Clinical trial NCT03011892
Conditions: Atopic Dermatitis
Keywords: Atopic dermatitis eczema pruritus Janus kinase (JAK) inhibitors
Sponsor: Incyte Corporation
Start date: 2017-01-09; Completion date: 2018-03-12
Enrollment: 307 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to establish the efficacy of each strength of ruxolitinib cream once daily (QD) or twice daily (BID) in participants with atopic dermatitis as compared with vehicle cream BID.

Detailed description:

Arms: arm 1: Participants applied vehicle cream twice daily (BID) for 8 weeks DB period. arm 2: Participants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period. arm 3: Participants applied ruxolitinib 0.15% cream QD for 8 weeks in DB period. arm 4: Participants applied ruxolitinib 0.5% cream QD for 8 weeks in DB period. arm 5: Participants applied ruxolitinib 1.5% cream QD for 8 weeks in DB period. arm 6: Participants applied ruxolitinib 1.5% cream BID for 8 weeks in DB period. arm 7: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. arm 8: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. arm 9: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. arm 10: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. arm 11: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. arm 12: Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
Interventions: intervention 1: Ruxolitinib 0.15% Cream QD intervention 2: Ruxolitinib 0.5% Cream QD intervention 3: Ruxolitinib 1.5% Cream QD intervention 4: Ruxolitinib 1.5% Cream BID intervention 5: Triamcinolone 0.1% Cream BID intervention 6: Vehicle Cream BID
Intervention descriptions: intervention 1: Ruxolitinib 0.15% cream QD intervention 2: Ruxolitinib 0.5% cream QD intervention 3: Ruxolitinib 1.5% cream QD intervention 4: Ruxolitinib 1.5% cream BID intervention 5: Triamcinolone 0.1% cream BID intervention 6: Vehicle cream BID

Protocol documents:
Prot_000.pdf: 
Incyte Corporation 
Page 1 of 72 
Protocol INCB 18424-206 
15 SEP 2016 
CONFIDENTIAL 
Clinical Study Protocol 
INCB 18424-206/NCT03011892   
A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and 
Triamcinolone 0.1% Cream–Controlled Study to Evaluate the 
Safety and Efficacy of INCB018424 Phosphate Cream Applied 
Topically to Adults With Atopic Dermatitis 
Product: 
INCB018424 Phosphate Cream 
IND Number: 
77,101 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Date of Protocol: 
15 SEP 2016 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
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 the prior 
written consent of Incyte Corporation. 


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Protocol INCB 18424-206 
15 SEP 2016 
CONFIDENTIAL 
INVESTIGATOR'S AGREEMENT 
I have read the INCB 18424-206 Protocol (dated 15 SEP 2016) 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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Protocol INCB 18424-206 
15 SEP 2016 
CONFIDENTIAL 
SYNOPSIS 
Name of Investigational Product:  INCB018424 Phosphate Cream 
Title of Study:  A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and Triamcinolone 
0.1% Cream–Controlled Study to Evaluate the Safety and Efficacy of INCB018424 Phosphate Cream 
Applied Topically to Adults With Atopic Dermatitis 
Protocol Number:  INCB 18424-206 
Study Phase:  2 
Indication:  Atopic Dermatitis 
Primary Objective: 
• To establish the efficacy of each dose of INCB018424 cream once daily (QD) or twice daily (BID) in 
subjects with atopic dermatitis (AD) compared with vehicle cream BID. 
Secondary Objectives: 
Key Secondary Objective: 
• To establish the efficacy of each dose of INCB018424 cream QD or BID in subjects with AD as 
compared with triamcinolone 0.1% cream BID. 
Other Secondary Objective: 
• To evaluate the safety and tolerability of INCB018424 cream when applied QD or BID to subjects with 
AD. 
Primary Endpoint: 
• Mean percentage change from baseline in Eczema Area and Severity Index (EASI) score at Week 4 in 
subjects treated with 1.5% INCB018424 BID compared with subjects treated with vehicle cream BID. 
Secondary Endpoints: 
Key Secondary Endpoints: 
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated with INCB018424 
compared with subjects treated with vehicle cream BID.  
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated with INCB018424 
compared with subjects treated with triamcinolone 0.1% cream BID. 
Other Secondary Endpoints: 
• Mean percentage change from baseline in EASI score at Week 2 and Week 8. 
• Proportion of subjects who achieve a ≥ 50% improvement from baseline in EASI (EASI-50) at 
Weeks 2, 4, and 8. 
• Assessment of dose response based on percentage change from baseline in EASI score at Week 4. 
• Time to achieve EASI-50. 


