Clinical trial NCT05906628
Conditions: Hand Eczema
Keywords: eczema chronic hand eczema (CHE) dermatitis skin disease JAK inhibitor
Sponsor: Incyte Corporation
Start date: 2023-07-31; Completion date: 2024-12-13
Enrollment: 186 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib cream in adult participants with diagnosis of chronic hand eczema (CHE) and moderate to severe disease activity (Investigator's Global Assessement (IGA) of CHE score 3 or 4).

Detailed description:

Arms: arm 1: Ruxolitinib cream 1.5% twice daily (BID) for 16 weeks followed by ruxolitinib cream 1.5% BID for an additional 16-week treatment extension period. arm 2: Vehicle cream for 16 weeks followed by crossover to ruxolitinib cream 1.5% BID in a 16-week treatment extension period.
Interventions: intervention 1: Ruxolitinib cream intervention 2: Vehicle
Intervention descriptions: intervention 1: Ruxolitinib cream is a topical formulation applied as a thin film to affected areas. intervention 2: Vehicle cream is a topical formulation applied as a thin film to affected areas.

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, 
Efficacy and Safety Study of Ruxolitinib Cream Followed by an 
Open-Label Extension Period in Adults With Chronic Hand Eczema 
NCT Number: 
NCT05906628 
Document Date: 
Protocol INCB 18424-226 Am 1 Version 2 19 APR 2023 
 
 
 


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Protocol INCB 18424-226 Am 1 
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CONFIDENTIAL 
 
Clinical Study Protocol 
 
TITLE PAGE 
INCB 18424-226 
A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, 
Efficacy and Safety Study of Ruxolitinib Cream Followed by an 
Open-Label Extension Period in Adults With Chronic Hand Eczema 
 
Product: 
INCB018424 
IND Number: 
77101 
EU CT Number: 
2022-502827-23-00 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 USA 
Original Protocol: 
12 DEC 2022 
Protocol Amendment 1: 
19 APR 2023 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki (Brazil 2013) and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and 
applicable laws and country-specific regulations, including WMO (Medical Research Involving Human Participants 
Act) and Clinical Trials Regulation (EU) No. 536/2014, in which the study is being conducted. 
The information in this document is confidential. No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-226 Protocol Amendment 1 (dated 19 APR 2023) 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. 
Chronic Hand Eczema Disease ...................................................................................17 
2.1.2. 
Population ...................................................................................................................17 
2.1.3. 
Inflammatory Pathways Involved in Chronic Hand Eczema .....................................18 
2.1.4. 
Current Treatment and Unmet Need in Chronic Hand Eczema .................................19 
2.2. 
Study Rationale ...........................................................................................................20 
2.2.1. 
Scientific Rationale for Study Design ........................................................................20 
2.2.2. 
Justification for Dose ..................................................................................................21 
 
 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................23 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.2. 
Overall Study Duration ...............................................................................................25 
4.3. 
Study Termination ......................................................................................................25 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................29 
5.4. 
Screen Failures ............................................................................................................29 
5.5. 
Replacement of Participants .......................................................................................29 
6. 
STUDY TREATMENT ..............................................................................................30 
6.1. 
Study Treatment Administered ...................................................................................30 
6.2. 
Preparation, Handling, and Accountability ................................................................31 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................32 
6.4. 
Study Treatment Compliance .....................................................................................32 


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6.5. 
Dose Modifications .....................................................................................................33 
 
 
 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................34 
6.6. 
Concomitant Medications and Procedures .................................................................35 
6.6.1. 
Permitted Medications and Procedures ......................................................................35 
6.6.2. 
Restricted Medications and Procedures ......................................................................36 
6.6.3. 
Prohibited Medications and Procedures .....................................................................36 
6.7. 
Treatment After the End of the Study .........................................................................36 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................37 
7.1. 
Discontinuation of Study Treatment ...........................................................................37 
7.1.1. 
Reasons for Discontinuation .......................................................................................37 
7.1.2. 
Discontinuation Procedures ........................................................................................37 
7.2. 
Participant Withdrawal From the Study .....................................................................38 
7.3. 
Lost to Follow-Up.......................................................................................................38 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................39 
8.1. 
Administrative and General Procedures .....................................................................39 
8.1.1. 
Informed Consent Process ..........................................................................................39 
8.1.2. 
Screening Procedures ..................................................................................................40 
8.1.3. 
Interactive Response Technology Procedure ..............................................................40 
8.1.4. 
Distribution of Reminder Cards and/or eDiaries ........................................................40 
8.1.5. 
Demography and Medical History ..............................................................................41 
8.1.5.1. 
Demographics and General Medical History .............................................................41 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................41 
8.2. 
Efficacy Assessments .................................................................................................41 
8.2.1. 
Investigator's Global Assessment–Chronic Hand Eczema .........................................41 
8.2.2. 
Hand Eczema Severity Index Score ...........................................................................42 
 
 
8.2.4. 
Body Surface Area ......................................................................................................43 
8.2.5. 
Photography ................................................................................................................43 
8.2.6. 
Patient-Reported Outcomes ........................................................................................43 
8.2.6.1. 
eDiary Assessments ....................................................................................................43 


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8.2.6.2. 
Dermatology Life Quality Index ................................................................................44 
8.2.6.3. 
Patient Global Impression of Change .........................................................................44 
8.2.6.4. 
Quality of Life in Hand Eczema Questionnaire .........................................................44 
8.2.7. 
Health Economics .......................................................................................................44 
8.2.7.1. 
EQ-5D-5L ...................................................................................................................44 
8.2.7.2. 
Work Productivity and Activity Impairment Questionnaire v2.0 in Chronic 
Hand Dermatitis ..........................................................................................................45 
8.3. 
Safety Assessments .....................................................................................................45 
8.3.1. 
Adverse Events ...........................................................................................................45 
8.3.2. 
Physical Examinations ................................................................................................46 
8.3.3. 
Vital Signs ..................................................................................................................46 
8.3.4. 
Laboratory Assessments .............................................................................................46 
8.3.4.1. 
Pregnancy Testing ......................................................................................................47 
8.3.4.2. 
Serology ......................................................................................................................48 
8.4. 
Pharmacokinetic Assessments ....................................................................................48 
8.5. 
Pharmacodynamic and Translational Assessments ....................................................48 
 
 
 
 
8.6. 
Unscheduled Visits .....................................................................................................48 
8.7. 
End of Treatment and Early Termination ...................................................................49 
8.8. 
Follow-Up ...................................................................................................................49 
9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................50 
9.1. 
Definition of Adverse Event .......................................................................................50 
9.2. 
Definition of Serious Adverse Event ..........................................................................51 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........52 
9.4. 
Reporting of Serious Adverse Events .........................................................................54 
9.5. 
Potential Drug-Induced Liver Injury ..........................................................................55 
9.6. 
Events of Clinical Interest ..........................................................................................55 
9.6.1. 
Adverse Events of Special Interest .............................................................................55 
9.7. 
Emergency Unblinding of Treatment Assignment .....................................................56 
9.8. 
Pregnancy ...................................................................................................................56 
9.9. 
Warnings and Precautions ..........................................................................................57 


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9.10. 
Product Complaints ....................................................................................................57 
9.11. 
Treatment of Overdose ...............................................................................................57 
10. 
STATISTICS ..............................................................................................................58 
10.1. 
Sample Size Determination ........................................................................................58 
10.2. 
Populations for Analysis .............................................................................................59 
10.3. 
Level of Significance ..................................................................................................59 
10.4. 
Statistical Analyses .....................................................................................................59 
10.4.1. 
Primary Analysis ........................................................................................................59 
10.4.2. 
Key Secondary Objective ...........................................................................................60 
10.4.3. 
Secondary Analysis ....................................................................................................60 
10.4.4. 
Safety Analyses ..........................................................................................................61 
10.4.5. 
Analysis Plan ..............................................................................................................61 
10.5. 
Interim Analysis ..........................................................................................................61 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................62 
11.1. 
Investigator Responsibilities .......................................................................................62 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................63 
11.2. 
Data Management .......................................................................................................63 
11.3. 
Data Quality Assurance ..............................................................................................65 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................65 
11.5. 
Financial Disclosure ...................................................................................................66 
11.6. 
Publication Policy .......................................................................................................66 
11.7. 
Study and Site Closure................................................................................................67 
12. 
REFERENCES ...........................................................................................................68 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................72 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................74 
APPENDIX C. 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 .......................................................................................10 
Table 3: 
Schedule of Activities .................................................................................................13 
Table 4: 
Objectives and Endpoints ...........................................................................................23 
Table 5: 
Study Treatment Information .....................................................................................31 
 
 
 
 
Table 8: 
Required Laboratory Analytes ....................................................................................47 
Table 9: 
Powering for Primary and Key Secondary Endpoints ................................................58 
Table 10: Populations for Analysis .............................................................................................59 
Table 11: Summary of Primary Analysis....................................................................................60 
Table 12: Summary of Analyses for Key Secondary Endpoints ................................................60 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
ACD 
allergic contact dermatitis 
AD 
atopic dermatitis 
AE 
adverse event 
AHE 
atopic hand eczema 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BID  
twice daily 
BSA 
body surface area 
CHE 
chronic hand eczema 
CI 
confidence interval 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DBVC 
double-blind vehicle-controlled 
DLQI 
Dermatology Life Quality Index 
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 
HE 
hand eczema 
HECSI 
Hand Eczema Severity Index 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV  
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator's Brochure 
ICD 
irritant contact dermatitis 
ICD-10 
International Classification of Diseases, 10th Revision 
ICD-11 
International Classification of Diseases, 11th Revision 
ICF 
informed consent form  


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Abbreviations and 
Special Terms 
Definition 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification 
IEC 
independent ethics committee 
IGA 
Investigator's Global Assessment 
IGA-CHE 
Investigator's Global Assessment–Chronic Hand Eczema 
IGA-CHE-TS 
Investigator's Global Assessment–Chronic Hand Eczema Treatment Success 
IGA-TS 
Investigator's Global Assessment–Treatment Success 
IL 
interleukin 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent-to-treat 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
Numerical Rating Scale 
OLE 
open-label extension 
PD 
pharmacodynamic(s) 
PGIC 
Patient Global Impression of Change 
QALY 
quality-adjusted life-year 
QOLHEQ 
Quality of Life in Hand Eczema Questionnaire 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SPF 
sun protection factor 
STAT 
signal transducers and activators of transcription 
TEAE 
treatment-emergent adverse event, AEs reported for the first time or worsening 
of a pre-existing event after first dose of study treatment 
Th 
T-helper 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
VAS 
visual analog scale 
WOCBP 
woman of childbearing potential 
WPAI-ChHD 
Work Productivity and Activity Impairment Questionnaire v2.0 in Chronic 
Hand Dermatitis  


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, Efficacy and Safety Study 
of Ruxolitinib Cream Followed by an Open-Label Extension Period in Adults With Chronic 
Hand Eczema 
Protocol Number: INCB 18424-226 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% 
cream BID in participants with CHE. 
• IGA-CHE-TSa at Week 16. 
Key Secondary 
To further assess the treatment effects of 
ruxolitinib 1.5% cream BID in participants with 
CHE. 
• ITCH4b response at Week 16. 
• ITCH4 response at Week 4.  
• ITCH4 response at Week 1 (Day 7). 
a IGA-CHE-TS is defined as an IGA-CHE score of 0 or 1 with ≥ 2-grade improvement from baseline. 
b ITCH4 response is defined as a ≥ 4-point improvement in CHE-related Itch NRS score from baseline. 
Overall Design: 
Table 2 presents the key study design elements. Further study details are presented after the 
table. 
Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of adult patients with moderate to severe CHE (IGA-CHE score 
of 3 or 4). 
Population 
Male and female participants ≥ 18 years of age with diagnosis of CHE for 
at least 6 months who have moderate to severe disease activity (IGA-CHE 
score of 3 or 4) and have been treated with at least 1 prescription CHE 
therapy. 
Number of Participants 
Approximately 180 participants will be randomized 1:1 to 1 of 2 treatment 
groups (ruxolitinib 1.5% cream BID or vehicle cream BID). The 
participants will be stratified by IGA-CHE score (3 or 4) at baseline and 
by region (North America or outside of North America).  
Study Design 
This is a randomized, 16-week, double-blind, vehicle-controlled study 
with a 16-week open-label treatment extension. 


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Table 2: 
Key Study Design Elements (Continued) 
Estimated Duration of 
Study Participation 
Estimated total duration of participants is up to approximately 40 weeks. 
• Screening: up to 4 weeks 
• DBVC period: 16 weeks 
• OLE period: 16 weeks 
• Safety follow-up: 30 days 
Data Safety Monitoring 
Board/Data Monitoring 
Committee 
No 
Coordinating Principal 
Investigator 
To be determined 
Treatment Groups and Duration: 
Approximately 180 adult participants with moderate to severe CHE with no history of (within 
the past 5 years) or current AD will be randomized 1:1 to either ruxolitinib 1.5% cream BID or 
vehicle cream BID (see Figure 1). During the DBVC period, participants will apply either 
ruxolitinib 1.5% cream or vehicle cream (both BID) to CHE-affected areas on the hands and 
wrists (if applicable) for 16 weeks. All areas identified at baseline should continue to be treated 
through the end of the DBVC period (Week 16) unless the participant meets criteria for stopping 
study drug (see Section 7.1). 
At Week 16, participants with no safety concerns will enter the 16-week OLE period, during 
which all participants will receive open-label ruxolitinib 1.5% cream. Affected areas will be 
treated as needed until they clear during the OLE period (see Section 6.1). Participants, 
investigators, and the sponsor will be blinded to each participant's treatment assignment during 
the DBVC period. During the OLE period, participants and investigators will remain blinded to 
the treatment assignment during the DBVC period until after all participants have completed 
treatment or discontinued and completed the safety follow-up period. 
Participants who develop additional areas of CHE may treat the additional areas with approval 
by the investigator as long as there are no safety concerns regarding the application of study 
drug. 
Table 3 presents the SoA. Adherence to the study design requirements, including those specified 
in the SoA, is essential and required for study conduct. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the outline of potential mitigation 
strategies described in Appendix B. 
Figure 1 presents the study design schema. 


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Figure 1:
Study Design Schema


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Table 3: 
Schedule of Activities 
Visit Day (Range) 
Days 
−28 to −1 
Vehicle-Controlled Treatment 
Open-Label 
Treatment 
Safety 
Follow-Up 
Notes 
Day 1 
Weeks 
Weeks 
Days 
Screening 
Baseline 
2a 
(± 3 d) 
4 
(± 3 d) 
8 
(± 3 d) 
12a 
(± 3 d) 
16b/ET1 
(± 3 d) 
24a 
(± 3 d) 
32/ET2c 
(± 3 d) 
30a,d (+ 7 d  
After Last 
Application) 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Contact IRT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Inclusion/exclusion 
criteria review 
X 
X 
 
 
 
 
 
 
 
 
 
Demography and 
medical history 
(general and disease 
specific)  
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Apply study drug in 
clinic* 
 
X 
X 
X 
X 
X 
X 
X† 
 
 
*On-site applications will be performed 
by participants. The application will be 
under supervision at baseline but not 
mandated for subsequent visits.  
†No study drug will be applied at 
Week 24 if BSA is 0 at the visit.  
Distribute reminder 
card 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Weigh/dispense study 
drug 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Collect/weigh 
returned study drug  
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Assess eDiary and 
study drug 
compliance 
X* 
X† 
X 
X 
X 
X 
X 
X 
X 
 
*At screening, eDiary will be issued 
and compliance check is not needed. 
eDiary for Itch and Skin Pain NRS is to 
be started at screening, and compliance 
should be checked starting at baseline. 
†eDiary for study medication is to be 
started at baseline, and compliance 
should be checked starting with the 
following visit. 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Days 
−28 to −1 
Vehicle-Controlled Treatment 
Open-Label 
Treatment 
Safety 
Follow-Up 
Notes 
Day 1 
Weeks 
Weeks 
Days 
Screening 
Baseline 
2a 
(± 3 d) 
4 
(± 3 d) 
8 
(± 3 d) 
12a 
(± 3 d) 
16b/ET1 
(± 3 d) 
24a 
(± 3 d) 
32/ET2c 
(± 3 d) 
30a,d (+ 7 d  
After Last 
Application) 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE is noted, that body system 
should be physically examined in a 
targeted physical examination. 
Comprehensive 
physical examination 
X* 
 
 
 
 
 
X† 
 
X 
 
*Including Fitzpatrick skin 
classification. 
†Only required for participants not 
continuing in the OLE period.  
Height and body 
weight 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy assessments 
%BSA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
The %BSA affected by CHE only 
(including hands and wrists [if 
applicable]).  
Target lesion 
 
X* 
 
 
X 
 
X 
 
 
 
*At select study sites participating in 
skin sampling for biomarker collection, 
a target lesion will be identified at 
baseline on a hand affected by CHE.  
IGA-CHE 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HECSI 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Photography 
 
X 
 
X 
X 
 
X 
X 
X 
 
Photographs of the hand and wrist 
(anterior and posterior) will be taken at 
all study sites. At select sites, 
photographs will be marked with the 
location of the target lesion and 
nonlesional area at the baseline visit. 
CHE-related Itch NRS 
X* 
Diary is completed each evening from screening through Week 32 or ET. 
 
*Average of 7-day (minimum 4/7 days) 
CHE-related Itch NRS directly prior to 
Day 1 will be used to determine study 
eligibility. 


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Table 3: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Days 
−28 to −1 
Vehicle-Controlled Treatment 
Open-Label 
Treatment 
Safety 
Follow-Up 
Notes 
Day 1 
Weeks 
Weeks 
Days 
Screening 
Baseline 
2a 
(± 3 d) 
4 
(± 3 d) 
8 
(± 3 d) 
12a 
(± 3 d) 
16b/ET1 
(± 3 d) 
24a 
(± 3 d) 
32/ET2c 
(± 3 d) 
30a,d (+ 7 d  
After Last 
Application) 
Efficacy assessments (continued) 
CHE-related Skin 
Pain NRS 
X 
Diary is completed each evening from screening through Week 32 or ET. 
 
 
DLQI 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
PGIC 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
QOLHEQ 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
EQ-5D-5L 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
WPAI-ChHD 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory assessments 
Chemistry 
assessments 
X 
X* 
 
 
X 
 
X 
X 
X 
X 
*Not necessary if screening assessment 
performed within 14 days of Day 1. 
Hematology 
assessments 
X 
X* 
 
 
X 
 
X 
X 
X 
X 
FSH 
X* 
 
 
 
 
 
 
 
 
 
*Women of nonchildbearing potential 
only.  
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
WOCBP will have a serum test at 
screening and a urine test at other visits 
noted. A positive urine test must be 
confirmed by a serum test. 
Urine pregnancy test 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
HIV serology 
X 
 
 
 
 
 
 
 
 
 
 
PD and translational assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 


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a Visits at Weeks 2, 12, and 24 and safety follow-up can be performed virtually (through telemedicine if applicable) only due to COVID-19–related reasons. No efficacy 
assessments can be performed virtually (see Appendix B). 
b All Week 16 assessments must be completed before the participant can continue in the OLE. Study drug will not be applied in the clinic at Week 16 for participants not 
continuing into the OLE period. 
c Participants who withdraw early should complete the ET and the safety follow-up visits. 
d For participants in the OLE period who have been in an observation/no treatment cycle with a total IGA-CHE score of 0 (clear) from Week 28 or earlier until Week 32, the 
Week 32/ET visit will also count as the safety follow-up visit. 


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2. 
INTRODUCTION 
Ruxolitinib cream is a topical formulation of ruxolitinib phosphate under development for a 
variety of dermatological conditions. Ruxolitinib 1.5% cream is approved by the US FDA for 
1) the topical short-term and noncontinuous chronic treatment of mild to moderate AD in 
nonimmunocompromised patients 12 years of age and older whose disease is not adequately 
controlled with topical prescription therapies or when those therapies are not advisable and 2) the 
topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and 
older (Opzelura™ 2022). Ruxolitinib phosphate is a JAK1/2 inhibitor. The JAK/STAT pathway 
mediates the effects of many inflammatory cytokines that are implicated in the pathogenesis of a 
number of inflammatory dermatosis (Chapman et al 2022). 
2.1. 
Background 
2.1.1. 
Chronic Hand Eczema Disease 
Hand eczema is a common disorder involving inflammation of the skin of the hands. The clinical 
manifestations of HE typically present in an acute (lasting for < 3 months and not occurring more 
than once per year) or chronic (lasting for > 3 months or recurring at least 2 times within a year) 
fashion (Diepgen et al 2015), with severity varying from mild to severe (Agner and Elsner 2020). 
Clinical signs include redness, thickening of the skin, scaling, edema, vesicles, areas of 
hyperkeratosis, and cracks (fissures). During the acute stage, HE usually presents with macules, 
papules, erythema, edema, weeping, and vesiculation. As lesions become subacute or chronic, 
the lesion morphology shifts to scaling, thickening, and fissuring of the skin. Lesions are usually 
bilateral and may involve the palmar or dorsal surface or both and/or the fingers. In 
long-standing disease, nail changes may be seen, including loss of the cuticle, thickening of the 
nail folds, ridging, and thickening of the nail plate. Symptoms typically include pruritus, burning, 
pain, stinging, sleep disturbances, and/or mood disturbances (Agner and Elsner 2020). 
2.1.2. 
Population 
The prevalence of HE and CHE is greater in the adult population than in the pediatric population. 
Hand eczema is common in the adult population (4%), with a 1-year prevalence of 
approximately 10% (Coenraads 2012) and a lifetime incidence of 15% (Thyssen et al 2010). An 
estimated < 5% of patients with HE develop chronic disease, and about one-half of these cases 
are steroid refractory (Crane et al 2017). Limited data exist regarding the epidemiology of 
chronic HE in the pediatric population. A study in the United Kingdom leveraging data from the 
Clinical Practice Research Datalink reported that HE is relatively uncommon (0.2%) in children 
younger than 18 years of age and CHE is extremely rare (0.004%) in children up to the age of 
14 years in 1-year prevalence (Crane et al 2017). Furthermore, the 10-year prevalence for CHE 
estimates near zero in children younger than the age of 14 years. The prevalence of CHE in late 
adolescence (15-19 years of age) is approximately 0.05%, increasing by the third decade 
(approximately 0.2%), maintaining this level throughout the occupational years, and declining in 
the eighth decade (Crane et al 2017). 
Chronic HE is often an occupational skin disease. While some patients with CHE may also have 
AD, the cause of CHE is considered multifactorial and distinct from AD in most patients. 


