ne d as n ot c o nc o mita nt. 


I nc yte C or p orati o n 
Pa ge 1 1  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
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V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
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, C ar y, N C; v 9 or later) will be us e d 
f or t he ge n erati 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 di a n, mi ni m u m, a n d ma xi m u m. Descri pti ve s u m maries f or cate g orical 
varia bles will i ncl u de t he n u m ber a n d perce nt a 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 n o pe n -la bel, si n gle treat me nt gr o u p st u d y. Partici pa nts will be s u m marize d o verall b y 
t otal o nl y. 
5. 3.  
A n al ysis P o p ul ati o ns  
5. 3. 1.  
F ull A n al ysis Set  
T he F A S 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. 
T he F A S will be use d f or t he s u m mar y of de m o gr a p hics, baseli ne c haracteristics, partici pa nt 
dis p ositi o n, a nal yses of all efficac y data, a n d s afet y f or t he C T peri o d a n d f or t he w h ole st u d y as 
well.  
5. 3. 2.  
P h ar m ac o ki netic/ H e m at ol o g y L a b E v al u a ble P o p ul ati o n  
T he P K -e val u a 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 d e d at least 1  p ost baseli ne P K sa m ple ( 1 P K meas ure me nt).  
T he he mat ol o g y la b e v al 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, pr o vi de d t he baseli ne he m at ol o g y bl o o d sa m ple, a n d at least 1  p ost baseli ne 
he mat ol o g y bl o o d sa m ple ( 1 he mat ol o g y meas ure me nt).  
T he P K/ he mat ol o g y la b e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o are b ot h P K 
e val ua ble a n d he mat ol o g y la b e val ua ble.  
5. 3. 3.  
L o n g -Ter m S afet y E v al u a ble P o p ul ati o n  
All partici pa nts w h o a p plie d  r u x oliti ni b crea m at l east o nce d uri n g t he L T S peri o d will c o nstit ute 
t he L T S-E V p o p ulati o n. All safet y a nal yses f or t h e L T S peri o d will be c o n d ucte d wit h t he 
L T S -E V p o p ulati o n.  


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C O N FI D E N TI A L  
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 data dis pla ys. 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.  
De m o gr a p hics, B aseli ne C h ar acteristics, a n d Dise ase Hist or y  
6. 1. 1.  
De m o gr a p hics a n d B aseli ne C h ar acteristi cs  
T he f oll o wi n g de m o gra p hics a n d baseli ne c haract eristics will be s u m marize d f or t he F A S: a ge, 
se x, race, et h nicit y, wei g ht, hei g ht, a n d B MI. 
6. 1. 2.  
B aseli ne Dise ase C h ar acteristi cs  
T he f oll o wi n g baseli ne disease c h aracteristics will be s u m marize d f or t he F A S:  
•  B aseli ne I G A sc ore ( 2 or 3)  
•  Baseli ne faci al I G A sc ore  
•  Baseli ne E A SI sc ore  
•  Baseli ne Itc h N R S  ( b y-visit, dail y)  
•  Ti me ( years) si nce first o nset of A D  
•  Pri or hist or y of ast h ma ( n o/ yes)  
•  Pri or aller gies (f o o d, e n vir o n me ntal; n o/ yes)  
•  Hist or y of c o ntact der matitis ( n o/ yes) 
•  C o m m o n c o m plicati o ns of A D  
•  Ti me si nce o nset of c urre nt A D e pis o de  
•  N u m ber of A D e pis o des/flare o v er t he last 1 2 m o nt hs  
•  Pri or t hera p y f or A D gi v e n i n t he past 1 2 m o nt hs ( n o/ yes)  
•  T otal % B S A i n v ol ve me nt i n c urre nt A D e pis o de  
•  Faci al a n d/ or nec k i n v ol ve me nt d uri n g past e pis o d es/flares ( n o/ y es)  
•  A vera g e d urati o n of e pis o des/flares  
6. 1. 3.  
Pri or T her a p y f or At o pic Der m atitis  
Pri or t hera pies f or A D, i ncl u di n g me dicati o n a n d ot her t y pes of t hera pies, d uri n g t he past 
1 2  m o nt hs will be c o de d usi n g t he W H O Dr u g Di cti o nar y a n d s u m marize d. T he t y pe of 
treat me nt a n d reas o n f or disc o nti n uati o n will be s u m marize d as w ell. 
6. 1. 4.  
Me dic al Hist or y  
F or partici pa nts i n t he F A S, me dical hist or y will be s u m marize d. T his s u m mati o n will i ncl u de 
t he n u m ber a n d perce nta ge of partici p a nts wit h me dical hist or y e ve nt f or eac h b o d y 
s yste m/ or ga n class as d o c u me nte d o n t he e C R F. 


