Clinical trial NCT04839380
Conditions: Atopic Dermatitis
Keywords: ruxolitinib Itch Chronic Pruritus
Sponsor: Incyte Corporation
Start date: 2021-10-12; Completion date: 2022-11-18
Enrollment: 49 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to evaluate the effect of ruxolitinib cream on itch in participants with Atopic Dermatitis.

Detailed description:

Arms: arm 1: ruxolitinib cream 1.5% will be applied twice daily as a thin film.
Interventions: intervention 1: ruxolitinib cream
Intervention descriptions: intervention 1: ruxolitinib cream 1.5% will be applied twice daily as a thin film

Protocol documents:
Prot_000.pdf: 
NCT Number:      NCT04839380
Document Date:  Clinical Study Protocol Version 4: 9-May-2022
Official Title:      An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% Cream 
on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 


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Protocol INCB 18424-901 Am 3 
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Clinical Study Protocol 
TITLE PAGE 
INCB 18424-901 
An Open-Label, Single-Arm Study to Evaluate the Effect of 
Ruxolitinib 1.5% Cream on Itch in Adult Participants With 
Atopic Dermatitis (SCRATCH-AD) 
Product: 
Ruxolitinib cream 
IND Number: 
 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
22 FEB 2021 
Amendment 1: 
30 MAR 2021 
Amendment 2: 
13 AUG 2021 
Amendment 3: 
09 MAY 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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Protocol INCB 18424-901 Am 3 
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INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-901 Protocol Amendment 3 (dated 09 MAY 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. 
Ruxolitinib ..................................................................................................................17 
2.1.2. 
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 ..................................................................................................18 
2.3. 
Benefit/Risk Assessment ............................................................................................19 
2.3.1. 
COVID-19 Pandemic ..................................................................................................20 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................21 
4. 
STUDY DESIGN .......................................................................................................23 
4.1. 
Overall Design ............................................................................................................23 
4.1.1. 
Study Conduct During the COVID-19 Pandemic ......................................................25 
4.2. 
Overall Study Duration ...............................................................................................26 
4.3. 
Study Termination ......................................................................................................26 
5. 
STUDY POPULATION .............................................................................................27 
5.1. 
Inclusion Criteria ........................................................................................................27 
5.2. 
Exclusion Criteria .......................................................................................................28 
5.3. 
Lifestyle Considerations .............................................................................................31 
5.4. 
Screen Failures ............................................................................................................31 
5.5. 
Replacement of Participants .......................................................................................32 
6. 
STUDY TREATMENT ..............................................................................................33 
6.1. 
Study Treatment Administered ...................................................................................33 
6.2. 
Preparation, Handling, and Accountability ................................................................34 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................35 
6.4. 
Study Treatment Compliance .....................................................................................35 


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6.5. 
Dose Modifications .....................................................................................................35 
6.5.1. 
Criteria and Procedures for Application Interruptions and Adjustments of 
Study Drug ..................................................................................................................36 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................37 
6.6. 
Concomitant Medications and Procedures .................................................................38 
6.6.1. 
Permitted Medications and Procedures ......................................................................38 
6.6.1.1. 
Emollients ...................................................................................................................38 
6.6.1.2. 
Other Permitted Therapies ..........................................................................................38 
6.6.2. 
Restricted Medications and Procedures ......................................................................39 
6.6.3. 
Prohibited Medications and Procedures .....................................................................39 
6.7. 
Treatment After the End of the Study .........................................................................40 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................41 
7.1. 
Discontinuation of Study Treatment ...........................................................................41 
7.1.1. 
Reasons for Discontinuation .......................................................................................41 
7.1.2. 
Discontinuation Procedures ........................................................................................41 
7.2. 
Participant Withdrawal From the Study .....................................................................42 
7.3. 
Lost to Follow-Up.......................................................................................................42 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................43 
8.1. 
Administrative and General Procedures .....................................................................43 
8.1.1. 
Informed Consent Process ..........................................................................................43 
8.1.2. 
Screening Procedures ..................................................................................................44 
8.1.3. 
Participant Numbering and Treatment Assignment ...................................................44 
8.1.4. 
Diaries .........................................................................................................................44 
8.1.5. 
Demography and Medical History ..............................................................................45 
8.1.5.1. 
Demographics and General Medical History .............................................................45 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................45 
8.2. 
Efficacy Assessments .................................................................................................45 
8.2.1. 
Health Economics .......................................................................................................45 
8.2.2. 
Assessed by Participant ..............................................................................................45 
8.2.2.1. 
Pruritus Numeric Rating Scale ...................................................................................45 
8.2.2.2. 
Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication ...............46 
8.2.3. 
Assessed by Investigator .............................................................................................46 


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8.2.3.1. 
Investigator's Global Assessment ...............................................................................46 
8.2.3.2. 
Body Surface Area ......................................................................................................47 
8.2.3.3. 
Eczema Area and Severity Index ................................................................................47 
8.2.3.4. 
Medical Photography ..................................................................................................47 
8.2.3.5. 
Transepidermial Water Loss .......................................................................................48 
8.3. 
Safety Assessments .....................................................................................................48 
8.3.1. 
Adverse Events ...........................................................................................................48 
8.3.2. 
Physical Examinations ................................................................................................49 
8.3.2.1. 
Comprehensive Physical Examination .......................................................................49 
8.3.2.2. 
Targeted Physical Examination ..................................................................................49 
8.3.3. 
Vital Signs ..................................................................................................................49 
8.3.4. 
Laboratory Assessments .............................................................................................49 
8.3.4.1. 
Chemistry, Serology, Hematology, and Urinalysis ....................................................52 
8.3.4.2. 
Pregnancy Testing ......................................................................................................52 
 
52 
 
52 
 
53 
 
54 
8.6. 
Unscheduled Visits .....................................................................................................54 
8.7. 
End of Treatment and/or Early Termination ..............................................................54 
8.8. 
Follow-Up ...................................................................................................................54 
8.8.1. 
Safety Follow-Up ........................................................................................................54 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................55 
9.1. 
Definition of Adverse Event .......................................................................................55 
9.2. 
Definition of Serious Adverse Event ..........................................................................56 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........57 
9.4. 
Reporting of Serious Adverse Events .........................................................................59 
9.5. 
Events of Clinical Interest ..........................................................................................60 
9.5.1. 
Adverse Events of Special Interest .............................................................................60 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................61 
9.7. 
Pregnancy ...................................................................................................................61 
9.8. 
Warnings and Precautions ..........................................................................................61 


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9.9. 
Product Complaints ....................................................................................................61 
9.10. 
Treatment of Overdose ...............................................................................................62 
10. 
STATISTICS ..............................................................................................................63 
10.1. 
Sample Size Determination ........................................................................................63 
10.2. 
Populations for Analysis .............................................................................................63 
10.3. 
Level of Significance ..................................................................................................63 
10.4. 
Statistical Analyses .....................................................................................................64 
10.4.1. 
General Considerations ...............................................................................................64 
10.4.2. 
Primary Analysis ........................................................................................................64 
10.4.3. 
Secondary Analysis ....................................................................................................64 
10.4.4. 
Safety Analyses ..........................................................................................................64 
 
65 
10.4.6. 
Other Analysis ............................................................................................................65 
10.5. 
Interim Analysis ..........................................................................................................65 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................66 
11.1. 
Investigator Responsibilities .......................................................................................66 
11.2. 
Data Management .......................................................................................................67 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................69 
11.4. 
Financial Disclosure ...................................................................................................69 
11.5. 
Publication Policy .......................................................................................................69 
11.6. 
Study and Site Closure................................................................................................70 
12. 
REFERENCES ...........................................................................................................71 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................73 
APPENDIX B. DIAGNOSTIC CRITERIA FOR ATOPIC DERMATITIS ..............................74 
APPENDIX C. PRURITUS NUMERIC RATING SCALE .......................................................75 
APPENDIX D. ECZEMA AREA AND SEVERITY INDEX ...................................................76 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................77 
 


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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: 
Objectives and Endpoints ...........................................................................................21 
Table 5: 
Sequence and Timing of mPP-NRS, PP-NRS, and Study Drug Applications 
on Days 1 and 2 ..........................................................................................................24 
Table 6: 
Study Treatment Information .....................................................................................33 
Table 7: 
Guidelines for Interruption and Restarting of Treatment Applications if 
Adverse Event is Deemed Related to the Study Drug ................................................37 
Table 8: 
Prohibited Therapies or Procedures ............................................................................40 
Table 9: 
Investigator's Global Assessment ...............................................................................47 
Table 10: Required Laboratory Analytes ....................................................................................51 
53 
Table 12: Populations for Analysis .............................................................................................63 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
COVID-19 
Coronavirus disease 2019 
CTCAE 
Common Terminology Criteria for Adverse Events 
EASI 
Eczema Area and Severity Index 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
ET 
early termination 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GFR 
glomerular filtration rate 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IGA 
Investigator Global Assessment 
IGA-TS 
Investigator Global Assessment-Treatment Success 
(IGA score of 0 or 1 with ≥ 2-grade improvement from baseline) 
IRB 
institutional review board 
ITT 
intent-to-treat 
JAK 
Janus kinase 
LMW 
low molecular weight 
MCID 
minimal clinically important difference 


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Abbreviations and 
Special Terms 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
mPP-NRS 
modified peak pruritus numerical rating scale (current itch intensity) 
NRS 
numerical rating scale 
NSAID 
nonsteroidal anti-inflammatory drug 
PDE-4 
phosphodiesterase-4 
PP-NRS 
peak pruritus numerical rating scale (24-hour recall period) 
PUVA 
psoralen plus ultraviolet A 
QD 
once daily 
RNA 
ribonucleic acid 
 
 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SRM 
Study Reference Manual 
study drug 
Incyte medicinal investigational product used for this study 
TEAE 
treatment-emergent adverse event 
TEWL 
transepidermal water loss 
TSQM-9 
Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication 
ULN 
upper limit of normal 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
Protocol Number:  INCB 18424-901 
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 efficacy of ruxolitinib 1.5% 
cream on pruritus in participants with AD. 
Change from baseline in PP-NRS at Day 2 (24-hour 
recall period after first application). 
Secondary 
To evaluate the efficacy of ruxolitinib 1.5% 
cream in participants with AD. 
• Change from baseline in mPP-NRS (current itch 
intensity) at 15 and 30 minutes and 1, 2, 4, 6, and 
12 hours postdose on Day 1; and in PP-NRS from 
Day 3 through Day 29. 
• Proportion of participants achieving at least a 
1-grade decrease from baseline in mPP-NRS at 
15 and 30 minutes and 1, 2, 4, 6, and 12 hours 
postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• Proportion of participants achieving at least a 
2-grade decrease from baseline in mPP-NRS at 
15 and 30 minutes and 1, 2, 4, 6, and 12 hours 
postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• Time to MCID (≥ 2-grade reduction in PP-NRS 
and mPP-NRS from baseline). 
• Change from baseline in IGA at Day 8, Day 15, 
and Day 29. 
• Proportion of participants achieving the IGA-TS 
(score of 0 or 1 in IGA with at least a 2-grade 
reduction from baseline) at Day 8, Day 15, and 
Day 29. 
To evaluate the local and systemic safety and 
tolerability of ruxolitinib 1.5% cream in 
participants with AD. 
Incidence and severity of local and systemic AEs. 
Note:  For efficacy endpoints related to PP-NRS, baseline is defined as the average of all nonmissing PP-NRS 
(24-hour recall period) scores reported during the 7‑day run-in period.  For the other efficacy variables (including 
the mPP-NRS), baseline is defined as the last nonmissing value before or on Day 1 (prior to first application of study 
drug). 


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Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table. 
Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Relief of itch in patients with AD. 
Population 
Men or women, aged 18 to 65 years (inclusive) at screening, who have a 
history of AD (1% to 20% BSA involvement) for at least 6 months, have a 
history of chronic itch (≥ 3 months) prior to screening, and a baseline mean 
PP-NRS score ≥ 4.0 during the run-in period. 
Number of 
Participants 
Approximately 48 participants will be included in the study. 
Study Design 
This is an open-label, single-arm study evaluating the effect of ruxolitinib 
1.5% cream on itch. 
Estimated Duration 
of Study 
Participation 
Up to 37 days for screening period (including 7 days for the run-in period), 
28 ( 2) days for the treatment period, and 15 (± 2) days for safety follow-up.  
It is estimated that an individual will participate in the study for up to 
approximately 3 months (80 days). 
Data Monitoring 
Committee 
No 
Coordinating 
Principal 
Investigator 
Not applicable. 
Treatment Groups and Duration: 
Participants will apply ruxolitinib 1.5% cream BID as a thin film for approximately 28 days (last 
application on the evening prior to the Day 29 visit).  The study drug will be applied on all AD 
lesions, with a maximum treated area ≤ 20% BSA.  All original areas of involvement identified 
on Day 1 (even in the event of lesions clearing), and any new lesions (a maximum of ≤ 20% 
BSA can be treated) must be treated until the evening prior to the Day 29 visit.  On Day 1, 
participants will remain at the study center until after the 6-hour mPP-NRS assessment 
(approximately an 8-hour stay at the site).  The 12-hour mPP-NRS assessment will be done at 
home just prior to the evening study drug application.  On Day 8 and Day 15, the morning 
application of the study drug will be at the study center under the supervision of study staff.  
Other study drug applications will be self-administered by the participants at home. 
Study drug application will occur in the morning and evening, with approximately 12 hours 
between applications.  The evening dose should be applied at least 1 hour before bedtime. On 
Day 1, the mPP-NRS assessments should occur as close as possible to the scheduled time 
relative to the first study drug application. In addition, the 12-hour mPP-NRS should be 
completed before the evening study drug application. On Day 2, the PP-NRS assessment should 
be completed approximately 24 hours after the first study drug application and before the Day 2 
morning dose. Refer to Table 5 for the sequence and timing of these assessments and allowed 


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windows on Day 1 and Day 2. From Day 3 until the Day 29 visit, the PP-NRS should be 
completed once daily, at approximately the same time in the morning, and prior to the study drug 
application. 
Efficacy will be evaluated using the PP-NRS (worst itch over a 24-hour period), the mPP-NRS 
(current itch at the time of assessment), and the 5‑point IGA. 
The BSA and EASI will be used to evaluate the participant's AD severity on Day 1 and will be 
characterized during the study. 
Medical photographs of the target lesion(s) and application site AEs will be taken during the 
study. 
Participants will be asked to complete the TSQM-9 at the end of the treatment period (or at ET). 
Safety will be assessed by collecting AEs, performing comprehensive and targeted physical 
examinations, and evaluating clinical laboratory assessments. 
 
 
 
The study schema is shown in Figure 1. 
Figure 1: 
Study Design Schema 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.  However, the Coronavirus Disease 2019 (COVID-19) pandemic 
may impact the ability to adhere to the study procedures described in the SoA (see Table 3) due 
to challenges that include but are not limited to participant preferences, site closures, travel 
restrictions, and quarantines.  See Section 4.1.1 for more details on allowable, as necessary, 
modifications to the protocol due to COVID-19 restrictions. 


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Table 3: 
Schedule of Activities 
Visit Day (Range) 
Screening Period 
Treatment Period 
 
Safety Follow-Up 
Notes 
Days −37 to −1 
(Including a 7-Day 
Run-In Period) 
Day 1a 
Day 8 
(± 2) 
Day 15 
(± 2) 
Day 29 
(± 2) 
ETb 
Day 43 
(15 ± 2 Days After 
Last Application) 
Visit Week 
Week 1 
Week 2 
Week 4 
Week 6 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
General and disease medical 
history 
X 
X 
 
 
 
 
 
 
Fitzpatrick skin type 
evaluation 
X 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
 
Identification of a target 
lesion 
X 
X 
 
 
 
 
 
The target lesion should be representative 
of the participant's overall disease and 
should be treated with study drug. 
A target lesion that could accommodate 
all skin samples (tape strips, biopsies, 
skin microbiome, and TEWL) is the 
preferred scenario.  However, a second 
target lesion could be selected, if needed. 
BSA for eligibility (1-20% 
involvement excluding palms, 
soles, scalp, genitals, and 
folds) 
X 
X 
 
 
 
 
 
 
Identification of all lesions on 
a body diagram (BSA of 
treated area [up to 20%]) 
 
X 
 
 
 
 
 
All body areas can be treated. 
If new lesions appear during the study, 
the BSA of treated area may need to be 
re-evaluated during the treatment period.  
Of note, BSA of treated area includes 
active, cleared, and new lesions. 
A maximum of ≤ 20% BSA can be 
treated during the study. 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening Period 
Treatment Period 
 
Safety Follow-Up 
Notes 
Days −37 to −1 
(Including a 7-Day 
Run-In Period) 
Day 1a 
Day 8 
(± 2) 
Day 15 
(± 2) 
Day 29 
(± 2) 
ETb 
Day 43 
(15 ± 2 Days After 
Last Application) 
Visit Week 
Week 1 
Week 2 
Week 4 
Week 6 
Application of study drug BID 
 
X--------------------------------------X 
 
 
The morning application will be on-site 
on Days 1, 8, and 15.  Other study drug 
applications will be self-administered by 
the participants at home. 
Last application is on the evening prior to 
the Day 29 visit. 
Give access to the 
participant's eDiary 
X 
 
 
 
 
 
 
eDiary for PP-NRS. 
Participants will be trained on eDiary at 
the screening visit. 
Distribution of paper diary 
 
X 
 
 
 
 
 
Paper diary for study drug application. 
Participants will be trained on how to 
complete the paper diary at the Day 1 
visit. 
Review the participant's diaries 
 
X 
X 
X 
X 
X 
 
At each visit the participant will need to 
bring back both the paper diary and 
eDiary (tablet) for site review. The site 
will need to make copies of the paper 
diary before returning it to the 
participant. 
Dispense study drug 
 
X 
 
X 
 
 
 
 
Study drug accountability 
 
 
X 
X 
X 
X 
 
 
Collect study drug  
 
 
 
X 
X 
X 
 
 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
 
Comprehensive physical 
examination 
X 
 
 
 
 
 
 
 
Targeted physical 
examination 
 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
 
 
 
 
 
 
 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening Period 
Treatment Period 
 
Safety Follow-Up 
Notes 
Days −37 to −1 
(Including a 7-Day 
Run-In Period) 
Day 1a 
Day 8 
(± 2) 
Day 15 
(± 2) 
Day 29 
(± 2) 
ETb 
Day 43 
(15 ± 2 Days After 
Last Application) 
Visit Week 
Week 1 
Week 2 
Week 4 
Week 6 
Efficacy assessments 
PP-NRS  
X--------------------------------------------------------------X 
 
 
Completed at screening, immediately after 
signing consent, and then should be 
completed daily (in the morning) from 
screening to Day −1 and Day 2 to the Day 29 
visit (ie, before morning study drug 
application from Day 2 until the day prior to 
the Day 29 visit).  The PP-NRS should be 
performed before other efficacy assessments 
on visit days. 
See Table 5 for the sequence and timing of 
assessments on Day 1 and Day 2. 
mPP-NRS 
 
X 
 
 
 
 
 
Evaluated onsite at the following intervals: 
predose, 15 minutes, 30 minutes, and 1, 2, 4, 
6, and 12 hours after the morning study drug 
application.  The 12-hour mPP-NRS 
evaluation will be done at home, prior to the 
second daily study drug application. 
See Table 5 for the sequence and timing of 
assessments on Day 1 and Day 2. 
Medical photographs 
 
X 
X 
X 
X 
X 
 
Photograph of the target lesion(s) and any 
application site AEs. 
IGA 
X 
X* 
X* 
X* 
X 
X 
X 
* Performed before morning application. 
TEWL 
 
X* 
 
 
X 
 
 
* Performed before morning application. 
Total BSA% affected by 
AD 
 
X* 
 
X* 
X 
X 
X 
* Performed before morning application. 
EASI 
 
X* 
 
X* 
X 
X 
X 
* Performed before morning application. 
TSQM-9 
 
 
 
 
X 
X 
 
 
Laboratory assessments 
HIV 
X 
 
 
 
 
 
 
 
Serum chemistries 
X 
X 
 
 
X 
X 
 
 
Hematology 
X 
X 
 
 
X 
X 
 
 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening Period 
Treatment Period 
 
Safety Follow-Up 
Notes 
Days −37 to −1 
(Including a 7-Day 
Run-In Period) 
Day 1a 
Day 8 
(± 2) 
Day 15 
(± 2) 
Day 29 
(± 2) 
ETb 
Day 43 
(15 ± 2 Days After 
Last Application) 
Visit Week 
Week 1 
Week 2 
Week 4 
Week 6 
Urinalysis 
X 
X 
 
 
X 
X 
 
 
Pregnancy testing 
X 
X 
 
 
X 
X 
X 
For WOCBP.  Serum test at screening.  Urine 
test at all other specified visits.  A positive 
urine test must be confirmed by a serum test. 
FSH 
X 
 
 
 
 
 
 
For female participants of nonchildbearing 
potential. 
Suture removal 
 
 
 
X 
 
 
X* 
Within 11-14 days after biopsy collection, if 
applicable. 
*If skin biopsies are collected at ET, a 
follow-up visit for suture removal may be 
performed after 11-14 days, if applicable. 
a On Day 1, participants will remain at the study center until after the 6-hour mPP-NRS assessment (approximately 8-hour stay at the site). 
b Participants who withdraw from the study prematurely should complete an ET visit.  Participants who are discontinued for safety reasons may be asked to come 
for additional follow-up visits, at the investigator's discretion, after the ET visit to ensure appropriate medical care and follow-up of AEs. 