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Individuals with occupational HE develop contact dermatitis on the hands and/or wrists due to 
exposure to irritants (up to 70% of cases) and/or allergens (up to 25% of cases) in the workplace 
(Agner et al 2015, Agner and Elsner 2020, Caroe et al 2014, Diepgen et al 2009, Menné et al 
2011). This has a significant professional impact, leading to > 20% job-related disability 
(Diepgen et al 2015). In addition to the occupational impact, individuals with CHE also 
experience poor quality of life (eg, sleep disturbances and domestic, social, and psychological 
impairment; Agner et al 2008, English 2010, Cortesi et al 2014). 
Furthermore, continuous exposure to other irritants may lead to CHE, including household 
detergents, fragrances, and preservatives in hand soaps; harsh chemicals found in common 
household and industrial cleaners, such as ammonia and solvents; raw fruits, vegetables, spices, 
and plants; and physical irritants, such as cold (Agner and Elsner 2020). Similarly, HE may be a 
manifestation of ACD, a specific T cell–mediated, delayed-type hypersensitivity reaction. 
Common allergens associated with HE are preservatives, fragrances, metals (eg, nickel or 
cobalt), rubber, and topical antibiotics (Agner and Elsner 2020). 
Hand eczema may not always be associated with AD. A meta-analysis indicated that the majority 
of patients with HE did not have past or current AD, although AD was associated with an 
increased prevalence of HE (odds ratio of 4.31 based on lifetime prevalence; Ruff et al 2018). An 
evaluation of 522 patients with HE in a dermatology practice found 19% of patients had past or 
current AD at the time of the evaluation (Veien et al 2008). Another study showed that 25% of 
427 patients with HE were reported to have previous or current AD (Agner et al 2015). 
Collectively, the data suggest that patients with HE are distinct from patients with AD and only a 
subset of patients have overlapping conditions.  
In the management of HE, identification and exposure avoidance to causative allergens and 
irritants are essential in the improvement and resolution of the condition. However, not all 
patients may find resolution to their condition. Patients who were originally diagnosed with ICD 
or ACD, in the absence of exposure to irritants or allergens, may still develop CHE 
(Thyssen et al 2020). Thus, individuals with CHE have a very prolonged course of disease, with 
an average reported duration of approximately 12 years (Anveden et al 2006). Furthermore, 
challenges remain in the recognition of CHE as a condition, since ICD-10 diagnosis codes only 
exist for ACD, ICD, and AD. In ICD-11, EA85.2 only states "dermatitis of hands" (Thyssen 
et al 2020). Nevertheless, after the underlying triggers (irritant and allergen) have been avoided, 
the persistent inflammation of CHE may require management with therapies delivered in an 
escalating fashion (Graham-Brown 2010). In establishing an accurate diagnosis of CHE, which 
excludes ICD and ACD, a detailed history and physical examination is required; if the symptoms 
of HE are prolonged, patch testing may be necessary. 
2.1.3. 
Inflammatory Pathways Involved in Chronic Hand Eczema 
In CHE, 3 etiologies (ie, ICD, ACD, and AHE) are associated with the progression of the HE 
condition, and the pathophysiology of HE may vary depending on the stage of each etiology. 
• Irritant contact dermatitis has an immune profile associated with Th1/Th17. Skin exposed 
to irritants elicits the activation of IL-1α, IL-1β, tumor necrosis factor α, 
granulocyte-macrophage colony-stimulating factor, and IL-8 from keratinocytes; 
keratinocytes break down, promoting neutrophils and mast cell infiltrates (de Jongh 
et al 2008, Gittler et al 2013, Leonard and Guttman-Yassky 2019). 


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• The immune profile for ACD may vary, depending on the allergen. Allergens associated 
with fragrance and rubber have shown to elicit a Th2/Th22 response, inducing cytokines 
IL-5, IL-13, IL-22, IL-32, CCL5, CCL13, CCL17, CCL18, and CTLA4 (Dhingra 
et al 2014, Leonard and Guttman-Yassky 2019, Ungar et al 2017). Allergens such as metal 
have shown induction of the Th1/Th17 response, with increased expression of IL-1β, 
IL-6, interferon α1, CXCL1, CXCL2, CXCL9, CXCL10, and CXCL11 (Dhingra 
et al 2014, Leonard and Guttman-Yassky 2019, Ungar et al 2017). 
• A large panel of cytokine-mediated signaling cascades have been identified as part of the 
immune signature of AHE, including Th1 (interferon gamma), Th2 (IL-4, IL-13, IL-31, 
CCL17, CCL18, and CCL22), Th22 (IL-22), Th17 (IL-17), and the JAK-STAT pathway 
(Brunner et al 2017, Gittler et al 2013, Leonard and Guttman-Yassky 2019, Pedersen 
et al 2007, Tauber et al 2020). 
 
 
 
 
2.1.4. 
Current Treatment and Unmet Need in Chronic Hand Eczema 
Currently, there are no FDA-approved treatments for CHE. The only approved therapy for CHE 
in adults is an oral retinoid (eg, alitretinoin) available in Europe, Canada, Israel, and South 
Korea. Thus, there is a large unmet medical need for effective and safe therapies for the 
management of CHE. Expert dermatologists recommend that CHE should be regarded as a 
chronic inflammatory disease similar to psoriasis and AD and treated with appropriate topical, 
systemic, and/or biologic medications after appropriate workup (Thyssen et al 2020). 
Currently, the initial, nonpharmacological therapies for patients with HE include avoidance of 
irritants and allergens and use of hydration and emollients (Graham-Brown 2010). After the 
avoidance of underlying triggers (irritants and allergens), the persistent inflammation of CHE is 
treated with pharmacological therapies. 
Individuals with mild to moderate HE are often treated with emollients and anti-inflammatory 
therapies including topical steroids as first-line therapy, followed by high-potency topical 
steroids, calcineurin inhibitors, or, in some regions/countries (Europe, Canada, Israel, and South 
Korea), oral retinoids (eg, alitretinoin) when topical steroids are not effective or not tolerated 
(Diepgen et al 2015, Dublin et al 2020, Silvestre Salvador et al 2020). Approximately 65% of 
patients experience a relapse or recurrent episodes after 5 years of treatment with topical agents 
(Agner et al 2008, Lee et al 2019). Moreover, long-term use of these therapies can result in 
significant side effects, including skin atrophy and barrier impairment. Individuals with moderate 
to severe chronic HE often become refractory to topical therapies over time.  


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2.2. 
Study Rationale 
Because the pathophysiology of CHE involves inflammation mediated through the JAK-STAT 
pathway, the primary purpose of this study is to assess the efficacy and safety of ruxolitinib 1.5% 
cream BID in participants with CHE. 
2.2.1. 
Scientific Rationale for Study Design 
As mentioned in Section 2.1.2, a large panel of cytokine-mediated signaling cascades has been 
identified as part of the pathophysiology of CHE, including Th2 (IL-4 and IL-13), Th22 (IL-22), 
Th17 (IL-17), Th1 (interferon gamma), and the JAK-STAT pathway (Brunner et al 2017, Gittler 
et al 2013, Pedersen et al 2007). Ruxolitinib, a JAK 1/2 inhibitor, mediates its clinical effects in 
AD and vitiligo through many of the same cytokines that have been identified in the 
pathogenesis of CHE. As such, it is anticipated that ruxolitinib will have an impact on CHE. 
The mechanism of ruxolitinib cream is well established in other inflammatory dermatoses (both 
in AD and vitiligo). Clinically, ruxolitinib cream has shown statistically significant and clinically 
meaningful efficacy in 2 Phase 3 registrational studies (INCB 18424-303 and INCB 18424-304) 
in participants with AD (including on the hands), which shares similarities with CHE (Papp 
et al 2021). In both Phase 3 studies of AD, more than 50% (53.8% and 51.3%, respectively) of 
participants (≥ 12 years of age) who applied ruxolitinib 1.5% cream BID for 8 weeks achieved 
an IGA-TS (defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline) 
compared with 15.1% and 7.6% of participants who applied vehicle cream. Participants on 
ruxolitinib cream also saw a substantial improvement in itch (ITCH4 response, defined as 
≥ 4-point improvement from baseline in Itch NRS score) compared with vehicle in both studies 
(50.7% and 52.2% for ruxolitinib cream vs 16.3% and 15.4% for vehicle, respectively). 
This study will examine the efficacy and safety of ruxolitinib 1.5% cream BID versus vehicle 
cream for the treatment of CHE. The vehicle-controlled period is 16 weeks. Participants who 
complete the Week 16 assessments with no safety concerns can continue into the 16-week OLE 
period, during which all participants will receive active treatment with ruxolitinib 1.5% cream 
BID to be applied as needed in affected areas. This design will provide a well-controlled 
assessment of the efficacy of ruxolitinib 1.5% cream in CHE compared to vehicle. 
The selection of 16 weeks for the vehicle-controlled period for this study reflects the goal to 
balance sufficient treatment duration for an inflammatory skin condition with the need to limit 
the DBVC period for participants. Due to the signs of highly inflamed skin such as 
hyperkeratosis, vesiculations, and fissures, the time required for ruxolitinib cream to achieve 
treatment success in patients with moderate to severe CHE will likely be more similar to that of 
other moderate to severe inflammatory skin conditions such as moderate to severe plaque 
psoriasis and moderate to severe AD than to the 8-week treatment duration of ruxolitinib cream 
for mild to moderate AD. The limited data from other JAK inhibitors in clinical studies also 
suggest that a duration of longer than 8 weeks is necessary to achieve optimal treatment effects 
in CHE. For example, in the delgocitinib (a pan-JAK inhibitor with a similar mechanism of 
action as ruxolitinib) Phase 2a study in participants with mild to moderate CHE, maximum 
treatment effect was not observed at the end of the 8-week DBVC period (Worm et al 2020). In 
the Phase 2b study of delgocitinib cream in participants with mild to severe CHE 
(NCT03683719), the treatment effect had not reached a plateau at the end of treatment 
(16 weeks), suggesting that longer-term use could offer additional benefits than what was 


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observed in the trial (Worm et al 2022). The primary endpoint, change in the modified Total 
Lesion Symptom Score over time, indicated a rapid onset of treatment effect as early as 2 weeks 
that continued to increase and plateaued after 12 to 16 weeks of treatment (depending on the 
dose).  
Therefore, a vehicle-controlled period of 16 weeks was selected for the Phase 2 study, similar to 
other studies involving patients with moderate to severe inflammatory skin conditions. In 
addition, based on the Phase 3 studies of AD (INCB 18424-303 and 304), which included 
treatment of up to 20% BSA during an 8-week vehicle-controlled period and a 44-week 
long-term safety extension period, there are no safety concerns associated with a 16-week 
vehicle-controlled treatment period followed by a 16-week OLE treatment extension period in 
the CHE studies, especially considering the limited %BSA to be treated in the CHE studies 
(maximum BSA is 4% if both hands are fully affected). It is also expected that the 16-week OLE 
period may decrease dropout rates in the vehicle arm by offering an incentive for participants to 
remain in the study beyond the initial 16-week DBVC period. 
2.2.2. 
Justification for Dose 
The ruxolitinib cream strength and application frequency for this study (ruxolitinib 1.5% cream 
BID) were selected primarily based on the following: 
• Data from the dose-ranging Phase 2 study (INCB 18424-206) and 2 Phase 3 studies 
(INCB 18424-303 and INCB 18424-304) in participants with mild to moderate AD, in 
which ruxolitinib 1.5% cream BID was shown to be the most efficacious regimen 
evaluated. The data from these studies supported the approval of ruxolitinib 1.5% cream 
BID for the AD indication in the US (Opzelura 2022). Because the inflammation and 
hyperkeratosis associated with moderate to severe CHE is typically more severe than that 
observed with mild to moderate AD, 
 to be 
efficacious for treatment of CHE. 
• 
 
 
• Due to the requirement to avoid hand washing, sanitizer use, or emollient use within 
1 hour following study drug application and the fact that many participants are working 
individuals, the burden from requiring more frequent application (eg, 3 times daily) than 
the BID regimen that is currently specified in the Protocol would be high, impractical, and 
lead to decreased compliance. Less frequent application (eg, once daily) of ruxolitinib 
1.5% cream is expected to be less efficacious than BID, as evident from the Phase 2 
dose-ranging study (INCB 18424-206) in mild to moderate AD. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 4 presents the objectives and endpoints. 
Table 4: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% 
cream BID in participants with CHE. 
•  IGA-CHE-TSa at Week 16. 
Key Secondary 
To further assess the treatment effects of 
ruxolitinib 1.5% cream BID in participants with 
CHE. 
• ITCH4b response at Week 16. 
• ITCH4b response at Week 4. 
• ITCH4b response at Week 1 (Day 7). 
Secondary 
To further evaluate the efficacy of ruxolitinib 
1.5% cream BID. 
• IGA-CHE-TS at each postbaseline visit. 
• ITCH4b response at Day 3. 
• Change from baseline in CHE-related Itch 
NRS score at each postbaseline visit. 
• Time to ≥ 4-point improvement from baseline 
in CHE-related Itch NRS score. 
• Change from baseline in CHE-related Skin 
Pain NRS score at each postbaseline visit. 
• Achieving ≥ 2-point improvement in 
CHE-related Skin Pain NRS score from 
baseline to Week 16. 
• Time to ≥ 2-point improvement from baseline 
in CHE-related Skin Pain NRS score. 
• Percentage change in HECSI from baseline to 
Week 16. 
• PGIC score at each postbaseline visit. 
To evaluate the participants' quality of life and 
other patient-reported outcomes. 
• Change from baseline in DLQI score at 
Weeks 2, 4, 8, 12, 16, 24, and 32. 
• Change from baseline in EQ-5D-5L score at 
Weeks 2, 4, 8, 12, 16, 24, and 32. 
• Change from baseline in QOLHEQ score at 
Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up. 
• Change from baseline in WPAI-ChHD score at 
Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up. 
To evaluate the safety and tolerability of 
ruxolitinib 1.5% cream BID. 
• The type, frequency, and severity of AEs as 
well as changes in vital signs and laboratory 
data for hematology and serum chemistry. 


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Table 4: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
a IGA-CHE-TS is defined as an IGA-CHE score of 0 or 1 with ≥ 2-grade improvement from baseline. 
b ITCH4 response is defined as a ≥ 4-point improvement in CHE-related Itch NRS score from baseline. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 2, randomized, double-blind, vehicle-controlled, 16-week study followed by a 
16-week open-label treatment extension period. Figure 1 presents the study design schema. 
Approximately 180 participants with moderate to severe CHE with no history of (within the past 
5 years) or current AD will be randomized 1:1 to either ruxolitinib 1.5% cream or vehicle cream. 
Participants will apply either ruxolitinib 1.5% cream or vehicle cream (both BID) to CHE lesions 
on the hands and wrists (if applicable) for 16 weeks. All areas identified at baseline should 
continue to be treated through the end of the DBVC period (Week 16) unless the participant 
meets criteria for stopping study drug (see Section 7.1). 
At Week 16, participants with no safety concerns will enter the 16-week OLE period, during 
which all participants will receive open-label ruxolitinib 1.5% cream. Affected areas will be 
treated as needed until they clear during the OLE period (see Section 6.1).  
Participants, investigators, and the sponsor will be blinded to each participant's treatment 
assignment during the DBVC period. During the OLE period, participants and investigators will 
remain blinded to the treatment assignment during the DBVC period until after all participants 
have completed treatment or discontinued and completed the safety follow-up period. 
Participants who develop additional areas of CHE may treat these additional areas with approval 
by the investigator as long as there are no safety concerns regarding the application of study 
drug. 
At Week 16, efficacy will be evaluated as the proportion of participants who achieve 
IGA-CHE-TS (the primary endpoint of the study). Additional efficacy assessments and 
patient-reported outcomes will be conducted as outlined in the SoA (see Table 3). 


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Participants will be assessed for safety and tolerability throughout the study by monitoring the 
type, frequency, and severity of AEs and measuring vital signs and clinical laboratory parameters 
(see Table 3). 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF. It is estimated that an individual 
will participate for approximately 40 weeks, including up to 28 days for screening, 16 weeks for 
DBVC study treatment, 16 weeks for OLE treatment, and up to 30 days for safety follow-up after 
the last application of study treatment. 
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if they have completed all study visits, 
including the safety follow-up visit. 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract. The investigator is to notify the IRB/IEC of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively if, for example, required by regulatory decision. 
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 this Protocol is essential. Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for the study.  
2. Age ≥ 18 years at the screening visit. 
3. Diagnosis of CHE for at least 6 months prior to screening.  
Diagnosis of CHE is defined as HE lasting > 3 months or ≥ 2 recurrences within the 
previous 12 months. 
Note: Participants with hyperkeratotic, vesicular (eg, pompholyx), and fingertip eczema 
may be included. 
4. Screening and baseline IGA-CHE score of 3 or 4. 
5. Baseline CHE-related Itch NRS score ≥ 4. Baseline Itch NRS score is defined as the 
7-day average of Itch NRS score directly before Day 1 (data from a minimum of 4 out of 
7 days prior to Day 1 is needed). 
6. Have been treated with at least 1 prescription CHE therapy or if such therapy was not 
advisable or contraindicated.  
7. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 90 days 
(a spermatogenesis cycle) after the last application of ruxolitinib cream and must 
refrain from donating sperm during this period. Permitted methods in preventing 
pregnancy (see Appendix A) should be communicated to the participants and their 
understanding confirmed. 
b. Female participants who are WOCBP must have a negative serum pregnancy test at 
screening and negative urine pregnancy test before the first application on Day 1 and 
must agree to take appropriate precautions to avoid pregnancy from screening 
through 30 days (1 menstrual cycle) after the last application of study ruxolitinib 
cream and must refrain from donating oocytes during this period. Permitted methods 
in preventing pregnancy (see Appendix A) should be communicated to the 
participants and their understanding confirmed. 
c. Female participants not considered to be of childbearing potential as defined in 
Appendix A are eligible. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Known triggers for CHE (allergic or irritant, such as those identified by previous patch 
tests) cannot be avoided during the course of the study. 
2. History of (within the past 5 years) or current AD or current psoriasis.  
Note: Participants with CHE due to AD are not eligible.  
3. Concurrent conditions and history of other diseases: 
a. Other active skin disease or infection on the hands, including tinea manuum. In 
addition, foot eczema is excluded. 
b. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, or 
Wiskott-Aldrich syndrome). 
c. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline. 
d. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chickenpox, or impetigo) within 1 week before baseline. 
e. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton 
syndrome), pigmentation, or extensive scarring that in the opinion of the investigator 
may interfere with the evaluation of CHE lesions or compromise participant safety. 
f. Unstable asthma or COPD requiring systemic treatment (such as intravenous steroids) 
or hospital admission or emergency department treatment within 3 months from 
baseline or stable asthma or COPD requiring budesonide more than 720 µg/day 
(2 puffs BID of 180-μg dose) or fluticasone more than 440 μg/day (2 puffs BID of 
110-μg dose) or other equivalent high dose of other inhaled corticosteroids. 
g. Current or history of hepatitis B or C virus infection. 
4. Any serious illness or medical, physical, or psychiatric condition(s) that, in the 
investigator's opinion, would interfere with full participation in the study, including 
administration of study drug and attending required study visits; pose a significant risk to 
the participant; or interfere with interpretation of study data. For example: 
a. Clinically significant or uncontrolled cardiovascular disease, including unstable 
angina, acute myocardial infarction, or stroke within 6 months from Day 1 of study 
drug application, New York Heart Association Class III or IV congestive heart 
failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood 
pressure > 150/90 mm Hg) unless approved by the medical monitor/sponsor. 
b. Participants with or a history of malignancy in the 5 years preceding the baseline 
visit, except for adequately treated nonmetastatic nonmelanoma skin cancer. 
c. Current and/or history of arterial or venous thrombosis, including deep venous 
thrombosis and pulmonary embolism. 
d. Current and/or history of active tuberculosis or current and/or history of latent 
tuberculosis unless adequately treated. 
e. History of severe anemia, severe thrombocytopenia, or severe neutropenia. 


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5. Any of the following clinical laboratory test results at screening: 
a. Cytopenias, defined as follows: 
− Hemoglobin < 100 g/L (ie, 10 g/dL) 
− Absolute neutrophil count < 1.5 × 109/L (ie, 1500/µL) 
− Platelet count < 1 × 1011/L (ie, 100,000/µL) 
b. Liver function tests: 
− AST or ALT ≥ 2.5 × ULN 
− Total bilirubin > 1.5 × ULN unless Gilbert syndrome 
c. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (using the Chronic Kidney 
Disease Epidemiology Collaboration 2021 Equation). 
d. Positive serology test results at screening for HIV antibody. 
e. Any other clinically significant laboratory result that, in the opinion of the 
investigator, poses a significant risk to the participant. 
6. Use of any of the following treatments within the indicated washout period before the 
baseline visit: 
a. 12 weeks or 5 half-lives, whichever is longer – biologic agents (eg, dupilumab). For 
biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult 
the medical monitor. 
b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs; 
cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or 
immunomodulating agents (eg, mycophenolate or tacrolimus); or oral alitretinoin or 
any other systemic treatment for CHE.  
c. 4 weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, 
baricitinib, brepocitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, 
ruxolitinib, tofacitinib, upadacitinib). 
d. 2 weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. 
e. 2 weeks – systemic antibiotics, immunizations with live-attenuated vaccines, or 
sedating antihistamines unless on a long-term stable regimen (nonsedating 
antihistamines are permitted). 
Note: Live-attenuated vaccines are not recommended during the DBVC period. 
COVID-19 vaccination is permitted. 
f. 1 week – use of any topical treatments for CHE (other than bland emollients, eg, 
Aveeno® creams, ointments, sprays, and soap substitutes), such as corticosteroids, 
calcineurin inhibitors, topical antipruritics (eg, doxepin cream), phosphodiesterase 4 
inhibitors, coal tar (shampoo), topical antibiotics or antifungals, and antibacterial 
cleansing body wash/soap. 
Note: Diluted sodium hypochlorite "bleach" baths are allowed as long as they do not 
exceed 2 baths per week and their frequency remains the same throughout the study. 
7. Psoralen ultraviolet A or ultraviolet B therapy for CHE within 4 weeks before baseline.  
8. Pregnant or lactating participants or those considering pregnancy during the period of 
their study participation. 


