An Open-Label, Single-Arm, Phase 4 Study of Ruxolitinib Cream in Adults With Atopic Dermatitis Experiencing Sleep Disturbance in the United States (MORPHEUS)
Phase: PHASE4
Conditions: Atopic Dermatitis
Sponsor: Incyte Corporation

Official Title: 
An Open-Label, Single-Arm, Phase 4 Study of Ruxolitinib Cream in 
Adults with Atopic Dermatitis Experiencing Sleep Disturbance in the 
United States (Morpheus) 
NCT Number: 
NCT05696392 
Document Date: 
Protocol INCB 18424-902 Version 1 21 JUNE 2022 
 
 
 

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Protocol INCB 18424-902 
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Clinical Study Protocol 
 
TITLE PAGE 
INCB 18424-902 
An Open-Label, Single-Arm, Phase 4 Study of Ruxolitinib Cream in 
Adults with Atopic Dermatitis Experiencing Sleep Disturbance in the 
United States (Morpheus) 
 
Product: 
Ruxolitinib Cream 
IND Number: 
 
Phase of Study: 
4 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 USA 
Original Protocol: 
21 JUNE 2022 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
The information in this document is confidential. No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 

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INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-902 Protocol (dated 21 JUNE 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 
2.1.1. 
Atopic Dermatitis and Itch ..........................................................................................17 
2.2. 
Study Rationale ...........................................................................................................18 
2.2.1. 
Scientific Rationale for Study Design ........................................................................18 
2.2.2. 
Justification for Dose ..................................................................................................20 
2.3. 
Benefit/Risk Assessment ............................................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................22 
4. 
STUDY DESIGN .......................................................................................................23 
4.1. 
Overall Design ............................................................................................................23 
4.2. 
Overall Study Duration ...............................................................................................24 
4.3. 
Study Termination ......................................................................................................24 
5. 
STUDY POPULATION .............................................................................................25 
5.1. 
Inclusion Criteria ........................................................................................................25 
5.2. 
Exclusion Criteria .......................................................................................................26 
5.3. 
Lifestyle Considerations .............................................................................................29 
5.4. 
Screen Failures ............................................................................................................30 
5.5. 
Replacement of Participants .......................................................................................30 
6. 
STUDY TREATMENT ..............................................................................................31 
6.1. 
Study Treatment Administered ...................................................................................31 
6.1.1. 
Study Treatment Application Guidance .....................................................................31 
6.2. 
Preparation, Handling, and Accountability ................................................................32 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................33 
6.4. 
Study Treatment Compliance .....................................................................................33 
6.5. 
Dose Modifications .....................................................................................................33 
6.5.1. 
Criteria and Procedures for Application Interruptions and Adjustments of 
Study Drug ..................................................................................................................33 

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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................34 
6.6. 
Concomitant Medications and Procedures .................................................................34 
6.6.1. 
Permitted Medications and Procedures ......................................................................35 
6.6.2. 
Restricted Medications and Procedures ......................................................................35 
6.6.3. 
Prohibited Medications and Procedures .....................................................................36 
6.7. 
Treatment After the End of the Study .........................................................................37 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................38 
7.1. 
Discontinuation of Study Treatment ...........................................................................38 
7.1.1. 
Reasons for Discontinuation .......................................................................................38 
7.1.2. 
Discontinuation Procedures ........................................................................................39 
7.2. 
Participant Withdrawal From the Study .....................................................................39 
7.3. 
Lost to Follow-Up.......................................................................................................39 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................41 
8.1. 
Administrative and General Procedures .....................................................................41 
8.1.1. 
Informed Consent Process ..........................................................................................41 
8.1.2. 
Screening Procedures ..................................................................................................42 
8.1.3. 
Interactive Response Technology Procedure ..............................................................42 
8.1.4. 
Visit Reminders and Distribution of eDiary and Sleep Monitoring Devices .............42 
8.1.5. 
Demography and Medical History ..............................................................................43 
8.1.5.1. 
Demography and General Medical History ................................................................43 
8.1.5.2. 
Medical and Treatment History ..................................................................................43 
8.2. 
Efficacy Assessments .................................................................................................43 
8.2.1. 
Health Economics .......................................................................................................43 
8.2.2. 
Monitoring Sleep ........................................................................................................43 
8.2.2.1. 
Total Sleep Time .........................................................................................................44 
8.2.3. 
Investigator's Global Assessment ...............................................................................45 
8.2.4. 
Body Surface Area ......................................................................................................46 
8.2.5. 
Photography of Target Lesion ....................................................................................46 

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8.3. 
Patient-Reported Outcomes ........................................................................................46 
8.3.1. 
STOP Criteria for High-Risk Obstructive Sleep Apnea .............................................47 
8.3.2. 
Itch Numerical Rating Scale .......................................................................................47 
8.3.3. 
PROMIS Sleep Questionnaires...................................................................................47 
8.3.3.1. 
PROMIS Sleep Disturbance – Short Form 8b ............................................................47 
8.3.3.2. 
PROMIS Sleep-Related Impairment – Short Form 8a ...............................................47 
8.4. 
Safety Assessments .....................................................................................................48 
8.4.1. 
Adverse Events ...........................................................................................................48 
8.4.2. 
Physical Examinations ................................................................................................48 
8.4.3. 
Vital Signs ..................................................................................................................49 
8.4.4. 
Laboratory Assessments .............................................................................................49 
8.4.4.1. 
Pregnancy Testing ......................................................................................................51 
8.4.4.2. 
Serology ......................................................................................................................51 
8.5. 
Pharmacokinetic Assessments ....................................................................................51 
8.6. 
Pharmacodynamic and Translational Assessments ....................................................51 
8.7. 
Unscheduled Visits .....................................................................................................51 
8.8. 
End of Treatment and/or Early Termination ..............................................................51 
8.9. 
Follow-Up ...................................................................................................................51 
8.9.1. 
Safety Follow-Up ........................................................................................................51 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................53 
9.1. 
Definition of Adverse Event .......................................................................................53 
9.2. 
Definition of Serious Adverse Event ..........................................................................53 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........55 
9.4. 
Reporting of Serious Adverse Events .........................................................................57 
9.5. 
Events of Clinical Interest ..........................................................................................58 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................58 
9.7. 
Pregnancy ...................................................................................................................59 
9.8. 
Warnings and Precautions ..........................................................................................59 
9.9. 
Product Complaints ....................................................................................................59 
9.10. 
Treatment of Overdose ...............................................................................................60 
10. 
STATISTICS ..............................................................................................................61 
10.1. 
Sample Size Determination ........................................................................................61 

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10.2. 
Populations for Analysis .............................................................................................61 
10.3. 
Level of Significance ..................................................................................................61 
10.4. 
Statistical Analyses .....................................................................................................61 
10.4.1. 
Sleep Assessment Endpoints ......................................................................................62 
10.4.2. 
Primary Analysis ........................................................................................................62 
10.4.3. 
Secondary Analysis ....................................................................................................63 
10.4.4. 
Exploratory Analysis ..................................................................................................63 
10.4.5. 
Safety Analyses ..........................................................................................................63 
10.4.6. 
Ad Hoc and Post Hoc Analyses ..................................................................................63 
10.5. 
Interim Analysis ..........................................................................................................64 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................65 
11.1. 
Investigator Responsibilities .......................................................................................65 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................66 
11.2. 
Data Management .......................................................................................................66 
11.3. 
Data Quality Assurance ..............................................................................................68 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................68 
11.5. 
Financial Disclosure ...................................................................................................69 
11.6. 
Publication Policy .......................................................................................................69 
11.7. 
Study and Site Closure................................................................................................70 
12. 
REFERENCES ...........................................................................................................71 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................74 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................76 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................78 
 

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LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................10 
Table 2: 
Key Study Design Elements .......................................................................................11 
Table 3: 
Schedule of Activities .................................................................................................13 
Table 4: 
Schedule of Laboratory Assessments .........................................................................16 
Table 5: 
Objectives and Endpoints ...........................................................................................22 
Table 6: 
Study Treatment Information .....................................................................................31 
Table 7: 
Guidelines for Interruption and Restarting of Treatment Applications if 
Adverse Event is Deemed Related to Study Drug ......................................................34 
Table 8: 
Investigator's Global Assessment ...............................................................................45 
Table 9: 
Required Laboratory Analytes ....................................................................................50 
Table 10: Populations for Analysis .............................................................................................61 
 
LIST OF FIGURES 
 
 
Figure 2: 
Study Drug Application Using a Fingertip Unit .........................................................32 
 

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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AD 
atopic dermatitis 
AE 
adverse event 
AI 
artificial intelligence 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
AST 
aspartate transaminase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
COVID-19 
Coronavirus disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EOT 
end of treatment 
ET 
early termination 
FDA 
Food and Drug Administration (US) 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GFR 
glomerular filtration rate 
GPS 
global positioning satellite 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator's Brochure 
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 

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Abbreviations and 
Special Terms 
Definition 
IRB 
institutional review board 
IRT 
interactive response technology 
JAK 
Janus kinase 
LOCF 
last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
numerical rating scale 
PDE-4 
phosphodiesterase-4 
PP 
per protocol 
PRO 
patient-reported outcome 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
PSG 
polysomnography 
REM 
rapid eye movement 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SCORAD 
scoring atopic dermatitis 
SE 
sleep efficiency 
SoA 
schedule of activities 
SOL 
sleep onset latency 
SOP 
standard operating procedure 
SPF 
sun protection factor 
STOP-BANG 
snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck 
circumference, and gender 
STP 
sufficiently treated population 
TEAE 
treatment-emergent adverse event 
TST 
total sleep time 
ULN 
upper limit of normal 
WASO 
wake after sleep onset 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential 

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1. 
PROTOCOL SUMMARY 
Protocol Title: 
An Open-Label, Single-Arm, Phase 4 Study of Ruxolitinib Cream in Adults with Atopic 
Dermatitis Experiencing Sleep Disturbance in the United States (Morpheus) 
Protocol Number: INCB 18424-902 
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 reduction in sleep disturbance 
after using ruxolitinib cream 
Change from baseline in TST as measured by 
Ōura Ring wearable device at Week 8 
Secondary 
To further evaluate the reduction in sleep 
disturbance after using ruxolitinib cream 
Change from baseline in PROMIS Sleep 
Disturbance – Short Form 8b score (24-hour 
recall) at Week 8 
Overall Design: 
Table 2 presents the key study design elements. Further study details are presented after the 
table. 