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Protocol INCB 18424-206 
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CONFIDENTIAL 
• Proportion of subjects achieving an Investigator's Global Assessment (IGA) score of 0 to 1 who have an 
improvement of ≥ 2 points from baseline at Weeks 2, 4, and 8. 
• Mean change from baseline in the Itch Numerical Rating Scale (NRS) score at Weeks 2, 4, and 8. 
• Safety and tolerability assessed by monitoring the frequency, duration, and severity of adverse events 
(AEs); performing physical examinations; collecting vital signs; and collecting laboratory data for 
hematology, serum chemistry, and urinalysis. 
Overall Study Design: 
This is a randomized, vehicle- and active (triamcinolone 0.1% cream)-controlled study in subjects with 
mild to moderate AD.  The study is double-blinded for vehicle, INCB018424 doses, and active control.  
Approximately 300 subjects will be randomized 1:1:1:1:1:1 to INCB018424 1.5% BID, 
INCB018424 1.5% QD, INCB018424 0.5% QD, INCB018424 0.15% QD, vehicle BID, and active 
control (triamcinolone 0.1% cream BID) and stratified by EASI score (≤ 7 and > 7).  Subjects receiving 
QD regimens will apply vehicle at the evening application.  Subjects will receive blinded study drug for 
8 weeks.  Subjects randomized to triamcinolone will apply triamcinolone 0.1% cream BID for 4 weeks 
and vehicle cream for 4 weeks to not exceed the allowable triamcinolone application duration. 
At Week 8, subjects who meet criteria (compliant with the Protocol and no safety concerns) will be 
offered open-label treatment with INCB018424 1.5% cream BID for 4 weeks. 
Through Week 8, subjects should continue to treat areas identified for treatment at baseline even if the 
area begins to improve.  After Week 8, areas which were treated before Week 8 that are no longer 
symptomatic are not required to be treated. 
Subjects will have follow-up assessments 1 month after the last application of study drug. 
Study drug (INCB018424 cream, vehicle, or triamcinolone) may not be applied to the face or 
intertriginous areas.  The face and intertriginous areas may be treated with hydrocortisone 2.5% cream 
during the study.  Assessments of BSA should be based on the areas treated with study drug (excluding 
the face and intertriginous areas that cannot be treated with study drug). 
Subjects who develop additional areas of AD after the initiation of treatment may treat these additional 


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Protocol INCB 18424-206 
15 SEP 2016 
CONFIDENTIAL 
areas (except the face and intertriginous areas) as long as the total treated BSA does not exceed 20% and 
there are no safety concerns regarding the additional application of study drug. 
Subjects may continue to use bland emollients that do not contain urea or ceramides during the study.  If 
bland emollients are used, the type of cream and amount of application should remain consistent for the 
duration of the study. 
An interim analysis will be conducted when at least half of the randomized subjects reach Week 4.  These 
data will be assessed by an unblinded team at the sponsor who does not have direct contact with the study 
sites. 
Sites and the sponsor are blinded to study drug; however, some personnel at Incyte (without direct contact 
with sites) will be unblinded. 
Study Population: 
Men or women, aged 18 to 70 years, who have been diagnosed with AD for at least 2 years, with an IGA 
score of 2 to 3, and BSA involvement (excluding the face and intertriginous areas) of 3% to 20%. 
Key Inclusion Criteria: 
A subject who meets all of the following criteria may be included in the study: 
• Adult men and women aged 18 to 70 years, inclusive. 
• Subjects diagnosed with AD as defined by the Hanifin and Rajka criteria. 
• Subjects with a history of AD for at least 2 years. 
• Subjects with an IGA score of 2 to 3 at screening and baseline. 
• Subjects with BSA of AD involvement, excluding the face and intertriginous areas, of 3% to 20% at 
screening and baseline. 
• Subjects who agree to discontinue all agents used to treat AD from screening through the final 
follow-up visit. 
Key Exclusion Criteria: 
A subject who meets any of the following criteria will be excluded from the study: 
• Subjects with evidence of active acute or chronic infections. 
• Use of topical treatments for AD (other than bland emollients) within 2 weeks of baseline. 
• Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, 
methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives of 
baseline (whichever is longer). 
• Subjects with other dermatologic disease besides AD whose presence or treatments could complicate 
the assessment of disease (eg, psoriasis). 
• Subjects with a history of other diseases besides dermatologic disorders (eg, other autoimmune 
diseases) taking treatments that could complicate assessments. 
• Subjects with cytopenias at screening, defined as: 
− Leukocytes < 3.0 × 109/L. 
− Neutrophils < lower limit of normal. 
− Hemoglobin < 10 g/dL. 
− Lymphocytes < 0.8 × 109/L. 
− Platelets < 100 × 109/L. 