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2. 
INTRODUCTION 
2.1. 
Background 
2.1.1. 
Ruxolitinib 
Ruxolitinib cream is a topical formulation of INCB018424 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 preliminary efficacy in some 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, 
aged 12 years and older, whose disease is not adequately controlled with topical prescription 
therapies or when those therapies are not advisable. 
2.1.2. 
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, Wolff et al 2008).  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, Wolff et al 2008).  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, National Eczema Association 2018, 
Rerknimitr et al 2017, Wolff et al 2008). 
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, Rerknimitr et al 2017, 
Wolff et al 2008, 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 (Wolff et al 2008).  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 (Yarbrough et al 2013, Pavlis and 
Yosipovitch 2018). 


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Free nerve endings in the skin are involved in pruritus as itching receptors (Urashima and 
Mihara 1998).  Histological examinations have revealed increased cutaneous 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 is a potent, 
selective inhibitor of JAK1 and JAK2, and its topical formulation may offer 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. 
2.2. 
Study Rationale 
Data from previous studies demonstrated that topical ruxolitinib cream is effective due to the 
dual anti-inflammatory and antipruritic properties.  The purpose of this study is to further 
understand the short-term clinical and molecular benefits of ruxolitinib in the control of pruritus 
(primary outcome measure) and reduction of disease severity in participants with AD. 
2.2.1. 
Scientific Rationale for Study Design 
During the study, all participants will apply ruxolitinib 1.5% cream on all AD lesions for 
28 (± 2) days.  The proposed design is considered appropriate to evaluate the onset of itch 
reduction following application of ruxolitinib 1.5% cream, to assess the efficacy of 
ruxolitinib 1.5% cream in participants with AD, to understand the effect of ruxolitinib on the 
skin, and to provide further insight on the safety of ruxolitinib in participants with AD. 
2.2.2. 
Justification for Dose 
The clinical efficacy and safety of ruxolitinib cream was investigated in several studies, 
including 2 ongoing Phase 3 studies (INCB 18424-303 and INCB 18424-304) with more than 
1235 participants with AD consisting of 1) a double‑blind, vehicle‑controlled period in which 
participants received ruxolitinib 0.75% or 1.5% or vehicle cream from Day 1 to Week 8, 
followed by 2) a double‑blind, long-term safety extension (Week 8 to Week 52) in which 
participants initially randomized to vehicle were rerandomized to ruxolitinib 0.75% or 
1.5% cream BID.  As of 28 JUN 2020, no participant had a fatal TEAE.  A few SAEs were 
reported, but all were considered by the investigator as unrelated to blinded study treatment. 
In the INCB 18424-303 study, a total of 191 participants (30.3%) had at least 1 TEAE in the first 
part of the study.  The most frequently reported TEAEs (≥ 1%) were nasopharyngitis 


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(n = 19 [3.0%]), upper respiratory tract infection (n = 18 [2.9%]), headache (n = 13 [2.1%]), 
dermatitis atopic (n = 12 [1.9%]), oropharyngeal pain and pruritus in 8 participants each (1.3%), 
and application site pain (n = 6 [1.0%]).  Of the 542 participants continuing blinded study 
treatment after Week 8, a total of 265 participants (48.9%) had at least 1 TEAE.  The most 
frequently reported TEAEs (≥ 2%) were upper respiratory tract infection (n = 49 [9.0%]); 
nasopharyngitis (n = 34 [6.3%]); headache (n = 20 [3.7%]); hypertension (n = 13 [2.4%]); 
bronchitis (n = 12 [2.2%]); and rhinitis (n = 11 [2.0%]). 
In the INCB 18424-304 study, a total of 169 participants (27.3%) had at least 1 TEAE in the first 
part of the study.  The most frequently reported TEAEs (≥ 1%) were nasopharyngitis 
(n = 13 [2.1%]), application site pain (n = 9 [1.5%]), application site pruritus (n = 8 [1.3%]), 
headache (n = 7 [1.1%]), and upper respiratory tract infection (n = 6 [1.0%]).  Of the 
529 participants continuing into the second part of the study, a total of 311 participants (58.8%) 
had at least 1 TEAE.  The most frequently reported TEAEs (≥ 2%) were nasopharyngitis 
(n = 49 [9.3%]); upper respiratory tract infection (n = 41 [7.8%]); bronchitis (n = 16 [3.0%]); 
asthma, influenza, and rhinitis in 13 participants each (2.5%); and hypertension and pharyngitis 
in 11 participants each (2.1%). 
In both studies, the majority of participants showed good local tolerability to study drug.  Pooled 
analysis from both Phase 3 studies confirmed that the AE profile was similar to that in the 
vehicle group, with low rate of application site reactions and no serious AEs. 
The efficacy data of these 2 Phase 3 studies revealed that either treatment regimen of ruxolitinib 
cream brought about rapid (within 12 hours of initiation of therapy), substantial, and sustained 
reduction in itch and showed superior efficacy versus vehicle in IGA-TS, ≥ 75% improvement in 
EASI score, and ≥ 4-point reduction in itch NRS score.  Of note, numerically better results were 
observed in the ruxolitinib 1.5% BID group (Papp et al 2020).  In addition, the Phase 2 study 
(INCB 18424-206) with 204 participants with AD randomized to treatment with ruxolitinib 
0.15% cream QD (n = 51), ruxolitinib 0.5% cream QD (n = 51), ruxolitinib 1.5% cream QD 
(n = 52), or ruxolitinib 1.5% cream BID (n = 50) revealed that all ruxolitinib treatment groups 
were superior to the vehicle group for the percent change from baseline in EASI score at Week 4.  
Of note, the greatest change from baseline was measured in the ruxolitinib 1.5% cream BID 
group (−71.57% versus −11.90%; p < 0.0001). 
Given the favorable safety and efficacy profile of ruxolitinib 1.5% cream BID in participants 
with AD, the 1.5% concentration of ruxolitinib cream applied BID was selected to evaluate the 
effect of ruxolitinib cream on itch in adult participants with AD in the present study. 
2.3. 
Benefit/Risk Assessment 
As of 28 JUN 2021, a total of 14 clinical studies with ruxolitinib cream had been completed 
(5 studies in healthy participants, 3 studies in participants with psoriasis, 1 study in participants 
with alopecia areata, and 5 studies in participants with AD) and 5 studies were ongoing 
(5 studies in participants with vitiligo).  A total of 2613 unique participants had been exposed to 
ruxolitinib cream in completed studies. 
An analysis of the clinical pharmacology of ruxolitinib cream applied in plaque psoriasis, 
alopecia areata, AD, and vitiligo uncovered that exposure to ruxolitinib is generally 
strength‑dependent, and presents a moderate intersubject variability.  In the psoriasis studies, 


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INCB 18424-201, INCB 18424-202, and INCB 18424-203, steady-state concentrations after 
application of ruxolitinib cream increased approximately proportional to the daily application 
strength.  However, the bioavailability for ruxolitinib cream was independent of the strength of 
the cream formulation and percent BSA. 
The most frequently reported (≥ 2%) TEAEs in participants with AD (n = 1595) were upper 
respiratory tract infection, nasopharyngitis, headache, atopic dermatitis, bronchitis, and rhinitis. 
Based on earlier studies with ruxolitinib 1.5% cream, it is anticipated that participants will 
clinically benefit from their participation in the current study.  Participation in this study may 
also help generate future benefit for larger groups of participants with inflammatory and pruritic 
skin conditions if ruxolitinib 1.5% cream proves to be efficient in prompt and maintained control 
of itch.  Ultimately, this study may deepen the understanding of ruxolitinib 1.5% cream's 
mechanism of action and inform on possible future uses of ruxolitinib 1.5% cream. 
All pharmacology and toxicology data and satisfactory safety and tolerability data demonstrated 
in nonclinical studies are considered sufficient to expect a positive benefit/risk ratio for the 
treatment of AD with ruxolitinib 1.5% cream and therefore to initiate this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ruxolitinib cream may be found in the IB. 
2.3.1. 
COVID-19 Pandemic 
As a consequence of the COVID-19 pandemic that has had a worldwide impact, including cases 
in North America, control measures in place in different regions may impact the ability to adhere 
to some of the study procedures described in this protocol.  Due to challenges that include but are 
not limited to participant preferences, site closures, travel restrictions, and quarantines, some 
modifications to study conduct during the COVID-19 pandemic may be necessary to ensure 
study continuity.  See Section 4.1.1 for more details on allowable, as necessary, modifications to 
the protocol due to COVID-19 restrictions. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 4 presents the objectives and endpoints. 
Table 4: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of ruxolitinib 1.5% 
cream on pruritus in participants with AD. 
Change from baseline in PP-NRS at Day 2 (24-hour 
recall period after first application). 
Secondary 
To evaluate the efficacy of ruxolitinib 1.5% 
cream in participants with AD. 
• Change from baseline in mPP-NRS (current itch 
intensity) at 15 and 30 minutes and 1, 2, 4, 6, and 
12 hours postdose on Day 1; and in PP-NRS from 
Day 3 through Day 29. 
• Proportion of participants achieving at least a 
1-grade decrease from baseline in mPP-NRS at 
15 and 30 minutes and 1, 2, 4, 6, and 12 hours 
postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• Proportion of participants achieving at least a 
2-grade decrease from baseline in mPP-NRS at 
15 and 30 minutes and 1, 2, 4, 6, and 12 hours 
postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• Time to MCID (≥ 2-grade reduction in PP-NRS 
and mPP-NRS from baseline). 
• Change from baseline in IGA at Day 8, Day 15, 
and Day 29. 
• Proportion of participants achieving the IGA-TS 
(score of 0 or 1 in IGA with at least a 2-grade 
reduction from baseline) at Day 8, Day 15, and 
Day 29. 
To evaluate the local and systemic safety and 
tolerability of ruxolitinib 1.5% cream in 
participants with AD. 
Incidence and severity of local and systemic AEs. 


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Table 4: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Exploratory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note:  For efficacy endpoints related to PP-NRS, baseline is defined as the average of all nonmissing PP-NRS 
(24-hour recall period) scores reported during the 7‑day run-in period.  For the other efficacy variables (including 
the mPP-NRS), baseline is defined as the last nonmissing value before or on Day 1 (prior to first application of 
study drug). 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, open-label, single-arm study evaluating the effect of ruxolitinib 1.5% cream on 
itch.  This study will include approximately 48 adult participants (18-65 years old, inclusively) 
who have at least a 6-month history of AD and at least a 3-month history of chronic itch. 
All participants will read and sign an ICF prior to any study procedures being performed and 
then undergo screening for study eligibility.  Participants who meet initial screening 
requirements will be given access to an eDiary to complete the PP-NRS each morning (24-hour 
recall period), from screening to Day −1 and from Day 2 to the Day 29 visit.  Participants must 
be willing and able to complete the eDiary on a daily basis for the duration of the study.  During 
the last 7 days prior to Day 1 (run-in period; Day −7 to Day −1), participants will be required to 
complete at least 4 of 7 PP-NRS assessments in their eDiary.  Inclusion of participants 
completing fewer than 4 of 7 PP-NRS questionnaires during the last 7 days of the screening 
period (run-in period) must be approved by the sponsor. 
After a screening period of no more than 37 days (from Day −37 to Day −1, including a 7-day 
run-in period), participants who fulfill all of the inclusion criteria, none of the exclusion criteria, 
and have a baseline mean PP-NRS score ≥ 4.0 during the run-in period will be eligible to start 
the treatment period.  The baseline mean PP-NRS score is defined as the average of all 
nonmissing PP-NRS scores reported during the run-in period. 
During the treatment period, participants will apply ruxolitinib 1.5% cream BID as a thin film for 
28 (± 2) days (last application on the evening prior to the Day 29 visit).  The study drug will be 
applied on all AD lesions, with a maximum treated area ≤ 20% BSA.  All original areas of 
involvement on Day 1 (even in the event of lesions clearing), and any new lesions (a maximum 
of ≤ 20% BSA can be treated) must be treated until the evening prior to the Day 29 visit.  On 
Day 1, participants will remain at the study center until after the 6-hour mPP-NRS assessment 
(approximately an 8-hour stay at the site).  The 12-hour mPP-NRS assessment will be done at 
home just prior to the evening study drug application.  On Day 8 and Day 15, the morning 
application of the study drug will be at the study center under the supervision of study staff.  
Other study drug applications will be self-administered by the participants at home.  The study 
schema is shown in Figure 1. 
Study drug application will occur in the morning and evening from Day 1 until the day prior to 
the Day 29 visit, with approximately 12 hours between applications.  The evening dose should be 
applied at least 1 hour before bedtime. On Day 1, the mPP-NRS assessments should occur as 
close as possible to the scheduled time relative to the first study drug application. In addition, the 
12-hour mPP-NRS should be completed before the evening study drug application. On Day 2, 
the PP-NRS assessment should be completed approximately 24 hours after the first study drug 
application and before the Day 2 morning dose. Refer to Table 5 for the sequence and timing of 
these assessments and allowed windows on Day 1 and Day 2. From Day 3 until the Day 29 visit, 
the PP-NRS should be completed once daily, at approximately the same time in the morning, and 
prior to the study drug application. 


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Table 5: 
Sequence and Timing of mPP-NRS, PP-NRS, and Study Drug Applications 
on Days 1 and 2 
Study Day 
Order of Assessments 
Scheduled Time (Window) 
Day 1 
Preapplication mPP-NRS 
Prior to first study drug application 
Morning study drug application (first 
application) 
— 
15-minutes postapplication mPP-NRS 
15 minutes (± 2 minutes) after first study drug application 
30-minutes postapplication mPP-NRS 
30 minutes (± 2 minutes) after first study drug application 
1-hour postapplication mPP-NRS 
1 hour (± 2 minutes) after first study drug application 
2-hours postapplication mPP-NRS 
2 hours (± 5 minutes) after first study drug application 
4-hours postapplication mPP-NRS 
4 hours (± 5 minutes) after first study drug application 
6-hours postapplication mPP-NRS 
6 hours (± 5 minutes) after first study drug application 
12-hours postapplication mPP-NRS 
12 hours (± 5 minutes) after first study drug application 
Evening study drug application 
(second application) 
Approximately 12 hours after first study drug application 
– After the 12-hour mPP-NRS 
Day 2 
PP-NRS 
24 hours (± 1 hour) after the first study drug application 
(ie, after Day 1 morning dose) 
Morning study drug application 
(third application) 
Approximately 12 hours after the Day 1 evening dose 
– After Day 2 PP-NRS 
Evening study drug application 
(fourth application) 
Approximately 12 hours after the Day 2 morning dose 
Note: From Day 3 until the Day 29 visit, the PP-NRS should be completed once daily, at approximately the same 
time in the morning, and prior to the study drug application. 
Efficacy will be evaluated using the PP-NRS (worst itch over a 24-hour period), the mPP-NRS 
(current itch at the time of assessment), and the 5‑point IGA. 
The BSA and EASI will be used to evaluate the participant's AD severity on Day 1 and will be 
characterized during the study. 
Medical photographs of the target lesion(s) and application site AEs will be taken during the 
study. 
Participants will be asked to complete the TSQM-9 at the end of the treatment period (or ET, if 
applicable). 
Safety will be assessed by collecting AEs, performing comprehensive and targeted physical 
examinations, and evaluating clinical laboratory assessments. 


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4.1.1. 
Study Conduct During the COVID-19 Pandemic 
As a consequence of the COVID-19 pandemic that has had a worldwide impact, including cases 
in North America, control measures in place in different regions may impact the ability to adhere 
to some of the study procedures described in this protocol.  Due to challenges that include but are 
not limited to participant preferences, site closures, travel restrictions, and quarantines, some 
modifications to study conduct during the COVID-19 pandemic may be necessary to ensure 
study continuity.  The following are allowable, as necessary, modifications to study conduct 
during the COVID-19 pandemic. 
• Prior to a study visit at the site, the participant may be contacted and screened for 
potential exposure or infection to COVID-19 per site, local, or federal requirements.  If 
the participant is suspected to have been exposed or infected with COVID-19, the on-site 
visit should either be rescheduled or a virtual visit may be performed instead, as 
applicable. 
• In the event that a participant cannot attend their regularly scheduled study visits 
in-person due to COVID-19 necessitating a limit on in-person contact, the investigator 
may perform safety and efficacy assessments by phone or video, except for the screening 
and Day 1 visits.  If the screening visit cannot be performed on-site, the participant 
should not be screened.  If the Day 1 visit cannot be performed on-site, the participant 
should be considered to have failed screening.  Participants who fail screening due to 
COVID-19 restrictions at screening or Day 1 may be rescreened at a later time, if 
feasible.  Every effort should be made to perform the Day 8 and Day 29 visits on-site to 
allow for skin and/or blood sample collection.  Protocol deviations due to missed study 
visits, missed applications, or missed study procedures as well as study discontinuations 
due to COVID-19 restrictions should be documented accordingly. 
• Participants should continue answering the daily PP-NRS via eDiary (tablet) and record 
their BID application of study drug in the paper diary.  Safety must be assessed during 
the virtual visit by collecting AEs and concomitant medications.  Other safety or efficacy 
assessments may be performed as reasonably practicable. 
• Clinical laboratory tests (eg, serum chemistries, hematology, urinalysis) and pregnancy 
tests may be performed by a local laboratory if these procedures cannot be performed at 
the study site due to COVID-19–related limitations, including but not limited to site 
closure.  Clinically significant abnormal laboratory results should be promptly 
communicated to the medical monitor within 72 hours of receipt, as per investigator's 
judgment.  Participant' anonymity must be maintained when communicating results to the 
medical monitor. 
• Source documentation should note that the visit was performed virtually (not 
face-to-face) and note the name of the local laboratory where laboratory tests were 
performed. 