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9. History of alcoholism or drug addiction within 1 year before screening or current alcohol 
or drug use that, in the opinion of the investigator, will interfere with the participant's 
ability to comply with the administration schedule and study assessments. 
10. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
the baseline visit with another investigational medication or current enrollment in another 
investigational drug protocol. 
11. Known allergy or reaction to any of the components of the study cream. 
12. In the opinion of the investigator are unable or unlikely to comply with the administration 
schedule and study evaluations. 
13. Committed to a mental health institution by virtue of an order issued either by the judicial 
or the administrative authorities. 
14. Employees of the sponsor or investigator or otherwise dependents of them. 
5.3. 
Lifestyle Considerations 
Participants should be cautioned to avoid excessive exposure to artificial sunlight (including 
tanning booths, sun lamps, etc). 
If sunscreen or other cosmetics have been applied to the areas to be treated, participants should 
follow the guidance in Section 6.6 regarding concomitant medications. 
It is recommended that swimming should not take place within 2 hours before and after the 
planned study cream application.  
Participants should not use hand sanitizer within 1 hour of study cream application. In addition, 
they should not wash or wet their hands or use hand sanitizer at a minimum within 1 hour after 
study cream application. In case of glove use, participants should ensure that the skin area where 
study cream is applied is completely dry before putting on glove(s).  
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study treatment. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error. Additionally, a participant who fails screening may 
repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status. Participants who rescreen must reconsent and be assigned a new participant ID 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. However, as noted in the 
COVID-19–related guidance (see Appendix B), due to the evolving situation of the COVID-19 
pandemic, the sponsor may decide to recruit additional participants in the study beyond the 
expected number (eg, if a substantial number of participants withdraw early from the study). 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
Ruxolitinib 1.5% cream or matching vehicle cream will be applied as a thin film BID, with 
applications at least 8 hours apart in the morning and in the evening at least 1 hour before 
bedtime. 
On the first clinic visit day and subsequent in-house clinic visits, participants should not apply 
the study cream at home. The first application of the study cream on the day of the clinic visit 
will be done at the clinic. 
At the baseline visit, an estimate of the %BSA to be treated (including hands and wrists [if 
applicable]) will be used by the IRT system to calculate the number of tubes of study cream to be 
dispensed. The participant will apply a thin film of study cream in front of site staff at the 
baseline/Day 1 visit by applying study cream until all the affected areas to be treated are covered. 
All areas identified at baseline should continue to be treated through the end of the DBVC period 
(Week 16) unless the participant meets criteria for stopping study cream. If there are new areas 
to be treated on the hands and wrists, including expansion of existing areas or development of 
new areas, after consultation with the investigator, study cream should be applied to these areas 
in addition to the areas treated at baseline, and the percentage of BSA to be treated will be 
recalculated and increased. This new estimate will be entered into the IRT system to calculate the 
number of tubes of study cream to be dispensed. 
During the OLE period starting at the Week 16 visit, CHE lesions will be evaluated by the 
investigator to confirm whether the participant still requires continuation of therapy (IGA-CHE 
score ≥ 1) or can otherwise (re)enter the observation/no treatment cycle (IGA-CHE score = 0). 
At Week 16, the IRT system will dispense a prespecified number of tubes according to the 
assessment of total BSA affected. 
Between OLE study visits, participants will self-evaluate recurrence of CHE (if applicable) and 
will treat all areas identified with active changes. If all signs and symptoms of CHE resolve 
between study visits, participants will stop treatment applications 3 days after they have 
disappeared. If this 3-day window is during a study visit and the IGA score for CHE (if 
applicable) is 0, as assessed by the investigator, treatment is to be stopped at the study visit.  
Participants will restart treatment of their CHE at the first sign of recurrence. In the event that 
new lesions are outside of the usual location and/or are more widespread than at baseline, the 
participant is required to contact the site for approval. Approval to treat additional areas may 
occur via telephone during the OLE period, although the investigator, at their discretion, may ask 
the participant to return for an unscheduled visit. 
All tubes (including caps) of study cream will be weighed before being dispensed. All returned 
tubes (including caps) of study cream will also be weighed. 
Application instructions will be provided by the site staff, and the participant will record their 
daily applications via eDiary. Refer to the Study Pharmacy Manual for participant instructions 
for handling study cream. 


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Table 5 presents the study treatment information. 
Table 5: 
Study Treatment Information 
 
Study Treatment 1 
Study Treatment 2 
Study treatment name: 
Ruxolitinib 
Vehicle 
Mechanism of action: 
JAK 1/2 inhibitor 
Not applicable 
Dosage formulation: 
Cream 
Cream 
Treatment strength: 
1.5% 
Not applicable 
Administration instructions: 
DBVC period: Apply a thin film to affected areas identified at 
baseline in the morning and at least 1 hour before bedtime with 
applications at least 8 hours apart for 16 weeks. 
OLE period: Apply a thin film to affected areas in the morning and 
at least 1 hour before bedtime with applications at least 8 hours 
apart as needed for 16 weeks. 
Packaging and labeling: 
Ruxolitinib or vehicle cream will be provided in 60-g tubes. 
Each tube will be labeled as required per country requirement. 
Storage: 
15°C-30°C (59°F-86°F) 
Status of treatment in 
participating countries: 
Investigational 
6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions 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 should not wash their hands, if possible, within 
1 hour after application of study cream. Refer to the Study Pharmacy Manual for participant 
instructions for handling of study cream. 
All study treatment must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff. Participants should store study treatment at ambient 
temperature conditions. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records). Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities. The 
investigator or designee must maintain records that document the following: 
• Delivery of study cream(s) to the study site. 
• Inventory of study cream(s) at the site. 


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• Participant use of the study cream(s), including tube counts from each supply dispensed. 
• Return of study cream(s) to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol. The investigator 
or designee will also maintain records adequately documenting that the participants were 
provided the specified study cream. These records should include dates, quantities, and any 
available batch or serial numbers or unique code numbers assigned to the investigational product 
and study participants. 
Completed accountability records will be archived by the site. The investigator or designee will 
be expected to collect and retain all used, unused, and partially used tubes of study cream until 
verified by the study monitor (unless otherwise agreed to by the sponsor). At the conclusion of 
the study, the investigator or designee will oversee the destruction of any remaining study drug 
according to institutional SOPs. If, however, local procedures do not allow on-site destruction, 
shipment of the study drug back to the sponsor is allowed. In this case, the site should (where 
local procedures allow) maintain the 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 cream is destroyed before monitor inspection, the 
monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the study materials provided to the sites. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT system. The IRT 
system will assign in a 1:1 ratio, stratified by baseline IGA-CHE score (3 or 4) and region (North 
America or outside of North America), the participant study number, track participant visits, 
randomize according to the defined parameters, maintain the blinding, and manage study cream 
inventory. Full details will be provided in the IRT Manual. 
Participants, investigators, and the sponsor will be blinded to each participant's treatment 
assignment during the DBVC period. During the OLE period, participants and investigators will 
remain blinded to the treatment assignment during the DBVC period. Emergency unblinding will 
occur if an AE requires the investigator to be made aware of the participant's treatment 
assignment (see emergency unblinding procedures in Section 9.7 and refer to the IRT Manual). 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by site 
personnel, and appropriate steps should be taken to optimize compliance during the study. 
Compliance will be assessed for frequency of administration of study cream by reviewing the 
participants' eDiaries. Participants will also be questioned regarding study cream application 
technique, missed applications, and use of any additional topical or systemic prescriptions of 
other products or over-the-counter products. Compliance with study cream will be evaluated by 
the participant's adherence to the BID application regimen (evaluation of actual number vs 
prescribed number of applications), documented by the site staff, and monitored by the 
sponsor/designee. 


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Qualified clinical staff will review the eDiary entries for compliance. Participants will be 
considered compliant with the treatment regimen if they apply at least 80% but no more than 
120% of the prescribed number of applications during participation in the DBVC period of the 
study. Participants who are noncompliant during the DBVC period and OLE period (if on a 
treatment cycle) will be reinstructed by the investigator (or designee), and the sponsor should be 
consulted by the investigator for instruction on the proper handling of the participant. 
Drug accountability will be assessed by documenting the quantities of drug used between study 
visits (tube counts and weighing). At the first clinic visit and subsequent study visits, all tubes 
(including caps) of study cream will be weighed before being dispensed and when returned. 
Participants will be instructed to bring all study cream with them to the study visits in order for 
site staff to assess study cream accountability. 
6.5. 
Dose Modifications 
There are no study drug application adjustments/modifications allowed (eg, frequency of 
application) except for drug interruption or permanent discontinuation if needed (eg, for 
management of an AE). 
Temporary interruption could be due to an AE during the DBVC or OLE period (see 
Section 6.5.1) or clearance of the CHE during the OLE period, as described in Section 6.1. 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease may require that 
the study drug be permanently discontinued. Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to the study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest. 
• Worsening of CHE that requires treatment with a prohibited concomitant medication. 
• An AE that requires an interruption of study drug for more than 2 weeks. 
• Confirmed Grade 4 laboratory abnormalities related to study drug (see Section 6.5.1). 
See Section 7 for discontinuation procedures. 


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6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF. All 
medications received up to 28 days before the first application of study treatment will be 
recorded in the eCRF. Any prior CHE treatments before the first application of study drug will 
be collected, including the reason for stopping the treatment (eg, inadequate response or 
intolerance). All medications received from the first application through 30 days after the last 
application of study treatment will be recorded in the eCRF. Any addition, deletion, or change in 
the dose/regimen of these medications will also be recorded. 
Other relevant medications or procedures received more than 28 days before the first dose of 
study drug may be recorded in the eCRF at the discretion of the investigator or at the request of 
the sponsor based on emerging events during the study. 
Any addition, deletion, or change in the strength/regimen of these medications will also be 
recorded. Concomitant medications administered 30 days after the last application of study 
treatment should be recorded for SAEs. Concomitant treatments/procedures that are required to 
manage a participant's medical condition during the study will also be recorded in the eCRF. The 
medical monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
6.6.1. 
Permitted Medications and Procedures 
The following are permitted during the study: 
• Participants may use/continue to use bland emollients (eg, Aveeno® creams, ointments, 
sprays, or soap substitutes). Participants may not change or introduce a new emollient 
within 4 weeks of the baseline visit. 
• Note: Emollients should not be used 4 hours before and at least 1 hour after study 
cream application. 
• If sunscreen is needed, a mineral-based sunscreen (such as zinc oxide or titanium oxide 
based) with an SPF of at least 30 may be used not less than 4 hours before and at least 
1 hour after study drug application. 
• Participants may use nonsedating, over-the-counter antihistamines. 
• Established treatment with sedating antihistamines (≥ 2 months prior to baseline) may be 
continued as long as no changes are made during the course of the study.  
• Inhaled corticosteroids for bronchial asthma or COPD are allowed with the dose 
equivalent of budesonide (not to exceed 720 µg/day or 2 puffs BID of a 180-μg dose) or 
fluticasone (not to exceed 440 μg/day or 2 puffs BID of a 110-μg dose) or other 
equivalent inhaled corticosteroids.  


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6.6.2. 
Restricted Medications and Procedures 
The use of the following medications and procedures is restricted to specified conditions:  
• Use of any over-the-counter, nonprescription preparations (including vitamins, minerals, 
and phytotherapeutic, herbal, or plant-derived preparations) if deemed acceptable by the 
investigator from 7 days before the baseline visit through the follow-up visit. 
• Use of any prescription medication to treat chronic medical conditions (such as 
hypertension) if on a stable regimen and if deemed acceptable by the investigator from 
7 days before the baseline visit through the follow-up visit. 
• Use of a short course of topical anti-infectives for an infection during the study (including 
antibacterial, antifungal, and antivirals) if used ≤ 5 days to treat skin infection. 
Anti-infective treatment should not be used for at least 4 hours before and 1 hour after 
application of study cream. 
• Short-term use (< 5 days) of systemic corticosteroids may be permitted to treat acute AEs 
(eg, asthma) during the OLE period, and the decision to keep the participant in the study 
(or to permanently discontinue study cream) will be made in consultation with the 
medical monitor. 
6.6.3. 
Prohibited Medications and Procedures 
No rescue treatment or therapy is allowed during the study (see Section 6.5.2). In addition, the 
following are not permitted during the study: 
• Any investigational medication other than the study drug. 
• Treatment known to affect the course of CHE. 
• Topical corticosteroids; topical calcineurin inhibitors; systemic corticosteroids (except 
short-term use of systemic corticosteroids to treat an AE during the OLE period, see 
Section 6.6.2); methotrexate, cyclosporin A, azathioprine and biological therapies, or 
other immunosuppressant agents; and oral alitretinoin or any other systemic treatment for 
CHE.  
• Strong systemic CYP3A4 inhibitors.  
• Phototherapy or tanning beds. 
• Live-attenuated vaccination during the DBVC period. 
Note: COVID-19 vaccination is permitted. 
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: 
• Disease worsens requiring treatment with prohibited medication. The participant should 
be discontinued at the discretion of the investigator or based on discussions with the 
medical monitor. 
• The participant becomes pregnant. 
• Consent is withdrawn.  
Note: Consent withdrawn means that the participant has explicitly indicated that they do 
not want to be followed any longer; in this case, no further data, except data in the public 
domain, may be solicited from or collected on the participant. Participants may choose to 
discontinue study treatment and remain in the study to be followed for disease 
progression and survival. 
• Further participation would be injurious to the participant's health or well-being, in the 
investigator's medical judgment. 
• Unacceptable toxicity as noted in Section 6.5. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, after 2 consecutive study visits and reinforcement of study drug application by site 
staff, a participant's drug usage exceeds one 60-g tube every 4 days; a participant who 
again fails to meet compliance benchmarks at a subsequent visit may be considered for 
withdrawal from the study. The medical monitor should be consulted for instruction on 
handling the participant. 
• If, during the course of the study, a participant is found not to have met eligibility criteria, 
the medical monitor, in collaboration with the investigator, will determine whether the 
participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug 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 treatment prior to the 
Week 16 or Week 32 visit, the ET visit should be conducted. Early termination will be referred 
to as ET1 if it occurs before Week 16 or ET2 if it occurs after Week 16 and before Week 32. 


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Reasonable efforts should be made to have the participant return for a follow-up visit. These 
visits are described in Table 3. The date and time of the last application of study cream and the 
reason for discontinuation of study cream will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The ET visit should be performed and the date recorded. 
• The status of the participant should be updated to ET in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at their own request or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If a participant withdraws from the study, they may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records. 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 they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 


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• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or their representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions regarding 
the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant. An ICF template 
will be provided by the sponsor or its designee. The sponsor or its designee must 
review and acknowledge the site-specific changes to the ICF template. The ICF 
must include a statement that the sponsor or its designee and regulatory 
authorities have direct access to participant records. 
− The ICF must contain all required elements including optional 
samples/procedures (eg, optional biopsy) and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the applicable requirements and regulations for the country(ies) in which the 
study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that their personal data collected for the study will be 
used by the sponsor in accordance with local data protection laws. The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
• The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 


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• 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 and must be assigned a 
new participant ID number. 
8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is 
enrolled/randomized in the study (Day 1). Screening may not exceed 28 days. Assessments that 
are required to demonstrate eligibility may be performed over the course of 1 or more days 
during the screening process. 
Procedures conducted as part of the participant's routine clinical management (eg, blood counts 
or physical examinations) and obtained before signing of the ICF may be used for screening or 
baseline purposes provided that the procedure meets the Protocol-defined criteria and has been 
performed in the timeframe of the study (ie, within 28 days or less prior to Day 1). For 
participants who are randomized/enrolled in the study, information associated with eligibility 
requirements must be entered into the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment/randomization and the administration of study drug. Tests with results that fail 
eligibility requirements may be repeated once during screening if the investigator believes the 
results to be in error. For screening assessments that are repeated, the most recent available result 
before randomization/treatment assignment will be used to determine eligibility. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the country's abbreviation, the site ID, and the participant ID number. Site staff 
should contact the IRT to obtain the participant ID number during screening. Upon determining 
that the participant is eligible for study entry, the IRT will be contacted to obtain the treatment 
assignment. Additionally, the IRT will be contacted at each regular study visit during both the 
DBVC period and the OLE period to update the study drug supply. Additional details are 
provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and/or eDiaries 
Starting at the Day 1 visit, a study drug–specific eDiary will be used by each participant to 
record the use of the study drug. The completed diary will be reviewed during each of the 
participant's study visits and the data uploaded will be confirmed by the study staff. 
Qualified clinical study staff will review the participants' eDiary entries for compliance. 
Participants who are noncompliant with their study drug schedule (defined as < 80% or > 120% 
of the expected number of applications between study visits) will have their administration 


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instructions reinforced by the investigator or a qualified designee, and the sponsor should be 
consulted by the investigator for instruction on the proper handling of participants who are not 
compliant during the DBVC period and the OLE period (see Section 6.4). Participants will be 
considered compliant with the treatment regimen if they apply at least 80% but no more than 
120% of the expected applications during participation in the DBVC period of the study. 
Participants will be provided with a reminder card starting on Day 1 and at all DBVC and all 
OLE visits through Week 32. The reminder card will indicate the date and time of the next visit 
and will also remind the participant that their morning application of study cream (if applicable) 
will take place at the clinic under site supervision after blood draws and safety evaluations have 
been completed. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses. Medical history will include relevant medical and 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 
Relevant medical and treatment history for CHE will be collected at screening by the investigator 
or qualified designee. Details regarding the participant's history of CHE, including date of 
diagnosis, relevant disease characteristics, prior treatments with outcome (eg, inadequate 
response or intolerance), and reason for stopping treatment will be recorded. Acceptable 
documentation includes a review of the participant's chart/medical records or investigator 
documentation based on communication with the participant's previous treating physician or the 
participant. A medical history of other conditions related to CHE will also be collected at this 
time. 
8.2. 
Efficacy Assessments 
8.2.1. 
Investigator's Global Assessment–Chronic Hand Eczema 
The IGA-CHE is an overall severity rating on a scale from 0 to 4 as noted in 
 The 
IGA-CHE-TS is defined as an IGA-CHE score of 0 or 1 with ≥ 2-grade improvement from 
baseline and will be measured at the timepoints indicated in the SoA (see Table 3).  


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8.2.2. 
Hand Eczema Severity Index Score 
The HECSI divides the hand into 5 areas for assessment (fingertips, fingers [except the tips], 
palms, back of hands, and wrists). Each of the 5 areas of the hand is assessed separately for 
erythema, induration/papulation, vesicles, fissuring, scaling, and edema using the following 
scale: 0, no skin changes; 1, mild disease; 2, moderate disease; and 3, severe disease. To 
determine the HECSI score, the affected area for each location (total of both hands) is given a 
score from 0 to 4 (0, 0%; 1, 1%-25%; 2, 26%-50%; 3, 51%-75%; and 4, 76%-100%) based on 
the extent of clinical symptoms. Finally, the score given for the extent at each location is 
multiplied by the total sum of the intensity of each clinical feature to calculate the HECSI score 
(range from 0 to a maximum severity score of 360 points; Held et al 2005). The HECSI score 
will be assessed at the timepoints indicated in the SoA (see Table 3).  


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8.2.4. 
Body Surface Area 
Total %BSA affected (including hands and wrists [if applicable]) will be estimated at each visit 
as outlined in the SoA (see Table 3). Body surface area assessment will be approximated to the 
nearest 0.1% using the Palmar Method as a guide (the palm plus 5 digits, with the fingers tucked 
together and the thumb tucked to the side [participant's handprint)] as 1% BSA and the thumb as 
0.1% BSA). 
8.2.5. 
Photography 
Photographs of the hands and wrists (anterior and posterior) will be taken at visits indicated in 
Table 3 at all sites. 
In addition, at select study sites that will collect skin samples (with tape discs), a note should be 
made in the medical record, and baseline photographs will be marked with the location of the 
target lesion and selected nonlesional area (see Section 8.2.3). 
Ad hoc photography for skin-related AEs is recommended. 
8.2.6. 
Patient-Reported Outcomes 
Patient-reported outcomes will be assessed as outlined in the SoA (see Table 3). 
8.2.6.1. 
eDiary Assessments 
Participants will be issued a handheld device (eDiary) for daily assessments at the screening 
visit. The participant will be instructed to complete and record the CHE-related Itch NRS and 
Skin Pain NRS via an eDiary daily, in the evening beginning on the day of screening through 
Week 32 or ET.  
Both the Itch NRS and Skin Pain NRS are a daily participant-reported measure (24-hour recall) 
of the worst level of itch or skin pain intensity related to CHE. 
The participants will rate the following: 
• CHE-related Itch NRS: Itch severity of their CHE by selecting a number from 0 (no 
itch) to 10 (worst imaginable itch) that best describes their worst level of itching in 
the past 24 hours. 