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Protocol INCB 18424-206 
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CONFIDENTIAL 
• Subjects with severely impaired liver function (Child-Pugh Class C) or end-stage renal disease on 
dialysis or at least 1 of the following: 
− Serum creatinine > 1.5 mg/dL. 
− Alanine aminotransferase or aspartate aminotransferase ≥ 1.5 × upper limit of normal. 
• Subjects taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 
5 half-lives, whichever is longer, before the baseline visit (topical agents with limited systemic 
availability are permitted). 
• Subjects who have previously received Janus kinase inhibitors, systemic or topical (eg, ruxolitinib, 
tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib). 
INCB018424 Cream/Study Drug, Dosage, and Mode of Administration: 
INCB018424 1.5% cream, INCB018424 0.5% cream, and INCB018424 0.15% cream will be supplied 
and applied topically as a thin film to the affected areas in the morning and in the evening at least 1 hour 
before bedtime.  The prescribed dose of study drug is to be determined by weighing a tube before and 
after the subject applies a thin film of study drug to the affected areas.  For each 1% of BSA (palm with 
fingers) to be treated with study drug, approximately 2 inches (5 cm) of study drug may be used.  Subjects 
will be advised to limit use to no more than 1 tube per application.  Application instructions will be 
provided at study visits and via a diary card given to the subjects.  If sunscreen, makeup, or other cream 
has been applied to the areas to be treated, subjects should wash the treatment areas with mild soap and 
water and pat dry before application of study drug.  If used, topical anti-infectives or other topical 
treatments should be avoided for at least 1 hour before and after application of study drug to an area.  
Subjects should be cautioned to avoid excessive exposure to either natural or artificial sunlight (including 
tanning booths, sun lamps, etc) and, when outdoors, should be advised to wear loose-fitting clothing that 
protects the treated area from the sun.  Immediately after application of study drug, subjects are to wash 
hands thoroughly with soap and warm water. 
Reference Therapy, Dosage, and Mode of Administration: 
Vehicle cream is matching in appearance to the INCB018424 creams, except it does not contain active 
drug.  Vehicle cream and triamcinolone 0.1% cream are to be applied in the same manner as 
INCB018424 cream.  Triamcinolone 0.1% cream treatment of 4 weeks will be followed by vehicle 
treatment for 4 weeks.  Subjects receiving QD regimens of INCB018424 cream will receive vehicle 
cream at the evening application. 
Study Schedule/Procedures: 
Study visits as follows: 
Screening:  Up to 28 days before enrollment.  Screening will begin at the time that the subject signs the 
informed consent and will continue until the date the subject is enrolled in the study (Day 1). 
Treatment:  Subjects will have study visits on Day 1 and at Weeks 2, 4, 8, 10, and 12 for assessment of 
safety and efficacy. 
Study drug will be applied in the clinic on the day of a study visit.  Subjects will be given a daily diary to 
record application times.  Subjects will also be instructed to bring all study drug tubes with them to each 
visit so that compliance can be assessed.  
Safety follow-up:  Subjects will have follow-up assessments 30 (± 7) days after the last dose of study 
drug to assess safety and efficacy.  If prohibited treatment for AD is started, then an earlier follow-up visit 
will be performed as a final, and thus end-of-study, visit. 
Safety assessments: 
At each scheduled study visits at the clinical site, targeted physical examinations, vital sign collection, 
laboratory assessments, collection of concomitant medications, and AE assessments will be performed.  A 
12-lead ECG will be performed at screening.  All laboratory assessments will be performed using a 




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Protocol INCB 18424-206 
15 SEP 2016 
CONFIDENTIAL 
TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................14 
1. 
INTRODUCTION ......................................................................................................16 
1.1. 
Atopic Dermatitis ........................................................................................................16 
1.2. 
Inflammation and Atopic Dermatitis ..........................................................................16 
1.3. 
Role of Janus Kinases in Atopic Dermatitis ...............................................................16 
 
17 
 
17 
 
18 
1.7. 
Clinical Experience .....................................................................................................20 
1.7.1. 
Clinical Efficacy With Topical INCB018424 in Psoriasis .........................................20 
1.7.2. 
Clinical  Experience With JAK Inhibition in Atopic Dermatitis ................................21 
 
21 
 
21 
 
21 
 
23 
1.7.5. 
Oral INCB018424 (Ruxolitinib) Safety......................................................................25 
 