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A detailed assessment of COVID-19–related risk and mitigation measures will be documented in 
the appropriate study plans. 
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 when all participants have completed the Day 43 visit or discontinued study drug 
(ET) and have completed all applicable follow-up assessments. 
It is estimated that an individual will participate in the study for up to approximately 3 months 
(80 days); inclusive of a maximum of 37 days for the screening period (including 7 days for the 
run-in period), 28 (± 2) days for the treatment period, and 15 (± 2) days for safety follow-up. 
A participant is considered to have completed the study if he/she has completed all parts of the 
study including the last visit or the last scheduled procedure shown in Table 3. 
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 decision.  In the 
event of significant safety findings, the study will be terminated.  If the study is terminated 
prematurely, the sponsor will notify the investigators, the IRBs and IECs, and the regulatory 
bodies of the decision and reason for termination of the study. 


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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female participant aged 18 to 65 years, inclusive, at screening. 
2. Participant is able to comprehend and willing to sign a written ICF for this study.  
Note:  Consent must be obtained prior to any study-related procedures. 
3. Participant has clinically confirmed diagnosis of active AD according to Hanifin and 
Rajka (1980) criteria (see Appendix B). 
4. Participant has at least a 6-month history of AD (information obtained from medical 
chart, participant's physician, or directly from the participant). 
5. Participant 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. Participant has an overall BSA (excluding palms, soles, scalp, genitals, and folds) 
affected by AD of 1% to 20% on Day 1. 
7. Participant has an IGA score of at least 2 on Day 1. 
8. Participant has 1 target AD lesion on Day 1 that can allow for the collection of skin 
samples as per study requirement (excluding face, scalp, genitals, axillae, groin, folds, 
palms, and soles).  The target lesion should be representative of the participant's overall 
disease and should be treated with study drug. 
Note:  A target lesion that could accommodate all skin samples (tape strips, biopsies, and 
skin microbiome) and TEWL assessment is the preferred scenario.  However, a second 
target lesion could be selected, if needed.  If selecting 2 target lesions on Day 1, they 
should be of similar severity and preferably from the same anatomical region. 
9. Participant has a single PP-NRS score ≥ 4 in the 24-hour period prior to the screening 
visit. 
10. Participant must be willing to complete the once-daily PP‑NRS (24-hour recall period) 
entries at approximately the same time each day during the study (from screening to 
Day −1 and from Day 2 to the Day 29 visit). 
Note:  Inclusion of participants completing fewer than 4 of 7 daily PP-NRS 
questionnaires during the last 7 days of the screening period (run-in period) must be 
approved by the sponsor. 


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11. Prior to the first application of study drug, participant has a baseline mean PP-NRS 
(24-hour recall period) score ≥ 4.0 during the run-in period, defined as the average of all 
nonmissing scores reported during the 7‑day run-in period. 
12. Participant has been using an emollient for at least 2 weeks prior to Day 1 (ie, 1 week 
prior to run-in period), and agrees to continue using that same emollient daily at the same 
frequency, applied on nontreated areas, throughout the study.  The chosen emollient 
should not contain urea, camphor, menthol, lactic acid, or pramoxine. 
13. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 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 on Day 1 
and must agree to take appropriate precautions to avoid pregnancy from screening 
through 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. 
14. Participant must be 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. 
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. Participant 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). 
3. Participant has clinically infected AD or has used antibiotics (systemic or topical) for 
their infected AD within 2 weeks prior to the run-in period. 
4. Participant 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). 
5. Participant has a presence of any tattoos, scratches, open sores, excessive hair, or skin 
damages that, in the opinion of the investigator, may interfere with study evaluations. 


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6. Participant 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. 
7. Participant is known to have immune deficiency or is immunocompromised 
(eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome). 
8. Participant has a history of cancer or lymphoproliferative disease within 5 years prior to 
Day 1, with the exception of successfully treated nonmetastatic cutaneous squamous cell 
or basal cell carcinoma and/or localized carcinoma in situ of the cervix. 
9. Participant had a major surgery within 8 weeks prior to Day 1 or has a major surgery 
planned during the study. 
10. Participant has any clinically significant medical condition or physical/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, including but not limited to 
participants with renal disease requiring dialysis. 
11. Participant has any of the following clinical laboratory test results at screening: 
a. Hemoglobin (< 10 g/dL) or absolute neutrophil count (ANC) of < 1000/uL or 
platelets count < 100,000/uL. 
b. Liver function tests: 
- 
AST or ALT ≥ 2.5 × ULN 
- 
Total bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if 
bilirubin is fractionated and direct bilirubin is < 35%). 
c. Estimated GFR < 30 mL/min/1.73 m2 (using the Modification of Diet in Renal 
Disease equation). 
d. Positive serology test results at screening for HIV antibody. 
e. Any other clinically significant laboratory result which in the opinion of the 
investigator, pose a significant risk to the participant. 
12. Removed during Protocol Amendment 2. 
13. Participant has used any oral, sedative, H1 antihistamine (including but not limited to 
diphenhydramine and hydroxyzine) within 2 weeks prior to the run-in period. 
Note:  Oral, nonsedative, H1 antihistamines to treat allergies will be permitted during the 
study only if the participant has been on a stable dose for at least 2 weeks prior to run-in 
and continues to use the same agent at the same frequency throughout the study. 
14. Participant has used doxepin within 2 weeks prior to the run-in period. 
15. Participant has used any topical medicated treatment that could affect AD and/or pruritus 
within 2 weeks prior to the run-in period, including but not limited to topical 
corticosteroids, crisaborole, calcineurin inhibitors, antihistamines, pramoxine, tars, 
antimicrobials, or stable doses of prescription or over-the-counter topical 
analgesics/moisturizers containing menthol, camphor, urea additives, or lactic acid. 


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16. Participant has used systemic corticosteroids (oral/injectable) within 4 weeks prior to the 
run-in period. 
Note:  Intranasal and inhaled corticosteroids are allowed.  Eye and ear drops containing 
corticosteroids are also allowed. 
17. Participant has used systemic treatments (other than biologics) that could affect AD 
and/or pruritus within 4 weeks prior to the run-in period (eg, retinoids, calcineurin 
inhibitors, PDE-4 inhibitors, methotrexate, cyclosporine, hydroxycarbamide 
[hydroxyurea], azathioprine, interferon-gamma, or opioids [agonist, partial 
agonist-mixed, or antagonist]). 
18. Participant has received any ultraviolet B phototherapy (including tanning beds) or 
excimer laser within 4 weeks prior to the run-in period. 
19. Participant has had PUVA treatment within 4 weeks prior to the run-in period. 
20. Participant has had excessive sun exposure, is planning a trip to a sunny climate, or has 
used tanning booths within 4 weeks prior to the run-in period or is not willing to 
minimize natural and artificial sunlight exposure during the study. 
21. Participant has received a nonbiological investigational product or device within 4 weeks 
prior to the run-in period, or is currently enrolled in another investigational drug study. 
22. Participant has received any marketed or investigational biological agent that could 
interfere with the course or assessments of AD within 12 weeks or 5 half-lives 
(whichever is longer) prior to the run-in period. 
23. Participant has used dupilumab within 26 weeks prior to the run-in period. 
24. Participant has received a live-attenuated vaccine within 4 weeks prior to the run-in 
period or plans to receive a live-attenuated vaccine during the study and up to 4 weeks or 
5 half-lives (of the study drug), whichever is longer, after the last application of study 
drug. 
25. Participant has received treatment with JAK inhibitors (systemic or topical) within 
4 weeks prior to the run-in period. 
26. Participant had prior treatment with a JAK inhibitor that was discontinued for safety 
reasons or tolerance problems. 
27. Participant has a known or suspected allergy to ruxolitinib or any component of the study 
drug. 
28. Participant has a known history of clinically significant drug or alcohol abuse in the last 
year prior to Day 1. 
29. Participant has a history of an allergic reaction or significant sensitivity to lidocaine or 
other local anesthetics. 
30. Participant has a history of hypertrophic scarring or keloid formation in scars or suture 
sites. 


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31. Participant has taken anticoagulant medication, such as heparin, LMW-heparin, warfarin, 
or antiplatelets (except low-dose aspirin ≤ 81 mg, which will be allowed), within 2 weeks 
prior to Day 1, or has a contraindication to skin biopsies. 
Note:  NSAIDs will not be considered antiplatelets and will be allowed. 
32. Participant is unlikely, in the opinion of the investigator, to be compliant with study 
procedures and requirements. 
33. Participant has a close affiliation (eg, a close relative) with the investigator, including any 
study staff of the sites or persons working at the contract research organization, or 
participant is an employee of the sponsor. 
34. History of hepatitis B virus or hepatitis C virus infection. 
5.3. 
Lifestyle Considerations 
Participants should abstain from taking a bath/shower within 2 hours following study drug 
application. 
Participants should abstain from physical activity that can cause significant sweating within 
2 hours following study drug application. 
Prolonged exposure to natural or artificial sources of ultraviolet radiation (eg, sun lamps, tanning 
booths) is prohibited within 4 weeks prior to the run-in period through the last study visit.  Use 
of sunscreen products and protective apparel are recommended when sun exposure cannot be 
avoided.  When outdoors, participants will be advised to wear loose‑fitting clothing that protects 
the treated area from the sun. 
Any sunscreen, makeup, or other cosmetics should be applied to the areas to be treated at least 
4 hours before and 2 hours after application of study drug.  If sunscreen, makeup, or other 
cosmetic has 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 the study drug. However, on the days 
of a study visit, participants should refrain from washing or applying cosmetics (makeup, 
creams, etc) to the target lesion area(s) and adjacent area(s) for at least 5 hours prior to the visit. 
Participants are to wash their hands thoroughly with soap and warm water prior to study drug 
application.  Participants with AD lesions on their hands must avoid washing their hands for 
approximately 2 hours after drug application.  Participants without AD lesions on their hands 
will be instructed to wash their hands thoroughly with soap and warm water after study drug 
application. 
Use of swimming pools during the treatment period of the study is not recommended.  If 
unavoidable, it is recommended that swimming should not take place within 2 hours before and 
after the planned study drug application. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the treatment period of the study. 
Tests with results that fail eligibility requirements may be repeated once during screening if 
deemed acceptable by the investigator.  Additionally, individuals who do not meet the criteria for 


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participation in this study (screen failure) may be rescreened once, if deemed acceptable by the 
investigator.  However, participants who do not meet the criteria for the single PP-NRS score at 
screening or the baseline mean PP-NRS score of eligibility for the 7-day run-in period may not 
be rescreened.  Participants who rescreen must reconsent and be assigned a new participant 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
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).  On Day 1, study 
staff will instruct participants on proper application of study drug. 
All participants will apply ruxolitinib 1.5% cream for 28 (± 2) days.  The study drug will be 
applied as a thin film, BID, on all AD lesions with a maximum treated area ≤ 20% BSA.  All 
original areas of involvement identified on Day 1 (even in the event of lesions clearing), and any 
new lesions (a maximum of ≤ 20% BSA can be treated) must be treated until the evening prior to 
the Day 29 visit.  The last application will be on the evening prior to the Day 29 visit.  On Day 1, 
participants will remain at the study center until after the 6-hour mPP-NRS assessment 
(approximately an 8-hour stay at the site).  The 12-hour mPP-NRS assessment will be done at 
home just prior to the evening study drug application.  On Day 8 and Day 15, the morning 
application of the study drug will be at the study center under the supervision of study staff.  
Other study drug applications will be self-administered by the participants at home. 
Participants will be instructed to apply the study drug at approximately the same time of the day 
(once in the morning and once in the evening, approximately 12 hours apart).  The evening dose 
should be applied at least 1 hour before bedtime.  On Day 1, the mPP-NRS assessments should 
occur as close as possible to the scheduled time relative to the first study drug application. In 
addition, the 12-hour mPP-NRS should be completed before the evening study drug application. 
On Day 2, the PP-NRS assessment should be completed approximately 24 hours after the first 
study drug application and before the Day 2 morning dose. Refer to Table 5 for of the sequence 
and timing of these assessments and allowed windows on Day 1 and Day 2. From Day 3 until the 
Day 29 visit, the PP-NRS should be completed once daily, at approximately the same time in the 
morning, and prior to the study drug application. 
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(s)/ 
dosage level(s): 
1.5% BID 
Administration instructions: 
Applied BID as a thin film, at an interval of approximately 12 hours, on all 
AD lesions (up to 20% BSA) for 28 (± 2) days. 
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: 
Investigational 


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6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions (ruxolitinib cream 
stored at ambient temperature 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 study treatment.  Participants are to wash their hands thoroughly with soap and 
warm water before application of ruxolitinib cream.  Participants with AD lesions on their hands 
must avoid washing their hands for approximately 2 hours after drug application.  Participants 
without AD lesions on their hands will be instructed to wash their hands thoroughly with soap 
and warm water after study drug application.  Refer to the SRM for participant instructions for 
handling of study drug. 
All study treatment at the site must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff.  Participants should store study 
treatment at ambient temperature conditions (15°C-30°C [59°F-86°F]). 
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 drug, including tube counts and weight from each supply 
dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the participants were provided the 
specified study drug.  These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the investigational product and study 
participants.  In case of missed visits related to the COVID-19 pandemic, alternative, secure 
delivery methods may be considered as well as changes in the dispensing schedule to ensure 
continued treatment with the study drug until the end of the treatment period.  Accountability 
processes will be maintained during the COVID-19 pandemic and all efforts will be made to 
ensure that all medication is returned at the site (even when last study visit is virtual). 
Completed accountability records will be archived by the site.  Returned study drug should not 
be redispensed to the participants.  The investigator or designee will be expected to collect and 
retain all used, unused, and partially used containers of study drug until verified by the study 
monitor (unless otherwise agreed to by the sponsor).  At the conclusion of the study, the 
investigator or designee will oversee shipment of any remaining study drug back to the sponsor 
or its designee for destruction according to institutional SOPs.  If local procedures mandate on-


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site destruction of the investigational supply, the site should (where local procedures allow) 
maintain the investigational supply until the study monitor inspects the accountability records in 
order to evaluate compliance and accuracy of accountability by the investigative site.  At sites 
where the study drug is destroyed before monitor inspection, the monitors rely on documentation 
of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the SRM. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
This is an open-label study; no comparisons will be made between participants or against 
historical controls.  Measurements of safety and efficacy are objective measurements, and only 
comparisons to pretreatment conditions will be made. 
6.4. 
Study Treatment Compliance 
Compliance with study-related treatment should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  To 
facilitate compliance assessment during the treatment period, participants will be supplied with a 
paper diary and instructed to record the time and date for each application of study drug. 
Study treatment compliance will be monitored at each visit.  Compliance will be assessed for 
frequency of application of study drug by reviewing the participant diary.  Qualified clinical staff 
will review the entries for compliance.  Participants will also be questioned regarding study drug 
application technique, missed applications, and use of any additional prescription or 
over-the-counter topical or systemic products.  For participants who miss more than 3 
consecutive study drug applications or have a compliance below 80%, the investigator should 
discuss with the medical monitor and/or sponsor for continued participation in the study. 
Participants will be considered compliant with the treatment regimen if they apply at least 80% 
but no more than 120% of the prescribed number of applications during the treatment period of 
the study.  Drug accountability will be assessed by documenting the quantities of drug used 
between study visits (tube counts and weighing).  Participants will be instructed to bring all study 
drugs with them at the visits specified in Table 3 in order for site personnel to assess study drug 
accountability.  The drug usage will be used by the sponsor to evaluate drug accountability. 
6.5. 
Dose Modifications 
During the 28 (± 2)-day treatment period, participants should treat all AD lesions identified for 
treatment on Day 1, even if lesions improve.  Participants who have additional areas of AD 
developing after the initiation of treatment should also treat these additional areas (a maximum 
of ≤ 20% BSA can be treated) with approval from the investigator.  Approval to treat additional 
areas may occur via telephone.  The site should consider having the participant come in for an 
unscheduled visit to document the new %BSA if the additional areas of AD constitute a 
clinically meaningful increase in BSA.  The change in %BSA treated should be documented in 
the eCRF.  It is recommended that, in such situations, an increase in the overall BSA to be 
treated does not exceed approximately 10% over the baseline BSA affected by AD.  If at any 
time during the study the participant’s BSA exceeds 20%, the participant should be considered 
for termination. 


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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 if the participant should continue or discontinue the study drug. 
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.  Except in cases 
of emergency, it is recommended that the investigator consult with the sponsor's medical monitor 
(or other representative of the sponsor) immediately upon occurrence or awareness before 
temporarily interrupting study drug.  Additionally, the investigator must obtain approval from the 
sponsor before restarting study drug that was temporarily interrupted because of an AE or 
laboratory abnormality. 
Individual participants may have administration interrupted at the discretion of the investigator, 
in consultation with the sponsor, for AEs or laboratory abnormalities until these have resolved. 
Instructions for application interruptions for ruxolitinib cream are outlined in Table 7.  Individual 
decisions regarding interruptions should be made using clinical judgment in consultation with the 
medical monitor (whenever possible), taking into account relatedness of the AE to the study 
treatment and the participant's underlying condition. 


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Table 7: 
Guidelines for Interruption and Restarting of Treatment Applications if 
Adverse Event is Deemed Related to the Study Drug 
Adverse Event Related to Study Druga 
Action Taken 
ANC < 750/uL (without fever); < 1000/uL (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 laboratory 
abnormalities are confirmed. 
Note:  Grading using the CTCAE v5.0. 
a In the opinion of the investigator. 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study treatment 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. 
• A worsening of AD that requires treatment with a prohibited concomitant medication. 
• A persistent AE requiring a delay of therapy for more than 2 weeks without resolution 
of the AE (unless a greater delay has been approved by the sponsor). 
See Section 7.1.2 for discontinuation procedures. 