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C O N FI D E N TI A L  
6. 2.  
Dis p ositi o n of P artici p a nt  
T he n u m ber a n d p erce nta ge of partici p a nts w h o w ere tr eate d, w h o c o m plet e d C T peri o d, w h o 
disc o nti n ue d st u d y treat me nt, or w h o wit h dra w fr o m  t he st u d y d uri n g t he C T peri o d wit h a 
pri mar y reas o n f or disc o nti n uati o n will be s u m marize d a n d liste d f or t he F A S  p o p ulati o n d uri n g 
t he C T peri o d. 
T he n u m ber a n d p erce nta ge of partici p a nts w h o w ere tr eate d, w h o c o m plet e d L T S peri o d, w h o 
disc o nti n ue d st u d y treat me nt, or w h o wit h dra w fr o m t he st u d y d uri n g t he L T S peri o d wit h a 
pri mar y reas o n f or disc o nti n uati o n will be s u m marize d a n d liste d f or t he L T S -E V  p o p ulati o n 
d uri n g t he L T S peri o 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 marize d a n d liste d  f or t he C T  a n d L T S peri o ds se paratel y.  
6. 4.  
E x p os ure  
F or partici pa nts i n t he F A S a n d L T S -E V p o p ulati o ns, descri pti ve statistics will be pr o vi de d f or 
d urati o n of treat me nt  (ie, t he a vera ge dail y a m o u nt of crea m a p plie d  [g ], a n d t he t otal a m o u nt of 
crea m a p plie d  [g ]), res p ecti vel y. D urati o n of treat me nt wit h r u x oliti ni b crea m is defi ne d as t he 
n u m ber of da ys fr o m Da y 1 t o t he date of last rec or d of r u x oliti ni b crea m a p plicati o n.  
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  d uri n g t he C T a n d L T S peri o d 
will be calc ulate d as f oll o ws:  
O verall 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 u all y a p plie d d uri n g t he st u d y a n d t he t otal n u m ber of i nte n d e d a p plicati o ns is t he 
n u m ber of da ys i n treat me nt –  t he n u m ber of d a ys wit h a n a p pr o ve d i nterr u pti o n. 
6. 6.  
Pri or a n d C o nc o mit a nt Me dic ati o n  
F or par ticip a nts in  th e F A S  p o p u latio n  d ur in g  th e C T per io d,  pr ior  a n d c o n c om ita nt m e dicatio ns  
w ill be  c ode d  us in g  the  W H O  D r u g D ictio n ar y an d  s um m arize d as n u m b er a n d pe rcen ta ge o f 
parti ci pa nts wi th  pr io r a n d c o nc om itan t m e dicatio ns  b y W H O  dr u g c lass  a n d W H O  dr u g term. 
A d diti o nall y, se parate pri or A D t hera p y will als o be s u m marize d f or t he F A S p o p ulati o n . 
F or p articip a n ts in  the  L T S per io d,  o n ly  c on c om ita nt m ed icatio ns  wi ll be s u m m arized . 


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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 data dis pla ys. 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  
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 v aila ble.  
7. 2.  
Effic ac y H y p ot heses  
N ot a p plica ble.  
7. 3.  
A n al ysis of E x pl or at or y Effic ac y P ar a meters  
All efficac y a n al yses are e x pl orat or y. He nce, n o p -val ues will be pr o vi de d, a n d m ulti ple 
a dj ust me nts will n ot be ma de.  
7. 3. 1.  
E x pl or at or y Effic ac y Me as ures  


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I nc yte C or p orati o n 
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V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  


I nc yte C or p orati o n 
Pa ge 1 7  of 3 0  
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V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
8.  
P H A R M A C O KI N E TI C S A N D P H A R M A C O D Y N A MI C S  
8. 1.  
P h ar m ac o ki netic A n al yses  
Tr o u g h plas ma c o nce ntrati o ns of r u x oliti ni b at 2  visits d uri n g t he C T peri o d will be s u m marize d 
usi n g descri pti ve statistics b y visit. Mea n tr o u g h plas ma c o nce ntrati o ns of r u x oliti ni b will be 
calc ulate d f or eac h i n di vi d ual a n d t he n s u m marize d usi n g descri pti ve statistics.  
Tr o u g h sali va c o nce ntrati o ns of r u x oliti ni b at 3 visits d uri n g t he C T peri o d a n d at 6 visits d uri n g 
t he L T S peri o d will be s u m marize d usi n g descri pti ve statistics b y visit. Mea n tr o u g h sali va 
c o nce ntr ati o ns of r u x oliti ni b will be calc ulate d f or eac h i n di vi d ual b y peri o d a n d t he n 
s u m marize d usi n g descri pti ve statistics.  
9.  
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 data dis pla ys. Sa m ple data dis pla ys are i ncl u de d i n a se para te 
d oc u me nt.  
9. 1.  
Ge ner al C o nsi der ati o ns  
S u m mar y ta bles ma y be re place d wit h listi n gs w he n a p pr o priate. F or i nsta nce, a n A E fre q u e 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 u e preferre d ter ms re p orte d o n 
relati vel y fe w partici pa nts.  
U nless ot her wise state d, t a ble s u m maries will be li mite d t o A Es occ urri n g wit hi n 3 0 da ys after 
t he last a p plicati o n of r u x oliti ni b crea m. 
9. 2.  
A d verse E ve nts  
9. 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 t he 
first a p plicati o n of st u d y dr u g u ntil 3 0  da ys after t he last a p plicati o n of st u d y dr u g . A nal ysis of 
A Es (as disc usse d b el o w) will be li mite d t o T E A Es, b ut data listi n gs will i ncl u de all A Es 
re gar dl ess of t heir ti mi n g i n relati o n t o st u d y 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 N CI C T C A E v 5. T he C T C A E re p orti n g g ui deli nes a n d gra di n g d etails are a vaila ble o n 
t he Ca ncer T h era p y E val uati o n Pr o gra m we bsite. 
T he s u bset of A Es c o nsi d ere 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 rel ati 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. The i nci de n ce of A Es a n d 
treat me nt-relate d A Es will be ta b ulate d. I n a d diti o n, seri o us T E A Es will als o be ta b ulate d. 
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 v erit 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 -relate d. 
•  A n u nres ol ve d missi n g se verit y will be i de ntifie d as a n u n k n o w n se v erit y.  