26 
 
26 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................27 
2.1. 
Study Objectives .........................................................................................................27 
2.1.1. 
Primary Objective .......................................................................................................27 
2.1.2. 
Secondary Objectives .................................................................................................27 
2.1.2.1. 
Key Secondary Objective ...........................................................................................27 
2.1.2.2. 
Other Secondary Objective .........................................................................................27 
 
28 
2.2. 
Study Endpoints ..........................................................................................................28 
2.2.1. 
Primary Endpoint ........................................................................................................28 
2.2.2. 
Secondary Endpoints ..................................................................................................28 
2.2.2.1. 
Key Secondary Endpoints ...........................................................................................28 
2.2.2.2. 
Other Secondary Endpoints ........................................................................................28 


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Protocol INCB 18424-206 
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CONFIDENTIAL 
 
29 
3. 
SUBJECT ELIGIBILITY ...........................................................................................29 
3.1. 
Subject Inclusion Criteria ...........................................................................................29 
3.2. 
Subject Exclusion Criteria ..........................................................................................30 
4. 
INVESTIGATIONAL PLAN .....................................................................................32 
4.1. 
Overall Study Design ..................................................................................................32 
4.2. 
Measures Taken to Avoid Bias ...................................................................................33 
4.3. 
Number of Subjects ....................................................................................................33 
4.4. 
Duration of Treatment and Subject Participation .......................................................33 
4.5. 
Overall Study Duration ...............................................................................................33 
4.6. 
Study Termination ......................................................................................................34 
5. 
TREATMENT ............................................................................................................34 
5.1. 
Treatment Assignment ................................................................................................34 
5.1.1. 
Subject Numbering and Treatment Assignment .........................................................34 
5.1.2. 
Randomization and Blinding ......................................................................................34 
5.2. 
INCB018424 Cream, Matching Vehicle, or Active Comparator ...............................35 
5.2.1. 
Description and Administration ..................................................................................35 
5.2.2. 
Supply, Packaging, and Labeling ...............................................................................35 
5.2.3. 
Storage ........................................................................................................................35 
 
36 
5.3. 
Treatment Compliance ................................................................................................36 
5.4. 
Treatment Interruptions and Adjustments ..................................................................37 
5.4.1. 
Dose Modifications .....................................................................................................37 
5.4.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................37 
5.4.3. 
Criteria for Permanent Discontinuation of Study Drug ..............................................37 
5.5. 
Withdrawal of Subjects From Study Treatment .........................................................38 
5.5.1. 
Withdrawal Criteria ....................................................................................................38 
5.5.2. 
Withdrawal Procedures ...............................................................................................38 
5.6. 
Concomitant Medications ...........................................................................................39 
 
39 
 
39 
 
39 


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CONFIDENTIAL 
6. 
STUDY ASSESSMENTS ..........................................................................................40 
6.1. 
Screening ....................................................................................................................42 
6.2. 
Baseline .......................................................................................................................43 
6.3. 
Treatment ....................................................................................................................43 
6.4. 
End of Treatment/Early Termination ..........................................................................43 
6.5. 
Follow-Up ...................................................................................................................44 
6.6. 
Unscheduled Visits .....................................................................................................44 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................44 
7.1. 
Administration of Informed Consent Form ................................................................44 
7.2. 
Interactive Response Technology Procedure ..............................................................44 
7.3. 
Demography and Medical History ..............................................................................44 
7.3.1. 
Demographics and General Medical History .............................................................44 
7.3.2. 
Disease Characteristics and Treatment History ..........................................................45 
7.4. 
Prior and Concomitant Medications and Procedures ..................................................45 
7.5. 
Safety Assessments .....................................................................................................45 
7.5.1. 
Adverse Events ...........................................................................................................45 
7.5.2. 
Physical Examinations ................................................................................................45 
7.5.2.1. 
Comprehensive Physical Examination .......................................................................45 
7.5.2.2. 
Targeted Physical Examination ..................................................................................45 
7.5.3. 
Vital Signs ..................................................................................................................46 
7.5.4. 
Electrocardiograms .....................................................................................................46 
7.5.5. 
Laboratory Assessments .............................................................................................46 
7.5.5.1. 
Chemistry ....................................................................................................................46 
7.5.5.2. 
Hematology .................................................................................................................46 
7.5.5.3. 
Urinalysis ....................................................................................................................46 
7.5.5.4. 
Pregnancy Testing ......................................................................................................47 
7.5.5.5. 
Serology ......................................................................................................................47 
7.6. 
Efficacy Assessments .................................................................................................47 
7.6.1. 
Eczema Area and Severity Index Score ......................................................................47 
7.6.2. 
Investigator's Global Assessment ...............................................................................47 
 