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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 4 
Clinical Indication 
Atopic dermatitis 
Population 
Male and female adults (≥ 18 years of age) with a diagnosis of AD for at least 
2 years, BSA involvement of 3% to 20% (excluding scalp), an IGA score ≥ 2, 
Itch NRS ≥ 4, PROMIS Sleep Disturbance – Short Form 8b score ≥ 21, 
average Total Sleep Time/night ≤ 6.5 hours, and no underlying sleep disorders 
Number of 
Participants 
Approximately 100 participants will be enrolled. The study will be conducted 
at approximately 30 sites in the US. 
Study Design 
Open-label, single-arm, Phase 4 study of ruxolitinib cream in patients with AD 
who experience sleep disturbance. 
Estimated Duration 
of Study 
Participation 
Participants will participate for a total of up to 128 days as follows: 
• Up to 42 days in the screening period (includes a 7-day screening sleep 
assessments used in determining eligibility and a 7-day pretreatment sleep 
assessment to further determine eligibility and to establish the participant’s 
baseline sleep pattern) 
• 56 days in the treatment period 
• 30 days in the safety follow-up period. 
DSMB/DMC 
No 
Coordinating 
Principal 
Investigators 
April Armstrong, MD, MPH 
Eric Simpson, MD, MCR 
Treatment Groups and Duration: 
This is a Phase 4, multicenter, open-label, single-arm study to evaluate the reduction in sleep 
disturbance among participants with AD after treatment with ruxolitinib cream. This study will 
enroll approximately 100 adults (≥ 18 years of age) with at least mild severity AD who have 
sleep disturbance. Individuals with known sleep-related conditions that are not associated with 
their AD diagnosis will be excluded from the study. 
A minimally invasive wearable device (Ōura Ring) and a 
 will be 
used to collect objective measures of sleep during the study. The Ōura Ring will be used during a 
7-day screening sleep assessment (to determine study eligibility), and both technologies will be 
used during a 7-day pretreatment sleep assessment (to further determine eligibility and to 
establish baseline sleep patterns) as well as throughout the 8-week treatment period (to monitor 
postbaseline sleep patterns). 
All participants will apply ruxolitinib cream at the FDA-approved strength (1.5%) BID over the 
8-week treatment period, during which participants will treat all baseline AD lesions BID, 
regardless of whether or not the lesion(s) improve. New and/or expanded areas of AD may also 
be treated but not in excess of a total of 20% BSA (for original plus new areas) per application. 
All participants will have follow-up assessments 30 (+ 7) days after the end of treatment 
(Week 8/EOT or ET) to evaluate safety. 

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Table 3: 
Schedule of Activities 
Visit Day (Range)/ 
Visit Week 
Screening Perioda 
Treatment Period 
Safety Follow-Up Period 
Notes 
Days -42 to -7 
Days -7 to -1 
Day 1/ 
Baseline 
Week 4 
(± 7 days) 
Week 8 
(+ 7 days)/ 
EOT/ET 
30 (+ 7) Days 
after Last Application 
Administrative Procedures 
Informed consent 
X 
 
 
 
 
 
Section 8.1.1 
Inclusion/exclusion criteria 
X 
 
X* 
 
 
 
*Reassess applicable 
inclusion/exclusion criteria; 
Section 5 
Demography and general medical 
history 
X 
 
 
 
 
 
Section 8.1.5.1 
Relevant medical and treatment 
history 
X 
 
 
 
 
 
Section 8.1.5.2 
Prior/concomitant medications 
X 
 
X 
X 
X 
X 
Section 6.6  
Contact IRT 
X 
 
X 
X 
X 
 
Section 8.1.3 
Ōura Ring wearable device set-up 
X 
 
 
 
 
 
 
eDiary set-up 
X 
 
 
 
 
 
Set-up includes giving participants 
access to the eDiary; Section 8.1.4 
Application of study drug BID 
 
 
X 
X 
X 
 
First application occurs on Day 1 at 
the site under direct site staff 
supervision; subsequent 
applications are at home; 
applications are recorded in the 
eDiary; Section 6.1 
Review the participant's eDiary 
 
 
X 
X 
X 
 
 
Dispense study drug 
 
 
X 
X 
 
 
 
Collect study drug 
 
 
 
X 
X 
 
 
Study drug accountability 
 
 
 
X 
X 
 
Section 6.4 

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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range)/ 
Visit Week 
Screening Perioda 
Treatment Period 
Safety Follow-Up Period 
Notes 
Days -42 to -7 
Days -7 to -1 
Day 1/ 
Baseline 
Week 4 
(± 7 days) 
Week 8 
(+ 7 days)/ 
EOT/ET 
30 (+ 7) Days 
after Last Application 
Efficacy Assessments 
Ōura Ring wearable device data 
collection 
X* 
X 
X 
X 
X 
 
*Includes collection of TST data 
for 7 days (screening sleep 
assessment) to confirm eligibility; 
Section 8.2.1 
IGA 
X 
 
X 
X 
X 
 
Section 8.2.3 
Total %BSA 
X 
 
X 
X 
X 
 
Section 8.2.4 
Photographs of target lesion 
 
 
X 
X 
X* 
 
Photographs taken on-site on Day 1 
and then at home weekly through 
Week 8. 
*The Week 8 photographs may be 
taken at home or at the site during 
the visit; Section 8.2.5 
Patient Reported Outcomes 
STOP-BANG 
X 
 
 
 
 
 
Only complete the 4 questions from 
STOP portion of questionnaire; 
Section 8.3.1 
PROMIS Sleep-Related 
Impairment – Short Form 8b 
X 
X* 
X* 
X* 
X* 
 
Completed via eDiary (in the 
morning); Section 8.3.3 
*Completed daily from 
pretreatment sleep assessment 
through last application of study 
drug. 

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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range)/ 
Visit Week 
Screening Perioda 
Treatment Period 
Safety Follow-Up Period 
Notes 
Days -42 to -7 
Days -7 to -1 
Day 1/ 
Baseline 
Week 4 
(± 7 days) 
Week 8 
(+ 7 days)/ 
EOT/ET 
30 (+ 7) Days 
after Last Application 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
Section 8.4.1  
Comprehensive physical 
examination 
X 
 
 
 
 
 
Section 8.4.2 
Targeted physical examination 
 
 
X 
X 
X 
X 
Conducted only when indicated by 
symptoms reported by participant 
(AEs or other findings); 
Section 8.4.2 
Vital signs 
X* 
 
X 
X 
X 
X† 
* Height and weight at screening 
only. 
†If this is a telehealth visit, vital 
signs are not collected; 
Section 8.4.3 
a The screening period includes two 7-day sleep assessments: the screening sleep assessment (Days −42 to −7) and the pretreatment sleep assessment (Days −7 to −1). 

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Table 4: 
Schedule of Laboratory Assessments 
Visit Day (Range)/ 
Visit Week 
Screening Perioda 
Treatment Period 
Safety Follow-Up Period 
Notes 
Days −42 to −7 
Days −7 to −1 
Day 1/ 
Baseline 
Week 4 
(± 7 days) 
Week 8 
(+ 7 days)/ 
EOT/ET 
30 (+ 7) Days after 
Last Application 
Laboratory Assessments 
Serum chemistries 
X 
 
 
 
X 
X 
Section 8.4.4  
Hematology 
X 
 
 
 
X 
X 
Section 8.4.4 
HIV 
X 
 
 
 
 
 
Section 8.4.4.2 
Pregnancy testing 
(WOCBP only) 
X 
 
X 
X 
X 
X 
Serum test at screening. Urine test 
at all other specified visits. A 
positive urine test must be 
confirmed by a serum test. 
Section 8.4.4.1  
FSH 
X 
 
 
 
 
 
For female participants of 
nonchildbearing potential. 
Section 8.4.4 
a The screening period includes two 7-day sleep assessments: the screening sleep assessment (Days −42 to −7) and the pretreatment sleep assessment (Days −7 to −1). 

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2. 
INTRODUCTION 
2.1. 
Background 
Ruxolitinib cream is a topical formulation of ruxolitinib phosphate, an investigational product 
that has been developed for the treatment of inflammatory diseases of the skin. Ruxolitinib 
phosphate is an inhibitor of the JAK family of protein tyrosine kinases, which play important 
roles in signal transduction downstream of cytokine and growth factor receptors. Ruxolitinib has 
shown efficacy in various chronic inflammatory conditions that present with an aberrant 
production of cytokines and growth factors, including psoriasis, vitiligo, and AD. In the US, 
Opzelura™ (ruxolitinib) cream is FDA-approved 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 2021). 
2.1.1. 
Atopic Dermatitis and Itch 
Atopic dermatitis is a chronic, recurring, and highly pruritic inflammatory skin condition 
characterized by erythematous lesions, xerosis, and frequent skin infections (Al-Shobaili 
et al 2016, Ong et al 2002). It typically begins early in infancy or childhood, although it can also 
develop in adulthood, and is more frequent among females than males (1.3 to 1.0 ratio; 
Eichenfield et al 2014, Leung et al 2012). Several environmental factors, such as small family 
size and increased education, can heighten one's likelihood to develop AD; however, recent 
advancement in the molecular genetics of the disease indicate that AD may result from the 
inheritance of disease susceptibility variants of genes coding for constituents of the skin barrier 
and immune system (Al-Shobaili et al 2016, Leung et al 2012). Evidence suggests that a 
complex interplay between these genes and environmental factors results in defective skin barrier 
integrity and altered immunologic/inflammatory responses and contributes to the development, 
progression, and chronicity of AD (Al-Shobaili et al 2016, Leung et al 2012, National Eczema 
Association 2018, Rerknimitr et al 2017). 
One of the most prominent and debilitating symptoms of AD is pruritus, also referred to as an 
"unpleasant sensation eliciting the urge to scratch" (Darsow et al 2011, Leung et al 2012, 
Rerknimitr et al 2017, Yarbrough et al 2013). In most cases, this urge to scratch arises following 
exposure to triggering factors, such as irritants, allergens, infectious agents, and/or emotional 
stressors, which elicit a cutaneous hyper-reaction (Darsow et al 2011). The mechanical injury 
from scratching contributes to skin inflammation and exacerbates the scratch‑itch cycle that 
perpetuates the disease (Leung et al 2012). Pruritus affects the majority of patients with AD, and 
can be significantly bothersome and undermine the affected patient's quality of life and overall 
well‑being (Farmer and Marathe 2017, Mochizuki et al 2017, Yosipovitch and Papoiu 2008). It 
can also disturb sleep and cause psychological problems such as depression and anxiety 
(Yarbrough et al 2013). Given the central role of pruritus in AD, it has become clear that the 
control of itch is critical to the management of the disease (Pavlis and Yosipovitch 2018, 
Yarbrough et al 2013). 
Free nerve endings in the skin are involved in pruritus as itching receptors 
(Urashima and Mihara 1998). Histological examinations have revealed increased cutaneous 