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6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  All 
prior medications for AD and any medications received within 28 days before the screening visit, 
throughout the study, and up to the safety follow-up visit will be recorded in the eCRF.  The 
medication record will be maintained after signing the ICF to document prior/concomitant 
medications, including any changes to the dose or regimen.  Concomitant treatments and/or 
procedures that are required to manage a participant's medical condition during the study will 
also be recorded in the eCRF.  Any addition, deletion, or change in the dose of these medications 
will also be recorded.  Concomitant medications administered within 15 (± 2) days after the last 
application of study treatment should be recorded for SAEs as defined in Section 9.4.  The 
medical monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
6.6.1. 
Permitted Medications and Procedures 
6.6.1.1. 
Emollients 
Participants must apply an emollient of their choice (except those containing urea, camphor, 
menthol, lactic acid, or pramixide) on their skin during the study.  Emollients should be applied 
everywhere on the body, including on AD lesions, during the screening and the follow-up 
periods.  Emollients should be applied everywhere on the body, except on treated AD lesions, 
during the treatment period.  Participants should continue on their established emollient 
application scheme and not initiate a new one at least 2 weeks prior to Day 1 (ie, 1 week prior 
to run-in period), and participants must continue using it at the same frequency (ideally QD or 
BID) throughout the study.  However, on the day of scheduled visits, participants cannot apply 
emollient before their scheduled visit time. 
Every effort should be made to keep the same emollient throughout the study for the same body 
region.  However, the chosen emollient may differ depending on the body region (eg, body vs 
face emollient may be different).  The commercial name of the selected emollient(s) will be 
recorded in the source document and the eCRF.  No other products may be applied to the lesions 
during the study. 
6.6.1.2. 
Other Permitted Therapies 
The following medications and procedures are permitted: 
• Intranasal corticosteroids and inhaled corticosteroids are allowed.  Eye and ear drops 
containing corticosteroids are also allowed. 
• Bathing during the study should be limited to once daily for no longer than 
15 minutes.  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. 
• Use of sunscreen products and protective apparel are recommended when sun 
exposure cannot be avoided.  If sunscreen is needed, a mineral-based sunscreen (such 
as zinc oxide– or titanium oxide–based) may be used at least 4 hours before and 
2 hours after study drug application. 


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6.6.2. 
Restricted Medications and Procedures 
The following are permitted during the study under specified conditions: 
• Oral, nonsedative, H1 antihistamines to treat allergies are allowed during the study 
only if the participant has been on a stable dose for at least 2 weeks prior to the run-in 
period and continues to use the same agent at the same frequency throughout the 
study. 
• Bleach baths are allowed as long as their frequency remains the same throughout the 
study. 
• Participants should abstain from taking a bath/shower within 2 hours following study 
drug application. 
• Use of swimming pools during the treatment period of the study is not recommended.  
If unavoidable, it is recommended that swimming should not take place within 
2 hours before and after the planned study drug application. 
• Participants should abstain from physical activity that can cause significant sweating 
within 2 hours following study drug application. 
6.6.3. 
Prohibited Medications and Procedures 
Table 8 lists prohibited medications that are not to be used from the defined washout periods 
prior to the run-in period through the last study visit. 
Participants who start prohibited medications or therapies that have been demonstrated to be 
effective for treatment of AD/pruritus during the study will be withdrawn from the study.  
Participants who start prohibited medications or therapies for other reasons during the study may 
be withdrawn from the study if an impact on efficacy assessment or safety of the participants is 
expected.  If in any doubt, investigators are advised to discuss medications with the medical 
monitor. 
Participants who present with a worsening of AD that requires treatment with a prohibited 
concomitant medication will have the study drug permanently discontinued. 


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Table 8: 
Prohibited Therapies or Procedures 
Prohibited Medications, Products, and Procedures 
Washout Period Prior to: 
Run-In Period 
Day 1 
Dupilumab 
26 weeks 
− 
Any marketed or investigational biological agent that may 
impact the course of AD or its assessments 
12 weeks or 5 half‑lives 
(whichever is longer) 
− 
Major surgery 
− 
8 weeks 
JAK inhibitor (systemic or topical) 
4 weeks 
− 
Nonbiological investigational product or device  
4 weeks 
− 
Live-attenuated vaccine  
4 weeks or 5 half‑lives 
(whichever is longer) 
− 
Systemic corticosteroid (oral/injectable)a 
4 weeks 
− 
Systemic treatment (other than biologics) that could affect 
AD and/or pruritusb 
4 weeks 
− 
PUVA treatment, UV-B phototherapy (including tanning 
beds) or excimer laser, excessive sun exposure  
4 weeks 
− 
Topical medicated treatment that could affect AD and/or 
pruritusc 
2 weeks 
− 
Doxepin 
2 weeks 
− 
Oral, sedative, H1 antihistamined 
2 weeks 
− 
Anticoagulant medicatione 
− 
2 weeks 
Antibiotics (systemic or topical) for infected AD 
2 weeks 
− 
a Intranasal corticosteroids and inhaled corticosteroids are allowed.  Eye and ear drops containing corticosteroids are 
also allowed. 
b For example, retinoids, calcineurin inhibitors, PDE-4 inhibitors, methotrexate, cyclosporine, hydroxycarbamide 
(hydroxyurea), azathioprine, interferon-gamma, or opioids (agonist, partial agonist-mixed, or antagonist). 
c Including but not limited to topical corticosteroids, crisaborole, calcineurin inhibitors, antihistamine, pramoxine, 
tars, antimicrobials, stable doses of prescription topical analgesics/moisturizers or over-the-counter topical 
analgesics/moisturizers containing menthol, camphor, urea additives, or lactic acid. 
d Including, but not limited to, diphenhydramine and hydroxyzine.  Note:  Oral, nonsedative, H1 antihistamines to 
treat allergies will be permitted during the study only if the participant has been on a stable dose for at least 
2 weeks prior to the run-in period and continues to use the same agent at the same frequency throughout the study. 
e For example, heparin, LMW-heparin, warfarin, antiplatelets (except low-dose aspirin ≤ 81 mg, which will be 
allowed).  Note:  NSAIDs will not be considered antiplatelets and will be allowed. 
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 
he/she does not want to be followed any longer; in this case no further data, except 
data in public domain, may be solicited from or collected on the participant.  
Participants may choose to discontinue study treatment and remain in the study to be 
followed for safety. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
− If this decision is made because of an SAE, the participant must discontinue study 
drug immediately, and appropriate measures are to be taken.  The investigator will 
notify the sponsor immediately. 
• If an application site reaction occurs, the investigator should use their best medical 
judgement as to whether to continue the participant's treatment. 
• Unacceptable toxicity as noted in Section 6.5.2. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, 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. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study drug, the ET visit 
should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit.  These visits are described in Table 3.  Participants who are discontinued for 
safety reasons may be asked to come for additional follow-up visits, at the investigator's 
discretion, after the ET visit to ensure appropriate medical care and AE follow-up.  The last date 
of the last application of study drug and the reason for discontinuation of study drug will be 
recorded in the eCRF. 


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If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The ET visit should be performed and date recorded. 
• The status of the participant should be updated to ET in the EDC system. 
• Unless the participant is lost to follow-up, the participant must be followed for safety 
until the time of the follow-up visit or until study drug–related toxicities resolve, 
return to baseline, stabilize, or are deemed irreversible, whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records.  If the 
participant withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
See Table 3 for data to be collected at the time of study withdrawal and follow-up and for any 
further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit (unless a virtual visit is scheduled due to COVID-19–related reasons): 
• 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, he/she will be considered to have 
withdrawn from the study, with "lost to follow-up" as a primary reason for 
withdrawal. 


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


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant receives the first 
application of study drug (Day 1).  Informed consent must be obtained before performing any 
study‑specific procedures.  Screening may not exceed 37 days (including 7 days for the run-in 
period).  Assessments that are required to demonstrate eligibility may be performed over the 
course of 1 or more days during the screening process.  Screening procedures are listed in 
Table 3. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before the 
first application of study drug.  Tests with results that fail eligibility requirements may be 
repeated once during screening, if deemed acceptable by the investigator.  For screening 
assessments that are repeated, the most recent available result before first application of study 
drug 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, following recovery 
from an infection).  Participants that do not meet the criteria for the single PP-NRS score at 
screening or for the baseline mean PP-NRS score of eligibility of the 7‑day run-in period may 
not be rescreened and will be considered screen failures. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Participant Numbering and Treatment Assignment 
All participant ID numbers will be 6 digits; the first 3 digits will be the site number, and the last 
3 digits will be the participant's number.  This participant number will be maintained throughout 
the study and will not be reassigned.  Participants who withdraw consent or withdraw from the 
study after being assigned a participant number will retain their initial number.  If a participant 
fails screening and is rescreened, a new participant number must be assigned. 
The investigator or designee will select the appropriate number of kits from their stock that 
corresponds to the %BSA affected by AD at baseline and dispense an individually customized 
number of kits to the participant.  All subsequent dispensing of study drug should follow this 
process (refer to the SRM). 
8.1.4. 
Diaries 
At the screening visit, participant email addresses will be collected and used for log-in access to 
an eDiary (tablet).  Participants will be trained to complete the eDiary once daily, starting from 
screening and up to the Day 29 visit, and will receive daily email reminders for completion.  The 
eDiary will capture the daily PP-NRS assessment starting at screening up to the Day 29 visit with 
the exception of Day 1. 
A paper diary will also be provided to participants to capture the date and time of twice daily 
study drug applications starting at the Day 1 visit. 
Participants may be contacted on Day 1 and Day 2 as a reminder to complete their dairies.  
The completed diaries will be reviewed during each study visit, and data will be confirmed by 
the study staff.  Qualified clinical staff will review the participants' entries for compliance.  


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Participants will be considered compliant with the treatment regimen if they apply at least 80% 
but no more than 120% of the expected number of applications during participation in the 
treatment period of the study.  Participants who are noncompliant will have their administration 
instructions reinforced by the investigator or a qualified designee. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data, general medical history, and the Fitzpatrick score will be collected at 
screening by the investigator or qualified designee and will include age, race, ethnicity, medical 
and surgical history, and current illnesses.  General medical history will be assessed on Day 1 for 
any changes from screening.  Medical history will include relevant medical or surgical treatment 
within the last 2 years that are considered to be clinically significant by the investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history for the past year will be collected at screening 
and assessed on Day 1 for any changes from screening by the investigator or qualified designee.  
Details regarding the participant's history of AD, including date of diagnosis, relevant disease 
characteristics, and prior treatments, including systemic treatments, radiation, and surgical 
procedures, will be recorded.  The participant's history of chronic itch and the participant's 
medical history of other conditions related to AD will also be collected at this time. 
8.2. 
Efficacy Assessments 
Clinical evaluations of AD will be performed by an experienced and qualified dermatologist 
(board certified or equivalent) or other suitably qualified and experienced physician.  To assure 
consistency and reduce variability, the same assessor should perform all assessments on a given 
participant whenever possible. 
Unless specified otherwise, the efficacy assessments scheduled during the study visits, as 
specified in Table 3, will be performed before study drug application.  In addition, assessments 
performed by participants (ie, PP-NRS, mPP-NRS, and TSQM-9 questionnaire) should be 
completed before the investigator assessments. In addition, refer to Table 5 for the sequence, 
timing, and allowed windows of mPP-NRS, PP-NRS, and study drug applications on Day 1 and 
Day 2. 
8.2.1. 
Health Economics 
Health Economics parameters are not evaluated in this study. 
8.2.2. 
Assessed by Participant 
8.2.2.1. 
Pruritus Numeric Rating Scale 
8.2.2.1.1. Peak-Pruritus Numerical Rating Scale (24-Hour Recall Period) 
As specified in Table 3, the intensity of pruritus (itch) will be recorded in the eDairy using an 
NRS (Phan et al 2012, Yosipovitch et al 2019).  Intensity will be evaluated by asking participants 


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to assign a numerical score representing their itch at the worst moment during the previous 
24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable.  This 
exercise will be completed daily, in the morning, from the screening visit until Day −1 and from 
Day 2 to the Day 29 visit. On Day 2, the PP-NRS should be completed approximately 24 (±1) 
hours after the Day 1 morning dose and before the Day 2 morning dose (refer to Table 5 for 
details). From Day 3 to the Day 29 visit, the PP-NRS should be completed at approximately the 
same time each morning and should be complete prior to each morning study drug application, 
per protocol. The PP-NRS (24-hour recall period) is presented in Appendix C.  To be eligible for 
this study, participants must complete at least 4 daily PP-NRS questionnaires during the last 7 
days of screening (the run-in period) and have a mean baseline PP-NRS score ≥ 4.0 during the 
run-in period, which is defined as the average of all nonmissing scores reported during the 7-day 
run-in period (Day −7 to Day −1).  Inclusion of participants completing fewer than 4 of 7 daily 
PP-NRS questionnaires during the last 7 days of screening (the run-in period) must be approved 
by the sponsor.  
8.2.2.1.2. Modified Peak-Pruritus Numerical Rating Scale (Current Itch Intensity) 
On Day 1 only, participants will be asked to evaluate the current intensity of their itch at the time 
of assessment (ie, prior to the morning study drug application, as well as at 15 and 30 minutes 
and 1, 2, 4, 6, and 12 hours after the morning study drug application; the 12-hour evaluation will 
occur prior to the second daily study drug application [refer to Table 5 for details and allowed 
windows]) on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst 
imaginable itch (Phan et al 2012, Verweyen et al 2019, Yosipovitch et al 2019).  The mPP-NRS 
(current itch intensity) was modified from the PP-NRS and is presented in Appendix C. 
8.2.2.2. 
Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication 
On Day 29 (or ET as applicable), participants will be asked to complete the TSQM-9.  The 
TSQM-9 is a 9-item measure that assesses the most common dimensions participants use to 
evaluate their medication (ie, global satisfaction, effectiveness, and convenience).  The results 
for each scale are presented from 0 to 100, where higher scores represent better satisfaction.  The 
questionnaire is provided separately from the protocol. 
8.2.3. 
Assessed by Investigator 
8.2.3.1. 
Investigator's Global Assessment 
The IGA of the current state of the disease will be performed at the visits specified in Table 3.  It 
is a 5-point morphological assessment of overall disease severity.  The grades for the IGA are 
shown in Table 9.  To be eligible for this study, participants must have an IGA score of at 
least 2 on Day 1. 


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Table 9: 
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. 
The IGA-TS is defined as an IGA score of 0 or 1 with at least a 2-grade reduction from baseline. 
8.2.3.2. 
Body Surface Area 
The overall BSA affected by AD (total BSA%) will be evaluated (from 0% to 100%) at the visits 
specified in Table 3.  The palmar surface of 1 hand (using the participant's hand and including 
the fingers and thumb) represents 1% of his or her total BSA (Thomas and Finlay 2007). 
In addition, at the screening and Day 1 visits, the BSA will be evaluated to verify each 
participant's eligibility, but excluding palms, soles, scalp, genitals, and folds.  To be eligible to 
enroll in this study, participants must have a BSA involvement between 1% and 20% (excluding 
palms, soles, scalp, genitals, and folds) on Day 1. 
Furthermore, on Day 1, the lesions to be treated will be identified on a body diagram.  All body 
areas can be treated.  If new lesions appear during the study, the BSA of treated area may need to 
be re-evaluated.  Of note, the BSA of treated area includes active, cleared, and new lesions and 
should not exceed 20% BSA. 
8.2.3.3. 
Eczema Area and Severity Index 
The EASI will be assessed at the visits specified in Table 3.  It quantifies the severity of a 
participant's AD based on both lesion severity and the percentage of BSA affected (Hanifin 
et al 2001).  The EASI is a composite score ranging from 0 to 72 that takes into account the 
degree of erythema, induration/infiltration (papules), excoriation, and lichenification (each 
scored from 0 to 3 separately) for each of 4 body regions, with adjustment for the percentage of 
BSA involved for each body region and for the proportion of the body region to the whole body.  
A detailed procedure of EASI score calculation is provided in Appendix D.  There is no 
minimum requirement in EASI to be eligible to enter this study. 
8.2.3.4. 
Medical Photography 
Medical photographs of the target lesion(s) (even if the AD lesion has cleared or disappeared) 
will be performed at the visits specified in Table 3 via 2 views (close-up and regional).  Medical 
photographs of application site AEs should also be taken. 


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Care will be taken to use the same camera, the same magnification, and the same settings for 
each photograph at each visit in order to obtain comparable pictures.  Medical photographs will 
be taken using a blue background. 
8.2.3.5. 
Transepidermial Water Loss 
Transepidermial water loss will be evaluated at the visits specified in Table 3. This measurement 
quantifies the clinical severity of AD and the associated effect on skin barrier function. 
Transepidermial water loss will be measured on the lesional (target lesion) and nonlesional skin 
on Day 1 and Day 29.  The TEWL assessment should be performed after medical photographs 
but prior to skin sample collection and at least 3 centimeters away from sites of skin sample 
collection and previous scars (for Day 29).  The location(s) of TEWL will be recorded.  On 
Day 1, TEWL assessments should be performed prior to study drug application.  On Day 29, 
TEWL should be performed on the same lesional and nonlesional skin identified on Day 1, even 
if the lesion has cleared.  Three TEWL readings will be taken at each location.  The readings 
should be taken in standard room ambient conditions (20°C to 22°C ± 1°C and < 60% relative 
humidity); the mean or median of the TEWL measurements will be used for analysis.  More 
details can be found in the SRM and SAP. 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in Table 3.  See Section 6.5 for 
guidelines regarding the management of relevant laboratory or other safety assessment 
abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
15 (± 2) days after the last study drug application.  Adverse events that begin or worsen after 
informed consent should be recorded on the Adverse Events Form in the eCRF regardless of the 
assumption of a causal relationship with the study drug.  Conditions that were already present at 
the time of informed consent should be recorded on the Medical History Form in the eCRF.  
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
considered related to the study drug/procedures, or that caused the participant to discontinue the 
study drug.  Care will be taken not to introduce bias when detecting AEs and/or SAEs.  
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?" is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 


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All SAEs will be reported to the sponsor or designee within 24 hours of the knowledge of the 
occurrence.  The investigator will submit any updated SAE data to the sponsor within 24 hours 
of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.3.2. 
Physical Examinations 
Physical examinations must be performed by a medically qualified individual, such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits.  Abnormalities identified after the first application 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. 
8.3.2.1. 
Comprehensive Physical Examination 
At the screening visit, a comprehensive physical examination should be conducted.  The 
comprehensive physical examination will include height, body weight, and assessment(s) of the 
following organ or body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief 
neurological examination. 
8.3.2.2. 
Targeted Physical Examination 
Targeted physical examinations will be performed as needed at the visits specified in Table 3. 
The targeted physical examination will be a symptom-directed evaluation and will include 
assessment of the body systems or organs as indicated by participant symptoms, AEs, or other 
findings and documented on the AE eCRF. 
8.3.3. 
Vital Signs 
Vital signs will be collected at the screening visit.  Vital sign measurements (to be taken before 
blood collection for laboratory tests) include systolic and diastolic blood pressure (mmHg), pulse 
(bpm), body temperature (°C), and respiratory rate (breaths/min).  If vital signs cannot be taken 
before blood collection for laboratory tests, there must be a minimum of 30 minutes from the 
completion of the blood collection procedures to the beginning of the vital signs collection.  
Blood pressure and pulse will be taken with the participant in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest. 
If deemed appropriate by the investigator, clinically significant findings in the vital signs 
assessment will exclude a participant from study participation.  Any abnormal finding related to 
vital signs that the investigator considers to be clinically significant must be recorded as an AE. 
8.3.4. 
Laboratory Assessments 
A central laboratory will perform all clinical laboratory assessments for safety.  See Table 10 for 
the list of clinical laboratory tests to be performed and Table 3 for the timing and frequency.  