47 
7.6.4. 
Itch Numerical Rating Scale .......................................................................................48 
 
48 


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Protocol INCB 18424-206 
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CONFIDENTIAL 
7.6.6. 
Photography ................................................................................................................48 
 
48 
 
48 
 
48 
 
48 
 
49 
 
49 
 
49 
7.10. 
Other Study Procedures ..............................................................................................49 
7.10.1. 
Distribution of Subject Diaries ...................................................................................49 
8. 
SAFETY MONITORING AND REPORTING .........................................................50 
8.1. 
Adverse Events ...........................................................................................................50 
8.1.1. 
Definitions ..................................................................................................................50 
8.1.2. 
Reporting ....................................................................................................................50 
8.2. 
Laboratory Test Abnormalities ...................................................................................51 
8.3. 
Serious Adverse Events ..............................................................................................52 
8.3.1. 
Definitions ..................................................................................................................52 
8.3.2. 
Reporting ....................................................................................................................52 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................53 
8.5. 
Pregnancy ...................................................................................................................54 
8.6. 
Warnings and Precautions ..........................................................................................54 
8.7. 
Data Monitoring Committee .......................................................................................54 
8.8. 
Product Complaints ....................................................................................................54 
9. 
STATISTICS ..............................................................................................................55 
9.1. 
Study Populations .......................................................................................................55 
9.2. 
Selection of Sample Size ............................................................................................55 
9.2.1. 
Graphical Procedure ...................................................................................................56 
9.2.1.1. 
Primary Analysis ........................................................................................................56 
9.2.1.2. 
Secondary Analysis ....................................................................................................57 
9.2.2. 
Noninferiority Margin ................................................................................................57 
9.2.3. 
Power Analysis ...........................................................................................................58 
9.3. 
Level of Significance ..................................................................................................58 
9.4. 
Statistical Analyses .....................................................................................................58 


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9.4.1. 
Efficacy Analyses .......................................................................................................58 
9.4.1.1. 
Efficacy Measures for Primary and Secondary Endpoints .........................................58 
9.4.1.2. 
Primary Efficacy Analyses .........................................................................................59 
9.4.1.3. 
Secondary Efficacy Analyses .....................................................................................59 
9.4.1.4. 
Other Efficacy Analyses .............................................................................................60 
9.4.2. 
Safety Analyses ..........................................................................................................60 
9.4.2.1. 
Adverse Events ...........................................................................................................60 
9.4.2.2. 
Clinical Laboratory Tests ...........................................................................................60 
9.4.2.3. 
Vital Signs ..................................................................................................................60 
9.4.2.4. 
Twelve-Lead Electrocardiograms ...............................................................................61 
 
61 
9.5. 
Analyses for the Data Monitoring Committee ............................................................61 
9.6. 
Interim Analysis ..........................................................................................................61 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ..........................................................................................................61 
10.1. 
Investigator Responsibilities .......................................................................................61 
10.2. 
Accountability, Handling, and Disposal of Study Drug .............................................63 
10.3. 
Data Management .......................................................................................................63 
10.4. 
Data Privacy and Confidentiality of Study Records ...................................................64 
10.5. 
Financial Disclosure ...................................................................................................64 
10.6. 
Publication Policy .......................................................................................................65 
11. 
REFERENCES ...........................................................................................................66 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................67 
APPENDIX B. ECZEMA AREA AND SEVERITY INDEX ....................................................68 
APPENDIX C. POTENT CYP3A4 INHIBITORS AND FLUCONAZOLE .............................70 
71 
APPENDIX E. STATISTICAL CONSIDERATIONS ...............................................................72 
 




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Protocol INCB 18424-206 
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CONFIDENTIAL 
LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Term 
Explanation 
AA 
alopecia areata 
AC 
active control 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANOVA 
analysis of variance 
AST 
aspartate aminotransferase 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cmax 
maximal plasma concentration 
COMFORT 
Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
EASI 
Eczema Area and Severity Index 
EASI-50 
≥ 50% improvement in EASI score 
ECG 
electrocardiogram 
eCRF 
electronic case report form  
EOT 
end of treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
H 
head 
HCV-RNA 
hepatitis C virus ribonucleic acid 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
IGA 
Investigator's Global Assessment 