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nerve densities in patients with AD and animal models, suggesting that this higher density may 
be at least partly responsible for intense itching in the skin. The increased nerve fibers in the 
epidermis may be also activated by exogenous mechanical, chemical, and biological stimuli, 
resulting in itch responses. Previous observations suggest that an increase in nerve density in the 
epidermis may be caused by weakness or disruption of skin barrier function, allowing the 
invasion of exogenous substances into the skin. As itch is a biological sign, it is important for 
antipruritic therapy in AD to target cutaneous nerve fibers, their triggers, and barrier function 
(Tominaga and Takamori 2014). 
Efforts have been made to find new and more appropriate treatment options to better meet the 
current and future medical needs of patients with AD. The results of recent trials indicated that 
oral JAK inhibitors may be effective in the treatment of AD and have elicited interest in the use 
of this drug class as a topical treatment for AD (Bissonnette et al 2019, Guttman-Yassky 
et al 2019, Levy et al 2015). Recent studies suggest that JAK inhibition may have antipruritic 
effects by acting directly on sensory nerve fibers (Hashimoto et al 2019). Ruxolitinib cream 
offers a novel therapeutic approach in AD with dual anti-inflammatory and antipruritic 
properties, providing a rationale for investigating the clinical utility of ruxolitinib cream for the 
treatment of this condition. Additionally, given that pruritus associated with AD causes 
significant patient discomfort, often leading to sleep deprivation or poor sleep quality, treatment 
of AD with ruxolitinib cream may positively impact patients' sleep-related qualify of life. 
2.2. 
Study Rationale 
Atopic dermatitis is the most common inflammatory skin disease that is chronically relapsing 
and characterized by associated pruritis (Leung and Guttman-Yassky 2014). Sleep disturbance is 
associated with AD and is a major contributing factor in reduced quality of life 
(Ricci et al 2007). In addition to the individuals with AD, family members also reported that 
sleep disturbance is one of the greatest factors affecting their quality of life (Ricci et al 2007). 
Sleep disturbance is reported in up to 83% of children with AD and up to 87% of adults with AD 
(Camfferman et al 2010, Chang and Chiang 2018). 
Data from previous studies demonstrated that topical ruxolitinib cream is effective in treating 
AD due to its dual anti-inflammatory and antipruritic properties. In addition to demonstrating a 
higher proportion of study participants with AD achieving clear or almost clear status 
(Papp et al 2021), participants also reported significant reduction in sleep disturbance through 
PROMIS® and SCORAD PROs compared to vehicle control group (Simpson et al 2021). 
The goal of the study is to demonstrate the reduction in sleep disturbance among participants 
with AD after the application of ruxolitinib cream using wearable and wireless technologies that 
enable objective measures of sleep. 
2.2.1. 
Scientific Rationale for Study Design 
In the 2 completed Phase 3 adult and adolescent AD trials of ruxolitinib cream versus vehicle 
control (INCB 18424-303  and INCB 18424-304 ), the ruxolitinib 1.5% cream group in each 
study demonstrated reduction in sleep disturbance based on PROs (PROMIS sleep disturbance 
questionnaire and SCORAD) at Week 8 (Papp et al 2021, Simpson et al 2021). In 
INCB 18424 -303, more participants reported clinically meaningful improvement in the 
PROMIS sleep disturbance questionnaire score (≥ 6-point improvement from baseline) at 

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Week 8 with ruxolitinib 1.5% cream versus vehicle (p < 0.01), and in INCB 18424-304, response 
rates were also higher with ruxolitinib 1.5% cream versus vehicle, although the differences were 
not statistically significant. 
Although PROMIS is a validated PRO measure of sleep, it has the limitation of subjectivity; 
while some subjective measures of sleep may correlate with sleep patterns of individuals, 
objective measures of sleep may provide a more robust assessment of the effect of ruxolitinib 
cream on sleep disturbance among patients with AD (O'Donnell et al 2009). Only a small 
number of studies in AD have been conducted using objective measures of sleep-related metrics 
(Chang and Chiang 2018, Chang et al 2014) while the majority of the studies rely on PROs. 
Polysomnography is traditionally used as the gold standard for determining sleep disturbance and 
other sleep-related conditions, and it is the standard to objectively measure sleep in clinical 
settings (Boe et al 2019, Shrivastava et al 2014). Polysomnography is usually conducted in a 
sleep laboratory and requires the participant to be connected to dozens of electrodes. However, 
due to the complexity of the usage and physical size of the machinery involved, the use of PSG 
devices would not be practical in an 8-week ambulatory study. 
In recent years, alternative technologies (eg, wearable and wireless devices) have been developed 
to assess sleep metrics using combinations of actigraphy and biometric data and have been 
shown to produce data comparable to PSG (Chee et al 2021, Kinnunen 2016). Such recent 
developments in wearable and wireless technologies allow for the measurement of sleep-related 
parameters without requiring polysomnographic machines (Boe et al 2019). This study will use a 
minimally invasive wearable device (Ōura Ring) 
 for 
collecting objective measures of sleep during the study. Ōura Ring is a commercially available 
device that participants will wear on their fingers and that can be used for monitoring sleep status 
The eligible study population will be similar to that in the ruxolitinib cream Phase 3 studies 
(INCB 18424-303 and INCB 18424-304; eg, BSA 3-20%); however, baseline Itch NRS ≥ 4 and 
PROMIS Sleep Disturbance – Short Form 8b score ≥ 21 are 2 key differences that have been 
included in this study. Also due to the high variability in sleep patterns among adolescents 
(Carskadon 1982), this study will be limited to adults (age ≥ 18 years). To establish eligibility, 
the sleep disturbance of participants will be assessed using the wearable device during the 
screening period. These additional measures are intended to more robustly evaluate participants 
who have at least moderate itch from AD and at least moderate sleep disturbance, so that the 
effect of ruxolitinib 1.5% cream on these particularly burdensome aspects of the disease can be 
better quantified (Eckert et al 2017). 
The sleep patterns of individuals are documented to be highly variable (Vallières et al 2005). 
Therefore, this study is designed to have each participant serving as their own control with a 
pretreatment sleep assessment prior to initiating the treatment with ruxolitinib cream. 

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2.2.2. 
Justification for Dose 
The results of the completed ruxolitinib cream Phase 3 AD trials (INCB 18424-303 and 
INCB 18424-304) demonstrated ruxolitinib 1.5% cream is a safe, well-tolerated, and effective 
treatment for participants with mild to moderate AD. All participants in this study will apply 
ruxolitinib cream with the FDA-approved strength (1.5%) and application frequency (BID) 
(Opzelura 2021), using the same treatment paradigm as in the Phase 3 AD trials. New and/or 
expanded areas of AD may also be treated but not in excess of a total of 20% BSA (for original 
plus new areas) per application. 
2.3. 
Benefit/Risk Assessment 
Ruxolitinib cream showed statistically significant and clinically meaningful improvement in AD. 
Given that participants in this study will have a diagnosis of active AD, it is likely that these 
participants will benefit from ruxolitinib cream treatment. Additionally, given that, participants 
in this study will also be experiencing sleep disturbance, which may be a result, in part, of the 
discomfort associated with AD, it is possible that these participants will have a benefit to their 
sleep following treatment of their AD with ruxolitinib cream. 
Safety data from the Phase 3 AD studies (INCB 18424-303 and INCB 18424-304) demonstrate 
that ruxolitinib 1.5% cream BID applied 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. 
Results from dermal safety studies 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 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 compared with the vehicle cream 
treatment group during the 8-week, vehicle-controlled period, which may be attributable to 
worsening of the underlying disease in the absence of active drug treatment. 
A comprehensive analysis of potential systemic safety concerns with oral ruxolitinib as well as 
additional events of interest for oral JAK inhibitors that have not been observed with oral 
ruxolitinib was performed in the Phase 3 studies. Events of interest included cytopenias, herpes 
zoster and other viral skin infections, other infections and infestations, nonmelanoma skin 
neoplasms, liver function test and lipid elevations, and arterial and venous thromboembolic and 
thrombocytosis events. As expected given the low bioavailability and the low plasma 
concentrations of ruxolitinib observed following topical application, ruxolitinib 1.5% cream BID 
was not associated with these safety concerns. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ruxolitinib cream may be found in the IB and the prescribing information for 
Opzelura (Opzelura 2021). 

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In addition, to address challenges associated with the COVID-19 global pandemic, the sponsor 
has issued Protocol considerations to ensure participant safety is maintained and adequate 
benefit/risk analyses are applied relative to the completion of study procedures and maintaining 
the investigational product supply chain (see Appendix B). 