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• CHE-related Skin Pain NRS: Pain severity of their CHE by selecting a number from 
0 (no pain) to 10 (worst imaginable pain) that best describes their worst level of pain 
in the past 24 hours. 
The average of 7-day CHE-related Itch NRS prior to the baseline visit (minimum 4 out of 7 days' 
data required) will be used to determine if a participant meets the inclusion criteria. 
Detailed directions for the administration of an eDiary will be provided in the Study Manual. 
8.2.6.2. 
Dermatology Life Quality Index  
The DLQI is a simple, 10-question validated questionnaire to measure how much the skin 
problem has affected the participant over the previous 7 days (Finlay and Khan 1994). The 
participant will answer the questionnaire as follows: 1) very much, 2) a lot, 3) a little, or 4) not at 
all. 
8.2.6.3. 
Patient Global Impression of Change 
The PGIC is a participant's self-reporting measure that reflects their belief about the efficacy of 
treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement of 
CHE and will be captured during site visits (Hurst and Bolton 2004).  
The participant will be asked to select 1 response from the response options that best describe the 
overall change in their CHE since they started study treatment: 1) very much improved, 2) much 
improved, 3) minimally improved, 4) no change, 5) minimally worse, 6) much worse, and 
7) very much worse. 
8.2.6.4. 
Quality of Life in Hand Eczema Questionnaire 
The QOLHEQ is a validated disease-specific instrument to assess disease-specific health-related 
quality of life in participants with CHE over the past 7 days (Ofenloch et al 2014). It consists of 
30 items that are summarized according to impairments because of 4 domains: 1) symptoms, 
2) emotions, 3) limitations in functioning, and 4) treatment and prevention. Each item is scored 
in a 5-point scale: 0) never, 1) rarely, 2) sometimes, 3) often, and 4) all the time.  
8.2.7. 
Health Economics 
8.2.7.1. 
EQ-5D-5L 
Participants will complete the EQ-5D-5L questionnaire at the designated study visits. The 
EQ-5D-5L questionnaire is a standardized, validated instrument for use as a measure of health 
outcome (Herdman et al 2011). The EQ-5D-5L questionnaire will provide data for use in 
economic models and analyses, including developing health utilities or QALYs. The EQ-5D-5L 
questionnaire consists of the following 2 sections: the EQ-5D descriptive system and the 
EQ VAS. 
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1 = no problems, 
Level 2 = slight problems, Level 3 = moderate problems, Level 4 = severe problems, and 
Level 5 = extreme problems. This part of the EQ-5D-5L questionnaire provides a descriptive 
profile that can be used to generate a health state profile. For example, a participant in "health 


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state 12345" would have no problems with mobility, slight problems with self-care (washing or 
dressing), moderate problems with doing usual activities, severe pain or discomfort, and extreme 
anxiety or depression. Each health state can potentially be assigned a summary index score based 
on societal preference weights for the health state. These weights, sometimes referred to as 
utilities, are often used to compute QALYs for use in health economic analyses. Health state 
index scores generally range from < 0 (where 0 is the value of a health state equivalent to dead; 
negative values represent values as worse than dead) to 1 (the value of full health), with higher 
scores indicating higher health utility. The health state preferences often represent national or 
regional values and can therefore differ between countries/regions. 
The EQ VAS records the participant's self-rated health on a vertical VAS (0-100), where the 
endpoints are labeled "the best health you can imagine" (100 score) and "the worst health you 
can imagine" (0 score). 
8.2.7.2. 
Work Productivity and Activity Impairment Questionnaire v2.0 in Chronic 
Hand Dermatitis 
The Work Productivity and Activity Impairment Questionnaire is a patient-reported quantitative 
assessment of the amount of absenteeism, presentism, and daily activity impairment attributable 
to a specific health problem. The WPAI-ChHD is a 6-item questionnaire used to assess the 
impact of chronic hand dermatitis (ChHD, the same as CHE in this context) on job performance 
and productivity in the past 7 days (Reilly et al 2003). 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see Table 3). 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last application of study drug. Adverse events for enrolled participants that 
begin or worsen after informed consent should be recorded on the Adverse Events Form in the 
eCRF regardless of the assumption of a causal relationship with the study drug. Conditions that 
were already present at the time of informed consent should be recorded on the Medical History 
Form in the eCRF. Adverse events (including laboratory abnormalities that constitute AEs) 
should be described using a diagnosis whenever possible rather than by individual underlying 
signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
that are considered related to the study drug/procedures, or that caused the participant to 
discontinue the study drug. Care will be taken not to introduce bias when detecting AEs and/or 
SAEs. Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences. Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 


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visits or through physical examinations, laboratory tests, or other assessments. The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee immediately, without undue delay and no 
later than within 24 hours (see Section 9.4). The investigator will submit any updated SAE data 
to the sponsor or designee immediately, without undue delay and no later than 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 AEs/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 
At the screening visit and the ET1 or ET2 visits, a comprehensive physical examination should 
be conducted. The comprehensive physical examination will include assessment(s) of the 
following organ or body systems: skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief 
neurological examination. Fitzpatrick skin classification will be included as part of the physical 
examination at screening. 
During the study, a targeted physical examination may be conducted by the investigator or 
medically qualified designee (per institutional policies and local standard of care) to assess AEs, 
symptoms/signs, laboratory abnormalities, or other findings. Findings from the targeted physical 
examination should be reported on the Adverse Events Form in the eCRF. 
Height and body weight will be assessed at screening. 
8.3.3. 
Vital Signs 
Vital sign measurements (to be taken before blood collection for laboratory tests) include blood 
pressure, pulse, respiratory rate, and body temperature and will be taken at the timepoints 
indicated in the SoA (see Table 3). Blood pressure and pulse will be taken with the participant in 
the sitting position after 5 minutes of rest. Abnormal vital sign results identified after the first 
dose of study treatment, 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. 
8.3.4. 
Laboratory Assessments 
See Table 8 for the list of clinical laboratory tests to be performed and Table 3 for the timing and 
frequency. A central laboratory will perform all clinical laboratory assessments for safety 
(eg, blood chemistries or hematology assessments) and will store the samples for PD analysis. 
Additional testing may be required by the sponsor based on emerging safety data. All 
Protocol-required laboratory assessments must be conducted in accordance with the Laboratory 
Manual and 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 


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abnormal during participation in the study or within 30 days after the last application of the study 
drug should be repeated until the values return to normal or baseline or are no longer considered 
clinically significantly abnormal by the investigator or medical monitor. 
It is not necessary to reassess chemistry or hematology at baseline (Day 1) if screening 
assessments were performed within 14 days of Day 1. 
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 
Table 8: 
Required Laboratory Analytes 
Chemistry 
Hematology 
Serology 
Pregnancy Testing 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Blood urea nitrogen or 
urea 
Creatinine 
Creatine kinase 
Glucose 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is elevated 
above ULN) 
Complete blood count, 
including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• Reticulocyte count 
• White blood cell 
count 
Differential count 
(absolute and %), 
including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
HIV 
Human chorionic 
gonadotropin 
(WOCBP only) 
FSH (women of 
nonchildbearing 
potential only) 
 
Note: Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data or to 
rule out a diagnosis. 
8.3.4.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening. Urine pregnancy tests 
will be performed locally, as outlined in the SoA (see Table 3), and as medically indicated (eg, in 
case of loss of menstrual cycle or when pregnancy is suspected). 
If a urine pregnancy test is positive, the results must be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.8 for reporting 
requirements. 


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8.3.4.2. 
Serology 
HIV screening assessment will be performed at the screening visit to rule out HIV infection. 
Generally, serology tests should be performed early in the screening process due to the length of 
time needed to obtain the results. Additional tests may be performed if clinically indicated. 
8.4. 
Pharmacokinetic Assessments 
Pharmacokinetic parameters will not be evaluated in this study. 
8.6. 
Unscheduled Visits 
Unscheduled visits may occur at any time medically warranted. Any assessments performed at 
those visits should be recorded in the eCRF. 


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8.7. 
End of Treatment and Early Termination 
A participant who completes the Week 16 visit will have reached the end of double-blind 
treatment (EOT1) with study drug. A participant who completes the Week 32 visit will have 
reached the end of open-label treatment (EOT2) with study drug. 
If a decision is made that the participant will permanently discontinue study drug prior to the 
Week 32 visit, then the ET visit should be conducted. Assessments for the ET visit will be the 
same as those for Week 32. Early termination will be referred to as ET1 if it occurs before 
Week 16 or ET2 if it occurs after Week 16 and before Week 32. If the ET visit coincides with a 
regular study visit, then the ET evaluations will supersede those of that scheduled visit, and the 
data should be entered in the ET page in the eCRF. If this decision does not coincide with a 
regular visit, reasonable efforts should be made to have the participant return to the site to 
complete the ET procedures. 
8.8. 
Follow-Up 
The safety follow-up period is the interval between the Week 32 or ET visit and the scheduled 
follow-up visit, which should occur 30 days (+ 7 days' visit window) after the Week 32 or ET 
visit. All participants will have a safety follow-up visit 30 days (+ 7 days) following the end of 
treatment (Week 32/ET) to evaluate safety and disease control parameters. One exception to this 
would be for participants in the OLE period who have been in an observation/no treatment cycle 
with a total IGA-CHE score of 0 (clear) from Week 28 or earlier until Week 32; for such 
participants, the Week 32/ET visit will also count as the safety follow-up visit. 
Adverse events and SAEs must be reported up until 1) 30 days after the last application of study 
drug or 2) until toxicities resolve, return to baseline, or are deemed irreversible, whichever is 
longer. Reasonable efforts should be made to have the participant return for the follow-up visit 
and report any AEs that may occur during this period. 


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9. 
ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 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 dose administration 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 department for observation and/or treatment that would 
not have been appropriate in the physician's office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious 
criteria, the event is serious. When in doubt as to whether hospitalization occurred or was necessary, 
the AE should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, or hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) is not considered an SAE. 
d. Results in persistent or significant disability/incapacity 
The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions. This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle) that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
An important medical event is an event that may not result in death, be immediately life-threatening, or 
require hospitalization but may be considered serious when, based on appropriate medical judgment, 
the event may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definition. Examples of such events include new invasive or 
malignant cancers; intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization; development of 
drug dependency or drug abuse; or suspected transmission of an infectious agent via a medicinal 
product.  


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


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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5. If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate 
the grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2: Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4: Life-threatening consequences; urgent treatment indicated. 
• Grade 5: Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB in making their assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that they have reviewed the 
AE/SAE and have provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report. However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements. Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change their opinion of causality in light of follow-up information and 
submit the updated causality assessment. 
Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 


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• Once an AE is detected, it should be followed in the Adverse Events Form in the eCRF until it has 
resolved or until it is judged to be permanent; assessment should be made at each visit (or more 
frequently if necessary) of any changes in severity, the suspected relationship to the study 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 (either via email/fax if paper SAE form is used or in the SAE EDC CRF) until 
resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) immediately, without undue delay but not later than within 24 hours of receipt 
of the information. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug or study procedure[s]), all SAEs 
occurring after the participant has signed the ICF through at least 30 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 30 days after the last dose of study drug. If the investigator learns of any SAE, including 
death, at any time during this period, and they consider the event to be reasonably related to the 
study drug or study participation, then the investigator must notify the sponsor (or designee) 
immediately, without undue delay but not later than within 24 hours of becoming aware of the 
event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities for 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 Clinical Trials Regulation (EU) No. 536/2014 or per national 
regulatory requirements in participating countries. 


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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 Events Form in the eCRF. 
• The investigator must report immediately, without undue delay but not later than within 24 hours of 
learning of its occurrence, any SAE via the EDC system (primary method) or by completing the 
Serious Adverse Event Report Form in English (only if the EDC system is not available). The 
contact information for Incyte Pharmacovigilance by email/fax is listed in the Study Reference 
Manual or the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Event Report Form. Once the EDC system is functional, 
the SAE report should be retrospectively added to the EDC system and follow-up should be 
completed through the EDC. The original copy of the Serious Adverse Event Report Form and the 
email or facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference 
Guide for Completing the Serious Adverse Event Report Form or Study Reference Manual for 
details and for the email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system. The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation). Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs. 
9.5. 
Potential Drug-Induced Liver Injury 
Not applicable. 
9.6. 
Events of Clinical Interest 
Not applicable. 
9.6.1. 
Adverse Events of Special Interest 
Not applicable. 


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9.7. 
Emergency Unblinding of Treatment Assignment 
In case of a medical emergency, for a participant's safety management, the procedure for 
emergency unblinding is provided to the investigator in the IRT Manual. The IRT system has an 
option to select for "Emergency Code Break" action for a given participant. After entering the 
study drug tube number and verification of the unmasking information, the 
investigator/subinvestigator will proceed to either final confirmation or cancellation of the code 
break procedure. 
If a participant's treatment assignment is unblinded, the sponsor or its designee should be notified 
immediately by telephone/email/IRT for awareness. 
If an investigator, the site personnel performing assessments, or a participant is unblinded, then 
the participant must discontinue study drug unless there are ethical reasons to have the 
participant remain on the study drug. In these cases, the investigator must obtain specific 
approval from the sponsor's (or its designee's) medical monitor for the participant to continue in 
the study. 
9.8. 
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. 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluations. 
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit. Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee. Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later. Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during the pregnancy of a study participant must be recorded and 
reported as described in Section 9.4. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4. If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 


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9.9. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB. Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications. Any 
important new safety information should be discussed with the participant during the study as 
necessary. If new significant risks are identified, they will be added to the ICF. 
There are no study-specific warnings or precautions in this study. 
9.10. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor. All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or their designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information. Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, they will return a copy of the 
product complaint communication with the product. 
9.11. 
Treatment of Overdose 
There has been no clinical experience with overdose resulting from excessive use of ruxolitinib 
cream. Treatment of overdose should consist of general supportive measures. 


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10. 
STATISTICS 
This section outlines the statistical analysis strategy and procedures for this study. If, after the 
study has begun, but before the final database lock, changes are made to primary and/or 
secondary analysis hypotheses or the statistical methods related to those hypotheses, the Protocol 
may be amended, consistent with ICH E9 (1998) and ICH E9 (R1) (2021). The detailed 
statistical analyses will be documented in the SAP. 
10.1. 
Sample Size Determination 
Approximately 180 participants will be randomized 1:1 to ruxolitinib 1.5% cream BID or vehicle 
cream BID. 
The sample size is calculated to provide sufficient power (> 80%) to detect a difference between 
ruxolitinib 1.5% cream BID and vehicle cream BID for the primary and key secondary 
endpoints. The powers for different endpoints are provided in Table 9. The chi-square test with a 
2-sided α of 0.05 is used to calculate the powers.  
In addition to providing sufficient power for efficacy variables, the sample size is determined to 
provide an adequate database for safety evaluations. 
Table 9: 
Powering for Primary and Key Secondary Endpoints 
Variables 
Response Rates With 
Ruxolitinib 1.5% 
Cream BID 
Response Rates 
With Vehicle Cream 
BID 
Power 
IGA-CHE-TS at Week 
16 
26%ab 
10%abc 
80% 
ITCH4 at Week 16 
40%bc 
18%bc 
90% 
ITCH4 at Week 4 
35%bc 
12%bc 
95% 
ITCH4 on Day 7 
30%bc 
10%bc 
92% 
a Based on the results from a Phase 2b study of topical delgocitinib in CHE (Worm 2022). 
b Based on the results from a Phase 3 study of topical delgocitinib in CHE (Bissonnette 2023). 
c Based on the results from the 2 Phase 3 registrational AD studies, INCB 18424-303 and INCB 18424-304. 


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10.2. 
Populations for Analysis 
Table 10 presents the populations for analysis. 
Table 10: 
Populations for Analysis 
Population 
Description 
ITT 
The ITT population incudes all randomized participants. 
Safety 
The safety population includes all participants who applied study drug at least once. 
Treatment groups for this population will be determined according to the actual 
treatment the participant received on Day 1. 
Open-label 
evaluable  
The open-label evaluable population includes all participants who applied at least 
1 dose of ruxolitinib cream during the OLE period. 
PD evaluable 
The PD evaluable population includes participants who applied study cream at least 
once and provided baseline PD sample and at least 1 postbaseline PD sample for 
analysis. The study translational scientist will review data listings of participant 
administration and sample records to identify participants to be excluded from the 
analysis. 
10.3. 
Level of Significance 
The gatekeeping testing strategy for the primary and key secondary analyses will be 
implemented to control the overall Type I error rate, 2-sided α = 0.05. These endpoints will be 
tested in a fixed sequence at 2-sided α = 0.05 level in the following order: 
• IGA-CHE-TS at Week 16 
• ITCH4 response at Week 16 
• ITCH4 response at Week 4 
• ITCH4 response at Week 1 (Day 7) 
10.4. 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the participant 
populations to be included in the analyses and procedures for accounting for missing, unused, 
and spurious data. This section is a summary of the planned statistical analyses of the primary 
and secondary endpoints. 
10.4.1. 
Primary Analysis 
The key parameters for the primary analysis are provided in Table 11. The primary analysis will 
be based on the ITT population. The primary alternative hypothesis (superiority of active 
ruxolitinib 1.5% cream BID compared with vehicle cream) will be tested at a 2-sided α = 0.05 
level using a Cochran-Mantel-Haenszel test stratified by IGA-CHE score (3 or 4) and region 
(North America or outside of North America). A summary of IGA-CHE-TS rates will be 
reported for each treatment group. The p-value and stratum-adjusted IGA-CHE-TS rate 
difference with 95% CI will be provided (Mantel and Haenszel 1959). 


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Table 11: 
Summary of Primary Analysis 
Parameter 
Definition 
Treatment 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population 
ITT population 
Variable 
IGA-CHE-TS at Week 16: defined as an IGA-CHE score of 0 or 1 with 
≥ 2-grade improvement from baseline 
Population-level 
summary 
Stratum-adjusted IGA-CHE-TS rate difference with 95% CI 
All nonresponders in the DBVC period, participants who discontinue study treatment at any time 
before the timepoint of interest, and participants who discontinue from the study for any reason 
will be defined as nonresponders for the nonresponder imputation analysis. Subgroup analysis by 
baseline characteristic (eg, IGA-CHE, region, or age) will be performed.  
10.4.2. 
Key Secondary Objective 
If the primary objective is achieved, the statistical hypotheses for the key secondary endpoint 
will be tested in the order specified in Section 10.3. Key secondary efficacy analysis at Week 16, 
Week 4, and Week 1 (Day 7) will be conducted in the ITT population. The statistical 
comparisons for binary outcomes (ITCH4) will be analyzed using a similar method as specified 
in the primary analysis. The stratum-adjusted ITCH4 rate difference (1.5% BID vs vehicle) and 
95% CI will be computed in a similar way as in the primary analysis. A summary of analyses for 
the key secondary endpoints is provided in Table 12. 
Table 12: 
Summary of Analyses for Key Secondary Endpoints 
Parameter 
Definition 
Treatment 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population  
ITT population 
Variables 
ITCH4 response at Week 16: Defined as a ≥ 4-point improvement in 
CHE-related Itch NRS score from baseline 
ITCH4 response at Week 4 
ITCH4 response at Week 1 (Day 7) 
Population-level 
summary 
Stratum-adjusted IGA-CHE-TS rate difference with 95% CI 
Note: Participants with missing observed data at the timepoint of interest, participants who discontinue study 
treatment at any time before the timepoint of interest, and participants who discontinue from the study for any 
reason will be defined as nonresponders. No rescue therapy or treatment switch is allowed in this study. 
10.4.3. 
Secondary Analysis 
All other secondary and exploratory efficacy variables will be summarized using descriptive 
statistics. For categorical measurements, summary statistics will include sample size, frequency, 
and percentages. For continuous measurements, summary statistics will include sample size, 
mean, median, standard deviation, standard error of the mean, minimum, and maximum. For the 


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time to achieve change from baseline in CHE-related Itch NRS score ≥ 4 and in CHE-related 
Skin Pain NRS score ≥ 2, a log-rank test stratified by randomization stratification factors will be 
used for comparisons between treatment groups. The hazard ratio and its 95% CI will be 
estimated based on the stratified Cox regression model using Efron's method accounting for ties. 
Kaplan-Meier curves will be presented by treatment groups. The number of participants, number 
of events, and number of censoring will be summarized by treatment groups. The Kaplan-Meier 
estimate of median time will be presented with its 95% CI. The 95% CI will be calculated using 
the method by Brookmeyer and Crowley (1982). 
10.4.4. 
Safety Analyses 
Safety analyses will be conducted for the safety population. 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first application of study drug. Analysis of AEs will be limited to TEAEs, but data listings will 
include all AEs regardless of their timing to study drug administration. Adverse events will be 
tabulated by the MedDRA preferred term and system organ class. Severity of AEs will be based 
on the National Cancer Institute CTCAE v5.0 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a causal relationship to study drug will 
be considered treatment-related AEs. If the investigator does not specify the relationship of the 
AE to study drug, then the AE will be considered treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. 
The clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned. Laboratory test values outside the normal range will be assessed for 
severity based on the normal ranges for the clinical reference laboratory. The incidence of 
abnormal laboratory values and shift tables relative to baseline will be tabulated. Descriptive 
statistics and mean change from baseline will be determined for vital signs (blood pressure, 
pulse, respiratory rate, and body temperature) at each assessment time. 
10.4.5. 
Analysis Plan 
There are 2 formal planned analyses: 
• The primary analysis will occur after the primary database lock, when all participants 
have completed the DBVC period. The sponsor will be unblinded after the primary 
database lock; however, investigators and participants will remain blinded to the 
individual study treatment assignment. 
• The final analysis will occur when all participants have completed or withdrawn from 
the study. 
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 and health authorities before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both health authorities and 
the IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and country-
specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to the 
Protocol procedures, with the exception of medical emergencies, must be discussed and 
approved, first, by the sponsor or its designee and, second, by the IRB/IEC. Each 
investigator is responsible for enrolling participants who have met the specified eligibility 
criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in an 
ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study during the 
retention period without receiving approval from the sponsor. The investigator must 
notify the sponsor or its designee in the event of accidental loss or destruction of any 
study records. If the investigator leaves the institution where the study was conducted, 
the sponsor or its designee must be contacted to arrange alternative record storage 
options. 


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− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made available 
at the site in compliance with applicable record retention regulations. The sponsor 
will retain the original eCRF data and audit trail. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study. As part of their responsibilities, the coordinating principal investigator will review the 
final CSR. Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system. The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF. The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements. Other data outside the EDC system required in the study conduct of 
the Protocol, such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and as designated by the sponsor, will have their own data flow 
management plans, study charters, or biomarker plans, as applicable. 
The sponsor (or designee) will be responsible for the following: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated and/or collected, including documents and 
results such as laboratory or imaging data analyzed centrally by a designated vendor of 
the sponsor. 
The investigator will be responsible for the following: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, or 
formulas relating to the study to the sponsor or designee electronically and/or centrally 
(eg, laboratory data, imaging data, biomarker data, photographs, diary data) or as 
otherwise specified in the Protocol. 