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Protocol INCB 18424-206 
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CONFIDENTIAL 
Term 
Explanation 
IgM 
immunoglobulin M 
IL 
interleukin 
IN 
Investigator Notification 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent-to-treat 
JAK 
Janus kinase 
LL 
lower limbs 
MedDRA 
Medical Dictionary for Regulatory Activities 
ni. 
noninferiority 
NOAEL 
no-observed-adverse-effect level 
NRS 
Numerical Rating Scale 
PK 
pharmacokinetic 
PV 
polycythemia vera 
QD 
once daily 
RA 
rheumatoid arthritis 
RNA 
ribonucleic acid 
 
 
s. 
superiority 
SAE 
serious adverse event 
STAT 
signal transducers and activators of transcription 
SUSAR 
suspected unexpected serious adverse reaction 
T 
trunk 
TSH 
thyroid-stimulating hormone 
UL 
upper limbs 
ULN 
upper limit of normal 
V 
vehicle 


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Protocol INCB 18424-206 
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1. 
INTRODUCTION 
INCB018424 cream is a topical formulation of INCB018424 phosphate under development for 
the treatment of subjects with psoriasis, alopecia areata (AA), and atopic dermatitis (AD).  
INCB018424 phosphate is an inhibitor of the Janus kinase (JAK) family of protein tyrosine 
kinases.  Isogenic and inflammatory cytokines are strongly implicated in the pathogenesis of 
psoriasis, AA, and AD.  Because JAKs serve to translate extracellular signals from a number of 
relevant cytokines and growth factors upregulated in inflammatory diseases such as psoriasis, 
AA, and AD, JAK inhibitors represent potential therapeutic agents for these disease states. 
1.1. 
Atopic Dermatitis 
Atopic dermatitis affects approximately 20% of children and 10% of adults (Silverberg and 
Hanifin 2013), is increasing in incidence, and costs $3.8 billion a year in direct medical costs 
alone (Ellis et al 2002).  Although not life-threatening, patients with AD are at higher risk for the 
development of other life-threatening disorders such as asthma and food allergy (Spergel 2010).  
Furthermore, according to the recent Global Burden of Disease project, worldwide AD is one of 
the 50 most prevalent diseases, and it has the second highest disability rank of all nonmalignant 
skin diseases (Hay et al 2014).  Strikingly, despite the advances in targeted biologic treatments 
for psoriasis, no targeted therapies currently exist for AD. 
Topical therapies are limited to topical steroids, which have associated side effects from 
long-term use, including glucocorticoid-induced folliculitis and localized skin atrophy.  The use 
of systemic glucocorticoids is also limited because of the adverse event (AE) profile.  If current 
topical therapies fail, then systemic immunosuppressive agents (eg, cyclosporine, methotrexate) 
are occasionally employed with highly variable efficacy and/or high risk of AEs.  However, 
recent studies indicate that oral JAK inhibitors are effective in the treatment of AD (Levy et al 
2015).  New approaches that improve AD symptoms and quality of life without introducing 
safety issues are urgently needed. 
1.2. 
Inflammation and Atopic Dermatitis 
Type 2 inflammation is widely known to underlie the pathogenesis of AD.  A number of studies 
have highlighted that T helper type 2 cells, group 2 innate lymphoid cells, and basophils, which 
all produce the type 2 cytokines interleukin (IL)-4, IL-5, and/or IL-13, are highly pathogenic in 
the setting of AD (Kim 2015).  Indeed, all of these cells are increased in frequency in lesional 
skin from AD patients.  Further blockade of these type 2 cytokines decreases disease in both 
murine models and in patients (Kim et al 2014, Beck et al 2014).  Taken together, simultaneous 
disruption of multiple type 2 inflammatory cytokine–associated pathways via JAK inhibition 
may serve as a novel therapeutic modality in AD. 
1.3. 
Role of Janus Kinases in Atopic Dermatitis 
The type 2 cytokines IL-4 and IL-13 signaling through JAK1.  A number of drugs in clinical 
studies for AD are designed to block these cytokines and are highly promising new biologic 
agents (eg, dupilumab and lebrikizumab; Beck et al 2014).  However, these new drugs employ 
humanized monoclonal antibody-mediated approaches, which cannot be used topically.  Thus, 


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topical JAK1 inhibition presents a unique approach to develop a novel nonsteroidal 
anti-inflammatory agent.  Studies with oral tofacitinib (JAK1- and JAK3-inhibitor) have already 
demonstrated efficacy in AD.  Thus, topical treatment with INCB018424 phosphate is a highly 
promising approach for the treatment of AD.  To date, a topical JAK inhibitor with sufficient 
skin penetration has not yet been approved in AD.  The JAK1/2 inhibitor INCB018424 has been 
used systemically successfully in myeloproliferative disorders, and a topical formulation of 
INCB018424 has been developed and demonstrated to be active in subjects with psoriasis. 