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F or p ur p os es of a n al 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 n a p plicati o n site reacti o n is a n A E t hat occ urs s olel y at o ne or m ore sites of r u x oliti ni b crea m 
a p plicati o n a n d c o ul d be relate d t o a p plicati o n of r u x oliti ni b crea m. A  s u m mar y of A S Rs will be 
pr o vi de d.  
9. 2. 2.  
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 peri o d will i ncl u de t he f oll o wi n g:  
•  N u m ber ( %) of partici pa nts w h o ha d a n y T E A Es  
•  N u m ber ( %) of partici pa nts w h o ha d a n y A S Rs  
•  N u m ber ( %) of partici pa nts w h o ha d a n y seri o us T E A Es  
•  N u m ber ( %) of partici pa nts w h o ha d a n y Gra de 3 or hi g her T E A Es  
•  N u m ber ( %) of partici pa nts w h o ha d a n y treat me nt -relate d T E A Es 
•  N u m ber ( %) of partici pa nts w h o te m p oraril y i nterr u pte d r u x oliti ni b crea m 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 r u x oliti ni b crea m beca us e 
of T E A Es  
•  N u m ber ( %) of partici pa nts w h o ha d a fat al T E A E  
S u b gr o u p a nal ysis (se x, race, et h nicit y) f or o verall T E A Es will als o be pr o vi de d.  
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 or fe wer partici pa nts  a p p ear 
i n a ta ble, a listi n g ma y be a p pr o pri ate): 
•  S u m mar y of T E A Es b y Me d D R A S O C a n d P T  
•  S u m mar y of T E A Es b y Me d D R A P T i n decreasi n g or der of fre q u e nc y  
•  S u m mar y of A S Rs b y Me d D R A P T i n decreasi n g or der of fre q u e nc y  
•  S u m mar y of Gra d e 3 or hi g her T E A Es b y Me d D R A S O C a n d P T  
•  S u m mar y of Gra d e 3 or hi g her T E A Es b y Me d D R A P T i n decreasi n g or der of 
fre q ue n c y 
•  S u m mar y of seri o us T E A Es b y Me d D R A S O C a n d P T  
•  S u m mar y of seri o us T E A Es b y Me d D R A P T i n decreasi n g or der of fre q u e nc y  
•  S u m mar y of treat me nt-relate d T E A Es b y Me d D R A 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 u e n c y 
•  S u m mar y of Gra d e 3 or hi g her treat me nt -relate d T E A Es b y Me d D R A 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 Me d D R A 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 M e d D R A S O C a n d P T  


I nc yte C or p orati o n 
Pa ge 1 9  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
•  S u m mar y of T E A Es lea di n g t o r u x oliti ni b crea m d ose i nterr u pti o n b y Me d D R A S O C 
a n d P T 
•  S u m mar y of T E A Es lea di n g t o disc o nti n uati o n of r u x oliti ni b crea m b y Me d D R A 
S O C a n d P T  
S u b gr o u p  a nal ysis (se x, r ace, et h nicit y) f or T E A Es b y Me d D R A P T will als o be pr o vi de d.  
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  
•  N o n mela n o ma s ki n ne o plas ms  
•  Li ver f u ncti o n test ele v ati o ns  
•  Mali g na ncies  
•  Maj or A d vers e Car di o vasc ular E ve nts  
•  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 v ate d mea n platel et v ol u me  
9. 3.  
Cli nic al L a b or at or y Tests  
9. 3. 1.  
L a b or at or y V al ue Defi niti o ns  
All la b orat or y assess me nts will be perf or me d usi n g a ce ntr al la b orat or y e xce pt f or uri ne 
pre g na nc y t ests (as a p pli ca ble). L a b orat or y val ues a n d c ha n g e fr o m bas eli ne val ues will be 
s u m marize 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.  
Baseli ne will be deter mi ne d acc o r di n g t o Secti o n 4. 1. 3 . If t here are m ulti ple val ues t hat meet t he 
criteria f or baseli ne, t h e val ue fr o m t he ce ntral la b orat or y has pri orit y o ver t he val ue fr o m t he 
l ocal la b orat or y. T h ereaft er, a d diti o nal r ules may b e pr o vi de d after c o ns ultati o n wit h t he me dical 
m o nit or t o deli neate w hic h val ue will be defi ne d as baseli ne.  
9. 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. If s pecifi c safet y iss ues arise, a d diti o nal u nsc he d ule d la b orat or y 
tests/a nal yses ma y be perf or me d at t he discreti o n of t he i n vesti gat or. 
All test res ults a n d ass oci ate d n or mal ra n ges fr o m ce ntral la b orat ories will be re p ort e d i n SI 
u nits. All tests wi t h n u meric val ues will ha ve a u ni q ue u nit per test. A n y la b orat or 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 2 0  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
W he n t here are m ulti ple la b orat or y n o n missi n g val ues f or a p artici pa nt's partic ular test wit hi n a 
visit wi n d o w, t he la b orat or y val ue wit h t he s mallest la b orat or y se q ue n ce n u m ber will be use d i n 
b y -visit s u m maries.  
F or test r es ults t hat will be s u m marize d wit h a vaila ble n or mal ra n ges, t he n u m ber a n d perce nt a ge 
of partici pa nts wit h la b orat or y val ue s bei n g l o w, n or mal, hi g h, 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 his s hift s u m mar y 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 i n t he C T peri o d, as well as t he L T S peri o d f or t he L T S -E V p o p ulati o n . S hift ta bles 
will be prese nte d s h o wi n g t he c ha n ge i n C T C A E gra de fr o m baseli ne t o w orst gra de p ost bas eli ne 
as well. T he de n o mi nat or f or t he perce nta ge calc ul ati o n will use t he n u m ber of partici pa nts i n t he 
baseli ne cat e g or y.  
9. 4.  
Vit al Si g ns  
Val ues at e ac h sc h e d ule d visit, c ha n ge, a n d perc e nta ge c ha n g e fr o m b aseli 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, t e m perat ure, a n d res pirat or y 
rate will be s u m marize d descri pti vel y. Hei g ht a n d wei g ht val ues at eac h sc he d ule d visit, c ha n ge, 
a n d perce nta ge c h a n g e fr o m baseli ne f or hei g ht a n d wei g ht will be s u m marize d descri pti vel y.  
Criteria f or cli nic all y n ota ble vital si g n a b n or malities are d efi ne d i n  Ta bl e  4  a n d Ta ble  5 . T h e 
a b n or mal val ues f or parti ci 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 b y a ge gr o u p. Alert vital si g ns are defi ne d as a n a bs ol ute val ue o utsi d e t he defi ne d n or mal 
ra n ge a n d p erce nta g e c ha n ge great er t ha n  2 5 %. T h e a b n or ma l val u es f or p artici pa nts e x hi biti n g 
alert vital si g n a b n or malities will be liste d.  
T a ble  4 : 
Criteri a f or Cli nic all y N ot a ble Vit al Si g n A b n or m alities f or A ge ≥ 1 2 t o 
<  1 6  Ye ars  
P a ra meter  
Hi g h  T hres h o l d 
L o w T hres h o ld  
S y sto lic b l o od p ress ure 
> 1 3 1 m m H g  
< 1 1 0 m m H g  
D iasto lic b lo o d p ressu re 
> 8 3 m m H g  
< 6 4 m m H g  
P u lse 
> 1 0 0 b p m  
< 6 0 b p m  
Te m p erat u re 
> 3 8. 0º C  
< 3 5. 5º C  
Res p irato r y rate 
> 2 0 breat hs/ mi n  
< 8 breat hs/ mi n  
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 alities f or A ge ≥ 1 6 t o 
<  1 8  Ye ars  
P a ra meter  
Hi g h  T hres h o l d 
L o w T hres h o ld  
S y sto lic b l o od p ress ure 
> 1 2 0 m m H g  
< 9 0 m m H g  
D iasto lic b lo o d p ressu re 
> 8 5 m m H g  
< 5 0 m m H g  
P u lse 
> 1 0 0 b p m  
< 4 5 b p m  
Te m p erat u re 
> 3 8. 0º C  
< 3 5. 5º C  
Res p irato r y rate 
> 2 0 breat hs/ mi n  
< 8 breat hs/ mi n  