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• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants. Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail). Source data are, in general, all information 
in original records and certified copies of original records of clinical findings, 
observations, or other activities in a clinical trial necessary for the reconstruction and 
evaluation of the trial. Source data are contained in source documents (original records or 
certified copies). 
• Verifying that data entries are accurate and correct by physically or electronically signing 
the eCRF. 
• Maintaining accurate documentation (source data) that supports the information entered 
in the eCRF, or sent to a central vendor designated by the sponsor or as described in other 
study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed and 
available at the investigator's site. Examples of source documents are original 
documents, data, and records (eg, hospital records; electronic hospital records; 
clinical and office charts; laboratory notes; memoranda; participants' diaries or 
evaluation checklists; pharmacy dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate 
copies; microfiches; photographic negatives; microfilm or magnetic media; x-rays; 
participants' files; and e-records/records kept at the pharmacy, at the laboratories, and 
at medico-technical departments involved in the clinical trial). 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, 
depending on the study. Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by the 
sponsor. 
− As required by privacy and data protection regulations and Incyte's privacy policies, 
if any photographs of participants are to be taken, the photographs must be limited to 
the area of the face or the body that is strictly necessary and the photographs should 
be masked (ie, identifying features such as eyes, mouth, scars, tattoos, or unique 
markings or features should be either obscured with a black bar or digitally pixelated 
so as to not permit the reidentification of the participants and preserve their 
confidentiality) by a specially designated photography vendor prior to sending the 
photographs to Incyte or any other third-party vendors for analysis or further 
processing. 


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• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring: Qualified representatives of the sponsor or its designee, study monitors, 
will monitor the study according to a predetermined plan. The investigator must allow 
the study monitors to review any study materials and participant records at each 
monitoring visit. 
− Auditing: Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, applicable 
local clinical study regulations, and overall study conduct. The investigator must 
allow the auditors to review original source records and study documentation for all 
participants. 
− Regulatory inspection: Regulatory authorities may conduct an inspection of the study 
and the site at any time during the development of an investigational product. The 
investigator and staff are expected to cooperate with the inspectors and allow access 
to all source documents supporting the eCRFs and other study-related documents. 
The investigator must immediately notify the sponsor when contacted by any 
regulatory authority for the purposes of conducting an inspection. 
11.3. 
Data Quality Assurance 
The sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations). The sponsor or designee is responsible for the data management of this 
study, including quality checking of the data. Further, monitoring details describing strategy, 
including definition of study-critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical 
risk-based monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues, Protocol deviations, and monitoring techniques (eg, central, remote, or 
on-site monitoring) are provided in the Monitoring Plan. 
Quality tolerance limits will be predefined in the Integrated Project Management Plan to identify 
systematic issues that can impact participants' safety, efficacy results and analysis, and/or 
reliability of study results. These predefined parameters will be monitored during the study and 
can be adjusted during the study upon data review. Important deviations from the quality 
tolerance limits and remedial actions taken, including reporting to IRBs/IECs and health 
authorities if applicable, will be summarized in the CSR. 
11.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations. The investigator and the sponsor or its designee are responsible for ensuring that 
personal information is handled in accordance with local data protection laws (including but not 
limited to HIPAA and GDPR) as applicable, and the sponsor operates comprehensive data 
privacy and data security programs that are applicable to this study. Appropriate notice, or notice 
and consent (as may be required by each applicable jurisdiction), for collection, use, disclosure, 
and/or transfer (if applicable) of personal information must be obtained in accordance with local 


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data protection laws. Appropriate data protection terms that comply with applicable laws will be 
included in relevant study agreements. 
To ensure confidentiality of records and protect personal data, 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. 
In the event of a data breach involving participant data, the sponsor or its designee will follow 
the sponsor's incident response procedures. The precise definition of a data breach varies in 
accordance with applicable law but may generally be understood as a breach of security leading 
to the accidental or unlawful destruction, loss, alteration, unauthorized disclosure of, or access to, 
personal data. In accordance with its incident response procedures, the sponsor will assess the 
breach to consider its notification and remediation obligations under applicable law. 
11.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure Form that 
sufficiently details any financial interests and arrangements that apply. For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator. These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Clinical Investigator Financial Disclosure Form. During a covered clinical 
study, any changes to the financial information previously reported by a clinical investigator 
must be reported to the sponsor or its designee. At the conclusion of the covered clinical study, 
the clinical investigators will be reminded of their obligations. In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.6. 
Publication Policy 
By signing the study Protocol, the investigator and their institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals. Study results will be published in accordance with applicable local and national 
regulations. If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement. The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee. A signed agreement will 
be retained by the sponsor or its designee. 


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The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.7. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
Agner T, Aalto-Korte K, Andersen KE, et al. Classification of hand eczema. J Eur Acad 
Dermatol Venereol 2015;29:2417-2422. 
Agner T, Andersen KE, Brandao FM, et al. Hand eczema severity and quality of life: a 
cross-sectional, multicentre study of hand eczema patients. Contact Dermatitis 2008;59:43-47. 
Agner T, Elsner P. Hand eczema: epidemiology, prognosis and prevention. J Eur Acad Dermatol 
Venereol 2020;34(suppl 1):4-12. 
Anveden I, Wrangsjö K, Järvholm B, Meding B. Self-reported skin exposure - a 
population-based study. Contact Dermatitis 2006;54:272-277. 
Bissonnette R. Efficacy and safety of delgocitinib cream in adults with moderate-to-severe 
chronic hand eczema: results of the Phase 3 DELTA 1 trial. In: Proceedings from the American 
Academy of Dermatology Annual Conference 2023; March 16 to March 21, 2023; New Orleans, 
LA. Oral presentation. 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of AD and its reversibility with 
broad-spectrum and targeted therapies. J Allergy Clin Immunol 2017;139:S65-S76. 
Caroe TK, Ebbehoj N, Agner T. A survey of exposures related to recognized occupational 
contact dermatitis in Denmark in 2010. Contact Dermatitis 2014;70:56-62. 
Chapman S, Kwa M, Gold LS, et al. Janus kinase inhibitors in dermatology: part I. 
A comprehensive review. J Am Acad Dermatol 2022;86:406-413. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Coenraads P-J. Hand eczema. N Engl J Med 2012;367:1829-1837. 
Cortesi PA, Scalone L, Belisari A, et al. Cost and quality of life in patients with severe chronic 
hand eczema refractory to standard therapy with topical potent corticosteroids. Contact 
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Crane MM, Webb DJ, Watson E, Cunliffe T, English J. Hand eczema and steroid-refractory 
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de Jongh CM, John SM, Bruynzeel DP, et al. Cytokine gene polymorphisms and susceptibility to 
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Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin 
identifies allergen-dependent differences in immune response. J Allergy Clin Immunol 
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Diepgen TL, Andersen KE, Brandao FM, et al. Hand eczema classification: a cross-sectional, 
multicentre study of the aetiology and morphology of hand eczema. Br J Dermatol 
2009;160:353-358. 


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Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and 
treatment of hand eczema. J Dtsch Dermatol Ges 2015;13:e1-e22. 
Dublin C, Del Duca E, Guttman-Yassky E. Drugs for the treatment of chronic hand eczema: 
successes and key challenges [erratum in Ther Clin Risk Manag 2021;17:233]. Ther Clin Risk 
Manag 2020;16:1319-1332. 
English J. Impact of CHE on society and the patient. J Eur Acad Dermatol Venereol 
2010;24(suppl 3):3-5. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) — a simple practical measure for 
routine clinical use. Clin Exp Dermatol 1994;19:210-216. 
Gittler JK, Krueger JG, Guttman-Yassky E. Atopic dermatitis results in intrinsic barrier and 
immune abnormalities: implications for contact dermatitis. J Allergy Clin Immunol 
2013;131:300-313. 
Graham-Brown R. Benefits and limitations of current treatment strategies. J Eur Acad Dermatol 
Venereol 2010;24(suppl 3):5-6. 
Held E, Skoet R, Johansen JD, Agner T. The hand eczema severity index (HECSI): a scoring 
system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability. Br 
J Dermatol 2005;152:302-307. 
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level 
version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727-1736. 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. E9: Statistical Principles 
for Clinical Trials. 1998. 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. E9 (R1): Statistical 
Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials. 
2021. 
Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand 
eczema. Dermatol Ther 2019;32:e12840. 
Leonard A, Guttman-Yassky E. The unique molecular signatures of contact dermatitis and 
implications for treatment. Clin Rev Allergy Immunol 2019;56:1-8. 
Lysdal SH, Søsted H, Andersen KE, Johansen JD. Hand eczema in hairdressers: a Danish 
register-based study of the prevalence of hand eczema and its career consequences. Contact 
Dermatitis 2011;65:151-158. 
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of 
disease. J Natl Cancer Inst 1959;22:719-748. 


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Menné T, Johansen JD, Sommerlund M, Veien NK. Hand eczema guidelines based on the 
Danish guidelines for the diagnosis and treatment of hand eczema. Contact Dermatitis 
2011;65:3-12. 
Ofenloch RF, Weisshaar E, Dumke A-K, Molin S, Diepgen TL, Apfelbacher C. The Quality of 
Life in Hand Eczema Questionnaire (QOLHEQ): validation of the German version of a new 
disease-specific measure of quality of life for patients with hand eczema. Br J Dermatol 
2014;171:304-312. 
Opzelura (ruxolitinib cream) [prescribing information]. Incyte Corporation; July 2022. 
Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the 
treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am 
Acad Dermatol 2021;85:863-872. 
Pedersen MB, Skov L, Menné T, Johansen JD, Olsen J. Gene expression time course in the 
human skin during elicitation of allergic contact dermatitis. J Invest Dermatol 
2007;127:2585-2595. 
Reilly MC, Lavin PT, Kahler KH, Pariser DM. Validation of the Dermatology Life Quality 
Index and the Work Productivity and Activity Impairment–Chronic Hand Dermatitis 
questionnaire in chronic hand dermatitis. J Am Acad Dermatol 2003;48:128-130. 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. Pharmacoeconomics 1993;4:353-365. 
Ruff SMD, Engebretsen KA, Zachariae C, et al. The association between atopic dermatitis and 
hand eczema: a systematic review and meta-analysis. Br J Dermatol 2018;178:879-888. 
Ruxolitinib Cream Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Silvestre Salvador JF, Heras Mendaza F, Hervella Garcés M, et al. Guidelines for the diagnosis, 
treatment, and prevention of hand eczema. Actas Dermosifiliogr (Engl Ed) 2020;111:26-40. 
Tauber M, Bérard E, Lourari S, et al. Latent class analysis categorizes chronic hand eczema 
patients according to skin barrier impairment. J Eur Acad Dermatol Venereol 
2020;34:1529-1535. 
Thyssen JP, Johansen JD, Linneberg A, Menné T. The epidemiology of hand eczema in the 
general population – prevalence and main findings. Contact Dermatitis 2010;62:75-87. 
Thyssen JP, Silverberg JI, Guttman-Yassky E. Chronic hand eczema understanding has 
ramifications on clinical management. J Eur Acad Dermatol Venereol 2020;34:e346-e432. 
Ungar B, Correa da Rosa J, Shemer A, et al. Patch testing of food allergens promotes Th17 and 
Th2 responses with increased IL-33: a pilot study. Exp Dermatol 2017;26:272-275. 
Veien NK, Hattel T, Laurberg G. Hand eczema: causes, course, and prognosis I. Contact 
Dermatitis 2008;58:330-334. 
Worm M, Bauer A, Elsner P, Mahler V, Molin S, Nielsen TSS. Efficacy and safety of topical 
delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, 
vehicle-controlled phase IIa study. Br J Dermatol 2020;182:1103-1110. 


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Worm M, Thyssen JP, Schliemann S, et al. The pan-JAK inhibitor delgocitinib in a cream 
formulation demonstrates dose response in chronic hand eczema in a 16-week randomized phase 
IIb trial. Br J Dermatol 2022;187:42-51. 


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


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


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APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical trials. The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the investigational 
product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the trial. Because of this risk and 
in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines 
In addition to the remote visits already specified in the Protocol, the evolving situation of the 
pandemic may require further travel restrictions and isolation requirements, or the investigator's 
benefit/risk assessment may determine it to be unsafe for participants to attend study visits at the 
investigational site. In such cases, the site staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (telephone or video calls). At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed. Periodic on-site visits 
should be conducted whenever feasible, in addition to the mandatory on-site visits 
outlined below. 
• No efficacy assessments can be performed via telemedicine (video call or phone call). 
• Laboratory sampling: In order to support investigator oversight of participant safety 
and disease management, off-site laboratory sampling (in accordance with the SoA, 
see Table 3) may be allowed in 1 of 2 ways: 
− Use of home nursing services. 
− Instruction of the participant to undergo some laboratory tests at a local (nearby) 
hospital laboratory or facility closer to the participant's residence rather than at the 
investigational site. In this case, the study physician will provide the participant 
with the list of parameters to be checked. These tests should be performed at 
certified laboratories and copies of results provided to the site. 


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Mandatory On-Site Visits 
The visits outlined below must be performed in person in order to capture the investigator's 
efficacy assessments and the patient-reported outcomes, even if the date that the participant 
eventually comes into the clinic deviates from the visit window. 
No efficacy assessments can be performed via telemedicine (video call, telephone call, or 
photography). 
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic. Further instructions 
will be provided if needed. 
During the placebo-controlled period, the following visits must be performed in person: 
• Screening 
• Day 1 (baseline) 
• Week 4, 8, and 16 visits 
During the extension period, the following visits must be performed in person: 
• Week 32 visit 
Investigational Medicinal Product Dispensing and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug via shipment 
to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study drug 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant. 
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment or maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the study site monitor will continue to employ off-site monitoring practices such as 
routine communication methods (eg, telephone calls, e-mails, or video visits) with the sites to get 
information on trial progress, participant status, and information on issue resolution. The study 
monitor may remotely review data entered into the EDC for accuracy and completeness. If 
allowed by local regulations, remote source data verification may be implemented with 
agreement of the principal investigator and institution, as applicable. 
If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 


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training. The study drug can be returned to the sponsor by the hospital pharmacy directly or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Other Considerations 
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight. In such situations, the investigator is required to provide the 
local physician with a delegation letter listing all delegated activities. The sponsor, through the 
study investigator or institution, will reimburse the local physician for the tests/procedures 
conducted outside of the standard of care. 
• In case of need, participants may refer to the local health care provider. Participants 
will be requested to obtain certified copies of the source data at the local health 
facility with the outcome of the contact and provide those to the investigator for 
appropriate oversight. The investigator/delegate will be requested to enter any 
relevant information into the EDC. 
• Should COVID-19–related restrictions be localized and have an effect on a limited 
number of sites, the affected sites may utilize direct contracting of third parties to 
support continuous study conduct (eg, home nursing services or couriers). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s] or the 
costs of local [nearby] laboratory tests). 


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APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
19 APR 2023 
Amendment 1 (19 APR 2023) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to increase the sample size and to remove the exit 
interview substudy. Additional changes are summarized below. 
1. Section 1, Protocol Summary (Table 2: Key Study Design Elements; Figure 1: Study 
Design Schema); Section 4.1, Overall Design; Section 10.1, Sample Size 
Determination (Table 9: Powering for Primary and Key Secondary Endpoints) 
Description of change: Increased sample size and updated the powering for endpoints. 
Rationale for change: Per recent results from a Phase 3 study of topical delgocitinib in 
CHE, the sample size was increased to detect the difference in response rates between 
ruxolitinib 1.5% cream and the vehicle cream. 
2. Section 1, Protocol Summary (Table 3: Schedule of Activities); 
 
 
Description of change: 
 
Rationale for change: Per sponsor decision. 
3. Section 1, Protocol Summary (Table 3: Schedule of Activities) 
Description of change: Removed photography from Week 2 and added to Week 4 visit. 
Rationale for change: Per sponsor decision. 
4. Incorporation of administrative changes. Other administrative changes have been 
incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-022379 v2.0
Signature Page for VV-CLIN-022379 v2.0
Approval Task
Approver
19-Apr-2023 21:39:52 GMT+0000
Approval Task
Approver
19-Apr-2023 22:30:22 GMT+0000
Approval Task
Approver
19-Apr-2023 23:26:22 GMT+0000
Approval Task
Approver
20-Apr-2023 12:37:11 GMT+0000
Approval Task
Approver
21-Apr-2023 14:57:56 GMT+0000

SAP_001.pdf: 
Official Title: 
A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, 
Efficacy and Safety Study of Ruxolitinib Cream Followed by an 
Open-Label Extension Period in Adults With Chronic Hand Eczema 
NCT Number: 
NCT05906628 
Document Date: 
INCB 18424-226 Statistical Analysis Plan 29 MAY 2024 
 
 
 


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Statistical Analysis Plan 
TITLE PAGE 
 
 
INCB 18424-226 
A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, 
Efficacy and Safety Study of Ruxolitinib Cream Followed by an 
Open-Label Extension Period in Adults With Chronic Hand Eczema 
 
IND Number: 
77101 
EU CT Number: 
2022-502817-23-00 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
INCB 18424-226 Protocol Amendment 1 dated 19 APR 2023 
CRF Approval Date: 
24 FEB 2024 
SAP Version: 
Original 
SAP Author: 
 
Principal Biostatistician, Biostatistics 
Date of Plan: 
29 MAY 2024 
 
 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
3. 
STUDY DESIGN .......................................................................................................10 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................11 
3.3. 
Sample Size Considerations .......................................................................................11 
3.4. 
Schedule of Assessments ............................................................................................11 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................12 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................12 
4.1.1. 
Day 1 ...........................................................................................................................12 
4.1.2. 
Study Day ...................................................................................................................12 
4.1.3. 
Baseline Value ............................................................................................................12 
4.1.4. 
Last Available Value ..................................................................................................13 
4.1.5. 
Handling of Missing and Incomplete Dates ...............................................................13 
4.2. 
Variable Definitions ....................................................................................................13 
4.2.1. 
Body Mass Index ........................................................................................................13 
4.2.2. 
Prior and Concomitant Medication .............................................................................13 
5. 
STATISTICAL METHODOLOGY ...........................................................................14 
5.1. 
General Methodology .................................................................................................14 
5.2. 
Treatment Groups .......................................................................................................14 
5.3. 
Analysis Populations ..................................................................................................14 
5.3.1. 
Intent-to-Treat Population ...........................................................................................14 
5.3.2. 
Safety Population ........................................................................................................14 
5.3.3. 
Open-Label Evaluable Population ..............................................................................14 
5.3.4. 
Pharmacodynamic-Evaluable Population ...................................................................15 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................16 


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6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................16 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................16 
6.1.2. 
Baseline Disease Characteristics ................................................................................16 
6.1.3. 
Prior Therapy for Chronic Hand Eczema ...................................................................17 
6.1.4. 
Medical History ..........................................................................................................17 
6.2. 
Disposition of Participant ...........................................................................................17 
6.3. 
Protocol Deviations ....................................................................................................17 
6.4. 
Exposure .....................................................................................................................17 
6.5. 
Study Drug Compliance .............................................................................................17 
6.6. 
Prior and Concomitant Medication .............................................................................18 
7. 
EFFICACY .................................................................................................................19 
7.1. 
General Considerations ...............................................................................................19 
7.2. 
Efficacy Hypotheses ...................................................................................................19 
7.3. 
Analysis of the Primary Efficacy Parameters .............................................................19 
7.3.1. 
Primary Efficacy Measures .........................................................................................19 
7.3.1.1. 
Investigator's Global Assessment–Chronic Hand Eczema .........................................19 
7.3.2. 
Primary Efficacy Analyses .........................................................................................19 
7.3.3. 
Subgroup Analyses for Primary Endpoints ................................................................20 
7.4. 
Analysis of the Secondary Efficacy Parameters .........................................................20 
7.4.1. 
Key Secondary Efficacy Measure ...............................................................................20 
7.4.1.1. 
Chronic Hand Eczema-Related Itch Numerical Rating Scale Score ..........................20 
7.4.2. 
Key Secondary Efficacy Analysis ..............................................................................21 
7.5. 
Analysis of Secondary Efficacy Parameters ...............................................................22 
7.5.1. 
Secondary Efficacy Measure ......................................................................................22 
7.5.1.1. 
Hand Eczema Severity Index Score ...........................................................................22 
7.5.1.2. 
Chronic Hand Eczema-Related Skin Pain Numerical Rating Scale Score .................22 
7.5.1.3. 
Patient Global Impression of Change .........................................................................22 
7.5.1.4. 
Dermatology Life Quality Index ................................................................................23 
7.5.1.5. 
EQ-5D-5L ...................................................................................................................23 
7.5.1.6. 
Quality of Life in Hand Eczema Questionnaire .........................................................24 
7.5.1.7. 
Work Productivity and Activity Impairment Questionnaire Specific Health 
Problem v2.0 in Chronic Hand Eczema .....................................................................26 
7.5.2. 
Secondary Efficacy Analysis ......................................................................................26 