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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 reduction in sleep disturbance 
after using ruxolitinib cream 
Change from baseline in TST as measured by 
Ōura Ring wearable device at Week 8 
Secondary 
To further evaluate the reduction in sleep 
disturbance after using ruxolitinib cream 
Change from baseline in PROMIS Sleep 
Disturbance – Short Form 8b score (24-hour 
recall) at Week 8 
Exploratory 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 4, multicenter, open-label, single-arm study to evaluate the reduction in sleep 
disturbance among participants with AD after treatment with ruxolitinib 1.5% cream. This study 
will enroll approximately 100 adults (≥ 18 years of age) with at least mild severity AD who have 
sleep disturbance. Individuals with known sleep-related conditions that are not associated with 
their AD diagnosis will be excluded from the study. The study will be conducted at 
approximately 30 sites in the US. 
A minimally invasive wearable device (Ōura Ring) and a 
 will be 
used to collect objective measures of sleep during the study. The Ōura Ring will be used during a 
7-day screening sleep assessment (to determine study eligibility), and both technologies will be 
used during a 7-day pretreatment sleep assessment (to further determine eligibility and to 
establish baseline sleep patterns) as well as throughout the 8-week treatment period (to monitor 
postbaseline sleep patterns). 
Figure 1 presents the study design schema, and Table 3 presents the SoA. 
The study begins with an up to 42-day screening period, which includes two 7-day sleep 
assessments (the screening sleep assessment and the pretreatment sleep assessment). During the 
screening period, participants will be given access to an electronic diary (eDiary) to complete 
PROs during the study, and participants will discontinue any current treatments for AD as well 
as other excluded treatments. 
Following completion of the pretreatment sleep assessment, participants will continue into an 
8-week treatment period. On Day 1 of the treatment period, all eligible participants will be 
enrolled in the study and will begin treating their AD with ruxolitinib cream at the 
FDA-approved strength (1.5%) BID, applied topically as a thin film. All original areas of AD 
involvement identified on Day 1 (baseline), regardless of whether or not the lesion(s) improve, 
and any new and/or expanded areas of AD lesions will be treated until the morning of the 
Week 8 visit, with a total maximum allowed treatment area of ≤ 20% BSA. Sleep data from each 
participant will be continuously collected during the treatment period (Day 1 through Day 56 
inclusive [or the day before the Week 8 visit]) with both sleep monitoring devices. 
Measurements of sleep at Week 8 will be compared to baseline in a pair-wise manner to 
determine the reduction in sleep disturbance. At the end of the treatment period (Week 8/EOT or 
ET), participants will discontinue treatment with ruxolitinib 1.5% cream (with the last 
application on the morning of this visit) and will be required to return the eDiary, Ōura Ring, and 
 
Following completion of the treatment period (or the last application of study drug for those who 
discontinue early), participants will have follow-up assessments 30 (+ 7) days after the end of 
treatment to evaluate safety. 
Throughout the study, at the times indicated in the SoA (see Table 3), participants will complete 
the following PROs using their eDiary: Itch NRS (daily), PROMIS Sleep Disturbance – Short 
Form 8b (daily), and PROMIS Sleep-Related Impairment – Short Form 8a (weekly). 
Additionally, the STOP portion of the STOP-BANG questionnaire will be completed during the 
screening visit as part of the eligibility assessment. Participants will be assessed for the safety 

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and tolerability of ruxolitinib cream throughout the study by monitoring the type, frequency, and 
severity of AEs, performing physical examinations, measuring vital signs, and conducting 
clinical laboratory assessments, as outlined in 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. 
It is estimated that an individual will participate for up to approximately 128 days (42-day 
screening period, 56-day treatment period, and 30-day safety follow-up period). A participant is 
considered to have completed the study if they have completed all study procedures of the study 
including the last visit or the last scheduled procedure shown in Table 3 as well as successfully 
submitted sleep data. 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract. The investigator is to notify the IRB/IEC of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, or if required by regulatory agency. In the event 
of significant safety findings, the study will be terminated. If the study is terminated prematurely, 
the sponsor will notify the investigators, the IRBs and IECs, and regulatory bodies of the 
decision and reason for termination of the study. 

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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety. Therefore, 
adherence to the criteria as specified in the Protocol is essential. Prospective approval of Protocol 
deviations to recruitment and enrollment criteria, also known as Protocol waivers or exemptions, 
are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for this study. 
Note: Consent must be obtained prior to any study-related procedures. 
2. Male or female participant ≥ 18 years of age at screening. 
3. Has clinically confirmed diagnosis of active AD according to Hanifin and Rajka (1980) 
criteria. 
4. Has at least a 2-year history of AD (information obtained from medical chart, 
participant's physician, or directly from the participant). 
5. Has chronic pruritus related to AD for at least 3 months before the screening visit 
(information obtained from medical chart, participant's physician, or directly from the 
participant). 
6. Has an overall BSA affected by AD of 3%-20% (excluding scalp) at the screening and 
baseline visits. 
7. Has an IGA score ≥ 2 at the screening and baseline visits. 
8. Has an Itch NRS score ≥ 4 at the screening and baseline visits. 
9. Willing to complete the once-daily Itch NRS (24-hour recall period) entries at 
approximately the same time each day during the study. 
10. Has a PROMIS Sleep Disturbance – Short Form 8b score ≥ 21 at the screening visit. 
11. Has an average TST/night of ≤ 6.5 hours during the 7-day screening sleep assessment, as 
measured by Ōura Ring wearable device. 
12. Has habitual amount of time in bed attempting to sleep of at least 7 hours, as reported by 
the participant. 
13. Has access to broadband wireless internet and is willing to connect wireless device to the 
wireless network. 
14. Agrees to spend at least 95% of nights in the household during the study period. 
15. Has habitual bedtime time that falls between 9:00 pm and 12:00 am (midnight) and 
habitual wake time that falls between 5:00 am and 9:00 am. 
16. Agrees to maintain a regular sleep schedule during the study period. 

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17. Generally does not experience sleep disturbance due to factors such as having young 
children (< 5 years) who live in the household or pets. 
18. Willing and able to follow required study procedures for measuring sleep for the duration 
of the study. 
19. Willing to avoid pregnancy or fathering children based on the below criteria: 
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 study drug 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 at 
baseline/Day 1 and must agree to take appropriate precautions to avoid pregnancy 
from baseline through 30 days (1 menstrual cycle) after the last application of study 
drug 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. 
20. Willing to comply with all study procedures and restrictions including discontinuation of 
all current therapies for AD and pruritus (unless otherwise specified), and must be 
available for the duration of the study. 
21. Willing to adhere to limited alcohol and caffeine use in a way that it does not impact 
general sleep pattern and willing to record alcohol and caffeine use for the duration of the 
study. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Participant is a female who is breastfeeding, pregnant, or planning to become pregnant 
during the study. 
2. Currently using a wearable or other device for monitoring sleep patterns and unwilling to 
discontinue its use during the study. 
3. Currently has a schedule that includes nighttime work shifts. 
4. Has had significant flares or unstable course in AD (ie, condition worsened significantly 
or required significant change in medications, as per medical judgment) in the previous 
4 weeks before screening (information obtained from medical chart, participant's 
physician, or directly from the participant). 
5. Has a clearly defined etiology for pruritus other than AD, including but not limited to 
urticaria, psoriasis, or other nonatopic dermatologic conditions; hepatic or renal disease; 
psychogenic pruritus; drug reaction; uncontrolled hyperthyroidism; and infection. 

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6. 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 unless approved by the 
medical monitor/sponsor: 
− 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). 
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 deep vein 
thrombosis and physical exam. 
d. Current and/or history of active tuberculosis or current and/or history of latent 
tuberculosis unless adequately treated. 
e. Has a current or prior diagnosis of any sleep-related condition (eg, insomnia not 
solely related to AD, severe sleep apnea, restless leg syndrome, narcolepsy). 
f. History of drug or alcohol dependency or abuse within approximately the previous 
1 year. 
g. Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom 
during the night. 
h. Participants answering yes to all 4 of the following STOP questions from the 
STOP-BANG questionnaire: 
− Do you snore loudly? (Louder than talking or loud enough to be heard through 
closed doors) 
− Do you often feel tired, fatigued, or sleepy during the daytime? 
− Has anyone observed you stop breathing during sleep? 
− Do you have (or are you being treated for) high blood pressure? 
i. Has clinically infected AD or has used antibiotics (systemic or topical) for their 
infected AD within 2 weeks prior to the screening period. 
j. Has immune deficiency or is immunocompromised (eg, lymphoma, acquired 
immunodeficiency syndrome, Wiskott-Aldrich syndrome). 
k. Has a history of skin disease or presence of skin condition that, in the opinion of the 
investigator, would interfere with the study assessments (eg, generalized 
erythroderma, Netherton syndrome, psoriasis, or any skin condition other than AD 
that may risk inducing a pruritus flare/worsening). 
l. Has had a major surgery within 8 weeks prior to screening or has a major surgery 
planned during the study. 
m. Is on maintenance dialysis. 
n. Current or history of hepatitis B virus or hepatitis C virus infection. 

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7. Has any clinically significant laboratory/vital sign abnormality that would, in the opinion 
of the investigator, put the participant at undue risk or interfere with interpretation of 
study results. 
8. Has any of the following clinical laboratory test results at screening: 
a. Hemoglobin < 100 g/L (ie, 10 g/dL) or ANC < 1000/μL 
b. Liver function tests: 
− AST or ALT ≥ 2.5 × ULN 
− Total bilirubin > 1.5 × ULN unless Gilbert syndrome 
c. Estimated GFR < 30 mL/min/1.73 m2 (using the Chronic Kidney Disease 
Epidemiology Collaboration equation). 
d. Positive serology test results at screening for HIV antibody. 
e. Any other clinically significant laboratory result that, in the opinion of the 
investigator, poses a significant risk to the participant. 
9. Use of any of the following treatments within the indicated washout duration prior to the 
pretreatment sleep assessment: 
a. 5 half-lives or 12 weeks, whichever is longer – marketed or investigational biologic 
agents (eg, dupilumab). For biologic agents with washout duration longer than 
12 weeks (eg, rituximab), consult the medical monitor. 
b. 4 weeks – systemic (oral/injectable) treatments that could affect AD and/or pruritus, 
such as corticosteroids, adrenocorticotropic hormone analogs, cyclosporin, 
methotrexate, azathioprine, retinoids, calcineurin inhibitors, PDE-4 inhibitors, other 
systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or 
tacrolimus), hydroxycarbamide [hydroxyurea], or opioids). 
Note: Intranasal and inhaled corticosteroids are allowed. Eye and ear drops containing 
corticosteroids are also allowed. 
c. 2 weeks – immunizations with live-attenuated vaccines; oral, sedative H1 
antihistamines (including but not limited to diphenhydramine and hydroxyzine). 
Note: Oral, nonsedative, H1 antihistamines will be permitted during the study. 
Note: Live-attenuated vaccines are not recommended during the treatment period. 
Note: COVID-19 vaccination is allowed. 
d. 1 week – use of other topical treatments that could affect AD and/or pruritus (other 
than bland emollients; eg, Aveeno® creams, ointments, sprays, soap substitutes), such 
as topical antipruritics (eg, doxepin cream), corticosteroids, calcineurin inhibitors, 
PDE-4 inhibitors (eg, crisaborole), coal tar (shampoo), topical 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. 
10. Has received any ultraviolet B phototherapy (including tanning beds) or excimer laser 
within 4 weeks prior to the screening period. 
11. Has had psoralen plus ultraviolet A treatment within 4 weeks prior to the screening 
period. 
12. Has received a nonbiological investigational product or device within 4 weeks prior to 
the screening period, or is currently enrolled in another investigational drug study. 