I nc yte C or p orati o n 
Pa ge 2 1  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
1 0.  
I N T E RI M A N A L Y S E S 
N o f or mal i nteri m a nal ysis is pla n ne d f or t his st u d y.  
1 1.  
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  
A ll versi o ns of t he S A P are liste d i n Ta ble  6 . 
T a ble  6 : 
St atistic al A n al ysis Pl a n Versi o ns  
S A P Versi o n  
D ate  
Ori gi nal  
1 0  M A Y  2 0 2 4  
1 1. 1.  
C h a n ges t o Pr ot oc ol -Defi ne d A n al yses  
N ot a p plica ble.  
1 1. 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 2 2  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
1 2.  
R E F E R E N C E S  
F o o d a n d Dr u g A d mi nistrati o n. Draft G ui da nce o n Pi mecr oli m us. Marc h 2 0 1 2.  
Ha nifi n  J M, T h urst o n M, O m ot o M, C herill R, T ofte SJ, Grae b er M. T he ecze ma area a n d 
se verit y i n de x ( E A SI): assess me nt of relia bilit y i n at o pic der matitis E A SI E val uat or Gr o u p. E x p 
Der mat ol 2 0 0 1; 1 0: 1 1 -1 8.  
Les he m  Y A, H ajar T, Ha nifi n J M, Si m ps o n E L. W hat t he Ecze ma Area a n d Se verit y I n de x sc ore 
tells us a b o ut t he se verit y of at o pic der m atitis: a n i nter preta bilit y st u d y. Br J Der mat ol 
2 0 1 5; 1 7 2: 1 3 5 3 -1 3 5 7.