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1.7. 
Clinical Experience 
1.7.1. 
Clinical Efficacy With Topical INCB018424 in Psoriasis 
In a double-blind, vehicle- or comparator-controlled, ascending dose, safety, tolerability, PK, and 
preliminary efficacy study of INCB018424 cream in subjects with plaque psoriasis 
(Study INCB 18424-201), efficacy was demonstrated with both the 1% cream applied QD and 
the 1.5% cream applied BID, with a trend toward a dose response.  Improvement in lesion 
thickness, erythema, scaling, and reduction in total lesion area were observed in comparison to 
the vehicle.  Reductions in mean lesion scores were 53% for 1% cream QD versus 32% for 
vehicle (p ≤ 0.05), 54% for 1.5% cream BID versus 27% for vehicle (p ≤ 0.05), 46% for 1.5% 
cream BID versus 40% for Dovonex® cream, and 58% for 1.5% cream BID versus 44% for 
Diprolene AF® cream. 
In an open-label, multicenter, sequential-cohort, dose-escalation, safety, tolerability, PK, 
pharmacodynamic, and preliminary efficacy study of INCB018424 1% or 1.5% cream applied to 
2% to 20% BSA QD or BID for 4 weeks in subjects with active, stable plaque psoriasis 
(Study INCB 18424-202), the efficacy analyses collectively revealed that all 5 regimens of 
INCB018424 cream, when applied for 28 days, were effective in decreasing the individual signs 
of lesion severity, lesion area, and the overall disease severity of psoriatic plaques.  Within each 
cohort, the mean individual and total psoriasis assessment scores for the treated lesions decreased 
from baseline to each subsequent assessment, indicating an overall lessening of disease severity.  
The total lesion scores for the control lesions within each cohort either increased from baseline, 
indicating a worsening of disease severity, or decreased marginally from baseline. 
Study INCB 18424-203 was a 12-week, randomized, multicenter, parallel-group, 
vehicle-controlled, double-blind, dose-ranging study designed to evaluate the safety and efficacy 
of QD application of  INCB018424 cream (0.5%, 1.0%, or 1.5%) relative to vehicle cream in 
subjects with stable plaque psoriasis.  Within each active treatment group, the mean scores for 
the individual and total psoriasis lesion assessments, the Psoriasis Area Severity Index, the 
Physician Global Assessment, and the mean treatable percentage of BSA decreased from 
baseline to each subsequent assessment, which indicated an overall lessening of disease severity.  
Thus, the efficacy analyses collectively revealed that all 3 doses of INCB018424 cream, when 
applied topically QD for 12 weeks, were effective in decreasing the individual signs of lesion 
severity, lesion area, and the overall disease severity of psoriatic plaques. 


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1.7.2. 
Clinical  Experience With JAK Inhibition in Atopic Dermatitis 
Topical tofacitinib 2% BID was studies in a Phase 2 randomized vehicle-controlled clinical study 
in subjects with mild to moderate AD.  Over a 4-week period, improvements were noted in 
disease activity (Eczema Area and Severity Index [EASI] and patient-reported pruritus) and it 
was generally safe and well-tolerated (Poulin et al 2015). 