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Additional testing may be required by the sponsor based on emerging safety data.  All 
Protocol-required laboratory assessments must be conducted in accordance with the Laboratory 
Manual and Table 3.  Information regarding collection, processing, and shipping of samples for 
laboratory assessment is provided in the Laboratory Manual. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.  All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 15 (± 2) 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 10: 
Required Laboratory Analytes 
Serum Chemistries 
Hematology 
Urinalysis  
Serology 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Blood urea nitrogen or urea 
Chloride 
Creatinine 
Gamma-glutamyl transferase 
Glucose random 
Lactate dehydrogenase 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total bilirubin 
is elevated above ULN) 
Lipid panel 
Uric acid 
Complete blood count, including: 
• Hemoglobin 
• Mean corpuscular hemoglobin 
• Hematocrit 
• Platelet count 
• Mean platelet volume 
• Red blood cell count 
• Mean corpuscular volume 
• WBC count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
 
Absolute values must be provided for: 
• WBC differential laboratory results 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen 
 
Microscopic analysis 
(as required) 
HIV 
Pregnancy Testing 
hCG (WOCBP only; serum and 
urine) 
Other 
FSH (only for female participants 
of nonchildbearing potential who 
had a cessation of menses for at 
least 12 months without an 
alternative medical cause) 
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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8.3.4.1. 
Chemistry, Serology, Hematology, and Urinalysis 
A panel of standard serum chemistries, hematology, and urinalysis tests will be analyzed at times 
shown in Table 3.  A list of required analytes is provided in Table 10.  All serum chemistries will 
be performed from blood samples collected without respect to food intake (ie, nonfasting). 
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 needed. 
8.3.4.2. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening.  Urine pregnancy tests 
will be performed at other specified visits outlined in Table 3.  If a urine pregnancy test is 
positive, the results should be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 


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8.6. 
Unscheduled Visits 
Unscheduled study visits may occur at any time as medically warranted.  Any assessments 
performed at those visits should be recorded in the eCRF. 
If the participant develops new areas of AD, documentation of the new BSA may occur at an 
unscheduled visit if appropriate. 
8.7. 
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, the ET evaluations 
will supersede those of that scheduled visit, and the data should be entered in the ET visit 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. 
8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the Day 29 visit and the scheduled follow-up 
visit and should occur 15 (± 2) days after the last application of study drug.  Adverse events and 
SAEs must be reported up until 1) within 15 (± 2) days after the last application of study drug or 
2) until toxicities resolve, return to baseline, stabilize, 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, vital signs measurements), including those that worsen from baseline, 
considered clinically significant in the medical and scientific judgment of the investigator (ie, not 
related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug.  Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin, platelet count 
decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study drug (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy assessments. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent.  If the condition is present before 
entering the study, then it should be captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs.  This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) 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 (including local and systemic reactions) that begins or worsens after informed consent is 
signed should be recorded on the Adverse Event Form in the eCRF.  AEs/SAEs should be reported 
for enrolled participants, but only SAEs need to be reported for screen failure participants.  For 
enrolled participants, conditions that were present at the time informed consent was given should be 
recorded on the Medical History Form in the eCRF.  For detailed information refer to the eCRF 
guidelines. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Event Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested.  In this 
case, all participant identifiers, with the exception of the participant number, will be redacted by the 
site staff on the copies of the medical records before submission.  These records can be submitted to 
Incyte Pharmacovigilance by email/fax per the contact information listed in the SRM. 
• 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 severity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug:  suspected 
(yes) or not suspected (no).  See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures and 
Non-Drug Therapy). 


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Assessment of Intensity 
The severity of AEs/SAEs 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.  For grading of AEs related to laboratory values; the CTCAE grading of the 
laboratory result should generally be followed (eg, for an AE of thrombocytopenia, the CTCAE 
grading of platelet count decreased should be followed). 
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 in making his/her assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report.  However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements.  Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
submit the updated causality assessment. 


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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the AE eCRFs until it has resolved, has stabilized, 
or until it is judged to be permanent; assessment should be made at each visit (or more frequently if 
necessary) of any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology. 
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance 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. 
In the event a participant experiences a skin reaction and that an allergic contact dermatitis is 
suspected, the event should be documented as an AE, and patch testing may be performed to 
confirm the diagnosis. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedures), all SAEs 
occurring after the participant has signed the ICF through the last safety visit or within 
15 (± 2) days after the last application of study drug must be reported to the sponsor (or 
designee) immediately, without undue delay but not later than within 24 hours of obtaining 
knowledge of its occurrence unless otherwise specified by the Protocol.  The investigator will 
submit any updated SAE data to the sponsor (or designee) immediately, without undue delay but 
not later than within 24 hours of it being available. 
Investigators are not obligated to actively seek SAE information after the safety follow-up visit 
or 15 (± 2) days after the last application of study drug.  However, if the investigator learns of 
any SAE, including death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study drug or study participation, 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). 


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Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB for the study drug (new occurrence) and is 
thought to be related to the study drug, the sponsor or its designee may urgently require further 
information from the investigator for expedited reporting to health authorities.  The sponsor or its 
designee may need to issue an Investigator Notification to inform all investigators involved in 
any study with the same drug that this SAE has been reported.  Suspected unexpected serious 
adverse reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC or as per national regulatory requirements 
in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation.  The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE by completing 
the Serious Adverse Event Report Form in English. 
• Follow-up information is also recorded and transmitted to Incyte Pharmacovigilance on an amended 
or new Serious Adverse Event Report Form, with an indication that it is follow-up to the previously 
reported SAE and the date of the original report.  The follow-up report should include information 
that was not provided on the previous Serious Adverse Event Report Form, such as the outcome of 
the event (eg, resolved or ongoing), treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation).  Each recurrence, complication, or progression of the original 
event should be reported as a follow-up to that event, regardless of when it occurs. 
• Contacts for SAE reporting can be found in SRM. 
9.5. 
Events of Clinical Interest 
Not applicable. 
9.5.1. 
Adverse Events of Special Interest 
Not applicable. 


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9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form or SRM. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or its designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.8. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 


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All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9.10. 
Treatment of Overdose 
Overdose is not an SAE unless it meets the criteria of an SAE (see Section 9.2). 
For this study, an overdose may consist of accidental or intentional ingestion of the study cream 
or excessive application onto the skin (eg, exposure to a meaningfully larger BSA than identified 
at baseline, using a greater quantity of cream versus the initial amount established at baseline, or 
applying more frequently than instructed). 
In the event of overdose, the investigator or treating physician should contact the medical 
monitor to discuss the event and proceed with the following as appropriate for the circumstances: 
• In case of excessive topical application, instruct the participant to wash ruxolitinib 
cream off of the skin and monitor for application site AEs. 
• Obtain a blood sample within 2 days from the date of the last application of study 
treatment or date of ingestion of cream to determine possible systemic exposure to 
ruxolitinib (if requested by the medical monitor; determined on a case-by-case basis). 
• Monitor the participant for systemic AEs/SAEs and laboratory abnormalities until 
ruxolitinib can no longer be detected systemically (at least 7 days). 
• In the event of ingestion of ruxolitinib cream, general symptomatic treatment should 
be given as necessary. 
• Document the quantity of ruxolitinib cream applied or ingested (eg, by weighing the 
tube of cream), as well as the duration of excessive application or exposure, in the 
CRF. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
Approximately 36 participants were planned to be enrolled into the study to receive ruxolitinib 
1.5% cream.  The sample size calculation was based on the CI for 1-sample mean.  With an 
approximate 10% missing assessment rate at 24 hours, a sample size of 36 is required to produce 
a 2-sided 95% CI for the expected change from baseline in PP-NRS (24-hour recall period), with 
a precision of 0.57.  The SD of 1.64 is estimated from 2 Phase 3, double-blind, randomized 
studies (INCB 18424-303 and INCB 18424-304). To ensure data quality and support study 
interpretation after deviations from protocol related to the timing of efficacy assessments were 
observed in the first participants enrolled, it was decided to enroll an additional 12 participants 
for a total of approximately 48 participants to be included. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 12. 
Table 12: 
Populations for Analysis 
Population 
Description 
Enrolled 
All participants who sign the ICF. 
ITT 
All enrolled participants who complete the run-in period and meet the inclusion 
and exclusion criteria.  The ITT population will be used for the summary of 
demographics, baseline characteristics, and participants disposition. 
mITT 
The mITT population is a subset of the ITT population, including participants 
who have both baseline and at least 1 postbaseline PP-NRS or mPP-NRS 
assessment within the treatment period. 
The mITT population will be used for all efficacy analyses. 
Per protocol 
The per protocol population is a subset of the mITT population, excluding 
participants with major protocol deviations that could potentially affect the 
efficacy evaluations. 
The per protocol population will be used as supportive information for all efficacy 
analyses. 
Safety 
The safety population will include all enrolled participants who received at least 
1 application of ruxolitinib 1.5% cream.  All safety analyses will be conducted 
using the safety population. 
 
 
 
 
 
10.3. 
Level of Significance 
No formal statistical comparisons will be performed.  All CIs will be 95%. 


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10.4. 
Statistical Analyses 
10.4.1. 
General Considerations 
The baseline value for a variable will be defined as the last nonmissing value before or on Day 1 
(prior to the first application of study drug), unless otherwise specified.  For PP-NRS, the 
baseline is defined as the average of all nonmissing PP-NRS scores reported during the 7‑day 
run-in period (Day −7 to Day −1). 
For continuous measurements, summary statistics will include sample size, mean, median, SD, 
standard error of the mean, minimum, and maximum.  Summary statistics for continuous 
measures will be provided for baseline, the actual measurements at each visit, and the change 
and percentage change from baseline at each visit, if applicable.  For categorical measurements, 
summary statistics will include sample size, frequency, and percentages. 
Any deviation(s) from the SAP will be described and justified in the final report, as appropriate. 
10.4.2. 
Primary Analysis 
The primary endpoint, change in PP-NRS from baseline at Day 2 (24-hour recall period after 
first application), will be analyzed descriptively.  The 95% CI will be provided for the mean 
change.  The baseline for this analysis will be the average of all nonmissing PP-NRS scores 
reported during the 7‑day run-in period (Day −7 to Day −1); at least 4 completed PP-NRS 
worksheets will be required prior to Day 1 (unless otherwise approved by the sponsor). 
10.4.3. 
Secondary Analysis 
All secondary efficacy endpoints will be analyzed descriptively, with summary statistics for 
continuous endpoints and frequency distribution for binary endpoints.  The onset of action will 
be analyzed using a change from baseline in mPP-NRS (current itch intensity) on Day 1, in 
which baseline is defined as the current itch (mPP-NRS) prior to the first application of study 
drug on Day 1.  The 95% CIs will also be provided.  The change in PP-NRS over time from 
baseline will be presented graphically.  The log-rank test with the Kaplan-Meier curves will be 
applied to the time-to-event endpoints. 
10.4.4. 
Safety Analyses 
Safety analyses will be conducted for the safety population. 
Adverse events (local and systemic) will be coded by the MedDRA dictionary, and TEAEs 
(ie, AEs reported for the first time or worsening of a pre-existing event after first application of 
study drug) will be tabulated by preferred term and system organ class for all events, related 
events, and events of Grade 3 or higher.  Quantitative safety variables (eg, laboratory 
assessments, vital signs) and their changes from baseline will be summarized with descriptive 
statistics.  Clinically notable abnormal values will be flagged and tabulated based on predefined 
criteria. 
The clinical laboratory data will be analyzed using summary statistics.  Descriptive statistics will 
be determined for vital signs.  Vital sign results will be reviewed for clinically notable 
abnormalities. 


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Measures of exposure (eg, days of exposure, number of applications) to study drug will be 
summarized by means of summary statistics. 
 
 
 
 
 
10.4.6. 
Other Analysis 
TSQM-9 data will be summarized using descriptive statistics. 
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 without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 


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11.2. 
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 (or delegate) 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 
, or data transfer 
specifications or agreements, as applicable. 
The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
, photographs, diary data), 
or as otherwise specified in the Protocol. 
• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants.  Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete.  Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail).  Source data are in general all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source data are contained in source 
documents (original records or certified copies). 
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 


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


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11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, 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. 


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


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12. 
REFERENCES 
Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z. Molecular genetic of atopic 
dermatitis: an update. Int J Health Sci (Qassim) 2016;10:96-120. 
Bissonnette R, Maari C, Forman S, et al. The oral Janus kinase/spleen tyrosine kinase inhibitor 
ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with 
moderate-to-severe atopic dermatitis: results from a randomized double-blind placebo-controlled 
study. Br J Dermatol 2019;181:733-742. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Darsow U, Pfab F, Valet M, et al. Pruritus and atopic dermatitis. Clin Rev Allergy Immunol 
2011;41:237-244. 
Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic 
dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J 
Am Acad Dermatol 2014;71:116-132. 
Farmer WS, Marathe KS. Atopic dermatitis: managing the itch. Adv Exp Med Biol 
2017;1027:161-177. 
Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-
to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled 
multiple-dose study. J Am Acad Dermatol 2019;80:913-921.e9. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl 
(Stockh) 1980;92:44-47. 
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and 
severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp 
Dermatol 2001;10:11-18. 
Hashimoto T, Sakai K, Sanders KM, Yosipovitch G, Akiyama T. Antipruritic effects of Janus 
kinase inhibitor tofacitinib in a mouse model of psoriasis. Acta Derm Venereol 2019;99:298-303. 
INCB018424 Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus 
kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 2015;73:395-399. 
Mochizuki H, Schut C, Nattkemper LA, Yosipovitch G. Brain mechanism of itch in atopic 
dermatitis and its possible alteration through non-invasive treatments. Allergol Int 2017;66:14-
21. 
National Eczema Association. Atopic Dermatitis. 2018. 
Ong PY, Ohtake T, Brandt C, et al. Endogenous antimicrobial peptides and skin infections in 
atopic dermatitis. N Engl J Med 2002;347:1151-1160. 
Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the 
treatment of atopic dermatitis: results from two phase 3, randomized, double-blind studies. 
Presented at: 2nd Annual Revolutionizing Atopic Dermatitis Conference; April 5, 2020; 
Chicago, IL. 


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Pavlis J, Yosipovitch G. Management of itch in atopic dermatitis. Am J Clin Dermatol 
2018;19:319-332. 
Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity 
and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 
patients with chronic pruritus. Acta Derm Venereol 2012;92:502-507. 
Rerknimitr P, Otsuka A, Nakashima C, Kabashima K. The etiopathogenesis of atopic dermatitis: 
barrier disruption, immunological derangement, and pruritus. Inflamm Regen 2017;37:14. 
Thomas CL, Finlay AY. The 'handprint' approximates to 1% of the total body surface area 
whereas the 'palm minus the fingers' does not. Br J Dermatol 2007;157:1080-1081. 
Tominaga M, Takamori K. Itch and nerve fibers with special reference to atopic dermatitis: 
therapeutic implications. J Dermatol 2014;41:205-212. 
Urashima R, Mihara M. Cutaneous nerves in atopic dermatitis. A histological, 
immunohistochemical and electron microscopic study. Virchows Arch 1998;432:363-370. 
Verweyen E, Ständer S, Kreitz K, et al. Validation of a comprehensive set of pruritus assessment 
instruments: The Chronic Pruritus Tools Questionnaire PRURITOOLS. Acta Derm Venereol 
2019;99:657-663. 
Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller AS, Leffell D. Fitzpatrick's Dermatology in 
General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. 
Yarbrough KB, Neuhaus KJ, Simpson EL. The effects of treatment on itch in atopic dermatitis. 
Dermatol Ther 2013;26:110-119. 
Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep 
2008;8:306-11. 
Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: psychometric 
validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br 
J Dermatol 2019;181:761-769. 


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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 
− 
Female participant who has had a cessation of menses for at least 12 months prior to the screening visit without an 
alternative medical cause, and an FSH test confirming nonchildbearing potential (refer to laboratory reference 
ranges for confirmatory levels). 
For male participants of reproductive potentialb 
The following methods during the Protocol-defined timeframe in Section 5.1 are considered effective: 
• Barrier method (use of a male condom or partner use of a female condom, cervical cap, diaphragm, or contraceptive 
sponge) in conjuction with spermicide 
• Vasectomy (performed ≥ 4 months prior to screening) 
• Partner use of hormonal contraceptives (eg, combined oral contraceptive, patch, vaginal ring, injectable, or implant), 
intrauterine devices, or intrauterine systems 
• Partner has had a tubal ligation 
• Sexual abstinencec 
− Abstinence from penile-vaginal intercourse  
The following are not acceptable methods of contraception: 
• Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhoea method 
• 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. 
For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 are considered effective: 
• Barrier method (use of a male condom or partner use of a female condom, cervical cap, diaphragm, or contraceptive 
sponge) in conjuction with spermicide 
• Hormonal contraception (eg, combined oral contraceptive, patch, vaginal ring, injectable, or implant) 
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Tubal ligation 
• Vasectomized partner (provided vasectomy was performed ≥ 4 months prior to screening) 
• 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 (excluding vasectomized participants) has a partner with childbearing potential the partner should also 
use contraceptives. 
c In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatments.  The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the 
participant. 
Source:  Clinical Trials Facilitation and Coordination Group (2020). 


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APPENDIX B. DIAGNOSTIC CRITERIA FOR ATOPIC DERMATITIS 
A participant is to have a clinical diagnosis of AD according to the criteria of Hanifin and Rajka 
(1980).  The criteria are as follows: 
Major Criteria (must have at least 3) 
• Pruritus 
• Typical morphology and distribution: 
− Adults:  flexural lichenification or linearity 
− Children and infants:  involvement of facial and extensor surfaces 
• Chronic or chronically relapsing dermatitis 
• Personal or family history of atopy (asthma, allergic rhinitis, AD) 
Minor Criteria (must have at least 3) 
• Xerosis 
• Ichthyosis/keratosis pilaris/palmar hyperlinearity 
• Immediate (Type 1) skin test reactivity 
• Elevated serum IgE 
• Early age at onset 
• Tendency to skin infections (Staphylococcus aureus, herpes simplex)/impaired 
cellular immunity 
• Tendency to nonspecific hand/foot dermatitis 
• Nipple eczema 
• Cheilitis 
• Recurrent conjunctivitis 
• Dennie-Morgan infraorbital fold 
• Keratoconus 
• Anterior subcapsular cataracts 
• Orbital darkening 
• Facial pallor/erythema 
• Pityriasis alba 
• Anterior neck folds 
• Itch when sweating 
• Intolerance to wool and lipid solvents 
• Perifollicular accentuation 
• Food intolerance 
• Course influenced by environmental/emotional factors 
• White dermographism/delayed blanch 


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APPENDIX C. PRURITUS NUMERIC RATING SCALE 
Peak Pruritus NRS (24-hour recall period) 
On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would 
you rate your itch at the worst moment during the previous 24 hours?  
Numeric Rating Scale 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No itch 
 
 
 
 
 
 
 
 
 
Worst itch 
imaginable 
 
©2019 Regeneron Pharmaceuticals, Inc and Sanofi SA.  All rights reserved.  Used with permission of Regeneron 
Pharmaceuticals, Inc and Sanofi SA. 
Modified Peak Pruritus NRS (current itch intensity) 
On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable', how would 
you rate your current itch? 
Numeric Rating Scale 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
No itch 
 
 
 
 
 
 
 
 
 
Worst itch 
imaginable 
 
Note:  This scale is a modified version of the PP-NRS (Phan et al 2012, Verweyen et al 2019). 