I nc yte C or p orati o n 
Pa ge 2 3  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
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, FI G U R E S, A N D LI S TI N G S  
T h is ap p en d ix  p ro v id es a  list of  the  p lan n ed  tab les, fig u res, an d  listi ng s fo r t he C li nical St u d y 
R ep o rt. St an d ard  tab les w ill fo llo w  the  co n v en tio ns  in  the  St an d ard  S afety  T ab les v 1. 6.  
T he  lists of  tab les, fig u re s, an d  listi ng s are to  b e u sed  as g u id elin es. M o dificati o ns of t he lists t hat 
d o n ot ot her wise affect t h e nat ure of t he a n al ysis will n ot warra nt a n a m e n d me nt t o t he S A P.  
T a bles  
T a ble N o.  
Title  
P o p ul ati o n  
B aseli ne a n d De m o gr a p hics C h ar a cteristics  
1. 1 Dis p ositi o n  
1. 1. 1  
A nal ysis P o p ulati o ns  
F A S  
1. 1. 2. 1  
S u m mar y of Partici pa nt Dis p ositi o n i n t he C T  Peri o d  
F A S  
1. 1. 2. 2  
S u m mar y of Partici pa nt Dis p ositi o n i n t he L T S Peri o d  
L T S -E V  
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  
1. 1. 4. 1  
S u m mar y of Pr ot oc ol De viati o ns f or t he C T  Peri o d  
F A S  
1. 1. 4. 2  
S u m mar y of Pr ot oc ol De viati o ns f or t he L T S Peri o d  
L T S -E V  
1. 2 De m o gr a p h y a n d B aseli n e C h ar a cteristics  
1. 2  
S u m mar y of De m o gra p hics a n d Baseli ne C haracteristics  
F A S  
1. 3 B aseli ne Dise ase C h ar acteristics  
1. 3  
S u m mar y of Baseli ne Disease C haracteristics  
F A S  
1. 4 Pri or Me dic ati o n a n d C o nc o mit a nt Me dic ati o n  
1. 4. 1  
S u m mar y of Pri or Me dicati o ns  
F A S  
1. 4. 2  
S u m mar y of Pri or Me dicati o ns f or At o pic Der matitis  
F A S  
1. 4. 3. 1  
S u m mar y of C o nc o mita nt Me dicati o ns i n t he C T Peri o d  
F A S  
1. 4. 3. 2  
S u m mar y of C o nc o mita nt Me dicati o ns i n t he L T S Peri o d  
L T S -E V  
1. 5 + Ot hers  
1. 5  
S u m mar y of Ge n eral Me dical Hist or y  
F A S  
Effic ac y  
2. 1 I G A 
2. 1. 1 . 1 
S u m mar y of Partici pa nts Ac hie vi n g I G A -T S b y Visit  
F A S  
2. 1. 1. 2   
S u m mar y of Partici pa nts i n Eac h Cate g or y of I G A Sc ore b y Visit  
F A S  
2. 1. 1. 3   
S u m mar y of Partici pa nts Ac hie vi n g a n I G A sc ore of 0 or 1 b y Visit  
F A S  
2. 1. 1. 4   
S u m mar y of Partici pa nts Ac hie vi n g a F acial I G A sc ore of 0 or 1 b y 
Visit  
F A S  
2. 2 E A SI  
2. 2. 1  
S u m mar y of Partici pa nts Ac hie vi n g E A SI 7 5 b y Visit D uri n g t he 
Treat me nt Peri o d  
F A S  
2. 2. 2  
S u m mar y of E A SI Sc ore b y Visit D uri n g t he Treat me nt Peri o d  
F A S  
2. 3 Itc h N R S Sc ore 
2. 3. 1  
S u m mar y of Partici pa nts Ac hie vi n g ≥ 4 -P oi nt I m pr o ve me nt i n Itc h 
N R S Sc ore b y Visit D uri n g t he Treat me nt Peri o d  
F A S wit h b aseli ne Itc h 
N R S sc ore ≥ 4  
2. 3. 2  
S u m mar y of B y -Visit Itc h N R S Sc ore  
F A S  
2. 3. 3  
S u m mar y of Partici pa nt Ac hie vi n g ≥ 4 -P oi nt I m pr o ve me nt i n Dail y 
Itc h N R S Sc ore  
F A S wit h baseli ne Itc h 
N R S sc ore ≥ 4  
2. 3. 4  
S u m mar y of Dail y Itc h N R S Sc ore  
F A S  


I nc yte C or p orati o n 
Pa ge 2 4  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
T a ble N o.  
Title  
P o p ul ati o n  
2. 4 B S A  
2. 4 . 1 
S u m mar y a n d A nal ysis of T otal % B S A Affecte d b y A D  
F A S  
S afet y  
3. 1 E x p os ure  
3. 1. 1. 1  
S u m mar y of E x p os ure i n t he C T  Peri o d  
F A S  
3. 1. 1. 2  
S u m mar y of E x p os ure i n t he L T S Peri o d  
L T S -E V  
3. 1. 1. 3  
S u m mar y of E x p os ure fr o m Baseli ne t o Wee k 5 2  
F A S  
3. 1. 2  
S u m mar y of St u d y Dr u g C o m plia nce i n t he C T Peri o d  
F A S  
3. 1. 3  
S u m mar y of St u d y Dr u g C o m plia nce i n t he L T S Peri o d  
L T S -E V  
3. 2 A d verse E ve nts  
3. 2. 1. 1. 1  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he C T 
Peri o d  
F A S  
3. 2. 1. 1. 2  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he C T 
Peri o d b y Se x  
F A S  
3. 2. 1. 1. 3  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he C T 
Peri o d b y Race  
F A S  
3. 2. 1. 1. 4  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he C T 
Peri o d b y Et h nicit y  
F A S  
3. 2. 1. 2. 1  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he L T S 
Peri o d  
L T S -E V  
3. 2. 1. 2. 2  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he L T S 
Peri o d b y Se x  
L T S -E V  
3. 2. 1. 2. 3  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he L T S 
Peri o d b y Race  
L T S -E V  
3. 2. 1. 2. 4  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts i n t he L T S 
Peri o d b y Et h nicit y  
L T S -E V  
3. 2. 1. 3. 1  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Fr o m 
Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1. 3. 2  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Fr o m 
Bas eli ne t o Wee k 5 2 b y Se x  
F A S  
3. 2. 1. 3. 3  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Fr o m 
Baseli ne t o Wee k 5 2 b y Race  
F A S  
3. 2. 1. 3. 4  
O verall S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Fr o m 
Baseli ne t o Wee k 5 2 b y Et h nicit y  
F A S  
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 i n t he C T Peri o d  
F A S  
3. 2. 2. 2  
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 i n t he L T S Peri o d  
L T S -E V  
3. 2. 2. 3  
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 Fr o m Baseli ne t o Wee k 5 2  
F A S  
3. 2. 3. 1. 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 i n t he C T Peri o d  
F A S  
3. 2. 3. 1. 2  
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 i n t he C T Peri o d b y 
Se x  
F A S  
3. 2. 3. 1. 3  
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 i n t he C T Peri o d b y 
Race  
F A S  