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13. Has received treatment with JAK inhibitors (systemic or topical) within 4 weeks prior to 
the screening period. 
14. Has had prior treatment with a JAK inhibitor that was discontinued for safety reasons or 
tolerance problems. 
15. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
baseline with a strong CYP3A4 inhibitor. 
16. Has a known or suspected allergy to ruxolitinib or any component of the study drug. 
17. Has a known history of clinically significant drug or alcohol abuse in the last year prior to 
screening. 
18. Had night shift work hours in the past 3 months prior to screening. 
19. Plans to work on an overnight shift during the study period. 
20. Plans to travel more than 2 time zones during the study period. 
21. Has other upcoming life events, or anticipates having life events, during the study period 
that would interrupt the participant's sleep at their household. 
22. Has excessive caffeine use that, in the opinion of the investigator, contributes to the 
participant's insomnia or habitually consumes caffeine-containing beverages after 
6:00 pm and is unwilling to forego caffeine after 6:00 pm for the duration of the study. 
23. Has a 7-day average TST/night of > 7.5 hours during the pretreatment sleep assessment, 
as measured by Ōura Ring wearable device. 
24. Is unlikely, in the opinion of the investigator, to be compliant with study procedures and 
requirements. 
5.3. 
Lifestyle Considerations 
Participants should be encouraged to sleep at home (or usual place of sleep) during the 14 days 
prior to Day 1, Week 4, and Week 8. 
Participants should be encouraged to attempt to sleep for at least 7 hours of sleep each night 
during the study (excluding time watching television, reading, etc in bed). 
 
 
Participants should be advised to limit alcohol intake to no more than 2 drinks per day or forego 
having alcohol within the 3 hours before bedtime for the duration of their participation in the 
study. 
Participants should be advised to avoid drastically different sleep patterns over the weekend 
nights compared to weekday nights for the duration of the study. 
Participants should be cautioned to avoid excessive exposure to natural or artificial sunlight 
(including tanning booths, sun lamps, etc). 

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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 
drug. 
It is recommended that swimming should not take place within 2 hours before and after the 
planned study drug application. 
Participants should be advised not to change medications taken for comorbid conditions unless 
deemed necessary by a healthcare professional. 
Participants should be advised not to change, add or remove, medications and supplements that 
would change general sleep patterns unless deemed necessary by a healthcare professional. 
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 treatment period of the study. 
Laboratory tests with results that fail eligibility requirements may be repeated once during 
screening if deemed acceptable by the investigator. Additionally, participants who do not meet 
the criteria for participation in this study (screen failure) may be rescreened once, if deemed 
acceptable by the investigator. Participants who rescreen must reconsent (if rescreened > 42 days 
after the initial screening) and be assigned a new participant number. 
Participants who do not meet the eligibility criteria for the Itch NRS score, PROMIS Sleep 
Disturbance – Short Form 8b score, or TST (during the screening sleep assessment or 
pretreatment sleep assessment, as measured by Ōura Ring) will be considered as screen failures 
and may not be rescreened. 
5.5. 
Replacement of Participants 
Participants meeting the following criteria may be replaced by enrolling additional participants: 
• Participants who received less than 23 applications in any interval of 14 consecutive 
days of BID study drug administration. 
• Participants with inadequate data (data missing for ≥ 3 days either during the 
pretreatment sleep assessment or between Days 49 and 56) to complete the primary 
analysis (eg, due to device malfunction, internet outage, unplanned travel, etc). 
• Participants experiencing major changes to their sleep patterns due to a medical 
condition or other life situation. 

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6. 
STUDY TREATMENT 
All participants enrolled in the study will be treated with open-label ruxolitinib 1.5% cream BID. 
6.1. 
Study Treatment Administered 
Table 6 presents the study treatment information. 
Table 6: 
Study Treatment Information 
Study treatment name: 
Ruxolitinib 
Mechanism of action: 
JAK1 and JAK2 inhibitor 
Dosage formulation: 
Cream 
Unit dose strength/ 
dosage level: 
1.5% 
Administration instructions: 
Apply BID as a thin film to the affected area(s) (up to 20% BSAa), at 
an interval of approximately 12 hours (but at least 8 hours) for 
8 weeks (from Day 1 until the morning of the Week 8visit). 
Packaging and labeling: 
Ruxolitinib will be provided in 60-g tubes. 
Tubes will include labeling in the local language, and each tube will 
be labeled as required per country requirement.  
Storage: 
Ambient (15°C-30°C/59°F-86°F) 
Status of treatment in 
participating countries: 
Approved in the USb 
a Affected areas identified at baseline will be treated for 56 days and new and/or expanded areas of AD may be 
treated but not in excess of a total of 20% BSA (for original plus new areas) per application. 
b Opzelura (ruxolitinib) cream 
Ruxolitinib 1.5% cream will be supplied in 60-g tubes. The study drug will be provided by the 
sponsor and dispensed at the study visits summarized in the SoA (see Table 3). 
6.1.1. 
Study Treatment Application Guidance 
On Day 1, study staff will instruct participants on proper application of study drug. Refer to the 
Study Pharmacy Manual for participant instructions for handling study of drug. 
Study drug should be applied optimally at equal intervals (ie, approximately 12 hours apart, but 
at least 8 hours apart) to the affected areas in the morning and in the evening, with the evening 
application done at least 1 hour before bedtime if possible. Participants should continue to apply 
study drug throughout the 56-day treatment period to the affected areas identified on Day 1 
(baseline) and any new AD lesions (up to a total maximum of 20% BSA for the original plus any 
new areas), regardless of whether the signs and symptoms of the participant's AD resolve during 
the treatment period. In the event that new lesions are outside of the original location(s) 
identified at baseline and/or are more widespread than at baseline, the participant is required to 
contact the site for approval to treat additional areas; this may occur via telephone, although the 
investigator, at their discretion, may ask the participant to return for an unscheduled visit. The 
last planned application will be on the morning of the Week 8/EOT visit. 

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Participants should remove study drug from the tube with their fingertip in small amounts until 
all of the areas to be treated are covered by a thin even film. A fingertip unit (see Figure 2) 
allows for the thin spreading of the study drug to cover approximately 2% of the participant's 
total BSA. 
Figure 2: 
Study Drug Application Using a Fingertip Unit 
 
Source: DermNet New Zealand (www.dermnetnz.org). 
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 treatments received and any discrepancies are reported and resolved before use of the study 
treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment. Immediately after application of ruxolitinib 
cream, participants are to wash hands thoroughly with soap and warm water. Refer to the Study 
Pharmacy Manual for participant instructions for handling of study drug. 
All study treatment must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records). Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities. The 
investigator or designee must maintain records that document the following: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drugs, including tube counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The study drug must be used only in accordance with the Protocol. The investigator or designee 
will also maintain records adequately documenting that the participants were provided the 
specified study drug. These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the study drug and study participants. 
Completed accountability records will be archived by the site. The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 

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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 according to institutional 
SOPs. If; however, local procedures do not allow on-site destruction, shipment of the study drug 
back to the sponsor is allowed. In this case, the site should (where local procedures allow) 
maintain the study drug supply until the study monitor inspects the accountability records in 
order to evaluate compliance and accuracy of accountability by the investigative site. At sites 
where the study drug is destroyed before monitor inspection, the monitors rely on documentation 
of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Study Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable (this is an open-label study with a single treatment arm). 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study. 
Compliance with study drug will be calculated by the sponsor based on participant responses in 
the eDiary about study drug application. 
Participants will be instructed to bring all empty, partially used, and unused tubes of study drug 
with them to the study visits in order for site personnel to confirm usage of the study drug. 
6.5. 
Dose Modifications 
No application adjustments/modifications (decrease or increase in study drug strength or 
frequency of application) are allowed during the study. 
The only modifications to the treatment regimen are either temporary interruption or permanent 
withdrawal of the study drug (eg, for management of an AE). 
6.5.1. 
Criteria and Procedures for Application Interruptions and Adjustments of 
Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine whether the participant should continue or discontinue study treatment. 
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or laboratory abnormalities that may have an unclear relationship to study drug. In the event an 
AE is present at a specific site of application, treatment may be 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 sponsor medical monitor (or 
other representative of the sponsor) before interrupting study drug applications. Additionally, the 
investigator must obtain approval from the sponsor before restarting study drug. Participants who 
experience a recurrence of the initial AE(s) upon restarting the study drug may need to 
permanently discontinue treatment with the study drug. 

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Instructions for application interruptions of study drug are outlined in Table 7. Individual 
decisions regarding interruptions should be made using clinical judgment in consultation with the 
medical monitor (whenever possible), taking into account relatedness of the AE to the study drug 
and the participant's underlying condition. 
Table 7: 
Guidelines for Interruption and Restarting of Treatment Applications if 
Adverse Event is Deemed Related to Study Drug 
Adverse Event Related to Study Druga 
Action Taken 
ANC < 750/μL (without fever); 
< 1000/μL (with fever) 
• Laboratory abnormalities should be confirmed with repeat testing 
within 48 hours whenever possible and immediate delivery of the 
laboratory results requested. 
• Study drug applications must be interrupted. At the discretion of 
the investigator, after consultation with the sponsor, study drug 
application may be restored once these have resolved. 
Any other Grade 3 laboratory 
abnormality (eg, hemoglobin with the 
exception of asymptomatic elevations in 
triglyceride, cholesterol, or amylase) 
• Laboratory abnormalities should be confirmed with repeat testing 
within 48 hours whenever possible and immediate delivery of the 
laboratory results requested. 
• Study drug applications must be interrupted. At the discretion of 
the investigator, after consultation with the sponsor, study drug 
application may be restored once these have resolved. 
Any Grade 4 laboratory abnormality or 
AST or ALT (> 20 × ULN) 
• Laboratory abnormalities should be confirmed with repeat testing 
within 48 hours whenever possible and immediate delivery of the 
laboratory results requested. 
• Discontinue study drug if lab abnormalities are confirmed. 
a In the opinion of the investigator. 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable severity of an AE not caused by the underlying disease will be 
presumed to be related to study drug and will require that the study drug be permanently 
discontinued. Unacceptable severity is defined as follows: 
• Occurrence of an AE that is related to treatment with study drug that, in the judgment 
of the investigator or the sponsor's medical monitor, compromises the participant's 
ability to continue study-specific procedures or is considered to not be in the 
participant's best interest. 
• Participant presents with a worsening of AD that requires treatment with a prohibited 
concomitant medication. 
• Persistent AE requiring a delay of therapy 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. Any 
prior medication received up to 28 days before the first dose of study drug and within 30 days 
after the last dose of study drug will be recorded in the eCRF. 