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7.5.2.1. 
Continuous Efficacy Endpoints ..................................................................................27 
7.5.2.2. 
Categorical Efficacy Endpoints ..................................................................................27 
7.5.2.3. 
Time-To-Event Efficacy Endpoints ............................................................................27 
7.6. 
Analysis of Exploratory Efficacy Parameters .............................................................28 
7.6.1. 
Exploratory Efficacy Analysis ....................................................................................28 
8. 
PHARMACODYNAMICS ........................................................................................29 
8.1. 
Pharmacodynamic Analyses .......................................................................................29 
9. 
SAFETY AND TOLERABILITY ..............................................................................29 
9.1. 
General Considerations ...............................................................................................29 
9.2. 
Adverse Events ...........................................................................................................29 
9.2.1. 
Adverse Event Definitions ..........................................................................................29 
9.2.2. 
Adverse Event Summaries ..........................................................................................30 
9.3. 
Clinical Laboratory Tests ...........................................................................................31 
9.3.1. 
Laboratory Value Definitions .....................................................................................31 
9.3.2. 
Laboratory Value Summaries .....................................................................................31 
9.4. 
Vital Signs ..................................................................................................................32 
10. 
INTERIM ANALYSES ..............................................................................................32 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................33 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................33 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................33 
12. 
REFERENCES ...........................................................................................................34 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................35 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Powering for Primary and Key Secondary Endpoints ................................................11 
Table 3: 
Investigator's Global Assessment-Chronic Hand Eczema ..........................................19 
Table 4: 
Summary of Primary Analysis....................................................................................20 
Table 5: 
Summary of Analyses for Key Secondary Endpoints ................................................21 
Table 6: 
Scoring of Quality of Life in Hand Eczema Questionnaire ........................................24 
Table 7: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................32 
Table 8: 
Statistical Analysis Plan Versions ..............................................................................33 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................10 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AD 
atopic dermatitis 
AE 
adverse event 
ASR 
application site reaction 
BID 
twice daily 
BMI 
body mass index 
BSA 
body surface area 
CHE 
chronic hand eczema 
CI 
confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBVC 
double-blind vehicle-controlled 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic Case Report Form 
ET 
early termination 
HE 
hand eczema 
HECSI 
Hand Eczema Severity Index 
IGA 
Investigator's Global Assessment 
IGA-CHE 
Investigator's Global Assessment-Chronic Hand Eczema 
IGA-CHE-TS 
Investigator's Global Assessment-Chronic Hand Eczema Treatment Success 
ITCH4 
≥ 4-point improvement in ITCH score 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
multiple imputation 
NCI 
National Cancer Institute 
NRS 
numerical rating scale 
OLE 
open-label extension 
PD 
pharmacodynamic(s) 
PGIC 
Patient Global Impression of Change 
PT 
preferred term 
QOLHEQ 
Quality of Life in Hand Eczema Questionnaire 
SAP 
Statistical Analysis Plan 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
VAS 
visual analog scale 
WPAI-ChHD 
Work Productivity and Activity Impairment Questionnaire v2.0 in Chronic 
Hand Dermatitis 


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1. 
INTRODUCTION 
This is a randomized, 16-week, double-blind, vehicle-controlled study with a 16-week open-label 
treatment extension period in participants with moderate to severe CHE with no history of 
(within the past 5 years) or current AD. Participants will be randomized 1:1 to ruxolitinib 1.5% 
cream BID or vehicle cream BID, with stratification by baseline IGA-CHE score and region. 
Participants will receive blinded study treatment (ruxolitinib 1.5% cream BID or vehicle) for 
16 weeks (DBVC period). All participants continuing in the OLE period will receive ruxolitinib 
1.5% cream BID and affected areas will be treated as needed until they clear. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the study Protocol. The Department of Biostatistics or designee will execute the scope of this 
plan. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 18424-226 Protocol Amendment 1 dated 19 APR 2023 and CRFs 
approved 24 FEB 2024. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of ruxolitinib 1.5% cream 
BID in participants with CHE. 
• IGA-CHE-TSa at Week 16. 
Key Secondary 
To further assess the treatment effects of ruxolitinib 
1.5% cream BID in participants with CHE. 
• ITCH4b response at Week 16. 
• ITCH4b response at Week 4. 
• ITCH4b response at Week 1 (Day 7). 
Secondary 
To further evaluate the efficacy of ruxolitinib 1.5% 
cream BID. 
• IGA-CHE-TS at each postbaseline visit. 
• ITCH4b response at Day 3. 
• Change from baseline in CHE-related Itch NRS 
score at each postbaseline visit. 
• Time to ≥ 4-point improvement from baseline in 
CHE-related Itch NRS score. 
• Change from baseline in CHE-related Skin Pain 
NRS score at each postbaseline visit. 
• Achieving ≥ 2-point improvement in CHE-related 
Skin Pain NRS score from baseline to Week 16. 
• Time to ≥ 2-point improvement from baseline in 
CHE-related Skin Pain NRS score. 
• Percentage change in HECSI from baseline to 
Week 16. 
• PGIC score at each postbaseline visit. 
To evaluate the participants' quality of life and other 
patient-reported outcomes. 
• Change from baseline in DLQI score at Weeks 2, 4, 
8, 12, 16, 24, and 32. 
• Change from baseline in EQ-5D-5L score at 
Weeks 2, 4, 8, 12, 16, 24, and 32. 
• Change from baseline in QOLHEQ score at 
Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up. 
• Change from baseline in WPAI-ChHD score at 
Weeks 2, 4, 8, 12, 16, 24, 32, and follow-up. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
To evaluate the safety and tolerability of ruxolitinib 
1.5% cream BID. 
• The type, frequency, and severity of AEs as well as 
changes in vital signs and laboratory data for 
hematology and serum chemistry. 
Exploratory 
a IGA-CHE-TS is defined as an IGA-CHE score of 0 or 1 with ≥ 2-grade improvement from baseline. 
b ITCH4 response is defined as a ≥ 4-point improvement in CHE-related Itch NRS score from baseline. 


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3.
STUDY DESIGN
This is a Phase 2, randomized, double-blind, vehicle-controlled, 16-week study followed by a 
16-week open-label treatment extension period. Approximately 180 participants with moderate
to severe CHE with no history of (within the past 5 years) or current AD will be randomized 
1:1 to either ruxolitinib 1.5% cream or vehicle cream. Participants will apply either ruxolitinib 
1.5% cream or vehicle cream (both BID) to CHE lesions on the hands and wrists (if applicable) 
for 16 weeks. All areas identified at baseline should continue to be treated through the end of the 
DBVC period (Week 16) unless the participant meets criteria for stopping study drug.
At Week 16, participants with no safety concerns will enter the 16-week OLE period, during 
which all participants will receive open-label ruxolitinib 1.5% cream. Affected areas will be 
treated as needed until they clear during the OLE period.
Participants, investigators, and the sponsor will be blinded to each participant's treatment 
assignment during the DBVC period. During the OLE period, participants and investigators will 
remain blinded to the treatment assignment during the DBVC period until after all participants 
have completed treatment or discontinued and completed the safety follow up period.
Figure 1 presents the study design schema.
Figure 1:
Study Design Schema
3.1.
Randomization
In the DBVC period, participants will be randomized 1:1 either to ruxolitinib 1.5% cream BID or 
vehicle cream BID. Additionally, participants will be stratified by baseline IGA-CHE score (3 or
4) and region (North America or outside of North America).


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3.2. 
Control of Type I Error 
The gatekeeping testing strategy for the primary and key secondary analyses will be 
implemented to control the overall Type I error rate, 2-sided α = 0.05. These endpoints will be 
tested in a fixed sequence at 2-sided α = 0.05 level in the following order: 
• IGA-CHE-TS at Week 16 
• ITCH4 response at Week 16 
• ITCH4 response at Week 4 
• ITCH4 response at Week 1 (Day 7) 
3.3. 
Sample Size Considerations 
Approximately 180 participants will be randomized 1:1 to ruxolitinib 1.5% cream BID or vehicle 
cream BID. 
The sample size is calculated to provide sufficient power (> 80%) to detect a difference between 
ruxolitinib 1.5% cream BID and vehicle cream BID for the primary and key secondary 
endpoints. The powers for different endpoints are provided in Table 2. The chi-square test with a 
2-sided α of 0.05 is used to calculate the powers. 
In addition to providing sufficient power for efficacy variables, the sample size is determined to 
provide an adequate database for safety evaluations. 
Table 2: 
Powering for Primary and Key Secondary Endpoints 
Variables 
Response Rates With 
Ruxolitinib 1.5% Cream BID 
Response Rates 
With Vehicle Cream BID 
Power 
IGA-CHE-TS at Week 16 
26%a,b 
10%a,b,c 
80% 
ITCH4 at Week 16 
40%b,c 
18%b,c 
90% 
ITCH4 at Week 4 
35%b,c 
12%b,c 
95% 
ITCH4 on Day 7 
30%b,c 
10%b,c 
92% 
a Based on the results from a Phase 2b study of topical delgocitinib in CHE (Worm et al 2022). 
b Based on the results from a Phase 3 study of topical delgocitinib in CHE (Bissonnette 2023). 
c Based on the results from the 2 Phase 3 registrational AD studies, INCB 18424-303 and INCB 18424-304. 
3.4. 
Schedule of Assessments 
Refer to INCB 18424-226 Protocol Amendment 1 dated 19 APR 2023 for a full description of all 
study procedures and assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first application of ruxolitinib cream or vehicle cream is administered to 
the participants. 
For randomized participants not treated with any study drug, Day 1 is defined as the day of 
randomization. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before or on the day of first application of 
ruxolitinib cream or vehicle cream for DBVC period. 
For randomized participants not treated with any study drug, baseline is defined as the last 
nonmissing assessment before or on the day of randomization for all parameters. 
For participants who continue in the OLE period, baseline for OLE is defined as follows: 
• For efficacy evaluation, baseline is the last nonmissing measurement obtained before 
or on the day of first application of study treatment in DBVC period. 
• For safety evaluation, for participants who cross over from vehicle group to 
ruxolitinib cream, the baseline is the last nonmissing measurement obtained before or 
on the day of first application of ruxolitinib cream in the OLE period; for participants 
on ruxolitinib cream in both periods, baseline is the last nonmissing measurement 
obtained before or on the day of first application of study treatment in DBVC period. 


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When scheduled assessments and unscheduled assessments occur on the same day and time of the 
assessment or time of first application is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first 
application and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first application and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Last Available Value 
The last available value is the last nonmissing measurement obtained after starting ruxolitinib 
cream or vehicle cream and within 30 days after the last application of ruxolitinib cream or 
vehicle cream, or before the first application of ruxolitinib cream in the next period, whichever is 
earlier. 
4.1.5. 
Handling of Missing and Incomplete Dates 
Methods for handling missing dates are specified in relevant sections. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
Body mass index (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first application of study 
treatment. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first application of study treatment and is ongoing throughout the 
study or ends on/after the date of first application of study treatment. 
• On/after the date of first application of study treatment and is ongoing or ends during 
the course of study treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after the first application of study treatment. In the listing, it will be indicated whether 
a medication is prior-only, concomitant-only, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9 or later) will be used 
for the generation of all tables, graphs, and statistical analyses. Descriptive summaries for 
continuous variables will include but not be limited to the number of observations, mean, 
standard deviation, median, minimum, maximum, first quartile, third quartile, and 95% CI. 
Descriptive summaries for categorical variables will include the number and percentage of 
participants in each category. 
5.2. 
Treatment Groups 
This is a randomized, DBVC study followed by an OLE period. Data will be summarized based 
on treatment regimen that was assigned (ITT) or that the participant actually applied (safety). 
For analyses in the ITT population and safety population, the treatment groups will be ruxolitinib 
1.5% cream BID and vehicle cream BID. 
For analyses in the open-label evaluable population, the treatment groups will be ruxolitinib 1.5% 
cream BID and vehicle cream BID to ruxolitinib 1.5% cream BID. 
5.3. 
Analysis Populations 
5.3.1. 
Intent-to-Treat Population 
All participants who are randomized to the study will constitute the ITT population. Treatment 
groups for this population will be defined according to the treatment assignment at the time of 
randomization regardless of the actual study treatment the participant might apply during their 
participation in the study. 
The ITT population will be used for the summary of demographics, baseline characteristics, 
participant disposition, and analyses of all efficacy data. 
5.3.2. 
Safety Population 
All randomized participants who applied study treatment at least once will constitute the safety 
population. Treatment groups for this population will be determined according to the actual 
treatment the participant applied on Day 1 regardless of assigned study treatment. 
All safety analyses in the DBVC period and throughout the study (from baseline to Week 32) will 
be conducted using the safety population. 
5.3.3. 
Open-Label Evaluable Population 
All participants who applied study treatment at least once during the OLE period will constitute 
the open-label evaluable population. All safety analyses for the OLE period will be conducted 
with the open-label evaluable population. 


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5.3.4. 
Pharmacodynamic-Evaluable Population 
The PD evaluable population includes participants who applied study treatment at least once and 
provided baseline PD sample and at least 1 postbaseline PD sample for analysis. The study 
translational scientist will review data listings of participant administration and sample records to 
identify participants to be excluded from the analysis. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics will be summarized for the ITT population during the DBVC period 
and open-label evaluable population in OLE period: age, age group, sex, race, ethnicity, weight, 
height, and BMI. 
6.1.2. 
Baseline Disease Characteristics 
Baseline disease characteristics summarized for the ITT population during the DBVC period 
include but are not limited to the following: 
• Time since initial diagnosis of CHE 
• Prior history of asthma (no/yes) 
• Prior allergies (food, conjunctivitis, rhinitis) (no/yes) 
• History of AD more than 5 years ago (no/yes) 
• Type of CHE 
• Diagnostic patch test result in the past 3 years (positive, negative, not available) 
• CHE related to occupational factors (no/yes) 
• Type of occupation if CHE related to occupational factor is yes 
• History of skin infection on hands (including wrists) related to CHE requiring 
antibiotic treatment (no/yes) 
• Time since onset of current CHE flare 
• Number of CHE flares in the last 12 months 
• Prior therapies for CHE received (no/yes) 
• Contraindication to oral alitretinoin within the last 12 months (no/yes) 
• Skin type using Fitzpatrick classification 
• Total %BSA affected with CHE in current flare 
• Baseline IGA-CHE score (3, 4) 
• Baseline CHE-related Itch NRS score (by visit and daily) 
• Baseline CHE-related Skin Pain NRS score (by visit and daily) 


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6.1.3. 
Prior Therapy for Chronic Hand Eczema 
Prior therapies for CHE which include medication and other type of therapies will be coded 
using the WHO Drug Dictionary and summarized by treatment group. The type of treatment and 
reason for discontinuation will be summarized as well. 
6.1.4. 
Medical History 
For participants in the ITT Population during the DBVC period, medical history will be 
summarized and listed by assigned treatment groups. This summation will include the number 
and percentage of participants with medical history event for each body system/organ class as 
documented on the eCRF. 
6.2. 
Disposition of Participant 
The number and percentage of participants who were randomized, treated, and completed the 
DBVC period and of participants who discontinued the treatment or withdrew from the study 
during the DBVC period with a primary reason for discontinuation will be summarized for ITT 
population during the DBVC period. 
The number and percentage of participants who completed the OLE period and discontinued 
treatment or withdrew from the study during the OLE period with a primary reason for 
discontinuation will be summarized for the open-label evaluable population in the OLE period. 
6.3. 
Protocol Deviations 
Protocol deviations will be summarized by treatment groups in the DBVC and OLE periods, 
separately. 
6.4. 
Exposure 
For participants in the safety population during the DBVC period and open-label evaluable 
population in OLE period, descriptive statistics will be provided. That is, by treatment group for 
duration of treatment, average daily amount of cream applied (g), and total amount of cream 
applied (g). Duration of treatment with ruxolitinib cream or vehicle cream is defined as the 
number of days from Day 1 to the last record of ruxolitinib cream or vehicle cream application in 
the specific period. 
6.5. 
Study Drug Compliance 
Overall compliance (%) for the application of ruxolitinib cream or vehicle cream during the 
DBVC period will be calculated for all participants in the safety population as follows: 
overall application compliance (%) = 100 × [total number of nonmissing applications] / [total 
number of intended applications], 
where the total number of nonmissing applications is the total number of applications that the 
participant actually applied during the study. The total number of intended applications is the 
number of planned applications minus the number of interrupted applications. 


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6.6. 
Prior and Concomitant Medication 
For participants in the ITT population during the DBVC period, prior medications and 
concomitant medications will be coded using the WHO Drug Dictionary and summarized as 
number and percentage of participants with prior and concomitant medications by WHO drug 
class and WHO drug term. For participants in the OLE period, only concomitant medications 
will be summarized. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
General Considerations 
For all continuous variables, both the actual value and change and/or percentage from baseline (if 
available) will be analyzed. 
All by-visit analyses will include the safety follow-up period if the data are available. 
7.2. 
Efficacy Hypotheses 
Not applicable. 
7.3. 
Analysis of the Primary Efficacy Parameters 
7.3.1. 
Primary Efficacy Measures 
7.3.1.1. 
Investigator's Global Assessment–Chronic Hand Eczema 
The IGA-CHE is an overall eczema severity rating on a 0 to 4 scale that will be assessed during 
site visits. The grades for the IGA-CHE are shown in Table 3. 
Table 3: 
Investigator's Global Assessment-Chronic Hand Eczema 
Grade 
Severity 
Features 
Intensity 
0 
Clear 
Erythema, scaling, hyperkeratosis/lichenification 
Absent 
Vesiculation, edema, fissures 
Absent 
1 
Almost 
clear 
Erythema, scaling, hyperkeratosis/lichenification 
At least 1 mild 
Vesiculation, edema, fissures 
Absent 
2 
Mild 
Erythema, scaling, hyperkeratosis/lichenification 
At least 1 mild 
Vesiculation, edema, fissures 
At least 1 mild 
3 
Moderate 
Erythema, scaling, hyperkeratosis/lichenification 
At least 1 mild or moderate 
Vesiculation, edema, fissures 
At least 1 moderate 
4 
Severe 
Erythema, scaling, hyperkeratosis/lichenification 
At least 1 moderate or severe 
Vesiculation, edema, fissures 
At least 1 severe 
Source: Adapted from Ruzicka et al 2008. 
The IGA-CHE-TS is defined as an IGA-CHE score of 0 or 1 with ≥ 2 grade improvement from 
baseline. 
7.3.2. 
Primary Efficacy Analyses 
The key parameters for the primary analysis are provided in Table 4. The primary analysis will 
be based on the ITT population in the DBVC period. The primary alternative hypothesis 
(superiority of active ruxolitinib 1.5% cream BID compared with vehicle) will be tested at a 
2-sided α = 0.05 level using a CMH test stratified by stratification factors IGA-CHE score (3 or 
4) and region (North America or outside of North America). The p-value and overall odds ratio 


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with 95% CI will be provided. Summary of IGA-CHE-TS rates will be reported for each 
treatment group. Stratum-adjusted IGA-CHE-TS rate difference (1.5% BID vs vehicle) and 
95% CI will be computed using Mantel-Haenszel weights (Mantel and Haenszel 1959). 
Table 4: 
Summary of Primary Analysis 
Parameter 
Definition 
Treatment 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population 
ITT Population 
Variable 
IGA-CHE-TS at Week 16: Defined as an IGA-CHE score of 0 or 1 with ≥ 2 grade 
improvement from baseline 
Population-level summary 
Stratum-adjusted IGA-CHE-TS rate difference with 95% CI 
All nonresponders during the DBVC period, as well as all participants missing Week 16 
assessment and who discontinue study treatment at any time before Week 16, or discontinue 
from the study for any reason, will be defined as nonresponders for the nonresponder imputation 
analysis. 
7.3.3. 
Subgroup Analyses for Primary Endpoints 
Subgroup analysis will be performed based on the following participant demographics and 
baseline disease characteristics variables for those participants whose data are available: 
• Baseline IGA-CHE score (3, 4) 
• Age (≥ 18 to 64, ≥ 65 years) 
• Sex (male, female) 
• Race 
• Region (North America or outside of North America) 
7.4. 
Analysis of the Secondary Efficacy Parameters 
7.4.1. 
Key Secondary Efficacy Measure 
7.4.1.1. 
Chronic Hand Eczema-Related Itch Numerical Rating Scale Score 
The CHE-related Itch NRS is a once-per-24 hours ("daily") patient-reported measure of the worst 
itch severity of their CHE assessed using an 11-point scale (0 = no itch to 10 = worst imaginable 
itch). Participants reported their worst itch severity in the evening beginning on the day of 
screening through Week 32 or ET. 
The CHE-related Itch NRS score for baseline will be determined by averaging the 7 daily NRS 
scores before Day 1 (Day –7 to Day –1). The by-visit CHE-related Itch NRS score for 
postbaseline visits will be determined by averaging the 7 daily NRS scores before the visit day. 
If 4 or more daily scores are missing (out of the 7), the CHE-related Itch NRS score at the visit 
will be set to missing. For all daily itch related analyses including time to achieve Itch NRS score 
improvement of at least 2 or 4 points, baseline will be defined as the last available Itch NRS 
score during the last week prior to Day 1 (from Day −7 to Day −1). 


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The proportion of participants with a clinically relevant change in CHE-related itch (ITCH4), 
defined as a ≥ 4-point improvement in CHE-related Itch NRS score from baseline, will be 
summarized by treatment groups. 
7.4.2. 
Key Secondary Efficacy Analysis 
Key secondary efficacy analyses will be conducted in the ITT population in the DBVC period. If 
the primary objective is achieved, the statistical comparisons for key secondary endpoints will be 
tested with the procedures specified in Section 3.2. The same nonresponder imputation method 
as specified in the primary analysis will be used to handle missing Week 4 and Week 16 itch 
data. 
For the key secondary endpoints of ITCH4 at Week 1 (Day 7), all participants who are missing 
Day 7 daily Itch NRS scores will be imputed using multiple imputation by fully conditional 
specification method. The variables to be included in the imputation regression model are 
treatment group, stratification factor, baseline itch score, and postbaseline daily itch score on 
Day 1 to Day 7. The corresponding binary response on Day 7 will be derived for each of the 
imputed datasets per the definition in Section 7.4.1.1. 
The following sample SAS code will be used for the MI: 
proc mi data=mi_wide seed=18424226 nimpute=30 out=impute_itch; 
class trt01p strat1 strat2; 
var trt01p strat1 strat2 base avald1 avald2 avald3 avald4 avald5 
avald6 avald7; 
fcs regpmm nbiter=30; 
run; 
All key secondary efficacy analyses will use stratified CMH test similar to the primary efficacy 
analysis. The summary of key secondary endpoints analysis is also provided in Table 5. 
Table 5: 
Summary of Analyses for Key Secondary Endpoints 
Parameter 
Definition 
Treatment 
Ruxolitinib 1.5% cream compared with vehicle cream 
Population  
ITT population 
Variables 
ITCH4 response at Week 16 
ITCH4 response at Week 4 
ITCH4 response at Week 1 (Day 7) 
Population-level summary 
Stratum-adjusted IGA-CHE-TS rate difference with 95% CI 
Note 1: Participants with missing observed data at the timepoint of interest (Week 4, Week 16), participants who discontinue 
study treatment at any time before the timepoint of interest (Week 4, Week 16), and participants who discontinue from the 
study for any reason will be defined as nonresponders. Participants with missing observed data at Day 7 will be imputed using 
multiple imputation by fully conditional specification method. No rescue therapy or treatment switch is allowed in this study. 
Note 2: ITCH4 is defined as a ≥ 4-point improvement in CHE-related Itch NRS score from baseline. 