I nc yte C or p orati o n 
Pa ge 2 5  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
T a ble N o.  
Title  
P o p ul ati o n  
3. 2. 3. 1. 4  
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 i n t he C T Peri o d b y 
Et h nicit y  
F A S  
3. 2. 3. 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 
Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y i n t he L T S Peri o d  
L T S -E V  
3. 2. 3. 2. 2  
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 
Preferr e d Ter m i n Decreasi n g Or der of Fre q ue nc y i n t he L T S Peri o d 
b y Se x  
L T S -E V  
3. 2. 3. 2. 3  
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 i n t he L T S Peri o d 
b y Race  
L T S -E V  
3. 2. 3. 2. 4  
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 i n t he L T S Peri o d 
b y Et h nicit y  
L T S -E V  
3. 2. 3. 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 Fr o m Baseli n e t o 
Wee k 5 2  
F A S  
3. 2. 3. 3. 2  
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 Fr o m Baseli ne t o 
Wee k 5 2 b y Se x  
F A S  
3. 2. 3. 3. 3  
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 Decre asi n g Or der of Fre q ue nc y Fr o m Baseli ne t o 
Wee k 5 2 b y Race  
F A S  
3. 2. 3. 3. 4  
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 Fr o m Baseli ne t o 
Wee k 5 2 b y Et h nicit y  
F A S  
3. 2. 3. 4. 1  
S u m mar y of A p plicati o n Site Reacti o ns b y Me d D R A Preferre d  Ter m 
i n Decreasi n g Or der of Fre q ue nc y i n t he C T Peri o d 
F A S  
3. 2. 3. 4. 2  
S u m mar y of A p plicati o n Site Reacti o ns b y Me d D R A Preferre d  Ter m 
i n Decreasi n g Or der of Fre q ue nc y i n t he L T S Peri o d 
L T S -E V  
3. 2. 3. 4. 3  
S u m mar y  of A p plicati o n Site Reacti o ns b y Me d D R A Preferre d  Ter m 
i n Decreasi n g Or der of Fre q ue nc y Fr o m Baseli ne t o Wee k 5 2 
F A S  
3. 2. 4. 1  
S u m mar y of Gra d e 3 or Hi g her 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 i n t he C T 
Peri o d  
F A S  
3. 2. 4. 2  
S u m mar y of Gra d e 3 or Hi g her 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 i n t he L T S 
Peri o d  
L T S -E V  
3. 2. 4. 3  
S u m mar y of Gra d e 3 or Hi g her 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 fr o m Baseli ne 
t o Wee k 5 2 
F A S  
3. 2. 5. 1  
S u m mar y of Gra d e 3 or Hi g her 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 i n t he 
C T Peri o d  
F A S  
3. 2. 5. 2  
S u m mar y of Gra d e 3 or Hi g her Treat me nt -E mer ge nt A d ve rse 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 i n t he 
L T S Peri o d  
L T S -E V  
3. 2. 5. 3  
S u m mar y of Gra d e 3 or Hi g her 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 Fr o m 
Baseli ne t o Wee k 5 2  
F A S  


I nc yte C or p orati o n 
Pa ge 2 6  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
T a ble N o.  
Title  
P o p ul ati o n  
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 i n  t he C T Peri o d  
F A S  
3. 2. 6. 2  
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 i n t he L T S Peri o d  
L T S -E V  
3. 2. 6. 3  
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 Fr o m Baseli ne t o 
Wee k 5 2  
F A S  
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 o f Fre q ue nc y i n t he C T 
Peri o d  
F A S  
3. 2. 7. 2  
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 i n t he 
L T S Peri o d  
L T S -E V  
3. 2. 7. 3  
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 Fr o m 
Baseli ne t o Wee k 5 2  
F A S  
3. 2. 8. 1  
S u m mar y of Treat me nt -Relate d 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 i n t he C T 
Peri o d  
F A S  
3. 2. 8. 2  
S u m mar y of Treat me nt -Relate d 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 i n t he L T S 
Peri o d  
L T S -E V  
3. 2. 8. 3  
S u m mar y of Treat me nt -Relate d 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 Fr o m Baseli ne 
t o Wee k 5 2 
F A S  
3. 2. 9. 1  
S u m mar y of Treat me nt -Relate d 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  i n t he 
C T Peri o d  
F A S  
3. 2. 9. 2  
S u m mar y of Treat me nt -Relate d 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  i n t he 
L T S Peri o d  
L T S -E V  
3. 2. 9. 3  
S u m mar y of Treat me nt -Relate d 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  Fr o m 
Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 0. 1  
S u m mar y of Gra de 3 or Hi g her Treat me nt -Relate d 
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  i n t he C T Peri o d 
F A S  
3. 2. 1 0. 2  
S u m mar y of Gra d e 3 or Hi g her Treat me nt -Relate d 
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  i n t he L T S Peri o d 
L T S -E V  
3. 2. 1 0. 3  
S u m mar y of Gra d e 3 or Hi g her Treat me nt -Relate d 
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  Fr o m Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 1. 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  i n t he 
C T Peri o d  
F A S  
3. 2. 1 1. 2  
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  i n t he 
L T S Peri o d  
L T S -E V  