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APPENDIX D. ECZEMA AREA AND SEVERITY INDEX 
Four anatomic sites (head, upper extremities, trunk, and lower extremities) are assessed for 
erythema, induration/infiltration (papules), excoriation, and lichenification as seen on the day of 
the examination.  The severity of each sign is assessed using the following 4-point scale (half 
steps are allowed; eg, 0.5, 1.5, and 2.5): 
• 0 = none 
• 1 = mild 
• 2 = moderate 
• 3 = severe 
The area affected by AD within a given anatomic site is estimated as a percentage of the total 
area of that anatomic site and assigned a numerical value according to the degree of AD 
involvement as follows: 
• 0 = no involvement 
• 1 = < 10% 
• 2 = 10% to < 30% 
• 3 = 30% to < 50% 
• 4 = 50% to < 70% 
• 5 = 70% to < 90% 
• 6 = 90% to 100% 
The EASI score is obtained by using the following formula: 
EASI = 0.1 (Eh + Ih + Exh + Lh) Ah + 0.2 (Eu + Iu + Exu + Lu) Au + 0.3 (Et + It + Ext + Lt) At + 
0.4 (El + Il + Exl + Ll) Al. 
Where E, I, Ex, L, and A denote erythema, induration, excoriation, lichenification, and area, 
respectively, and h, u, t, and l denote head, upper extremities, trunk, and lower extremities, 
respectively. 


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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1  
30 MAR 2021 
Amendment 2 
13 AUG 2021 
Amendment 3 
09 MAY 2022 
Amendment 3 (09 MAY 2022) 
The primary purpose of this amendment is two-fold: to clarify the sequence and timing of events 
on Day 1 and Day 2 for the mPP-NRS, PP-NRS, and study drug applications, and to increase the 
number of participants to be included in the study. 
1. Section 1, Protocol Summary (Treatment Groups and Duration; Table 3:  Schedule 
of Activities); Section 4.1, Overall Design; Section 6.1, Study Treatment 
Administered (Table 6:  Study Treatment Information); Section 8.2, Efficacy 
Assessments; Section 8.2.2.1.1, Peak-Pruritus Numerical Rating Scale (24-Hour 
Recall Period); Section 8.2.2.1.2, Modified Peak-Pruritus Numerical Rating Scale 
(Current Itch Intensity) 
Description of change:  Updated with additional text and added new table (ie, Table 5) 
to clarify mPP-NRS and PP-NRS timing, and to allow windows of mPP-NRS, PP-NRS, 
and study drug applications on Day 1 and Day 2. 
Rationale for change:  Timing of mPP-NRS and PP-NRS are critical, and should take 
precedence on Day 1 and Day 2. 
2. Section 1, Protocol Summary (Table 2:  Key Study Design Elements); Section 4.1, 
Overall Design; Section 10.1, Sample Size Determination 
Description of change: Increased the number of participants from 36 to 48. 
Rationale for change:  To ensure data quality and support study interpretation after 
deviations from protocol related to the timing of efficacy assessments were observed in 
the first participants enrolled. 
3. Section 1, Protocol Summary (Treatment Groups and Duration); Section 4.1, 
Overall Design; Section 6.1, Study Treatment Administered 
Description of change:  Removed the ± 2 hours window for the every 12 hours (BID) 
study drug application. 
Rationale for change:  To avoid confusion and potential error regarding the sequence of 
NRS completion and IP application. 
4. Section 1, Protocol Summary (Table 3:  Schedule of Activities); Section 4.1.1, Study 
Conduct During the COVID-19 Pandemic; Section 6.4, Study Treatment 
Compliance; Section 8.1.4, Diaries 
Description of change:  Clarified that the twice daily study drug application will be 
captured in a paper diary, and only the daily PP-NRS assessment will be captured in the 
eDiary. 


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Rationale for change:  The eDiary does not collect time of study drug applications as 
indicated in Protocol Section 6.4. 
5. Section 1, Protocol Summary (Treatment Groups and Duration; Table 3:  Schedule 
of Activities); Section 4.1.1, Overall Design; Section 5.1, Inclusion Criteria 
(Criterion #10); Section 6.1, Study Treatment Administered; Section 8.2.2.1.1, 
PP-NRS 
Description of change:  Clarified that the PP-NRS should be completed from screening 
to Day −1 and from Day 2 to the Day 29 visit (before morning study drug application). 
Rationale for change:  As the PP-NRS efficacy endpoints are up to Day 29, the PP-NRS 
needs to be collected up to the Day 29 visit. 
6. Section 2.1.1, Ruxolitinib 
Description of change:  Updated to acknowledge the recent FDA approval of ruxolitinib 
1.5% cream for treatment of atopic dermatitis. 
Rationale for change:  Ruxolitinib 1.5% cream received FDA approval on 21 SEP 2021 
for the atopic dermatitis indication. 
7. Section 2.3, Benefit/Risk Assessment 
Description of change:  Updated to be aligned with the latest version of the IB. 
Rationale for change: A new IB dated 16 AUG 2021 is now available. 
8. Section 5.3, Lifestyle Considerations 
Description of change:  Addition of text for participants to refrain from washing or 
applying cosmetics to the targeted lesions(s) and adjacent areas. 
Rationale for change:  To align with current microbiome skin swab kit 
recommendations and with the laboratory manual. 
9. Section 10.2, Populations for Analysis (Table 13:  Populations for Analysis) 
Description of change:  Added a per protocol population as supportive information for 
the efficacy analyses. 
Rationale for change:  To exclude participants with major protocol deviations that could 
potentially affect the efficacy evaluations. 
10. Section 10.4.4, Safety Analyses  
Description of change:  Removed the distributions of key laboratory parameters over 
time and the change from baseline in vital signs. 
Rationale for change:  As laboratory values are only measured at baseline and 
Week 4/ET, laboratory values will not be plotted over time. Similarly, as vital signs are 
only collected at screening, no change from baseline will be reported. 
11. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 2 (13 AUG 2021) 
The primary purpose of this amendment is to revise exclusion criteria, translational assessments 
and analyses, as well as provide other general clarifications. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; 
Table 3:  Schedule of Activities); Section 2.2.1, Scientific Rationale for Study 
Design; Section 4.1, Overall Design; Section 4.2, Overall Study Duration; 
Section 6.1, Study Treatment Administered (Table 5:  Study Treatment 
Information); Section 6.5, Dose Modifications; Section 8.1.4, Electronic Diaries 
Description of change: 
• Added  2 days to the treatment period to be 28 ( 2) days, and updated the 
estimated time an individual will participate in the study to 80 days. 
• Updated that treatment will be approximately 28 days, and the last application to 
occur the evening prior to the Day 29 visit. 
• Clarified that any new lesions must be treated until the evening prior to the 
Day 29 visit. 
Rationale for change:  The intent is for participants to continue to apply the study drug 
up until the evening prior to the Day 29 visit.  With the allowed visit window of  2 days, 
there may be situations where a participant does not have their Day 29 visit until Day 31, 
but would have stopped application of study drug on the evening of Day 28.  This allows 
the participant to continue treatment up to their Day 29 visit. 
2. Section 1, Protocol Summary (Table 3:  Schedule of Activities); Section 8.2.2.1.2, 
Modified Peak-Pruritis Numerical Rating Scale (Current Itch Intensity) 
Description of change:  Removed the mPP-NRS assessment from the participant's 
eDiary notes of the SoA, and updated the mPP-NRS 0.25 and 0.5 hour time points to 
15 and 30 minutes in the PP-NRS and mPP-NRS notes of the SoA and in 
Section 8.2.2.1.2. 
Rationale for change:  The mPP-NRS is completed on paper, and therefore, not linked 
to the eDiary.  The time points for the mPP-NRS assessments were updated to align with 
the objectives and endpoints and improve clarity. 
3. Section 3, Objectives and Endpoints (Table 4:  Objectives and Endpoints) 
Description of change:  
 
 
Rationale for change:  Analyses was no longer logistically feasible given the study 
timelines and was removed. 
4. Section 5.2, Exclusion Criteria (Criteria #10, #11, #12, and #34) 


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Description of change:  Updated criterion #10 to include renal disease requiring dialysis 
as one of the limiting medical conditions.  Revised the list of clinical lab test results at 
screening in criterion #11.  Removed criterion #12 regarding the positive result for HIV 
as it was moved into criterion #11.  Added new criterion #34 for a history of hepatitis B 
virus or hepatitis C virus infection. 
Rational for change:  The criterion #10 addition of renal disease was to add more 
clarification for the limiting medical conditions.  Criterion #11 was determined to be 
overly restrictive and could potentially limit enrollment.  This revision also ensures 
consistency across the ruxolitinib cream AD program and does not impose additional 
risks to participants.  The estimated GFR criterion was also updated to a more 
conservative value to ensure participant safety.  Criterion #12 removal was due to it being 
moved into a screening exclusion in criterion #11.  Criterion #34 was added to capture 
the history of hepatitis B or hepatitis C viruses since it was previously omitted. 
5. Section 6.5, Dose Modifications 
Description of change:  Added that at any time during the study the participant’s BSA 
exceeds 20%, the participant should be considered for termination. 
Rational for change:  In response to agency feedback as well as to ensure consistency 
across the ruxolitinib AD program. 
6. Section 6.5.1, Criteria and Procedures for Application Interruptions and 
Adjustments of Study Drug (Table 6:  Guidelines for Interruption and Restarting of 
Treatment Applications if Adverse Event is Deemed Related to the Study Drug) 
Description of change:  Replaced the AE related to study drug list in the table. 
Rationale for change:  The changes were implemented to better align with the revised 
exclusion criterion. 
7. Section 8.1.4, Electronic Diaries 
Description of change:  Revised text to include collection of each participant's email 
address for log-in access to an eDiary, receipt of twice daily email reminders, and that the 
eDiary will capture twice daily study drug applications. 
Rationale for change:  To clarify procedures related to use and programming of the 
eDiary. 
  
 
 
 
 
 
 
 
 


Incyte Corporation 
Page 81 of 82 
Protocol INCB 18424-901 Am 3 
Version 4 
09 MAY 2022 
VV-CLIN-013593 
CONFIDENTIAL 
 
 
 
10. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Incyte Corporation 
Page 82 of 82 
Protocol INCB 18424-901 Am 3 
Version 4 
09 MAY 2022 
VV-CLIN-013593 
CONFIDENTIAL 
Amendment 1 (30 MAR 2021) 
The primary purpose of this amendment is to incorporate Health Authority comments. 
1. Section 5.2, Exclusion Criteria 
Description of change:  Exclusion Criterion 11b was revised to include any participant 
who is on maintenance dialysis or has an estimated GFR ≤ 15 mL/min/1.73 m2. 
Rationale for the change:  To incorporate Health Authority comments. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 
 


Signature Page for VV-CLIN-013593 v4.0
Signature Page for VV-CLIN-013593 v4.0
Approval
09-May-2022 15:47:47 GMT+0000
Approval
09-May-2022 15:56:13 GMT+0000
Approval
09-May-2022 17:05:57 GMT+0000
Approval
10-May-2022 08:00:52 GMT+0000
Approval
Approver
10-May-2022 12:23:16 GMT+0000

SAP_001.pdf: 
NCT Number:      NCT04839380
Document Date:  Statistical Analysis Plan Version Final: 17-Jun-2022
Official Title:      An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% Cream 
on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 


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Statistical Analysis Plan 
 
 
Study Title: 
An Open-Label, Single-Arm Study to Evaluate the Effect 
of Ruxolitinib 1.5% Cream on Itch in Adult Participants 
With Atopic Dermatitis (SCRATCH-AD) 
 
Protocol Number and Version: 
INCB 18424-901 Amendment 3 dated 09-MAY-2022 
Product: 
Ruxolitinib cream 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off, 
Wilmington, Delaware, USA 19803 
 
Date: 
17-Jun-2022 
 
 
 
Version: 
Final v1.0 
 
 
Prepared by: 
 
 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
STATISTICAL ANALYSIS PLAN REVISION SUMMARY 
Version 
Version Date 
Author 
Summary of Changes 
Final v1.0 
17-Jun-2022 
 
Initial version 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
SIGNATURE PAGE 
AUTHOR(S): 
 
 
 
 EDT 
APPROVALS: 
 
 
 
 
 
 
 
 
 
EDT 
 
 
 
 
 
 
EDT 
 
 
 
 
This statistical analysis plan will be reviewed and revised as needed. The most recent version will replace 
the previous version in place. 
 
EDT 
Name 
Signature 
Title 
Date 
(DD-MMM-YYYY) 
 
05-Oct-2022 | 16:09:46 
Name 
Signature 
Title 
Date 
(DD-MMM-YYYY) 
 
06-Oct-2022 | 10:17:29 
 
cyte Corporation 
05-Oct-2022 | 22:45:23 
 
05-Oct-2022 | 16:12:38 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
TABLE OF CONTENT 
1 
INTRODUCTION .................................................................................................................... 8 
2 
STUDY OBJECTIVES AND ENDPOINTS .......................................................................... 8 
3 
STUDY DESIGN .................................................................................................................... 10 
3.1 
Overall Design ................................................................................................................ 10 
3.2 
Schedule of Events .......................................................................................................... 12 
3.3 
Treatment ........................................................................................................................ 12 
3.4 
Randomization, Replacement, and Unblinding Procedures ....................................... 12 
3.5 
Changes to the Analysis from the Protocol ................................................................... 12 
4 
POPULATIONS FOR ANALYSIS ...................................................................................... 12 
4.1 
Enrolled Analysis Set ..................................................................................................... 12 
4.2 
Intent-to-Treat Analysis Set........................................................................................... 13 
4.3 
Modified Intent-to-Treat Analysis Set .......................................................................... 13 
4.4 
Safety Analysis Set .......................................................................................................... 13 
5 
GENERAL CONSIDERATIONS ......................................................................................... 13 
5.1 
Sample Size ..................................................................................................................... 13 
5.2 
Baseline ............................................................................................................................ 14 
5.3 
Reference Start Date and Analysis Day ........................................................................ 14 
5.4 
Windowing Conventions ................................................................................................ 14 
5.5 
Descriptive Statistics ....................................................................................................... 14 
5.6 
Statistical Tests ............................................................................................................... 15 
5.7 
Handling of Retests, Unscheduled Visits, and Early Termination Data .................... 15 
5.8 
Software Version ............................................................................................................ 15 
6 
STATISTICAL CONSIDERATIONS .................................................................................. 15 
6.1 
Adjustments for Covariates ........................................................................................... 15 
6.2 
Handling of Dropouts or Missing data ......................................................................... 15 
6.3 
Interim Analysis and Data Monitoring ......................................................................... 15 
6.4 
Multicenter Studies ........................................................................................................ 15 
6.5 
Multiple Comparisons/Multiplicity ............................................................................... 16 
6.6 
Examination of Subgroups ............................................................................................ 16 
7 
STUDY PARTICIPANTS ..................................................................................................... 16 
7.1 
Disposition of Participants ............................................................................................. 16 
7.2 
Protocol Deviations ......................................................................................................... 17 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
8 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................. 17 
9 
SURGICAL AND MEDICAL HISTORY ............................................................................ 18 
10 
PRIOR AND CONCOMITANT MEDICATIONS AND THERAPIES ............................ 19 
10.1 
Prior and Concomitant Medications ............................................................................. 19 
10.2 
Non-drug Therapies and Surgical Procedures ............................................................. 19 
11 
STUDY TREATMENT EXPOSURE AND TREATMENT COMPLIANCE ................... 20 
12 
EFFICACY ANALYSIS ........................................................................................................ 21 
12.1 
Primary Endpoint ........................................................................................................... 21 
12.1.1 
Peak-Pruritus Numerical Rating Scale ........................................... 21 
12.1.2 
Primary Analysis ............................................................................ 21 
12.2 
Secondary Endpoints ...................................................................................................... 21 
12.2.1 
Modified Peak-Pruritus Numerical Rating Scale ........................... 21 
12.2.2 
Peak-Pruritus Numerical Rating Scale ........................................... 22 
12.2.3 
Minimal Clinically Important Difference ...................................... 22 
12.2.4 
Investigator's Global Assessment ................................................... 22 
12.2.5 
Secondary Endpoints Analysis ....................................................... 23 
 
 23 
 
 23 
 
 24 
 
 24 
12.4 
Other Analyses ................................................................................................................ 24 
12.4.1 
Abbreviated 9-Item Treatment Satisfaction Questionnaire 
for Medication ................................................................................ 24 
12.4.2 
Transepidermal Water Loss ........................................................... 24 
12.4.3 
Eczema Area and Severity Index ................................................... 25 
12.4.4 
Total BSA Affected by AD ............................................................ 25 
13 
SAFETY ANALYSIS ............................................................................................................. 25 
13.1 
Adverse Events ............................................................................................................... 25 
13.2 
Clinical Laboratory ........................................................................................................ 27 
13.3 
Vital Signs ....................................................................................................................... 27 
14 
REFERENCES ....................................................................................................................... 28 
15 
APPENDICES ........................................................................................................................ 29 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
ABBREVIATIONS 
AD 
Atopic Dermatitis 
AE 
adverse event 
ATC 
anatomical therapeutic chemical 
BID 
twice daily 
BSA 
body surface area 
CI 
confidence interval 
COVID-19 
Coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
EASI 
Eczema Area and Severity Index 
eCRF 
electronic case report form 
ET 
early termination 
IGA 
Investigator Global Assessment 
IGA-TS 
Investigator Global Assessment-Treatment Success 
(IGA score of 0 or 1 with ≥ 2-grade improvement from baseline) 
ITT 
intent-to-treat (population) 
MCID 
minimal clinically important difference 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat (population) 
mPP-NRS 
modified peak pruritus numerical rating scale (current itch intensity) 
NRS 
numerical rating scale 
PP-NRS 
peak pruritus numerical rating scale (24-hour recall period) 
PT 
preferred term 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System® 
SD 
standard deviation 
SOC 
system organ class 
TEAE 
treatment emergent adverse event 
TLF 
tables, listings, and figures 
TSQM-9 
Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication 
WHO-DD 
World Health Organization Drug Dictionary 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
1 INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the planned analysis and reporting for Incyte 
Corporation clinical protocol INCB 18424-901. The analyses described in the SAP are based upon 
the protocol version Amendment 3 dated 09-MAY-2022. 
This SAP has been developed prior to database lock and final analyses. All final analyses will be 
performed after the clinical trial data are entered into the database, any discrepancies in the data 
are resolved, the lock of the database, and following the signature of the SAP. 
 