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Any addition, deletion, or change in the dose of these medications will also be recorded. 
Concomitant medications administered after 30 days after the last dose of study treatment should 
be recorded for SAEs as defined in Section 9.3. 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 the following periods from the application 
of study drug: 4 hours before and 2 hours after application. 
• Bathing during the study should be limited to once daily for no longer than 
15 minutes and not within 2 hours following study drug application. During baths, 
tepid (not hot) water and mild cleansing agents (eg, Basis® bar or Dove®) should be 
used. Showers should be limited in time with warm water and mild cleansing agents 
used. See Section 5.3 for swimming guidance. 
• 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 drug application. 
• Participants may use nonsedating, over-the-counter antihistamines as needed during 
the study. 
6.6.2. 
Restricted Medications and Procedures 
The following are permitted during the study under specified conditions: 
• Use of any over-the-counter, nonprescription preparations or prescription medications 
deemed acceptable by the investigator are permitted under an established and stable 
treatment regimen (as long as not otherwise prohibited under this Protocol). 
• Allergen immunotherapy (desensitization) is not recommended during the study 
unless deemed necessary by the investigator. 
• 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 drug 
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 drug. 

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6.6.3. 
Prohibited Medications and Procedures 
Refer to the study exclusion criteria (Section 5.2) for the full list of medications (and their 
required washout duration) that are prohibited during the study, which include, but are not 
limited to, the following: 
• Prescription medication for sleep or over-the-counter sleep aids (including H1 
sedating antihistamines) 
• Hypnotics (prescribed or over-the-counter) 
• Melatonin 
• Valerian 
• Nonstimulant diet pills 
• Barbiturates 
• Benzodiazepines 
• GABA analogues 
• Hydantoins 
• Phenyltriazines 
• Antihistamines (centrally-acting H1, including over-the-counter) with known sedating 
effects; nonsedating antihistimines (eg, Claritin™) are not prohibited 
− Diphenhydramine HCl 
− Carbinoxamine 
− Doxylamine 
− Dimenhyrinate 
− Triprolidine 
− Bromopheniramine 
− Chlorphemamine 
− Hydroxyzine 
• Anxiolytics with known sedating effects 
− Lorazepam 
− Alprazolam 
− Buspirone 
• Stimulants 
− Amphetamines 
− Modafinil 
− Armodafinil 
− Methylfenidate 
− WAKIX (pitolisant) 
− Sunosi (solriamfetol) 
• Herbal preparations with sedating effects 
• Any investigational medication other than the study drug, including systemic or other 
topical JAK inhibitors. 
• Topical corticosteroids, tacrolimus, pimecrolimus, and PDE-4 inhibitors (Eucrisa®) 
• Other topical agents for AD (except bland emollients as noted in Section 6.6.1). 
• Treatment known to affect the course of AD. 

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• Systemic corticosteroids, methotrexate, cyclosporine A, azathioprine and biological 
therapies, or other immunosuppressant agents. 
• Phototherapy or tanning beds 
• Live-attenuated vaccination 
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: 
• 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. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
• Major changes to individual sleep pattern (eg, acute sickness, hospitalization, surgery, 
family emergency, unplanned vacation, etc) or travel plans that would interfere with 
sleep assessment during the study. 
• Device malfunction or other reason that would interfere with sleep data collection 
during the 7 days prior to baseline (ie, during Day −7 to Day -1) or prior to the 
Week 8 visit (ie, during Day 49 to Day 56). 
• The participant's AD worsens during the treatment period to an extent that, in the 
opinion of the investigator, it requires treatment with study drug over an area 
exceeding 20% BSA. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug/treatment 
administration in the investigator's opinion, the sponsor should be consulted for 
instruction on handling the participant. 

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7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the ET 
visit should be conducted. Reasonable efforts should be made to have the participant return for a 
follow-up visit (see Table 3 and Table 4). The last date of the last application of study drug and 
the reason for discontinuation of study drug will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The ET visit should be performed and date recorded in eCRF. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug-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 discontinuation and follow-up and for any further 
evaluations should conform to the requirements of the ET visit (see Table 3 and Table 4). 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. 

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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
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. An ICF 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 including optional 
samples/procedures (eg, optional biopsy) and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the country in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that 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. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF must be provided to the participant or the participant's legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICF (if rescreened > 42 days after the 
initial screening) and must be assigned a new participant number. 

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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (first day of the treatment period). Informed consent must be obtained before performing 
any study-specific procedures. The screening period may not exceed 42 days. Assessments that 
are required to demonstrate eligibility may be performed over the course of 1 or more days 
during the screening process, including collecting 7-day averages of the number of hours the 
participant sleeps at night during the screening and pretreatment sleep assessments. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment or the administration of study drug. Tests with results that fail eligibility requirements 
may be repeated once during screening if the investigator believes the results to be in error. For 
screening assessments that are repeated, the most recent available result before the treatment 
period 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); however, participants who do not meet 
the criteria for the Itch NRS score, PROMIS Sleep Disturbance – Short Form 8b score, and TST 
requirements (determined using data from the Ōura Ring wearable device 
 
wireless device) during screening may not be rescreened. The participant is not required to sign 
another ICF if the rescreening occurs within the participant's screening period (which may be up 
to 42 days in duration, depending on medications a participant is taking that require a washout) 
from the previous ICF signature date. 
During the screening period, participants will washout any AD treatments or other excluded 
treatments. The screening sleep assessment may occur during or after this washout; the 
pretreatment sleep assessment will occur after completion of the washout. 
See Section 5.4 for information regarding screen failures and the rescreening procedure for 
participants. See Section 5.5 for information regarding replacement of participants. 
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 assignment. Additionally, the IRT system will be 
contacted at each clinic visit (see Table 3) to update the study drug supply. The IRT system will 
also be used, during the study visits, to recalculate the amount of study drug to be dispensed if 
the participant's %BSA of AD lesions to be treated has changed. In addition, the IRT system will 
be utilized to distribute the wireless and wearable sleep monitoring devices. Additional details 
are provided in the IRT Manual. 
8.1.4. 
Visit Reminders and Distribution of eDiary and Sleep Monitoring Devices 
Participants will be provided with a reminder notification indicating the date/time of the next 
visit. 
At screening, participants will be issued a handheld device (eDiary) to complete PROs (see 
Section 8.3) and to record application of study drug. Each participant will be provided 

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instructions for completing the diary from screening through Week 8 or treatment 
discontinuation. Compliance with the eDiary will be assessed electronically at the visits noted in 
the SoA (see Table 3). If the participant is not completing the eDiary frequently enough, the site 
staff will be informed so compliance can be addressed in a timely manner. 
Study sites will contact participants 1 week before the baseline visit to confirm compliance with 
eDiary assessments. Detailed directions for the administration of the eDiary will be provided in 
the Study Manual. 
During screening, participants will also be provided with a wearable device (Ōura Ring) and a 
 (see Section 8.2.1). It may take up to 
7 days during the screening period for the devices to be installed and/or configured and ready for 
sleep monitoring. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demography and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses. Medical history will include relevant medical or surgical treatment 
within the past 2 years that are considered to be clinically significant by the investigator. 
8.1.5.2. 
Medical and Treatment History 
Relevant medical and treatment history for the past year will be collected at screening by the 
investigator or qualified designee. Details regarding the participant's current and history of AD 
and any comorbid sleep-related disorders, including date of diagnosis, relevant disease 
characteristics, and prior treatments, including systemic treatments, radiation, and surgical 
procedures, will be recorded. A medical history of other conditions related to AD will also be 
collected at this time. 
8.2. 
Efficacy Assessments 
8.2.1. 
Health Economics 
Health economic parameters are not evaluated in this study. 
8.2.2. 
Monitoring Sleep 
Sleep patterns of participants enrolled in the study will be monitored during the screening period 
recording, or GPS capabilities. The mobile device application does not collect any additional 
data outside of the required data for this study. 

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During the screening period, the participant will be provided with an Ōura Ring wearable device, 
which will be used initially to determine the degree of sleep disturbance during the screening 
sleep assessment (ie, to confirm the participant meets the eligibility requirement for a 7-day 
average TST ≤ 6.5 hours/night). If the 7-day average TST during the screening sleep assessment 
is > 6.5 hours/night and the participant was undergoing a washout for AD treatments or other 
excluded treatments at the time, the participant may continue to monitor sleep for up to an 
additional 7 days while not on medication as part of the eligibility assessment. 
Participants who have a 7-day average TST ≤ 6.5 hours/night during the screening sleep 
assessment and who meet all other inclusion criteria and none of the exclusion criteria will then 
The sponsor of the study will not receive any identifiable data from either device. No identifiable 
data will be reported as a part of the study results. The participant ICF will include details of 
device functionality, data collected, and intended use of the data. Both devices will report 
sleep-related measurements: TST, 
 
 
8.2.2.1. 
Total Sleep Time 
Total sleep time is the total amount of time spent during a planned sleep episode. Participants 
with AD may experience reduced TST due to episodes of awakening due to itching. Decreased 
TST is indicative of increased sleep disturbance. A treatment alleviating itch among participants 
with AD may increase TST. 