I nc yte C or p orati o n 
Pa ge 2 7  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
T a ble N o.  
Title  
P o p ul ati o n  
3. 2. 1 1. 3  
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  Fr o m 
Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 2. 1  
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Wit h a Fatal 
O utc o me b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m  i n t he 
C T Peri o d  
F A S  
3. 2. 1 2. 2  
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Wit h a Fatal 
O utc o me b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m  i n t he 
L T S Peri o d  
L T S -E V  
3. 2. 1 2. 3  
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts Wit h a Fatal 
O utc o me b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m  Fr o m 
Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 3. 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 b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m i n 
t he C T Peri o d 
F A S  
3. 2. 1 3. 2  
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 b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m i n 
t he L T S Peri o d 
L T S -E V  
3. 2. 1 3. 3  
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 b y Me d D R A S yste m Or ga n Class a n d Preferre d Ter m 
Fr o m Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 4. 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  R u x oliti ni b Crea m  b y Me d D R A S yste m Or ga n 
Class a n d Preferr e d Ter m i n t he C T Peri o d  
F A S  
3. 2. 1 4. 2  
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 R u x oliti ni b Crea m b y Me d D R A S yste m Or ga n 
Class a n d Preferre d Ter m i n t he L T S Peri o d  
L T S -E V  
3. 2. 1 4. 3  
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 R u x oliti ni b Crea m b y Me d D R A S yste m Or ga n 
Class a n d Preferre d Ter m Fr o m Baseli ne t o Wee k 5 2  
F A S  
3. 2. 1 5 . 1 
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts of I nterest b y  
Me d D R A S yste m Or ga n Class a n d Preferre d Ter m i n t he C T  P eri o d 
F A S  
3. 2. 1 5 . 2 
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts of I nterest b y  
Me d D R A S yste m Or ga n Class a n d Preferre d Ter m i n t he L T S P eri o d  
L T S -E V  
3. 2. 1 5 . 3 
S u m mar y of Treat me nt -E mer ge nt A d verse E v e nts of I nterest b y  
Me d D R A S yste m Or ga n Class a n d Preferre d Ter m Fr o m B aseli ne t o 
Wee k 5 2  
F A S  
3. 2. 1 6 . 1 
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts of I nterest b y  
Me d D R A Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y i n  t he C T 
P eri o d  
F A S  
3. 2. 1 6 . 2 
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts of I nterest b y  
Me d D R A Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y i n  the 
L T S P eri o d  
L T S -E V  
3. 2. 1 6 . 3 
S u m mar y of Treat me nt -E mer ge nt A d verse E ve nts of I nterest b y  
Me d D R A Preferre d Ter m i n Decreasi n g Or der of Fre q ue nc y Fr o m 
B aseli ne t o Wee k 5 2  
F A S  
3. 3 L a b or at or y  
3. 3. 1  
S u m mar y of La b orat or y Val ues - He mat ol o g y i n t he Treat me nt Peri o d  
F A S  
3. 3. 2  
S u m mar y of La b orat or y Val ues - C he mistr y i n t he Treat me nt Peri o d  
F A S  
3. 3. 3. 1  
S hift S u m mar y of He m at ol o g y La b orat or y Val ues i n C T C A E Gra de - 
to t he W orst A b n or mal Val u e i n t he C T Peri o d  
F A S  


I nc yte C or p orati o n 
Pa ge 2 8  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
T a ble N o.  
Title  
P o p ul ati o n  
3. 3. 3. 2  
S hift S u m mar y of He m at ol o g y La b orat or y Val ues i n C T C A E Gra de - 
to t he W orst A b n or mal Val u e i n t he L T S Peri o d  
L T S -E V  
3. 3. 4. 1  
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 Gra de - to 
t he W orst A b n or mal Val u e i n t he C T Peri o d 
F A S  
3. 3. 4. 2  
S hift S u m ma r y of C he mistr y La b orat or y Val ues i n C T C A E Gra de - to 
t he W orst A b n or mal Val u e i n t he L T S Peri o d 
L T S -E V  
3. 3. 5. 1  
S hift S u m mar y of He m at ol o g y Val ues - to t he W orst A b n or mal Val ue 
i n t he C T Peri o d 
F A S  
3. 3. 5. 2  
S hift S u m mar y of He m at ol o g y Val ues - to t he W orst A b n or mal Val ue 
i n t he L T S Peri o d 
L T S -E V  
3. 3. 6. 1  
S hift S u m mar y of C he mistr y Val ues - to t he W orst A b n or mal Val ue i n 
t he C T Peri o d 
F A S  
3. 3. 6. 2  
S hift S u m mar y of C he mistr y Val ues - to t he W orst A b n or mal Val ue  i n 
t he L T S Peri o d 
L T S -E V  
3. 4 Vit al Si g ns  
3. 4. 1  
S u m mar y of S yst olic Bl o o d Press ure i n t he Treat me nt Peri o d  
F A S  
3. 4. 2  
S u m mar y of Diast olic Bl o o d Press ure i n t he Treat me nt Peri o d  
F A S  
3. 4. 3  
S u m mar y of P ulse i n t he Treat me nt Peri o d  
F A S  
3. 4. 4  
S u m mar y of Res pirat or y Rate i n t he Treat me nt Peri o d  
F A S  
3. 4. 5  
S u m mar y of B o d y Te m perat ure i n t he Treat me nt Peri o d  
F A S  
3. 4. 6  
S u m mar y of Hei g ht i n t he Treat me nt Peri o d  
F A S  
3. 4. 7  
S u m mar y of Wei g ht i n t he Treat me nt Peri o d  
F A S  
Fi g ures  
Fi g ure N o.  
Title  
P o p ul ati o n  
4. 1 I G A 
4. 1. 1  
Pr o p orti o n of Partici pa nts Ac hie vi n g a n I G A Sc ore of 0 or 1 b y Visit 
F A S  
4. 1. 2  
Pr o p orti o n of Partici pa nts Ac hie vi n g a facial I G A Sc ore of 0 or 1 b y Visit 
F A S  
4. 2 E A SI  
4. 2. 1  
Pr o p orti o n of Partici pa nts Ac hie vi n g E A SI 7 5 b y Visit  
F A S  
4. 2. 4. 1  
Mea n a n d Sta n dar d Err or Pl ot of E A SI Sc ore b y Visit  
F A S  
4. 2. 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 E A SI Sc ore b y 
Visit  
F A S  
4. 2. 4. 3  
Mea n a n d Sta n dar d Err or Pl ot of Perce nt C ha n ge Fr o m Baseli ne i n E A SI Sc ore 
b y Visit  
F A S  
4. 3 Itc h N R S  
4. 3. 1  
Pr o p orti o n of Partici pa nts Ac hie vi n g ≥ 4 -P oi nt I m pr o ve me nt i n Itc h N R S Sc ore 
b y Visit  
F A S w it h 
b aseli ne Itc h 
N R S sc ore ≥ 4  
4. 3. 2. 1  
Mea n a n d Sta n dar d Err or Pl ot of Itc h N R S Sc ore b y Visit  
F A S  
4. 3. 2. 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 Itc h N R S Sc ore b y 
Visit  
F A S  
4. 3. 2. 3  
Mea n a n d Sta n dar d Err or Pl ot of Perce nt C ha n ge Fr o m Baseli ne i n Itc h N R S 
Sc ore b y Visit  
F A S  
4. 3. 3  
Pr o p orti o n of Partici pa nts Ac hie vi n g ≥ 4 -P oi nt I m pr o ve me nt i n Dail y Itc h N R S 
Sc ore  
F A S w it h 
b aseli ne Itc h 
N R S sc ore ≥ 4  