 
2   STUDY OBJECTIVES AND ENDPOINTS 
 
 
OBJECTIVES 
ENDPOINTS 
Primary 
To evaluate the efficacy of 
ruxolitinib 1.5% cream on 
pruritus in participants with 
atopic dermatitis (AD). 
Primary efficacy endpoint: 
• Change from baseline in Peak-Pruritus Numerical Rating Scale 
(PP-NRS) at Day 2 (24-hour recall period after first application). 
Secondary 
To evaluate the efficacy of 
ruxolitinib 1.5% cream in 
participants with AD. 
Secondary efficacy endpoints: 
• 
Change from baseline in Modified Peak-Pruritus Numerical 
Rating Scale (mPP-NRS) (current itch intensity) at 15 and 
30 minutes and 1, 2, 4, 6, and 12 hours postdose on Day 1; and 
in PP-NRS from Day 3 through Day 29. 
• 
Proportion of participants achieving at least a 1-grade decrease 
from baseline in mPP-NRS at 15 and 30 minutes and 1, 2, 4, 6, 
and 12 hours postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• 
Proportion of participants achieving at least a 2-grade decrease 
from baseline in mPP-NRS at 15 and 30 minutes and 1, 2, 4, 6, 
and 12 hours postdose on Day 1; and in PP-NRS from Day 2 
through Day 29. 
• 
Time to minimal clinically important difference (MCID) (≥ 2- 
grade reduction in PP-NRS and mPP-NRS from baseline). 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
OBJECTIVES 
ENDPOINTS 
• 
Change from baseline in Investigator's Global Assessment 
(IGA) at Day 8, Day 15, and Day 29. 
• Proportion of participants achieving the Investigator's Global 
Assessment-Treatment Success (IGA-TS) (score of 0 or 1 in 
IGA with at least a 2-grade reduction from baseline) at Day 8, 
Day 15, and Day 29. 
To evaluate the local and 
systemic safety and 
tolerability of ruxolitinib 
1.5% cream in participants 
with AD. 
Secondary safety/efficacy endpoints: 
• Incidence and severity of local and systemic adverse events (AEs). 
Exploratory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
3 STUDY DESIGN 
3.1 Overall Design 
This is a Phase 2, open-label, single-arm study evaluating the effect of ruxolitinib 1.5% cream on 
itch. This study will include approximately 48 adult participants (18-65 years old, inclusively) who 
have at least a 6-month history of AD and at least a 3-month history of chronic itch. 
All participants will read and sign an Informed Consent Form (ICF) prior to any study procedures 
being performed and then undergo screening for study eligibility. Participants who meet initial 
screening requirements will be given access to an eDiary to complete the PP-NRS each morning 
(24-hour recall period), from screening to Day −1 and from Day 2 to the Day 29 visit. Participants 
must be willing and able to complete the eDiary on a daily basis for the duration of the study. 
During the last 7 days prior to Day 1 (run-in period; Day −7 to Day −1), participants will be 
required to complete at least 4 of 7 PP-NRS assessments in their eDiary. Inclusion of participants 
completing fewer than 4 of 7 PP-NRS questionnaires during the last 7 days of the screening period 
(run-in period) must be approved by the sponsor. 
After a screening period of no more than 37 days (from Day −37 to Day −1, including a 7-day run- 
in period), participants who fulfill all of the inclusion criteria, none of the exclusion criteria, and 
have a baseline mean PP-NRS score ≥ 4.0 during the run-in period will be eligible to start the 
treatment period. The baseline mean PP-NRS score is defined as the average of all nonmissing 
PP-NRS scores reported during the run-in period. 
During the treatment period, participants will have topical treatment with ruxolitinib 1.5% cream 
applied BID as a thin film for 28 (±2) days (last application on the evening prior to the Day 29 
visit). The study drug will be applied on all AD lesions, with a maximum treated area ≤ 20% BSA. 
All original areas of involvement on Day 1 (even in the event of lesions clearing), and any new 
lesions (a maximum of ≤ 20% BSA can be treated) must be treated until the evening prior to the 
Day 29 visit. On Day 1, participants will remain at the study center until after the 6-hour mPP- 
NRS assessment (approximately an 8-hour stay at the site). The 12-hour mPP-NRS assessment 
will be done at home just prior to the evening study drug application. On Day 8 and Day 15, the 
morning application of the study drug will be at the study center under the supervision of study 
staff. Other study drug applications will be self-administered by the participants at home. The 
study schema is shown in Figure 1 in the protocol. 
Study drug application will occur in the morning and evening from Day 1 until the day prior to 
the Day 29 visit, with approximately 12 hours between applications. The evening dose should be 
applied at least 1 hour before bedtime. On Day 1, the mPP-NRS assessments should occur as 
close as possible to the scheduled time relative to the first study drug application. In addition, the 
12-hour mPP-NRS should be completed before the evening study drug application. On Day 2, 
the PP-NRS assessment should be completed approximately 24 hours after the first study drug 
application and before the Day 2 morning dose. Refer to Table 5 for the sequence and timing of 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
these assessments and allowed windows on Day 1 and Day 2. From Day 3 until the Day 29 visit, 
the PP-NRS should be completed once daily, at approximately the same time in the morning, and 
prior to the study drug application. 
Efficacy will be evaluated using the PP-NRS (worst itch over a 24-hour period), the mPP-NRS 
(current itch at the time of assessment), and the 5‑point IGA. 
The Body Surface Area (BSA) and Eczema Area and Severity Index (EASI) will be used to 
evaluate the participant's AD severity on Day 1 and will be characterized during the study. 
Medical photographs of the target lesion(s) and application site adverse events (AEs) will be taken 
during the study. Participants will be asked to complete the Abbreviated 9-Item Treatment 
Satisfaction Questionnaire for Medication (TSQM-9) at the end of the treatment period (or ET, if 
applicable). 
Safety will be assessed by collecting AEs, performing comprehensive and targeted physical 
examinations, and evaluating clinical laboratory assessments. 
 
 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
3.2 Schedule of Events 
Table 3 of the protocol provides a description of the procedures planned at each visit. 
Figure 1: 
Study Design Schema 
 
 
3.3 Treatment 
The treatment group is: ruxolitinib 1.5%, BID for 28 days. 
3.4 Randomization, Replacement, and Unblinding Procedures 
This is an open-label, single-arm study. No participants will be replaced at any time during this 
study. 
3.5 Changes to the Analysis from the Protocol 
No changes were made from the planned analysis in protocol. 
 
4 POPULATIONS FOR ANALYSIS 
4.1 Enrolled Analysis Set 
The Enrolled analysis set will include all participants who sign the ICF. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
4.2 Intent-to-Treat Analysis Set 
The Intent-to-Treat (ITT) analysis set will include all enrolled participants who complete the run- 
in period (ie, not be a screen failed) and meet the inclusion and exclusion criteria. The ITT analysis 
set will be used for the summary of demographics, baseline characteristics, and participants 
disposition. 
4.3 Modified Intent-to-Treat Analysis Set 
The modified Intent-to-Treat (mITT) analysis set is a subset of the ITT analysis set, including 
participants who have both baseline and at least 1 post-baseline PP-NRS or mPP-NRS assessment 
within the treatment period. The mITT analysis set will be used for all efficacy analyses. 
4.4 Per Protocol Analysis Set 
The per protocol analysis set is a subset of the mITT analysis set, excluding participants with major 
protocol deviations that could potentially affect the efficacy evaluations. The per protocol analysis 
set will be used as supportive information for all efficacy analyses. 
4.5 Safety Analysis Set 
The Safety analysis set will include all enrolled participants who received at least 1 application of 
ruxolitinib 1.5% cream. All safety analyses will be conducted using the safety analysis set. 
 
5 GENERAL CONSIDERATIONS 
Formats and layouts of tables, listings, and figures (TLF) will be provided in a separate document 
(output general layout is described in Appendix 1). 
5.1 Sample Size 
Approximately 36 participants were planned to be enrolled into the study to receive ruxolitinib 
1.5% cream. The sample size calculation was based on the CI for 1-sample mean. With an 
approximate 10% missing assessment rate at 24 hours, a sample size of 36 is required to produce 
a 2-sided 95% CI for the expected change from baseline in PP-NRS (24-hour recall period), with 
a precision of 0.57. The SD of 1.64 is estimated from 2 Phase 3, double-blind, randomized 
studies (INCB 18424-303 and INCB 18424-304). To ensure data quality and support study 
interpretation after deviations from protocol related to the timing of efficacy assessments were 
observed in the first participants enrolled, it was decided to enroll an additional 12 participants 
for a total of approximately 48 participants to be included. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
5.2 Baseline 
Unless otherwise specified, baseline value will be defined as the last non-missing assessment 
before or on Day 1 and prior to the first application of study drug (including unscheduled 
assessments). If the last non-missing assessment is performed on the same date as the first study 
treatment and time or timepoint is not available, the assessment will be considered as baseline, 
except for adverse events (AEs) and medications starting on the first study treatment dose date 
which will be considered post-baseline. 
For PP-NRS, the baseline is defined as the average of all non-missing PP-NRS scores reported 
during the 7‑day run-in period (Day −7 to Day −1). 
5.3 Reference Start Date and Analysis Day 
Analysis Day will be calculated from the first study treatment date and will be used to show 
start/end day of assessments or events. 
Analysis day = (Date of event – Date of first dose administration) + 1 if date of event is on or after 
the date of first dose administration of study treatment; 
= (Date of event – Date of first dose administration) if date of event is before the date 
of first dose administration of study treatment. 
In the situation where the assessment/event date is partial or missing, Analysis Day will be missing. 
5.4 Windowing Conventions 
No windowing conventions apply for this study. 
5.5 Descriptive Statistics 
All continuous variables will be summarized by presenting the number of participants, mean, 
standard deviation, standard error of the mean, median, minimum and maximum. Categorical 
variables will be presented as frequencies and percentages. Summary tables will be presented by 
visit, when applicable. 
Change from baseline will be calculated as: 
Assessment value at post-baseline visit X – Baseline value. 
Percent change from baseline (%) will be calculated as: 
(Assessment value at postbaseline visit X – Baseline value) / Baseline value * 100. 
Percent change from baseline will be missing in situation where Baseline value equals to 0. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
5.6 Statistical Tests 
No formal statistical comparisons will be performed. Confidence intervals (CIs) will be two-sided 
with 95% coverage. Unless otherwise specified, confidence intervals for proportions will be 
calculated using the Clopper-Pearson method, as applicable. 
5.7 Handling of Retests, Unscheduled Visits, and Early Termination Data 
When retests measurements are done, the retest measurement will be considered for the summary 
analysis. All data from retest visits will be listed. 
 
Unscheduled measurements will not be summarized in by-visit summary tables or figures. 
However, they will be included in shift summary tables. All data from unscheduled visits will be 
listed. 
 
Early Termination visit assessments will be summarized as a separate visit in by-visit outputs. All 
data from early termination visits will be listed. 
5.8 Software Version 
All analyses will be performed using SAS® software Version 9.4 or higher. 
 
6 STATISTICAL CONSIDERATIONS 
6.1 Adjustments for Covariates 
Not applicable. 
6.2 Handling of Dropouts or Missing data 
No imputation will be made for efficacy data. See Appendix 2 for handling of completely or 
partially missing dates for prior and concomitant medications and adverse events. 
6.3 Interim Analysis and Data Monitoring 
No formal interim analysis is planned for this study. 
6.4 Multicenter Studies 
Not applicable. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
6.5 Multiple Comparisons/Multiplicity 
No adjustments for multiple comparison will be made for this study. 
6.6 Examination of Subgroups 
No subgroup analysis is planned for this study. 
 
7 STUDY PARTICIPANTS 
7.1 Disposition of Participants 
All participants who provide informed consent will be accounted for in this study. The number of 
participants screened, rescreened, and who failed screening (screen failures) will be presented. The 
reason for screen failure will be presented for all screened participants who failed screening and 
rescreening, if applicable. The percentage of participants screen failures will be calculated using 
the number of participants screened as denominator. The percentage of reasons for screen failure 
will be calculated using the number of screen failures as denominator. The number of participants 
enrolled (who provide informed consent) and included in each analysis set will be presented and 
percentages will be based on the number of enrolled participants. 
End of treatment status and treatment discontinuation related to COVID-19 or not will be 
presented. The percentage of end of treatment status will be calculated using the number of 
participants in the ITT analysis set. The percentage of treatment discontinuation related to COVID- 
19 or not will be calculated using the number of participants in the ITT analysis set who did not 
complete the treatment. Study completion status and the reason for study discontinuation will also 
be presented, including discontinuation related to COVID-19. The percentage of reasons for study 
discontinuation will be calculated using the number of participants in the ITT analysis set who did 
not complete study as denominator (and related or not to COVID-19, if applicable). Otherwise, 
the percentages will be calculated using the number of participants included in the ITT analysis 
set as denominator. 
Number of days in the study will be calculated as follows and summarized: 
Number of days in study = Date of completion/discontinuation – 1st dose date +1. 
If a participant had no dose, the number of days in the study will be left as missing. A listing of 
participants’ disposition and a listing of participants included in each of the analysis sets will also 
be provided based on the Enrolled analysis set. Information on first screening for participants who 
were rescreened, including the rescreened participant identifier, will be presented under the first 
screening participant identifier. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
7.2 Protocol Deviations 
Protocol deviations will be classified as major or minor prior to database lock. 
The number of participants with at least one major protocol deviation will be summarized by 
deviation category on the safety analysis set. Important protocol deviations will be summarized in 
a similar way. A listing of all protocol deviations will also be provided. 
The number of events and the number and percentage of participants with at least one protocol 
deviation associated with COVID-19 will be summarized by deviation category using the safety 
analysis set. A listing of all protocol deviations associated with COVID-19 will also be provided. 
 
8 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographics and baseline characteristics will be summarized with descriptive statistics based on 
the ITT analysis set and on the per protocol analysis set. The list of demographics and baseline 
characteristics to be summarized will include: 
• Age (years) – as recorded in the CRF 
• Sex at birth 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Unknown) 
• Race* (White, American Indian or Alaska native, Asian, Native Hawaiian or other Pacific 
islander, Black or African American, Unknown) 
• Baseline Height (cm) 
• Baseline Weight (kg) 
• Fitzpatrick skin type 
• Baseline Body Surface Area for eligibility (%) (excluding palms, soles, scalp, genitals, and 
folds) 
• Baseline Total Body Surface Area affected (%) 
• Baseline Body Surface Area treated (%) 
• Baseline Peak-Pruritus Numerical Rating Scale (run-in period mean score) 
• Baseline Modified Peak-Pruritus Numerical Rating Scale 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
• Baseline Investigator Global Assessment 
• Baseline Eczema Area and Severity Index 
• Baseline Transepidermal Water Loss (TEWL) (lesional and non-lesional) 
*Participants who reported more than one race will be summarized as ‘Multiple’ race in the table. 
All races selected will be displayed in the listing. 
A listing of all demographics and baseline characteristics will be provided for the ITT analysis set. 
 
9 SURGICAL AND MEDICAL HISTORY 
Medical history will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA), Version 24.0. 
General surgical and medical history will be summarized by system organ class (SOC) and 
preferred term (PT) on the safety analysis set. A participant who experienced the same surgical 
and medical history event multiple times will be counted only once for the corresponding PT. 
Similarly, if a participant experienced multiple surgical and medical history events within the same 
SOC, the participant will be counted only once for that SOC. Surgical and medical history events 
will be sorted alphabetically by SOC and within each SOC the PT will be presented by decreasing 
order. 
A listing of all general surgical and medical history events will be provided. 
Disease-targeted Atopic Dermatitis (AD) medical history will be summarized based on the safety 
analysis set. Disease duration, chronic itch (yes/no), prior history of asthma (yes/no), prior allergies 
(yes/no), history of contact dermatitis (yes/no), common complications associated, time from 
onset, presence of head and neck, facial and periorbital involvement (yes/no), and the number of 
AD episodes/flare-ups over the last 12 months will be reported. 
The disease duration (in years) will be calculated as follow: 
Disease duration = (Date of first dose of study treatment – Date of initial AD diagnostic)/365.25. 
The time from onset (in years) will be calculated as follow: 
Time from onset = (Date of first dose of study treatment – Current date of onset of AD 
episode)/365.25. 
Completely or partially missing dates for the date of AD diagnostic and the current date of onset 
of AD will be imputed as follow: 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
• Completely missing: Leave missing. 
• Missing day and month: Impute to January 1st. 
• Missing day: Impute to the 1st of the month. 
A listing of all disease-specific AD history, including date of AD diagnostic and date of current 
onset, will be provided. 
 
10  PRIOR AND CONCOMITANT MEDICATIONS AND THERAPIES  
10.1 Prior and Concomitant Medications 
Medications will be coded according to the World Health Organization Drug Dictionary (WHO- 
DD), B3 March 2021. 
Prior medications are defined as any medication started and discontinued prior to the first study 
treatment dose. Concomitant medications are defined as any medication taken after the first study 
treatment dose, including those who started prior to the first study treatment date and continued 
past that date. See Appendix 2 for handling of completely or partially missing dates for prior and 
concomitant medications. 
Incidence of prior and concomitant medications will be tabulated separately by ATC level 3 and 
PT on the safety analysis set. A participant with the same medication taken multiple times will be 
counted only once for the corresponding PT. Similarly, if a participant has taken more than one 
medication within the same ATC level, then the participant will be counted only once for that 
ATC. A listing of all prior and concomitant medications will be provided. 
All disease-specific (AD) prior medications and therapies will be tabulated separately in a similar 
way and based on the safety analysis set. Additionally, a listing of all prior medications and 
therapies related to AD will be provided. 
10.2 Non-drug Therapies and Surgical Procedures 
Non-drug therapies and surgical procedures will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA), Version 24.0. 
Prior non-drug therapies and surgical procedures are defined as any non-drug therapy and surgical 
procedure started and discontinued prior to the first study treatment dose. Concomitant non-drug 
therapies and surgical procedures are defined as any non-drug therapy and surgical procedure taken 
after the first study treatment dose, including those who started prior to the first study treatment 
date and continued past that date. See Appendix 2 for handling of completely or partially missing 
dates for non-drug therapies and surgical procedures. 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
Incidence of prior and concomitant non-drug therapies and surgical procedures will be tabulated 
separately by system organ class (SOC) and preferred term (PT) on the safety analysis set. A 
participant who experienced the same non-drug therapies and surgical procedures event multiple 
times will be counted only once for the corresponding PT. Similarly, if a participant experienced 
multiple non-drug therapies and surgical procedures events within the same SOC, the participant 
will be counted only once for that SOC. Non-drug therapies and surgical procedures will be sorted 
alphabetically by SOC and within each SOC the PT will be presented by decreasing order. 
A listing of all non-drug therapies and surgical procedures will be provided. 
 
11 STUDY TREATMENT EXPOSURE AND TREATMENT 
COMPLIANCE 
 
 
Duration of exposure to study treatment, in days, will be computed as follows: 
 
Duration of exposure = [(Date of last dose of study treatment – Date of first dose of study 
treatment) + 1] 
 
Compliance with study treatment (%) will be calculated as follows: 
 
Number of applications per participant eDiary 
Total number of intended applications 
 
× 100 
For each participant, the total number of intended applications corresponds to 2 applications per 
day from the day of first dose until the end of treatment date: 
 
Total number of intended applications = [(Date of end of treatment – Date of first dose of study 
treatment) + 1] x 2. 
 