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7.5. 
Analysis of Secondary Efficacy Parameters 
7.5.1. 
Secondary Efficacy Measure 
7.5.1.1. 
Hand Eczema Severity Index Score 
The HECSI divides the hand into 5 areas for assessment (fingertips, fingers [except the tips], 
palms, back of hands, and wrists). Each of the 5 areas of the hand are assessed separately for 
erythema, induration/papulation, vesicles, fissuring, scaling, and edema using the following 
scale: 0, no skin changes; 1, mild disease; 2, moderate disease; and 3, severe disease. To 
determine the HECSI score, the affected area for each location (total of both hands) is given a 
score from 0 to 4 (0, 0%; 1, 1%-25%; 2, 26%-50%; 3, 51%-75%; and 4, 76%-100%) based on 
the extent of clinical symptoms. Finally, the score given for the extent at each location is 
multiplied by the total sum of the intensity of each clinical feature to calculate the total HECSI 
score, varying from 0 to a maximum severity score of 360 points (Held et al 2005). 
The binary variable HECSI-75 will be equal to 1 for percentage improvement from baseline in 
HECSI-75 of ≥ 75% and will be equal to 0 for percentage improvement of < 75%. Hand Eczema 
Severity Index-90 is defined with the same pattern. 
7.5.1.2. 
Chronic Hand Eczema-Related Skin Pain Numerical Rating Scale Score 
The CHE-related Skin Pain NRS is a once-per-24 hours ("daily") patient-reported measure of the 
worst skin pain severity of their CHE assessed using an 11-point scale (0 = no pain to 10 = worst 
imaginable pain), in the evening beginning on the day of screening through Week 32 or ET. 
The CHE-related Skin Pain NRS score for baseline will be determined by averaging the 7 daily 
NRS scores before Day 1 (Day –7 to Day –1). The by-visit CHE-related Skin Pain NRS score for 
postbaseline visits will be determined by averaging the 7 daily NRS scores before the visit day. 
If 4 or more daily scores are missing (out of the 7), the CHE-related Skin Pain NRS score at the 
visit will be set to missing. For all the daily pain-related analyses, baseline will be defined as the 
last available pain NRS score during the last week prior to Day 1 (from Day −7 to Day −1). 
The proportion of participants with a clinically relevant change in CHE-related Skin Pain, defined 
as a ≥ 2-point improvement in CHE-related skin pain NRS score from baseline to Week 16, will 
be summarized by treatment groups. 
7.5.1.3. 
Patient Global Impression of Change 
The PGIC is a participants' self-reporting measure that reflects their belief about the efficacy of 
treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement of 
CHE and will be captured during postbaseline visits (Hurst and Bolton 2004). 
The participant will be asked to select 1 response from the response options that best describe the 
overall change in their CHE since they started study treatment: 1) very much improved, 2) much 
improved, 3) minimally improved, 4) no change, 5) minimally worse, 6) much worse, and 
7) very much worse. Missing values will not be imputed. 


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7.5.1.4. 
Dermatology Life Quality Index 
The DLQI is a simple, 10-question validated questionnaire to measure how much the skin 
problem has affected the participant over the previous 7 days in all the scheduled visits in both 
DBVC and OLE period (Finlay and Khan 1994). 
The questionnaire is analyzed under 6 subscales as follows: 
• Symptoms and feelings (Questions 1 and 2) 
• Daily activities (Questions 3 and 4) 
• Leisure (Questions 5 and 6) 
• Work and school (Question 7) 
• Personal relations (Questions 8 and 9) 
• Treatment (Question 10) 
The scoring of each question is as follows: Very much = 3; A lot = 2; A little = 1; Not at all = 0; 
Not relevant = 0; Question 7, "Prevented work or studying" Yes = 3. 
The following imputation will be applied for incorrectly completed questionnaires: 
• If 1 question is left unanswered, this is scored 0 and the scores are summed and 
expressed as usual out of a maximum of 30. 
• If 2 or more questions are left unanswered, the questionnaire is not scored. 
• If question 7 is answered "yes," this is scored 3. If Question 7 is answered "no," but 
then either "a lot" or "a little" is ticked, this is then scored 2 or 1. If 'Not relevant" is 
ticked, the score for Question 7 is 0. If it is answered "no," but the second half is left 
incomplete, the score will remain 0. 
• For the 6 subscales, if the answer to one question in a subscale is missing, that 
subscale should not be scored. 
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a 
minimum of 0. The higher the score, the more quality of life is impaired. 
7.5.1.5. 
EQ-5D-5L 
Participants will complete the EQ-5D-5L questionnaire at the scheduled visits in DBVC and 
OLE periods. The EQ-5D-5L questionnaire is a standardized, validated instrument for use as a 
measure of health outcome (Herdman et al 2011). The EQ-5D-5L questionnaire consists of the 
following 2 sections: the EQ-5D descriptive system and the EQ VAS. 
The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1 = no problems, 
Level 2 = slight problems, Level 3 = moderate problems, Level 4 = severe problems, and 
Level 5 = extreme problems. 
The EQ VAS records the participant's self-rated health on a vertical VAS (0-100), where the 
endpoints are labeled "the best health you can imagine" (100 score) and "the worst health you 
can imagine" (0 score). 


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Missing values will not be imputed. The categorical outcomes for the 5 dimensions (mobility, 
self-care, usual activity, pain/discomfort, and anxiety/depression) will be summarized. The 
change from baseline in EQ-5D VAS score will be analyzed. 
7.5.1.6. 
Quality of Life in Hand Eczema Questionnaire 
Participants will complete the QOLHEQ at the scheduled visits in DBVC and OLE periods. The 
QOLHEQ is a validated disease-specific instrument to assess disease-specific health-related 
quality of life in participants suffering from CHE over the past 7 days (Ofenloch et al 2014). It 
consists of 30 items that are summarized according to impairments for 4 subscales: 1) symptoms, 
2) emotions, 3) limitations in functioning, and 4) treatment and prevention. Each item is scored 
in a scale of never, rarely, sometimes, often, all the time. The overall score is calculated by 
summing up all items. 
Table 6 shows the scoring for each QOLHEQ item with the item number corresponds with the 
position of the item in the QOLHEQ. 
Table 6: 
Scoring of Quality of Life in Hand Eczema Questionnaire 
Item Number 
Scoring of the item 
(never-rarely-sometimes-often-all the time) 
Symptoms 
1 
0 – 1 – 2 – 3 – 4 
6 
0 – 1 – 2 – 3 – 4 
9 
0 – 1 – 2 – 3 – 4 
11 
0 – 1 – 2 – 3 – 4 
20 
0 – 1 – 2 – 3 – 4 
23 
0 – 1 – 2 – 3 – 4 
28a 
0 – 1 – 1 – 2 – 3 
Emotions 
5 
0 – 1 – 2 – 3 – 4 
8 
0 – 1 – 2 – 3 – 4 
10a 
0 – 1 – 1 – 2 – 3 
16 
0 – 1 – 2 – 3 – 4 
19 
0 – 1 – 2 – 3 – 4 
21 
0 – 1 – 2 – 3 – 4 
27 
0 – 1 – 2 – 3 – 4 
30 
0 – 1 – 2 – 3 – 4 


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Table 6: 
Scoring of Quality of Life in Hand Eczema Questionnaire (Continued) 
Item Number 
Scoring of the item 
(never-rarely-sometimes-often-all the time) 
Limitations in functioning 
2 
0 – 1 – 2 – 3 – 4 
3 
0 – 1 – 2 – 3 – 4 
12 
0 – 1 – 2 – 3 – 4 
14 
0 – 1 – 2 – 3 – 4 
15 
0 – 1 – 2 – 3 – 4 
17 
0 – 1 – 2 – 3 – 4 
25 
0 – 1 – 2 – 3 – 4 
29 
0 – 1 – 2 – 3 – 4 
Treatment and prevention 
4a 
0 – 1 – 1 – 2 – 3 
7 
0 – 1 – 2 – 3 – 4 
13 
0 – 1 – 2 – 3 – 4 
18 
0 – 1 – 2 – 3 – 4 
22 
0 – 1 – 2 – 3 – 4 
24 
0 – 1 – 2 – 3 – 4 
26 
0 – 1 – 2 – 3 – 4 
a In general, all items are scored 0-4 and only 3 items differ in their scoring structure. 
The following imputation will be applied for incorrectly completed questionnaires 
(QOLHEQ 2024): 
• If 1 question is left unanswered, this is scored as 0 and the subscale score is 
calculated by summing up all items. 
• For the 4 subscales, if the answer to more than 1 question in a subscale is missing, 
that subscale should not be scored. 
• If 4 or more questions are left unanswered, the overall score is set to missing and 
should not be scored. 


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7.5.1.7. 
Work Productivity and Activity Impairment Questionnaire Specific Health 
Problem v2.0 in Chronic Hand Eczema 
Participants will complete the WPAI-ChHD questionnaire at the scheduled visits in DBVC and 
OLE periods. The Work Productivity and Activity Impairment Questionnaire is a 
patient-reported quantitative assessment of the amount of absenteeism, presentism, and daily 
activity impairment attributable to a specific health problem (Reilly et al 1993). The 
WPAI-ChHD is a 6-item questionnaire used to assess the impact of chronic hand dermatitis 
(ChHD, the same as CHE in this context) on job performance and productivity in the last 7 days. 
Work Productivity and Activity Impairment outcomes are expressed as impairment percentages, 
with higher numbers indicating greater impairment and less productivity, ie, worse outcomes, as 
follows: 
Questions: 
• 1 = currently employed 
• 2 = hours missed due to CHE 
• 3 = hours missed other reasons 
• 4 = hours actually worked 
• 5 = degree CHE affected productivity while working 
• 6 = degree CHE affected regular activities 
Scores: 
Multiply below scores by 100 to express in percentages (%). 
• Percent work time missed due to CHE: Q2 / (Q2 + Q4) 
• Percent impairment while working due to CHE: Q5 / 10 
• Percent overall work impairment due to CHE: [Q2 / (Q2 + Q4)] + ({1 – [Q2 / 
(Q2 + Q4)]} × [Q5 / 10]) 
• Percent activity impairment due to CHE: Q6 / 10 
These impairment percentages will be summarized by visit and by treatment. Missing values will not 
be imputed. 
7.5.2. 
Secondary Efficacy Analysis 
All secondary efficacy analyses will be conducted based on the ITT population during the 
treatment period (DBVC and OLE periods). 


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7.5.2.1. 
Continuous Efficacy Endpoints 
By-visit summary statistics for the following continuous measurements, including change from 
baseline and percentage change from baseline will be presented: 
• CHE-related Itch NRS score 
• CHE-related Skin Pain NRS score 
• HECSI score 
• DLQI total score 
• EQ-5D-5L VAS score 
• QOLHEQ total score 
• WPAI-ChHD scores 
The summary statistics includes sample size, mean, median, standard deviation, minimum, 
maximum, 1st quartile, 3rd quartile, and 95% CI will be presented by visits. 
For PGIC score, summary statistics will be presented by treatment group at each postbaseline 
visit. 
7.5.2.2. 
Categorical Efficacy Endpoints 
For the following categorical parameters, summary statistics including sample size, frequency, 
and percentages will be presented by visits. 
• Proportion of participants achieving an IGA-CHE-TS 
• Proportion of participants achieving ≥ 2-point improvement in CHE-related Skin Pain 
NRS score up to Week 16 from baseline. 
• Proportion of participants achieving ≥ 4-point improvement in CHE-related daily Itch 
NRS score from baseline to Day 14. 
Statistical analysis for the ITCH4 response at Day 3 will be conducted using models similar to 
the key secondary endpoint of ITCH4 at Day 7, specified inSection 7.3.2. 
For the following categorical endpoints, the number and percentage of participants will be 
summarized by treatment at each postbaseline visit: 
• Proportion of participants in each category of EQ-5D-5L score 
• Proportion of participants with each score on the PGIC 
7.5.2.3. 
Time-To-Event Efficacy Endpoints 
For the time to achieve CHE-related Itch NRS score improvement of at least 4 points and time to 
achieve CHE-related Skin Pain NRS score improvement of at least 2 points, a log-rank test 
stratified by randomization stratification factors will be used for between treatment group 
comparisons. The hazard ratio and its 95% CI will be estimated based on the stratified Cox 
regression model using Efron’s method accounting for ties. Kaplan-Meier curves will be 
presented by treatment groups. The number of participants, number of events and number of 


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I N C B 1 8 4 2 4-2 2 6  Statistical A nal ysis Pla n  
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ce ns orin g  w ill b e s um m arize d b y treatm e nt gr o u ps. T he  K a pla n-M eier estim ate of  m e dia n  tim e 
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7. 6.  
A n a lys is o f E x p lo ra to r y E ffica cy  P a ra m eters 
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E x pl or at or y  Eff ic a c y A n al ysis  
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8. 
PHARMACODYNAMICS 
8.1. 
Pharmacodynamic Analyses 
Pharmacodynamic parameters will be summarized descriptively. 
9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the DBVC and 
open-label evaluable population in the OLE period. Cumulative TEAEs across the treatment 
periods (DBVC and OLE periods) will be summarized. Summary tables may be replaced with 
listings when appropriate. For instance, an AE frequency table may be replaced with a listing if it 
only contains a few unique PTs reported on relatively few participants. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first application of study drug and within 30 days of the last application of study drug. For 
participants who crossover treatments, the first application date is period-specific, and the end 
date is 30 days after the last application date in this period, or the first application date in the next 
period, whichever comes first. Analysis of AEs (as discussed below) will be limited to TEAEs, 
but data listings will include all AEs regardless of their timing in relation to study drug 
application. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the NCI CTCAE v5.0 (Grade 1 to 5). The CTCAE reporting guidelines and grading details 
are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered 
treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered treatment-related. The incidence of AEs and treatment-related 
AEs will be tabulated. Serious AEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution. Unresolved missing 
causality and severity will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 


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Application site reactions are AEs that occur at the site of drug application. A summary of ASRs 
will be provided. 
9.2.2. 
Adverse Event Summaries 
An overall summary of AEs by treatment period will include: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants who had any ASRs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any treatment-related TEAEs 
• Number (%) of participants who temporarily interrupted study drug in any of the 
treated areas because of TEAEs 
• Number (%) of participants who permanently discontinued study drug because of 
TEAEs 
• Number (%) of participants who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if 2 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of ASRs by MedDRA PT in decreasing order of frequency 
• Summary of Grade 3 or higher AEs by SOC and PT 
• Summary of Grade 3 or higher AEs by PT in decreasing order of frequency 
• Summary of serious TEAEs by SOC and PT 
• Summary of serious TEAEs by PT in decreasing order of frequency 
• Summary of treatment-related TEAEs by SOC and PT 
• Summary of treatment-related TEAEs by PT in decreasing order of frequency 
• Summary of Grade 3 or higher treatment-related TEAEs by SOC and PT 
• Summary of treatment-related serious TEAEs by SOC and PT 
• Summary of TEAEs with a fatal outcome by SOC and PT 
• Summary of TEAEs leading to dose interruption by SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by SOC and PT 


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Adverse events of interest will be summarized in the following categories: 
• Cytopenias 
− Anemia 
− Thrombocytopenia 
− Neutropenia 
• Herpes zoster 
• Nonmelanoma skin neoplasms 
• Liver function test elevations 
• Malignancies 
• Major Adverse Cardiovascular Events 
• Venous and arterial thromboembolic events 
• Thrombocytosis and elevated mean platelet volume 
9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
All laboratory assessments will be performed using a central laboratory except for urine 
pregnancy tests (as applicable). Laboratory values and change from baseline values will be 
summarized descriptively by visit, and non-numeric test values will be tabulated when necessary. 
The baseline value will be determined using the last nonmissing value collected before the first 
study drug application, prioritizing scheduled assessments for baseline identification over 
unscheduled visits. The last record before administration in the highest priority will be 
considered the baseline record. For baseline laboratory candidates with the same date and time in 
the same priority category, additional rules may be provided after consultation with the medical 
monitor to delineate which value will be defined as baseline. 
9.3.2. 
Laboratory Value Summaries 
Clinical laboratory tests, including hematology and serum chemistry, will be performed at the 
Protocol-specified visits. If specific safety issues arise, additional unscheduled laboratory 
tests/analyses may be performed at the discretion of the investigator. 
All test results and associated normal ranges from central laboratories will be reported in SI 
units. All tests with numeric values will have a unique unit per test. Any laboratory test results 
and associated normal ranges from local laboratories will be converted to SI units. 
When there are multiple laboratory nonmissing values for a participant's particular test within a 
visit window, the laboratory value with the smallest laboratory sequence number will be used in 
by-visit summaries. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low (but never high), normal, high (but never 


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low), and both low and high will be calculated for each test. This shift summary will be produced 
for each test for the safety population in the DBVC period, as well as the open-label evaluable 
population in the OLE period. Shift tables will be presented showing change in CTCAE grade 
from baseline to worst grade postbaseline as well. The denominator for the percentage 
calculation will use the number of participants in the baseline category. 
9.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, temperature, and respiratory 
rate will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 7. The abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed along 
with their assigned treatment group. Alert vital signs are defined as an absolute value outside the 
defined range and percentage change from baseline greater than 25%. The abnormal values for 
participants exhibiting alert vital sign abnormalities will be listed. 
Table 7: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
≤ 155 mmHg 
≥ 85 mmHg 
Diastolic blood pressure 
≤ 100 mmHg 
≥ 40 mmHg 
Pulse 
≤ 100 bpm 
≥ 45 bpm 
Temperature 
≤ 38°C 
≥ 35.5°C 
Respiratory rate 
≤ 24 breaths/min 
≥ 8 breaths/min 
10. 
INTERIM ANALYSES 
No formal interim analysis is planned for this study. There are 2 formal planned analyses: 
• The primary analysis will occur after the primary database lock, when all participants 
have completed the DBVC period. The sponsor will be unblinded after the primary 
database lock; however, investigators and participants will remain blinded to the 
individual study treatment assignment. 
• The final analysis will occur when all participants have completed or withdrawn from 
the study. 


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11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 8. 
Table 8: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
29 MAY 2024 
11.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
11.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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12. 
REFERENCES 
Bissonnette R. Efficacy and safety of delgocitinib cream in adults with moderate-to-severe 
chronic hand eczema: results of the Phase 3 DELTA 1 trial. In: Proceedings from the American 
Academy of Dermatology Annual Conference 2023; March 16 to March 21, 2023; New Orleans, 
LA. Oral presentation. 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) — a simple practical measure for 
routine clinical use. Clin Exp Dermatol 1994;19:210-216. 
Held E, Skoet R, Johansen JD, Agner T. The hand eczema severity index (HECSI): a scoring 
system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability. Br 
J Derm 2005;152;302-307. 
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level 
version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727-1736. 
Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther 2004;27:26-35. 
Mantel N, Haenszel W. Statistical aspects of analysis of data from retrospective studies of 
disease. J Natl Cancer Inst 1959;22:719-748. 
Ofenloch RF, Weisshaar E, Dumke A-K, Molin S, Diepgen TL, Apfelbacher C. The Quality of 
Life in Hand Eczema Questionnaire (QOLHEQ): validation of the German version of a new 
disease-specific measure of quality of life for patients with hand eczema. Br J Derm 
2014:171;304-312. 
Quality of Life in Hand Eczema Questionnaire. Accessed May 16, 2024. 
https://qolheq.dermis.net/content/faq/index_eng.html 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. PharmacoEconomics 1993;4:353-365. 
Ruzicka T, Lynde CW, Jemec GB, et al. Efficacy and safety of oral alitretinoin (9-cis retinoic 
acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of 
a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol 2008;158:808-
817. 
Worm M, Thyssen JP, Schliemann S, et al. The pan-JAK inhibitor delgocitinib in a cream 
formulation demonstrates dose response in chronic hand eczema in a 16-week randomized phase 
Iib trial. Br J Dermatol 2022;187:42-51. 