I nc yte C or p orati o n 
Pa ge 2 9  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
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. 4 . 1 
Mea n a n d Sta n dar d Err or Pl ot of Dail y Itc h N R S Sc ore  
F A S  
4. 3. 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 Dail y  Itc h N R S 
Sc ore  
F A S  
4. 3. 4 . 3 
Mea n a n d Sta n dar d Err or Pl ot of Perce nt C ha n ge Fr o m Baseli ne i n Dail y Itc h 
N R S Sc ore  
F A S  
4. 4 B S A  
4. 4 . 1 
Mea n a n d Sta n dar d Err or Pl ot of A D -Aff e ct e d % B S A  b y Visit  
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 A D -Aff ect e d 
% B S A  b y Visit  
F A S  
4. 4 . 3 
Mea n a n d Sta n dar d Err or Pl ot of Perce nt C ha n ge Fr o m Baseli ne i n 
A D -Aff ect e d % B S A  b y Visit  
F A S  
4. 5 L a b or at or y  D at a  
4. 5 . 1 
Mea n a n d Sta n dar d Err or Pl ot of Selecte d La b orat or y He mat ol o g y Val ues b y 
Visit  
F A S  
4. 5 . 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 Selecte d La b orat or y 
He m at ol o g y Val u es b y Visit  
F A S  
4. 5 . 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 Baseli ne i n Selecte d 
La b orat or y He m at ol o g y Val ues b y Visit  
F A S  
4. 6 . 1 
Mea n a n d Sta n dar d Err or Pl ot of Selecte d La b orat or y C he mistr y Val ues b y 
Visit  
F A S  
4. 6 . 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 Selecte d La b orat or y 
C he mistr y Val u es b y Visit  
F A S  
4. 6 . 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 Baseli ne i n Selecte d 
La b orat or y C he mistr y Val u es b y Visit  
F A S  
Listi n gs  
Listi n g N o.  
Title  
2. 1 P artici p a nt Dis p ositi o n  
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 nt I ncl usi o n a n d E xcl usi o n Criteria Vi olati o ns 
2. 2 Pr ot oc ol De vi ati o ns  
2. 2  
Pr ot oc ol De viati o ns  
2. 3 D at a E xcl u de d Fr o m P K, Effic ac y, a n d/ or S afet y A n al yses  
2. 3  
A nal ysis P o p ulati o ns  
2. 4 De m o gr a p hic a n d B aseli ne C h ar a cteristics (I ncl u di n g Pri or a n d C o nc o mit a nt Me dic ati o ns)  
2. 4. 1  
De m o gra p hic C haracteristics  
2. 4. 2  
Baseli ne Disease C haracteristi cs  
2. 4. 3  
Pri or a n d C o nc o mita nt Me dicati o ns  
2. 4. 4  
Pri or Me dicati o ns f or At o pic Der matitis  
2. 4. 5  
Me dical Hist or y  
2. 5 Dr u g C o m pli a nce  
2. 5  
St u d y Dr u g E x p os ure a n d C o m plia nce  
2. 6 Effic ac y  
2. 6. 1  
I G A Sc ore 
2. 6. 2  
Facial I G A Sc ore  
2. 6. 3  
E A SI Sc ore  


I nc yte C or p orati o n 
Pa ge 3 0  of 3 0  
I N C B 1 8 4 2 4-3 1 5  Statistical A nal ysis Pla n  
1 0  M A Y  2 0 2 4  
V V -C LI N -0 2 6 6 9 1  
C O N FI D E N TI A L  
Listi n g N o.  
Title  
2. 6. 4  
Itc h N R S Sc ore 
2. 6. 5  
A D -Affecte d % B S A  
2. 7 A d verse E ve nts  
2. 7. 1  
A d verse E ve nts  
2. 7. 2  
A d verse E ve nts Lea di n g t o 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 -Relate 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. 7  
A d verse E ve nts wit h Gra d e 3 or Hi g her  
2. 7. 8  
A p plicati o n Site Reacti o ns  
2. 7. 9  
A d verse E ve nts of I nterest  
2. 8 L a b or at or y D at a  
2. 8. 1  
Cli nical La b orat or y Val u es –  He mat ol o g y  
2. 8. 2  
Cli nical La b orat or y Val u es –  Ser u m C he mistr y  
2. 8. 3  
A b n or mal Cli nical La b orat or y Val ues –  He mat ol o g y  
2. 8. 4  
A b n or mal Cli nical La b orat or y Val ues –  Ser u m C he mistr y  
2. 9 Vit al Si g ns  
2. 9. 1  
Vital Si g ns  
2. 9. 2  
Cli nicall y N ota ble Vital Si g n Val ues  
2. 9. 3  
Alert Vital Si g n Val u es