Descriptive statistics for the duration of exposure, number of applications (based on the 
participant’s eDiary) and compliance to study treatment will be presented based on the safety 
analysis set. Frequency distribution will also be presented for the following compliance categories: 
<80% , 80% to 120%, >120%. 
 
A summary of cumulative dose applied will be presented based on the safety analysis set. 
Cumulative dose will be derived based on the information on the dispensed tubes weight and 
returned tubes weight captured in the drug accountability form. Cumulative dose (in grams) will 
be computed as follow: 
 
(Sum of tubes weight dispensed – Sum of tubes weight returned). 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
If the information on tube weight is missing (i.e. tube not returned), cumulative dose will be 
missing. 
A listing of exposure, compliance, study treatment administrations, treatment interruptions and 
study treatment accountability will be provided. 
 
12 EFFICACY ANALYSIS 
Unless otherwise noted, all efficacy analysis will be performed on the mITT analysis set. The per 
protocol analysis set will be used as supportive information for all efficacy analyses. 
12.1 Primary Endpoint 
12.1.1 Peak-Pruritus Numerical Rating Scale 
The intensity of pruritus (itch) will be recorded daily in the eDiary from the screening visit until 
Day −1 and from Day 2 to the Day 29 visit, using the Peak-Pruritus Numerical Rating Scale (PP- 
NRS) (24-hour recall period). This NRS will be evaluated by asking participants to assign a 
numerical score representing their itch at the worst moment during the previous 24 hours on a scale 
of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable. 
The PP-NRS will be analyzed as follow: 
• Change from baseline in PP-NRS at Day 2 (24-hour recall period after first application). 
12.1.2 Primary Analysis 
The primary endpoint, change in PP-NRS from baseline at Day 2 (24-hour recall period after first 
application), will be analyzed descriptively. The 95% CI will be provided for the mean change. 
 
12.2 Secondary Endpoints 
12.2.1 Modified Peak-Pruritus Numerical Rating Scale 
On Day 1 only, participants will be asked to evaluate the current intensity of their itch at the time 
of assessment (ie, prior to the morning study drug application and 15, 30 minutes, 1, 2, 4, 6, and 
12 hours after the morning study drug application; the 12-hour evaluation will occur prior to the 
second daily study drug application) on a scale from 0 to 10, with 0 indicating no itch and 10 
indicating the worst imaginable itch. The modified Peak-Pruritus Numerical Rating Scale (mPP- 
NRS) (current itch intensity) was modified from the PP-NRS. 
The mPP-NRS will be analyzed as follow: 


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Page 22 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
• Change from baseline in mPP-NRS (current itch intensity) at 15 and 30 minutes and 1, 2, 
4, 6, and 12 hours postdose on Day 1. 
• Proportion of participants achieving at least a 1-grade decrease from baseline in mPP-NRS 
at 15 and 30 minutes and 1, 2, 4, 6, and 12 hours postdose on Day 1. 
• Proportion of participants achieving at least a 2-grade decrease from baseline in mPP-NRS 
at 15 and 30 minutes and 1, 2, 4, 6, and 12 hours postdose on Day 1. 
12.2.2 Peak-Pruritus Numerical Rating Scale 
The PP-NRS is defined in section 12.1.1. The PP-NRS will be analyzed as follow: 
• Change from baseline in PP-NRS from Day 3 through Day 29. 
• Proportion of participants achieving at least a 1-grade decrease from baseline in PP-NRS 
from Day 2 through Day 29. 
• Proportion of participants achieving at least a 2-grade decrease from baseline in PP-NRS 
from Day 2 through Day 29. 
 
12.2.3 Minimal Clinically Important Difference 
The minimal clinically important difference (MCID) corresponds to an achievement of ≥ 2-grade 
reduction in PP-NRS and mPP-NRS from baseline. 
The MCID will be analyzed as follow: 
• Time to MCID for PP-NRS (≥ 2-grade reduction in PP-NRS from baseline). 
• 
Time to MCID for mPP-NRS (≥ 2-grade reduction in mPP-NRS from baseline). 
The time to MCID will be defined as the time from the date (time) of first dose to the date (time) 
of first occurrence of MCID. The time to MCID for the PP-NRS will be reported in days, and the 
time to MCID for the mPP-NRS will be reported in hours. 
12.2.4 Investigator's Global Assessment 
The Investigator's Global Assessment (IGA) of the current state of the disease is a 5-point 
morphological assessment of overall disease severity. 
The IGA will be analyzed as follow: 
• Change from baseline in IGA at Day 8, Day 15, and Day 29. 
 
The Investigator's Global Assessment-Treatment Success (IGA-TS) is defined as an IGA score of 
0 or 1 with at least a 2-grade reduction from baseline. The IGA-TS will be analyzed as follow: 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
•  Proportion of participants achieving the IGA-TS (score of 0 or 1 in IGA with at least a 2- 
grade reduction from baseline) at Day 8, Day 15, and Day 29. 
 
12.2.5 Secondary Endpoints Analysis 
Descriptive statistics will be presented for all secondary efficacy endpoints, by visit and timepoint 
(if applicable). The change from baseline and percent change from baseline in PP-NRS, mPP-NRS 
and IGA, and proportion endpoints for PP-NRS, mPP-NRS, and IGA-TS, will be analyzed 
descriptively at each visit. The 95% CI will be provided for the mean change, percent change and 
the proportions (using the Clopper-Pearson method). For proportion endpoints, percentages will 
be based on the number of participants with a response at the specified visit and timepoint. 
 
The proportion of participants achieving an IGA score of 0 or 1 and associated 95% CI (using the 
Clopper-Pearson method) will also be reported descriptively. 
 
The time to MCID will be analyzed using Kaplan Meier estimation for PP-NRS and mPP-NRS. A 
participant will be considered censored if he has not met the event of interest at the end of the 
study or if the participant is lost to follow up at last observation. Those participants will be censored 
at their last available mPP-NRS or PP-NRS assessment date or time. Survival curves will also be 
presented. 
 
A line graph presenting the value and a line graph presenting the change from baseline in mPP- 
NRS over time will be produced. The value and change from baseline in PP-NRS over time and 
value and change from baseline in IGA will be presented similarly. 
 


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STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
 
 
 
12.4 Other Analyses 
12.4.1 Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication 
The Abbreviated 9-Item Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a 9- 
item measure that assesses the most common dimensions participants use to evaluate their 
medication (ie, global satisfaction, effectiveness, and convenience). The results for each scale 
(global satisfaction, effectiveness, and convenience) are presented from 0 to 100, where higher 
scores represent better satisfaction. Scoring method for each scale is presented in Appendix 3. 
TSQM-9 data for each scale will be summarized separately by visit using descriptive statistics. All 
TSQM-9 data will be listed. 
12.4.2 Transepidermal Water Loss 
Transepidermal water loss (TEWL) quantifies the clinical severity of AD and the associated effect 
on skin barrier function. Three TEWL readings are taken at each location (lesional and non- 
lesional), and the median will be calculated for these three readings. If the participant performs 
less than 3 readings, the median will still be calculated based on available readings. Descriptive 
statistics for the median of the three TEWL measurements will be presented by location and visit, 


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Page 25 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
and the corresponding change from baseline when appropriate. The 95% CI will be provided for 
the mean change from baseline. All Transepidermal Water Loss measurements will be listed. 
12.4.3 Eczema Area and Severity Index 
The Eczema Area and Severity Index (EASI) is a composite score ranging from 0 to 72 that takes 
into account the degree of erythema, induration/infiltration (papules), excoriation, and 
lichenification (each scored from 0 to 3 separately) for each of 4 body regions, with adjustment 
for the percentage of BSA involved for each body region and for the proportion of the body region 
to the whole body. Scoring method for the Eczema Area and Severity Index is presented in 
Appendix 4. 
Descriptive statistics for the EASI will be presented by visit, and the corresponding change and 
percent change from baseline when appropriate. The 95% CI will be provided for the mean change 
and percent change. 
 
Additionally, the proportion of participants with at least a 75% reduction from baseline in EASI 
(EASI-75) and associated 95% CI (using the Clopper-Pearson method) will be reported 
descriptively. 
 
All EASI assessments will be listed. A line graph presenting the value in EASI and a line graph 
presenting the change from baseline in the EASI over time will be produced. 
 
12.4.4 Total BSA Affected by AD 
The overall BSA affected by AD (total BSA%) will be presented by visit, and the corresponding 
change and percent change from baseline when appropriate. The 95% CI will be provided for the 
mean change and percent change. All total BSA affected assessments will be listed. A line graph 
presenting the value and a line graph presenting the change from baseline in the total BSA affected 
over time will be produced. 
 
13 SAFETY ANALYSIS 
All safety analyses will be conducted using the safety analysis set. 
13.1 Adverse Events 
Adverse events (AEs) will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA), Version 24.0. 
Treatment emergent adverse events (TEAEs) are derived as any AEs with onset date during or 
after the first study treatment dose. AEs starting on the first study treatment dosing date and related 


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Page 26 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
to a pre-dose study assessment will not be considered as TEAE. See Appendix 2 for handling of 
completely or partially missing dates for AEs. In the case where it is not possible to define an AE 
as treatment emergent or not, the AE will be classified as treatment emergent. 
An overall summary table of adverse events will be provided. The number of events and the 
number and percentage of participants who experienced AE, TEAE, TEAE at application site, 
TEAE by relationship, TEAE by toxicity grade, related TEAE by toxicity grade, TEAE of CTCAE 
Grade 3 or higher, serious TEAE, serious TEAE by toxicity grade, TEAE leading to study drug 
interruption, TEAE leading to study drug discontinuation, TEAE leading to study discontinuation 
and AE leading to death will be presented. 
Unless otherwise specified, a participant experiencing the same TEAE multiple times will be 
counted only once for the corresponding PT. Similarly, if a participant experiences multiple 
TEAEs within the same SOC, the participant will be counted only once for that SOC. TEAEs will 
be sorted alphabetically by SOC and within each SOC the PT will be presented by decreasing 
order. 
Frequency and percentage of participants who experience TEAE will be summarized by SOC and 
PT within SOC. 
Frequency and percentage of participants who experience TEAE will be summarized by SOC, PT 
and relationship (causality). A treatment-related AE is defined as any TEAE that is assessed by 
the Investigator as possibly related to study treatment. TEAE that is assessed as not possibly related 
will be defined as not treatment-related. TEAE with an unknown relationship will be considered 
as treatment-related. If a participant experiences more than one TEAE within different relationship 
categories within the same SOC/PT, the participant will be counted once for that SOC/PT in each 
relationship category. 
Frequency and percentage of participants who experience TEAE will be summarized by SOC, PT 
and intensity grade. TEAE with an unknown intensity grade will be considered missing. If a 
participant experiences more than one TEAE within different intensity grade categories within the 
same SOC/PT, the participant will be counted once for that SOC/PT in each intensity grade 
category. Similarly, frequency and percentage of participants who experience treatment-related 
TEAE will be summarized by SOC, PT and intensity grade. 
Frequency and percentage of participants who experience serious TEAE will be summarized by 
SOC and PT within SOC. 
Frequency and percentage of participants who experience TEAE of intensity of Grade 3 or higher 
will be summarized by SOC and PT within SOC. 
Frequency and percentage of participants who experience serious TEAE will be summarized by 
SOC, PT and intensity grade. TEAE with an unknown intensity grade will be considered missing. 


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Page 27 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
If a participant experiences more than one TEAE within different intensity grade categories within 
the same SOC/PT, the participant will be counted once for that SOC/PT in each intensity grade 
category. 
Frequency and percentage of participants who experience Application Site TEAE will be 
summarized by SOC and PT. 
Frequency and percentage of participants who experience TEAE of Application site pain Preferred 
Term will be summarized by Lowest Level Term. 
Listings of all AEs, all AEs leading to death, all serious AEs, all TEAEs leading to study treatment 
discontinuation, all TEAEs leading to study treatment interruption and all TEAEs leading to study 
discontinuation will be provided. A listing of drug overdose will be provided. 
13.2 Clinical Laboratory 
Descriptive statistics will be presented for data related to serum chemistry, hematology and 
quantitative urinalysis. Change from baseline values will be presented for each post-baseline 
assessment. Frequencies and percentages for each result will be provided for qualitative urinalysis 
data. 
Shift tables from baseline to each post-baseline visits describing shifts to abnormality will be 
provided as well based on abnormality in the CRF. Only participants with a baseline result and a 
result at the specified visit for the parameter will be considered. 
Separate listings of all data for serum chemistry, hematology and urinalysis will be provided. 
Pregnancy tests results will be listed. 
In addition, separate listings of data for serum chemistry, hematology and urinalysis will be 
provided for each parameter where a participant had at least one abnormal clinically significant 
result. 
13.3 Vital Signs 
Descriptive statistics will be presented for data related to vital signs (systolic blood pressure 
diastolic blood pressure, pulse, respiratory rate and body temperature). A listing of all vital signs 
assessments will be provided. 


DocuSign Envelope ID: 31209E82-CF15-4345-9D8C-78912BEA71F8 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
 Proprietary & Confidential 
Page 28 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
14 REFERENCES 


DocuSign Envelope ID: 31209E82-CF15-4345-9D8C-78912BEA71F8 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
 Proprietary & Confidential 
Page 29 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
15 APPENDICES 
 
Output Conventions 
 
Appendix 1 
TLF will be generated using SAS® and will be displayed on letter size paper with landscape 
orientation, 1 inch margins and 9 pt Courier New font. 
The header section will comprise the Sponsor’s name, the protocol number, the delivery 
description, the data cut-off date (if applicable), the TLF number, the TLF title, the analysis set, 
and the page number (Page X of Y). The footer section will include the TLF footnotes, the CRO’s 
name, the date and time of the execution of the program, the reference listings and the name of the 
program. 
Mean, median and quantiles will be displayed to one more decimal place than the original 
value; minimum and maximum will keep the same number of decimal places as the original value; 
standard deviation, standard error and CI will be displayed to two more decimal places than the 
original value. If derived parameters are to be summarized, the number of decimals of the derived 
values is to be chosen on a case-by-case basis, but the rule above applies. 
For categorical summary tables, percentages will be reported to one decimal place. Percentages 
between 0 and 0.1 (both exclusive) will be displayed as “<0.1”. The denominator for each 
percentage will be the number of participants within the population per treatment group unless 
otherwise specified. 
Listings will be ordered by participant number, date and visit (where applicable). Imputed dates 
will not be presented in the listings. 
Dates & Times Format 
Date and time (if available) will be presented in the format yyyy-mm-dd/hh:mm. 
Presentation of Treatment Groups 
When applicable, study treatments will be represented as follows in the different outputs: 
 
Study Treatment Full Name 
Study Treatment Output Name 
Ruxolitinib 1.5% BID 
Ruxolitinib 


DocuSign Envelope ID: 31209E82-CF15-4345-9D8C-78912BEA71F8 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
 Proprietary & Confidential 
Page 30 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
Appendix 2 
Algorithm for Imputation of Start/End Date of Adverse Events, 
Prior/Concomitant Medications and Prior/Concomitant Non-Drug Therapies 
and Surgical Procedures 
Event Start Date Imputation 
• Imputation of event end date should be done before imputation of event start date. 
• Completely missing: Impute to the first study treatment date. 
• Missing day and month: Impute to January 1st, unless year is the same as year of first study 
treatment dose then impute to the first study treatment date. 
• Missing day: Impute to the 1st of the month, unless month and year are the same as month 
and year of first study treatment dose then impute to the first study treatment date. 
• If imputed event start date is after event end date (imputed or not), set the event start date 
to the imputed event end date. 
 
Event End Date Imputation 
• Completely Missing: Impute to the last contact date. 
• Missing day and month: Impute to December 31st, unless year is the same as last contact 
date then impute to the last contact date. 
• Missing day: Impute to the last day of the month, unless year and month are the same as 
year and month of last contact date then impute to the last contact date. 


DocuSign Envelope ID: 31209E82-CF15-4345-9D8C-78912BEA71F8 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
 Proprietary & Confidential 
Page 31 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
Appendix 3 
Scoring Method for the Abbreviated 9-Item Treatment Satisfaction 
Questionnaire for Medication (TSQM-9) 
Scores for each domain are computed by adding the TSQM items in each domain and then 
transforming the composite score into a value ranging from 0 to 100. Of note, a score can be 
computed for a domain only if no more than one item is missing from that domain. The calculations 
specific to each domain are presented in detail below. 
1. Global Satisfaction 
([Sum(Item 7 to Item 9) – 3] divided by 14) * 100 
If either Item 7 or 8 is missing 
([(Sum(the two completed items)) – 2] divided by 10) * 100 
If Item 9 is missing 
([(Sum(Item7 and Item8)) – 2] divided by 8) * 100 
 
2. Effectiveness 
([(Item 1 + Item 2 + Item 3) – 3] divided by 18) * 100 
If one item is missing 
([(Sum(the two completed items – 2] divided by 12) * 100 
 
3. Convenience 
([Sum(Item 4 to Item 6) – 3] divided by 18) * 100 
If one item is missing 
([(Sum(the two completed items)) – 2] divided by 12) * 100 


DocuSign Envelope ID: 31209E82-CF15-4345-9D8C-78912BEA71F8 
SOP-STAT-03-TOOL.01 Version 4 
Effective Date: 03-Jun-2018 
 Proprietary & Confidential 
Page 32 of 32 
 
 
 
STATISTICAL ANALYSIS PLAN, Version 
Final v1.0 
Protocol Number: INCB 18424-901 
Sponsor: Incyte Corporation 
Study Title: An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% 
Cream on Itch in Adult Participants With Atopic Dermatitis (SCRATCH-AD) 
 
Appendix 4 
Scoring Method for the Eczema Area and Severity Index 
 
Four anatomic sites (head, upper extremities, trunk, and lower extremities) are assessed for 
erythema, induration/infiltration (papules), excoriation, and lichenification as seen on the day of 
the examination. The severity of each sign is assessed using the following 4-point scale (half 
steps are allowed; eg, 0.5, 1.5, and 2.5): 
 
• 0 = none 
• 1 = mild 
• 2 = moderate 
• 3 = severe 
 
The area affected by AD within a given anatomic site is estimated as a percentage of the total 
area of that anatomic site and assigned a numerical value according to the degree of AD 
involvement as follows: 
 
• 0 = no involvement 
• 1 = < 10% 
• 2 = 10% to < 30% 
• 3 = 30% to < 50% 
• 4 = 50% to < 70% 
• 5 = 70% to < 90% 
• 6 = 90% to 100% 
 
The EASI score is obtained by using the following formula: 
 
EASI = 0.1 (Eh + Ih + Exh + Lh) Ah + 0.2 (Eu + Iu + Exu + Lu) Au + 0.3 (Et + It + Ext + Lt) At + 
0.4 (El + Il + Exl + Ll) Al. 
 
Where E, I, Ex, L, and A denote erythema, induration, excoriation, lichenification, and area, 
respectively, and h, u, t, and l denote head, upper extremities, trunk, and lower extremities, 
respectively. 
 
The EASI score will be set as missing if at least one question value is missing. 


 
 
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