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8.2.3. 
Investigator's Global Assessment 
IGA is an overall eczema severity rating on a 0 to 4 scale that will be assessed during site visits 
as outlined in the SoA (see Table 3). 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: www.homeforeczema.org 

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8.2.4. 
Body Surface Area 
Total %BSA afflicted by AD will be estimated at each visit as outlined in the SoA (see Table 3). 
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 scalp) of 3% to 20% to be eligible for the 
study. 
8.2.5. 
Photography of Target Lesion 
Photography of the participant’s target lesion will be performed as outlined in the SoA (see 
Table 3). On Day 1, the photographs will be taken at the clinic site, and after Day 1, participants 
will take photographs of the same lesion at home weekly up to Week 8 (the Week 8 photographs 
may be taken by the participant at home prior to the visit or may be taken at the clinic site during 
the visit). 
The target lesion will be selected by the investigator at the Day 1 (baseline) visit and should be at 
least 5 cm2 in size. Photographs will be taken via 2 views (close-up and regional body area) 
throughout the treatment period, even if the AD lesion has cleared or disappeared. A note should 
be made in the participant's source documents of the target lesion location, and the photographs 
can be marked with the location of the target lesion at each visit. 
Participants will be instructed to avoid taking pictures of areas that may lead to the identification 
of the participant (eg, face). Any pictures that may include identifiable information will be 
de-identified prior to the investigator accessing the pictures. The participants will be encouraged 
to take pictures more frequently than required. 
Participants will be provided with a device (eg, the eDiary) that is equipped with a camera 
capable of taking photographs. Participants will be instructed to take each picture with the same 
consistency (background, lighting, etc). De-identified pictures will be stored in a secure server 
and will be used to demonstrate the effectiveness of the treatment using a visual medium. 
8.3. 
Patient-Reported Outcomes 
The frequency of collection for each PROs is specified in the SoA (see Table 3). 
The 4 questions comprising the STOP portion of the STOP-BANG (see Section 8.3.1) 
questionnaire will be completed as part of the screening assessment. The following other PROs 
will be completed by the participants at home using an eDiary that will be issued at the time of 
screening. 
• 
• 

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8.3.1. 
STOP Criteria for High-Risk Obstructive Sleep Apnea 
The STOP criteria from the STOP-BANG questionnaire will be administered during screening to 
determine if a participant is at high risk for obstructive sleep apnea. Participants answering "Yes" 
to all 4 questions below will not be enrolled into the study: 
1. Do you snore loudly? (Louder than talking or loud enough to be heard through closed 
doors) 
2. Do you often feel tired, fatigued, or sleepy during the daytime? 
3. Has anyone observed you stop breathing during sleep? 
4. Do you have (or are you being treated for) high blood pressure? 

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8.4. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see Table 3). 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.4.1. 
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 that begin or worsen after 
informed consent should be recorded on the Adverse Events Form in the eCRF regardless of the 
assumption of a causal relationship with the study drug. Conditions that were already present at 
the time of informed consent should be recorded on the Medical History Form in the eCRF. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
that are considered related to the study drug/procedures, or that caused the participant to 
discontinue the study drug. Care will be taken not to introduce bias when detecting AEs and/or 
SAEs. Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences. Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments. The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.4.2. 
Physical Examinations 
Physical examinations will be conducted at the timepoints listed in the SoA (see Table 3). 
At the screening visit, a comprehensive physical examination should be conducted. The 
comprehensive physical examination will include assessments of the following organ or body 

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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. 
During the study, participants will be assessed by the investigator or medically qualified 
designee per institutional standard of care. These assessments should be an evaluation as 
indicated by participant symptoms, AEs, or other findings and documented on the AE eCRF. 
Abnormalities identified after the first dose of study treatment constitute an AE if they are 
considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug. Investigators should pay special attention to clinical 
signs related to previous serious illnesses. 
8.4.3. 
Vital Signs 
Vital signs will be collected at the time points listed in the SoA (see Table 3). 
Vital sign measurements (to be taken before blood 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. Height and weight will also be 
assessed at screening. 
Abnormal vital sign results identified after the first dose of study treatment constitute an AE if 
they are considered clinically meaningful, induce clinical signs or symptoms, or require 
concomitant therapy. 
8.4.4. 
Laboratory Assessments 
See Table 9 for the list of clinical laboratory tests to be performed and Table 4 for the timing and 
frequency. A central laboratory will perform all clinical laboratory assessments for safety 
(ie, blood chemistries, hematology assessments, coagulation tests, and urinalysis). Additional 
testing may be required by the sponsor based on emerging safety data. Additional tests may also 
be performed if clinically indicated. 
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 
drug should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 

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Table 9: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology 
Serology 
• Albumin 
• ALP 
• ALT 
• AST 
• Bicarbonate or CO2 
• 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 1.5 × ULN) 
• Total protein 
Complete blood count, including: 
• Hemoglobin 
• Mean corpuscular volume 
• Hematocrit 
• Platelet count 
• Mean platelet volume 
• In samples with abnormalities in platelet count 
or size distribution (as indicated by an 
automated analyzer), a blood film should be 
examined. 
• Red blood cell count 
• Red blood cell distribution width 
• WBC count 
Differential count (% and absolute values), 
including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
• HIV antibody 
Pregnancy Testing 
Women of nonchildbearing potential will have 
FSH tested at screening. 
Women of childbearing potential will require the 
following: 
• Serum pregnancy test at screening. 
• Urine pregnancy test at all other in-clinic visits 
and as medically indicated or per country or 
institutional requirements. 
Pregnancy tests (serum or urine) should be 
repeated if required by local regulations. 
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. 

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8.4.4.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening. Urine pregnancy tests 
will be performed locally as outlined in Table 4, and as medically indicated (eg, in case of loss of 
menstrual cycle, when pregnancy is suspected). 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 drug/treatment and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 
8.4.4.2. 
Serology 
HIV assessments will be performed at the screening visit to rule out HIV infection. Serology 
tests should be performed early in the screening process due to the length of time needed to 
obtain the results. Additional tests may be performed if clinically indicated. 
8.5. 
Pharmacokinetic Assessments 
There is no plan to assess pharmacokinetic parameters in this study. 
8.6. 
Pharmacodynamic and Translational Assessments 
Pharmacodynamic parameters are not evaluated in this study. 
8.7. 
Unscheduled Visits 
Unscheduled study visits may occur at any time medically warranted including when participants 
develop new areas of AD. Any assessments performed at those visits should be recorded in the 
eCRF. 
8.8. 
End of Treatment and/or Early Termination 
If a decision is made that the participant will permanently discontinue study drug, then the ET 
visit should be conducted. If the ET visit coincides with a regular study visit, then the ET 
evaluations will supersede those of that scheduled visit, and the data should be entered in the ET 
page in the eCRF. If this decision does not coincide with a regular visit, reasonable efforts should 
be made to have the participant return to the site to have the ET procedures completed. The 
participant should be encouraged to return for the follow-up visit. 
8.9. 
Follow-Up 
8.9.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT (Week 8) visit (or ET visit, if 
applicable) and the scheduled follow-up visit, which should occur 30 days after the EOT visit (or 
after the last dose of study drug if the EOT visit was not performed). Adverse events and SAEs 
must be reported up until at least 30 days after the last dose of study drug, the date of the 

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follow-up visit, or until toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. Reasonable efforts should be made to have the participant return for the 
follow-up visit and report any AEs that may occur during this period. 

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

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

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

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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5. If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2: Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4: Life-threatening consequences; urgent treatment indicated. 
• Grade 5: Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB for study drug in making 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 drug administration, 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 eCRFs until it has 
resolved or until it is judged to be permanent; assessment should be made at each visit (or more 

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frequently if necessary) of any changes in severity, the suspected relationship to the study drug, the 
interventions required to treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology. 
• New or updated SAE information will be recorded in the originally completed eCRF and reported to 
Incyte Pharmacovigilance (either via email/fax if paper SAE form is used or in the SAE EDC CRF) 
until resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
9.4. 
Reporting of Serious Adverse Events 
All SAEs, regardless of suspected causality (eg, relationship to study drug or study 
procedure[s]), occurring after the participant has signed the ICF through the last study visit or 
30 days after the last application of study drug, whichever occurs later, must be reported to the 
sponsor (or designee) immediately, without delay but not later than within 24 hours of learning 
of its occurrence, unless otherwise specified by the Protocol. The investigator will submit any 
updated SAE data to the sponsor (or designee) immediately, without delay but not later than 
within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and they consider the event to be 
reasonably related to the study drug or study participation, 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 of a SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the ruxolitinib cream IB for the study drug (new occurrence) 
and is thought to be related to the sponsor's study drug, the sponsor or its designee may urgently 
require further information from the investigator for reporting to health authorities. The sponsor 
or its designee may need to issue an Investigator Notification to inform all investigators involved 
in any study with the same drug that this SAE has been reported. Suspected unexpected serious 
adverse reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC, or as per national regulatory requirements 
in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 

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will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Events Form in the eCRF. 
• The investigator must also complete the Incyte Serious Adverse Event Report Form, in English. 
Refer to the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Facsimile or email transmission of the Serious Adverse Event Report Form is the preferred method 
to transmit this information to the PhV/designee. The contact information of the sponsor's 
study-specific representatives is listed in the investigator manual provided to each site. The original 
copy of the Serious Adverse Event Report Form and the confirmation sheet must be kept at the study 
site. 
• Follow-up information is recorded on an amended or new Serious Adverse Event Report Form, with 
an indication that it is follow-up to the previously reported SAE and the date of the original report. 
The follow-up report should include information that was not provided on the previous Serious 
Adverse Event Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or participant disposition (eg, continued or withdrew from study participation). Each 
recurrence, complication, or progression of the original event should be reported as follow-up to that 
event, regardless of when it occurs. 
• In rare circumstances and in the absence of facsimile or computer equipment, notification by 
telephone is acceptable with a copy of the Incyte Serious Adverse Event Report Form sent by 
overnight mail or courier service. Initial notification via telephone does not replace the need for the 
investigator to complete and sign the Serious Adverse Event Report Form within the designated 
reporting time frames. 
• Contacts for SAE reporting can be found in the Study Manual. 
9.5. 
Events of Clinical Interest 
Not applicable. 
9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 

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9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method. When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety 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 drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later. Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy of a study participant must be recorded 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 drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB. Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications. Any 
important new safety information should be discussed with the participant during the study, as 
necessary. If new significant risks are identified, they will be added to the ICF. 
There are no study-specific special warnings or precautions in this study. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor. All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 

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The investigator or 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 Overdose 
There has been no clinical experience with overdose of ruxolitinib cream. Treatment of overdose 
should consist of general supportive measures. 