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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report.  
The lists of tables, figures, and listings are to be used as guidelines. Modifications of the lists that 
do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Baseline and Demographic Characteristic 
1.1 Disposition 
1.1.1 
Analysis Populations 
All 
1.1.2.1 
Summary of Participant Disposition in the DBVC Period 
ITT 
1.1.2.2 
Summary of Participant Disposition in the OLE Period 
Open-Label 
Evaluable 
1.1.3 
Summary of Number of Participants Enrolled by Country and Site 
ITT 
1.1.4.1 
Summary of Protocol Deviations in the DBVC Period 
ITT 
1.1.4.2 
Summary of Protocol Deviations in the OLE Period 
Open-Label 
Evaluable 
1.2 Demography and Baseline Characteristics 
1.2 
Summary of Demographics and Baseline Characteristics 
ITT 
1.3 Baseline Disease Characteristics 
1.3 
Summary of Baseline Disease Characteristics 
ITT 
1.4 Prior Medication and Concomitant Medication 
1.4.1 
Summary of Prior Medications 
ITT 
1.4.2 
Summary of Prior Therapies for CHE 
ITT 
1.4.3.1 
Summary of Concomitant Medications in the DBVC Period 
ITT 
1.4.3.2 
Summary of Concomitant Medications in the OLE Period 
Open-Label 
Evaluable 
1.5+ Others 
1.5 
Summary of General Medical History  
ITT 
Efficacy 
2.1 IGA-CHE-TS 
2.1.1 
Summary and Analysis of Participants Achieving IGA-CHE-TS in the 
Treatment Period 
ITT 
2.1.2 
Summary and Analysis of Participants Achieving IGA-CHE-TS in the 
Treatment Period With Nonresponder Imputation 
ITT 
2.1.3 
Summary and Analysis of Participants Achieving IGA-CHE-TS by Baseline 
IGA-CHE Score in the Treatment Period 
ITT 
2.1.4 
Summary and Analysis of Participants Achieving IGA-CHE-TS by Age Group 
in the Treatment Period 
ITT 
2.1.5 
Summary and Analysis of Participants Achieving IGA-CHE-TS by Sex in the 
Treatment Period 
ITT 
2.1.6 
Summary and Analysis of Participants Achieving IGA-CHE-TS by Race in the 
Treatment Period 
ITT 
2.1.7 
Summary and Analysis of Participants Achieving IGA-CHE-TS by Region in 
the Treatment Period 
ITT 


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Table No. 
Title 
Population 
2.2 CHE-Related Itch NRS Score 
2.2.1 
Summary and Analysis of Participants Achieving ≥ 4-Point Improvement in 
CHE-Related Itch NRS Score in the Treatment Period by Visit 
ITT  
2.2.2 
Summary and Analysis of Participants Achieving ≥ 4-Point Improvement in 
CHE-Related Itch NRS Score in the Treatment Period with Nonresponder 
Imputation by Visit 
ITT  
2.2.3 
Summary and Analysis of By-Visit CHE-Related Itch NRS Score in the 
Treatment Period 
ITT 
2.2.4 
Summary and Analysis of Time to ≥ 4-Point Improvement in CHE-Related Itch 
NRS Score in the Treatment Period 
ITT 
2.2.5 
Summary and Analysis of Daily CHE-Related Itch NRS Score  
ITT 
2.2.6 
Summary and Analysis of Participants Achieving ≥ 4-Point Improvement in 
CHE-Related Itch NRS Score From Day 1 to Day 7 
ITT 
2.3 CHE-Related Skin Pain NRS Score 
2.3.1 
Summary of Participants Achieving ≥ 2-Point Improvement in CHE-Related 
Skin Pain NRS Score in the Treatment Period 
ITT 
2.3.2 
Summary of By-Visit CHE-Related Skin Pain NRS Score in the Treatment 
Period 
ITT 
2.3.3 
Summary of Time to ≥ 2-Point Improvement in CHE-Related Skin Pain NRS 
Score in the Treatment Period 
ITT 
2.4 HECSI 
2.4.1 
Summary of By-Visit HECSI Score in the Treatment Period 
ITT 
2.4.2 
Summary of Participants Achieving HECIS-75 in the Treatment Period 
ITT 
2.4.3 
Summary of Participants Achieving HECIS-90 in the Treatment Period 
ITT 
2.5 PGIC 
2.5.1 
Summary of By-Visit PGIC Score in the Treatment Period 
ITT 
2.5.3 
Summary of Participants Achieving a PGIC Score of 1 or 2 in the Treatment 
Period 
ITT 
2.6 DLQI 
2.6.1 
Summary of Total DLQI Total Score in the Treatment Period 
ITT 
2.7 EQ-5D-5L 
2.7.1 
Summary of EQ-5D VAS Score in the Treatment Period 
ITT 
2.7.2 
Summary of Participants in Each Category of EQ-5D Score in the Treatment 
Period 
ITT 
2.8 QOLHEQ 
2.8.1 
Summary of QOLHEQ Total Score in the Treatment Period 
ITT 
2.9 WPAI-ChHD 
2.9.1 
Summary of WPAI-ChHD Score in the Treatment Period 
ITT 
Safety 
3.1 Exposure 
3.1.1.1 
Summary of Exposure in the DBVC Period  
Safety 
3.1.1.2 
Summary of Exposure in the OLE Period 
Open-Label 
Evaluable 
3.1.1.3 
Summary of Exposure From Baseline to Week 32 
Safety 
3.1.2 
Summary of Study Drug Compliance in the DBVC Period 
Safety 


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INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Table No. 
Title 
Population 
3.2 Adverse Events 
3.2.1.1.1 
Overall Summary of Treatment-Emergent Adverse Events in the DBVC Period 
Safety 
3.2.1.1.2 
Overall Summary of Treatment-Emergent Adverse Events in OLE Period 
Open-Label 
Evaluable 
3.2.1.1.3 
Overall Summary of Treatment-Emergent Adverse Events for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.2.1.1 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term in the DBVC Period 
Safety 
3.2.2.1.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.2.1.3 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term for Participants Who Applied Ruxolitinib Cream 
Throughout the Study (Baseline to Week 32) 
Safety 
3.2.2.1.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term From Baseline to Week 32 
Safety 
3.2.3.1.1 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency in the DBVC Period 
Safety 
3.2.3.1.2 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.3.1.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency for Participants Who Applied Ruxolitinib 
Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.3.1.4 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency From Baseline to Week 32 
Safety 
3.2.3.3.1 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency in the DBVC Period 
Safety 
3.2.3.3.2 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.3.3.3 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency for Participants who Applied Ruxolitinib 
Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.3.3.4 
Summary of Application Site Reactions by MedDRA Preferred Term in 
Decreasing Order of Frequency From Baseline to Week 32 
Safety 
3.2.4.1.1 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term in the DBVC Period 
Safety 
3.2.4.1.2 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term in OLE Period 
Open-Label 
Evaluable 
3.2.4.1.3 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.5.1.1 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency in the DBVC 
Period 
Safety 
3.2.5.1.2 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.5.1.3 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency for Participants 
Who Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.6.1.1 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term in DBVC Period 
Safety 


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INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Table No. 
Title 
Population 
3.2.6.1.2 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.6.1.3 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term for Participants Who Applied Ruxolitinib 
Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.7.1.1 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency in the DBVC Period 
Safety 
3.2.7.1.2 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.7.1.3 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.8.1.1 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term in DBVC Period 
Safety 
3.2.8.1.2 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.8.1.3 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.9.1.1 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency in DBVC Period 
Safety 
3.2.9.1.2 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.9.1.3 
Summary of Treatment-Related Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency for Participants 
Who Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.10.1.1 
Summary of Grade 3 or Higher Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term in 
DBVC Period 
Safety 
3.2.10.1.2 
Summary of Grade 3 or Higher Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term in the 
OLE Period 
Open-Label 
Evaluable 
3.2.10.1.3 
Summary of Grade 3 or Higher Treatment-Related Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term for 
Participants Who Applied Ruxolitinib Cream Throughout the Study (Baseline 
to Week 32) 
Safety 
3.2.11.1.1 
Summary of Treatment-Related Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term in the DBVC Period 
Safety 
3.2.11.1.2 
Summary of Treatment-Related Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.11.1.3 
Summary of Treatment-Related Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.12.1.1 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term in the DBVC Period 
Safety 
3.2.12.1.2 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.12.1.3 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 


Incyte Corporation 
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INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Table No. 
Title 
Population 
3.2.13.1.1 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption 
in any of the Treated Areas by MedDRA System Organ Class and Preferred 
Term in the DBVC Period 
Safety 
3.2.13.1.2 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption 
in any of the Treated Areas by MedDRA System Organ Class and Preferred 
Term in the OLE Period 
Open-Label 
Evaluable 
3.2.13.1.3 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption 
in any of the Treated Areas by MedDRA System Organ Class and Preferred 
Term for Participants Who Applied Ruxolitinib Cream Throughout the Study 
(Baseline to Week 32) 
Safety 
3.2.14.1.1 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Study Drug by MedDRA System Organ Class and Preferred Term in the 
DBVC Period 
Safety 
3.2.14.1.2 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Study Drug by MedDRA System Organ Class and Preferred Term in the 
OLE Period 
Open-Label 
Evaluable 
3.2.14.1.3 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Study Drug by MedDRA System Organ Class and Preferred Term for 
Participants who Applied Ruxolitinib Cream Throughout the Study (Baseline to 
Week 32) 
Safety 
3.2.15.1.1 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
System Organ Class and Preferred Term in the DBVC Period 
Safety 
3.2.15.1.2 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
System Organ Class and Preferred Term in the OLE Period 
Open-Label 
Evaluable 
3.2.15.1.3 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
System Organ Class and Preferred Term for Participants Who Applied 
Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.2.16.1.1 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
Preferred Term in Decreasing Order of Frequency in the DBVC Period 
Safety 
3.2.16.1.2 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
Preferred Term in Decreasing Order of Frequency in the OLE Period 
Open-Label 
Evaluable 
3.2.16.1.3 
Summary of Treatment-Emergent Adverse Events of Interest by MedDRA 
Preferred Term in Decreasing Order of Frequency for Participants Who 
Applied Ruxolitinib Cream Throughout the Study (Baseline to Week 32) 
Safety 
3.3 Laboratory 
3.3.1 
Summary of Laboratory Values – Hematology in the DBVC Period 
Safety 
3.3.1.2 
Summary of Laboratory Values – Hematology in the OLE Period 
Open-Label 
Evaluable 
3.3.2.1 
Summary of Laboratory Values – Chemistry in the DBVC Period 
Safety 
3.3.2.2 
Summary of Laboratory Values – Chemistry in the OLE Period 
Open-Label 
Evaluable 
3.3.3.1 
Shift Summary of Hematology Laboratory Values in CTCAE Grade – to the 
Worst Abnormal Value in the DBVC Period 
Safety 
3.3.3.2 
Shift Summary of Hematology Laboratory Values in CTCAE Grade – to the 
Worst Abnormal Value in the OLE Period 
Open-Label 
Evaluable 
3.3.4.1 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade – to the 
Worst Abnormal Value in the DBVC Period 
Safety 
3.3.4.2 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade – to the 
Worst Abnormal Value in the OLE Period 
Open-Label 
Evaluable 


Incyte Corporation 
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INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Table No. 
Title 
Population 
3.3.5.1 
Shift Summary of Hematology Values – to the Worst Abnormal Value in the 
DBVC Period 
Safety 
3.3.5.2 
Shift Summary of Hematology Values – to the Worst Abnormal Value in the 
OLE Period 
Open-Label 
Evaluable 
3.3.6.1 
Shift Summary of Chemistry Values – to the Worst Abnormal Value in the 
DBVC Period 
Safety 
3.3.6.2 
Shift Summary of Chemistry Values – to the Worst Abnormal Value in the 
OLE Period 
Open-Label 
Evaluable 
3.4 Vital Signs 
3.4.1.1 
Summary of Systolic Blood Pressure in the DBVC Period 
Safety 
3.4.1.2 
Summary of Systolic Blood Pressure in the OLE Period 
Open-Label 
Evaluable 
3.4.2.1 
Summary of Diastolic Blood Pressure in the DBVC Period 
Safety 
3.4.2.2 
Summary of Diastolic Blood Pressure in the OLE Period 
Open-Label 
Evaluable 
3.4.3.1 
Summary of Pulse in the DBVC Period 
Safety 
3.4.3.2 
Summary of Pulse in the OLE Period 
Open-Label 
Evaluable 
3.4.4.1 
Summary of Respiratory Rate in the DBVC Period 
Safety 
3.4.4.2 
Summary of Respiratory Rate in the OLE Period 
Open-Label 
Evaluable 
3.4.5.1 
Summary of Body Temperature in the DBVC Period 
Safety 
3.4.5.2 
Summary of Body Temperature in the OLE Period 
Open-Label 
Evaluable 
Figures 
Figure No. 
Title 
Population 
4.1 IGA-CHE-TS 
4.1.1.1 
Proportion of Participants Achieving IGA-CHE-TS in the Treatment Period  
ITT 
4.1.1.2 
Proportion of Participants Achieving IGA-CHE-TS in the DBVC Period With 
Nonresponder Imputation 
ITT 
4.1.2.1 
Proportion of Participants Achieving IGA-CHE-TS By Baseline IGA-CHE 
Score in the Treatment Period 
ITT 
4.1.2.2 
Proportion of Participants Achieving IGA-CHE-TS by Age Group in the 
Treatment Period 
ITT 
4.1.2.3 
Proportion of Participants Achieving IGA-CHE-TS by Sex in the Treatment 
Period 
ITT 
4.1.2.4 
Proportion of Participants Achieving IGA-CHE-TS by Race in the Treatment 
Period 
ITT 
4.1.2.5 
Proportion of Participants Achieving IGA-CHE-TS by Region in the Treatment 
Period 
ITT 
4.1.3 
Forest Plot of Response Rate Difference in Achieving IGA-CHE-TS at Week 16 
ITT 


Incyte Corporation 
Page 41 of 44 
INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Figure No. 
Title 
Population 
CHE-Related Itch NRS Score 
4.3.1.1 
Proportion of Participants Achieving ≥ 4-point Improvement in CHE-Related 
Itch NRS Score in the Treatment Period 
ITT 
4.3.1.2 
Proportion of Participants Achieving ≥ 4-point Improvement in CHE-Related 
Itch NRS Score in the DBVC Period With Nonresponder Imputation 
ITT 
4.3.2.1 
Mean and Standard Error Plot of CHE-Related Itch NRS Score by Visit in the 
Treatment Period 
ITT 
4.3.2.2 
Mean and Standard Error Plot of Change From Baseline in CHE-Related Itch 
NRS Score by Visit in the Treatment Period 
ITT 
4.3.3.1 
Proportion of Participants Achieving ≥ 4-point Improvement in CHE-Related 
Daily Itch NRS Score from Day 1 to Day 14 
ITT 
4.3.3.2 
Proportion of Participants Achieving ≥ 4-point Improvement in CHE-Related 
Daily Itch NRS Score from Day 1 to Day 7 using Multiple Imputation 
ITT 
4.3.4.1 
Mean and Standard Error Plot of CHE-Related Daily Itch NRS Score in the 
Treatment Period  
ITT 
4.3.4.2 
Mean and Standard Error Plot of Change From Baseline in CHE-Related Daily 
Itch NRS Score in the Treatment Period 
ITT 
4.3.5.1 
Kaplan-Meier Curve of the Time to ≥ 4-Point Improvement in Itch NRS Score in 
the DBVC Period 
ITT 
CHE-Related Skin Pain NRS 
4.4.1 
Proportion of Participants Achieving ≥ 2-point Improvement in CHE-Related 
Skin Pain NRS Score in the Treatment Period 
ITT 
4.4.2.1 
Mean and Standard Error Plot of CHE-Related Skin Pain NRS Score by Visit in 
the Treatment Period 
ITT 
4.4.2.2 
Mean and Standard Error Plot of Change From Baseline in CHE-Related Skin 
Pain NRS Score by Visit in the Treatment Period 
ITT 
4.4.3 
Kaplan-Meier Curve of the Time to ≥ 2-Point Improvement in CHE-Related 
Skin Pain NRS Score in the DBVC Period 
ITT 
HECSI 
4.6.1 
Proportion of Participants Achieving HECSI-75 in the Treatment Period 
ITT 
4.6.2 
Proportion of Participants Achieving HECSI-90 in the Treatment Period 
ITT 
4.6.3 
Mean and Standard Error Plot of HECSI Score by Visit in the Treatment Period 
ITT 
4.6.4 
Mean and Standard Error Plot of Change From Baseline in HECSI Score by 
Visit in the Treatment Period 
ITT 
4.6.5 
Mean and Standard Error Plot of Percent Change From Baseline in HECSI Score 
by Visit in the Treatment Period 
ITT 
PGIC 
4.7.1 
Mean and Standard Error Plot of PGIC Score by Visit in the Treatment Period 
ITT 
4.7.2 
Proportion of Participants Achieving a PGIC Score of Either 1 or 2 in the 
Treatment Period 
ITT 
DLQI 
4.8.1 
Mean and Standard Error Plot of DLQI Total Score in the Treatment Period 
ITT 
4.8.2 
Mean and Standard Error Plot of Change From Baseline in DLQI Total Score in 
the Treatment Period 
ITT 
EQ-5D-5L 
4.9.1 
Mean and Standard Error Plot of EQ-5D-5L VAS Score in the Treatment Period 
ITT 
4.9.2 
Mean and Standard Error Plot of Change From Baseline in EQ-5D-5L VAS 
Score in the Treatment Period 
ITT 


Incyte Corporation 
Page 42 of 44 
INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Figure No. 
Title 
Population 
QOLHEQ 
4.10.1 
Mean and Standard Error Plot of QOLHEQ Total Score in the Treatment Period 
ITT 
4.10.2 
Mean and Standard Error Plot of Change From Baseline in QOLHEQ Total 
Score and Subscale Score in the Treatment Period 
ITT 
WPAI-ChHD 
4.12.1 
Mean and Standard Error Plot of WPAI-ChHD Score in the Treatment Period 
ITT 
4.12.2 
Mean and Standard Error Plot of Change From Baseline in WPAI-ChHD Score 
in the Treatment Period 
ITT 
Laboratory 
4.13.1.1 
Box Plot of Hemoglobin (g/L) by Visit in the Treatment Period 
Safety 
4.13.1.2 
Box Plot of Change From Baseline in Hemoglobin (g/L) by Visit in the DBVC 
Period 
Safety 
4.13.1.3 
Box Plot of Percentage Change From Baseline in Hemoglobin (g/L) by Visit in 
the DBVC Period 
Safety 
4.13.2.1 
Box Plot of Platelets (10^9/L) by Visit in the Treatment Period 
Safety 
4.13.2.2 
Box Plot of Change From Baseline in Platelets (10^9/L) by Visit in the DBVC 
Period 
Safety 
4.13.2.3 
Box Plot of Percentage Change From Baseline in Platelets (10^9/L) by Visit in 
the DBVC Period 
Safety 
4.13.3.1 
Box Plot of Neutrophils (10^9/L) by Visit in the Treatment Period 
Safety 
4.13.3.2 
Box Plot of Change From Baseline in Neutrophils (10^9/L) by Visit in the 
DBVC Period 
Safety 
4.13.3.3 
Box Plot of Percentage Change From Baseline in Neutrophils (10^9/L) by Visit 
in the DBVC Period 
Safety 
4.13.4.1 
Box Plot of Leukocytes (10^9/L) by Visit in the Treatment Period 
Safety 
4.13.4.2 
Box Plot of Change From Baseline in Leukocytes (10^9/L) by Visit in the 
DBVC Period 
Safety 
4.13.4.3 
Box Plot of Percentage Change From Baseline in Leukocytes (10^9/L) by Visit 
in the DBVC Period 
Safety 
4.13.5.1 
Box Plot of Lymphocytes (10^9/L) by Visit in the Treatment Period 
Safety 
4.13.5.2 
Box Plot of Change From Baseline in Lymphocytes (10^9/L) by Visit in the 
DBVC Period 
Safety 
4.13.5.3 
Box Plot of Percentage Change From Baseline in Lymphocytes (10^9/L) by 
Visit in the DBVC Period 
Safety 
4.13.6.1 
Box Plot of Erythrocytes (10^12/L) by Visit in the Treatment Period 
Safety 
4.13.6.2 
Box Plot of Change From Baseline in Erythrocytes (10^12/L) by Visit in the 
DBVC Period 
Safety 
4.13.6.3 
Box Plot of Percentage Change From Baseline in Erythrocytes (10^12/L) by 
Visit in the DBVC Period 
Safety 
4.13.7.1 
Box Plot of Reticulocytes (10^9/L) by Visit in the Treatment Period 
Safety 
4.13.7.2 
Box Plot of Change From Baseline in Reticulocytes (10^9/L) by Visit in the 
DBVC Period 
Safety 
4.13.7.3 
Box Plot of Percentage Change From Baseline in Reticulocytes (10^9/L) by 
Visit in the DBVC Period 
Safety 


Incyte Corporation 
Page 43 of 44 
INCB 18424-226 Statistical Analysis Plan 
29 MAY 2024 
VV-CLIN-027138 
CONFIDENTIAL 
Listings 
Listing No. 
Title 
2.1 Participant Disposition 
2.1.1.1 
Participant Enrollment and Disposition Status in the DBVC Period 
2.1.1.2 
Participant Enrollment and Disposition Status in the OLE Period 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2 Protocol Deviations 
2.2 
Protocol Deviations 
2.3 Data Excluded From PK, Efficacy, and/or Safety Analyses 
2.3 
Analysis Populations 
2.4 Demographic and Baseline Characteristics (Including Prior and Concomitant Medications) 
2.4.1 
Demographic Characteristics 
2.4.2 
Baseline Disease Characteristics 
2.4.3 
Prior and Concomitant Medications 
2.4.4.1 
Prior Therapies for CHE 
2.4.5 
Medical History 
2.5 Drug Compliance 
2.5.1 
Study Drug Exposure and Compliance in the DBVC Period 
2.5.2 
Study Drug Exposure in the OLE Period 
2.5.3 
Study Drug Exposure from Baseline to Week 32 
2.6 Efficacy 
2.6.1 
IGA-CHE-TS Score 
2.6.2.1 
CHE-Related Itch NRS Daily Score 
2.6.2.2 
CHE-Related Itch NRS By-Visit Score  
2.6.2.3 
Time to CHE-Related Itch NRS Response 
2.6.3.1 
CHE-Related Skin Pain NRS Daily Score 
2.6.3.2 
CHE-related Skin Pain NRS By-Visit Score 
2.6.3.3 
Time to CHE-Related Skin Pain NRS Response 
2.6.5 
HECSI Score 
2.6.6 
PGIC Score  
2.6.8 
DLQI Score  
2.6.10 
EQ-5D-5L Score 
2.6.11 
QOLHEQ Score 
2.6.13 
WPAI-ChHD Score 
2.7 Adverse Events 
2.7.1 
Adverse Events 
2.7.2 
Adverse Events Leading to Drug Discontinuation 
2.7.3 
Serious Adverse Events 
2.7.4 
Treatment-Related Adverse Events 
2.7.5 
Adverse Events With a Fatal Outcome 
2.7.6 
Adverse Events Leading to Interruption of Study Drug 
2.7.8 
Adverse Events with Grade 3 or Higher 
2.7.9 
Application Site Reactions 
2.7.10 
Adverse Events of Interest 


Incyte Corporation 
Page 44 of 44 
INCB 18424-226 Statistical Analysis Plan 
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CONFIDENTIAL 
Listing No. 
Title 
2.8 Laboratory Data 
2.8.1 
Clinical Laboratory Values – Hematology 
2.8.2 
Clinical Laboratory Values - Serum Chemistry 
2.8.3 
Abnormal Clinical Laboratory Values – Hematology 
2.8.4 
Abnormal Clinical Laboratory Values - Serum Chemistry 
2.9 Vital Signs 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values