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10. 
STATISTICS 
10.1. 
Sample Size Determination 
All participants will receive treatment with ruxolitinib cream 1.5% BID. The primary analysis 
will compare the difference in TST between baseline and Week 8 (see Section 10.4.1). If the true 
increase in TST is 30 minutes, a sample size of 70 participants will provide > 90% power to 
reject the null hypothesis at α = 0.05. Accounting for loss to follow-up and device malfunction, a 
total of 100 participants will be enrolled into the study. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 10. The primary analysis will be performed in 
the PP population. 
Table 10: 
Populations for Analysis 
Population 
Description 
STP 
The STP is defined as study eligible participants who received at least 
23 applications in any interval of 14 consecutive days of study drug 
administration BID (ie, participants with ≤ 5 missed applications out of 28 in any 
14-day interval across the 8-week treatment period are included). 
PP 
The PP population includes all participants in the STP population who are 
considered to be sufficiently compliant with the Protocol. 
Safety 
The safety population includes all participants who received at least 1 application 
of study drug during the treatment period. 
10.3. 
Level of Significance 
The hypotheses for the primary and secondary endpoints (Section 10.4) will be tested at level of 
significance 0.05. All analyses described in primary, secondary, and exploratory objectives will 
be conducted and will be assessed at 0.05 level of significance. No adjustments for multiple 
testing will be performed. 
10.4. 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the participant 
populations to be included in the analyses and procedures for accounting for missing, unused, 
and spurious data. This section is a summary of the planned statistical analyses of the primary, 
secondary, and exploratory endpoints. 

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10.4.1. 
Sleep Assessment Endpoints 
The following endpoints will be evaluated to determine reduction in sleep disturbance: 
• TST: The total amount of time spent during a planned sleep episode 
• 
• 
• 
• 
The baseline assessments of sleep will be determined as the average of the 7 days prior to Day 1. 
Participants with data for at least 4 days out of the 7 days prior to Day 1 will be included in the 
analysis. The Week 4 and Week 8 sleep assessments will be determined using the average of the 
sleep measurements during the 7 days prior to Week 4 (Day 21 to Day 28) and Week 8 (Day 49 
to Day 56), respectively. Participants with at least 4 days of sleep measurements during Week 4 
and Week 8 assessment periods will be included in the analysis. The number of days with 
available data will be used to calculate the average for the week. The reduction in sleep 
disturbance will be calculated as the difference between the sleep assessment measures between 
Week 8 and baseline assessments. 
10.4.2. 
Primary Analysis 
The primary endpoint of the study is change from baseline in mean TST as measured by Ōura 
Ring wearable device at Week 8. A paired t-test will be used to test the hypothesis below for 
participants with both TST measurements at baseline (as determined during the pretreatment 
sleep assessment) and Week 8 (Day 49 to Day 56): 
H0: TST(Week 8) – TST (Baseline) = 0 
H1: TST(Week 8) – TST (Baseline) ≠ 0 
Mean, standard deviation, 95% confidence interval of TST at each evaluable timepoint will be 
presented. Mean pair-wise difference and 95% confidence interval of the difference will be 
presented. The hypotheses above will be tested at level of significance 0.05. The primary 
analysis will include participants with both baseline and Week 8 TST assessments available. 
Missing data imputation (LOCF) may be considered as a sensitivity analysis. 

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10.4.3. 
Secondary Analysis 
The secondary endpoint is the PROMIS Sleep Disturbance – Short Form 8b score. A paired t-test 
will be used to test the hypothesis below for participants with PROMIS Sleep Disturbance – 
Short Form 8b score at both baseline and Week 8. 
H0: PROMIS Sleep Disturbance – Short Form 8b score (Week 8) – PROMIS Sleep Disturbance 
– Short Form 8b score (Baseline) = 0 
H1: PROMIS Sleep Disturbance – Short Form 8b score (Week 8) – PROMIS Sleep Disturbance 
– Short Form 8b score (Baseline) ≠ 0 
Mean, standard deviation, and 95% confidence interval of overall sleep score at each evaluable 
timepoint will be presented. Mean pair-wise difference and 95% confidence interval of the 
difference will be presented. The hypotheses above will be tested at level of significance 0.05. 
The secondary analysis will include participants with both baseline and Week 8 PROMIS Sleep 
Disturbance – Short Form 8b scores available. Missing data imputation (LOCF) may be 
considered as a sensitivity analysis. 
10.4.4. 
Exploratory Analysis 
10.4.5. 
Safety Analyses 
Safety analyses will be conducted for the safety population. 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug. Analysis of AEs will be limited to TEAEs, but data listings will include 
all AEs regardless of their timing to study drug administration. Adverse events will be tabulated 
by the MedDRA preferred term and system organ class. Severity of AEs will be based on the 
National Cancer Institute CTCAE v5.0 using Grades 1 through 5. The subset of AEs considered 
by the investigator to have a relationship to study drug will be considered to be treatment-related 
AEs. If the investigator does not specify the relationship of the AE to study drug, then the AE 
will be considered treatment-related. The incidence of AEs and treatment-related AEs will be 
tabulated. 
Descriptive statistics and mean change from baseline will be determined for quantitative 
variables (eg, laboratory assessments, vital signs [blood pressure, pulse, respiratory rate, and 
body temperature]) at each assessment time. 
10.4.6. 
Ad Hoc and Post Hoc Analyses 
Additional ad hoc and/or post hoc analyses including, but not limited to, assessing the 
association between different sleep assessment measures, the association between PROs and 
sleep assessment measures, changes in additional sleep-related metrics reported by wearable and 

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wireless devices, etc may be conducted upon completion of the primary analysis. All ad hoc and 
post hoc analyses will be documented in a separate ad hocSAP. 
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, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC. Each investigator is responsible for enrolling participants who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study 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, 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, 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 
or further processing. 

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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. 
• Data from the wireless and wearable devices will not be integrated into the eCRFs. 
The data from the wireless and wearable devices will be directly integrated into the 
study database. 
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 monitoring plan. 
Quality tolerance limits will be predefined in the operational manual subsection (or equivalent) 
to identify systematic issues that can impact participant’s 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 
QTLs and remedial actions taken, including reporting to IRBs/ECs if applicable, will be 
summarized in the clinical study report. 
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 

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limited to HIPAA and GDPR) as applicable. Appropriate notice, or notice and consent (as may 
be required for each applicable jurisdiction), for collection, use, disclosure, and/or transfer (if 
applicable) of personal information must be obtained in accordance with local data protection 
laws. 
Participant names will not be supplied to the sponsor or its designee. Only the participant number 
will be recorded in the eCRF; if the participant's name appears on any other document (eg, 
laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee. Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
11.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply. For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator. These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form. During a covered clinical study, any 
changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee. At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations. In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.6. 
Publication Policy 
By signing the study Protocol, the investigator and their institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals. Study results will be published in accordance with applicable local and national 
regulations. If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement. The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee. A signed agreement will 
be retained by the sponsor or its designee. 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 

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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 treatment development. 

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12. 
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Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl 
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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.  
− Female participants 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 
• 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 of 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 treatment. 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 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 
drop-out 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 
If there are local travel restrictions, isolation requirements, or the investigator determines it to be 
unsafe for participants to attend the participant's scheduled study visit, the site staff may conduct 
the visit via telemedicine (phone or video calls) to minimize participant risk as follows: 
• Screening Period: 
− The screening visit must be performed in person. 
• Treatment Period: 
− The Day 1/baseline visit must be performed in person. If the baseline visit cannot 
be performed on-site at the end of the 7-day pretreatment sleep assessment, the 
participant will be considered to have failed screening. Participants who screen 
failed due to COVID-19 may be rescreened at a later time, if feasible. 
− The Week 4 and Week 8/EOT/ET visits must be performed in person. 
• Safety Follow-Up Period: 
− The follow-up visit may be conducted via telemedicine, if necessary. 
• Telemedicine Visits: 
− At a minimum, a review of AEs, concomitant medications, and study drug 
application compliance must be completed and recorded in the EDC. 
− No BSA assessments can be performed even if the telemedicine visit is a video 
call or photography of the active lesion areas are provided. 
− Patient reported outcomes measurements recorded in the eDiary should be 
completed as scheduled prior to the telemedicine visit, but collected at the next 
on-site visit of the participant. 
− All assessments not performed will be recorded in the EDC as Protocol deviations 
and reason documented as COVID-19. 

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Investigational Medicinal Product Dispensation and Distribution 
In the event a participant is not be able to attend an on-site study visit due to COVID-19, and in 
order to ensure the continuity of providing participants' clinical supplies within the constraints 
imposed by the pandemic, the site staff may decide to supply study treatment to participant as 
follows: 
• Adequate supplies of study drug can be shipped to the participant by the study staff 
using a third-party service with approval from the participant. The third-party vendor 
will be agreed upon with the sponsor. 
• The participant may request, with prior arrangement/agreement with the site, an 
authorized individual (a relative or delegate) to retrieve the study drug from the study 
site if the participant is unable to personally to do so. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed; however, the site monitor will continue to employ 
off-site monitoring practices such as routine communication methods (eg, phone calls, emails, 
video visits) with the sites to get information on trial progress, participant status, and information 
on issue resolution as detailed in the Data Monitoring Guidelines. 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 carry out the final drug accountability for 
reconciliation purposes, and the operation cannot be postponed, it may be carried out by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training. The study treatment can be returned to the sponsor by the hospital pharmacy directly, or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Direct Contracts with Third Parties/Specialized Service Companies 
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight. In such situations, the investigator is required to provide the 
local physician with a delegation letter listing all delegated activities. The sponsor, through the 
study investigator or institution, will reimburse the local physician for the test/procedures 
conducted outside of the standard of care. 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participant (participant's parent[s]/legal guardian) for any 
extraordinary expenses with prior sponsor approval for AEs that are related to study drug, 
keeping appropriate documentation as evidence (eg, travel expenses for the local laboratory 
visit[s], the costs of local [proximate] laboratory tests). 

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APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Not applicable. 

Signature Page for VV-CLIN-020842 v1.0
Signature Page for VV-CLIN-020842 v1.0
Approval
r
 Data Science, Dermatology
21-Jun-2022 19:22:12 GMT+0000
Approval
prover
 Medical Affairs, Inflammation & Auto
21-Jun-2022 20:50:09 GMT+0000