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1.7.5. 
Oral INCB018424 (Ruxolitinib) Safety 
In the randomized period of the 2 pivotal studies in myelofibrosis, Controlled Myelofibrosis 
Study With Oral JAK Inhibitor Treatment (COMFORT)-I and COMFORT-II, discontinuation 
because of AEs regardless of causality was observed in 11.3% of subjects.  The most frequently 
reported adverse drug reactions were thrombocytopenia and anemia.  Hematological adverse 
reactions (any CTCAE grade) included anemia (82.4%), thrombocytopenia (69.8%), and 
neutropenia (16.6%).  Anemia, thrombocytopenia, and neutropenia are dose-related effects.  The 
3 most frequent nonhematological adverse reactions were bruising (21.6%), dizziness (15.3%), 
and headache (14.0%).  The 3 most frequent nonhematological laboratory abnormalities were 
increased alanine aminotransferase (ALT; 27.2%), increased aspartate aminotransferase (AST; 
18.6%), and hypercholesterolemia (16.9%). 
Long-term follow-up in subjects with myelofibrosis (including 615 subjects treated with 
ruxolitinib during the controlled and extension phases of Studies INCB 18424-251 cutoff 
01 OCT 2012, COMFORT-I cutoff 02 SEP 2012, and COMFORT-II cutoff 01 SEP 2012 has 
shown that, as expected, the numbers and proportions of AEs and SAEs has increased; however, 
no new safety signals have emerged (median duration of exposure for this population is 
27.6 months, with 1345.78 patient-years of exposure). 
In Study INCB 18424-258, in subjects with myelofibrosis with a platelet count between 50 and 
100 × 109/L, beginning treatment with 5 mg BID was well-tolerated, avoided levels of 
thrombocytopenia associated with a high risk of significant bleeding, and provided an 
opportunity to increase the dose of ruxolitinib in a safe manner. 
Overall, the safety profile of ruxolitinib in the polycythemia vera (PV) population is generally 
consistent with that observed in the myelofibrosis population.  Ruxolitinib was generally 
well-tolerated in subjects with PV, and only a small proportion of subjects discontinued 
ruxolitinib because of AEs (3.6%).  Most of the AEs were managed by dose modifications.  
Hematological toxicities were less frequent and less severe in subjects with PV as compared with 
those observed in subjects with myelofibrosis.  No new safety signals emerged from a study in 
pancreatic cancer in combination with capecitabine.   
The AE profile of ruxolitinib was also assessed in 198 healthy subjects, subjects with various 
degrees of renal (n = 32) or hepatic (n = 24) impairment, and subjects with rheumatoid arthritis 
(RA; n = 59).  Adverse events were, in general, mild and resolved without interventions. 


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A thorough QT study was conducted in 50 healthy subjects.  There was no indication of a 
QT/QTc-prolonging effect of ruxolitinib in single doses up to a supratherapeutic dose of 200 mg, 
indicating that ruxolitinib has no effect on cardiac repolarization. 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
• To establish the efficacy of each dose of INCB018424 QD or BID in subjects with 
AD compared with vehicle cream BID. 
2.1.2. 
Secondary Objectives 
2.1.2.1. 
Key Secondary Objective 
• To establish the efficacy of each dose of INCB018424 cream QD or BID in subjects 
with AD as compared with triamcinolone 0.1% cream BID. 
2.1.2.2. 
Other Secondary Objective 
• To evaluate the safety and tolerability of INCB018424 cream when applied QD or 
BID to subjects with AD. 


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2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoint 
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with 1.5% INCB018424 BID compared with subjects treated with vehicle cream BID. 
2.2.2. 
Secondary Endpoints 
2.2.2.1. 
Key Secondary Endpoints 
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with INCB018424 compared with subjects treated with vehicle cream BID.  
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with INCB018424 compared with subjects treated with triamcinolone 0.1% cream 
BID. 
2.2.2.2. 
Other Secondary Endpoints 
• Mean percentage change from baseline in EASI score at Week 2 and Week 8. 
• Proportion of subjects who achieve a ≥ 50% improvement from baseline in EASI 
(EASI-50) at Weeks 2, 4, and 8. 
• Assessment of dose response based on percentage change from baseline in EASI 
score at Week 4. 
• Time to achieve EASI-50. 
• Proportion of subjects achieving an Investigator's Global Assessment (IGA) score of 
0 to 1 who have an improvement of ≥ 2 points from baseline at Weeks 2, 4, and 8. 
• Mean change from baseline in the Itch Numerical Rating Scale (NRS) score at 
Weeks 2, 4, and 8. 
• Safety and tolerability assessed by monitoring the frequency, duration, and severity of 
AEs; performing physical examinations; collecting vital signs; and collecting 
laboratory data for hematology, serum chemistry, and urinalysis. 


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3. 
SUBJECT ELIGIBILITY 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or subject safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential. 
3.1. 
Subject Inclusion Criteria 
A subject who meets all of the following criteria may be included in the study: 
1. Adult men and women aged 18 to 70 years, inclusive. 
2. Subjects diagnosed with AD as defined by the Hanifin and Rajka (1980) criteria. 
3. Subjects with a history of AD for at least 2 years. 
4. Subjects with an IGA score of 2 to 3 at screening and baseline. 
5. Subjects with BSA of AD involvement, excluding the face and intertriginous areas, of 
3% to 20% at screening and baseline. 
6. Subjects who agree to discontinue all agents used to treat AD from screening through the 
final follow-up visit. 


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7. Willingness to avoid pregnancy or fathering of children based on the criteria below: 
a. Woman of nonchildbearing potential (surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR postmenopausal, defined by last menstrual period 
> 12 months before screening). 
b. Woman of childbearing potential who has a negative serum pregnancy test at 
screening and a negative urine pregnancy test before the first dose on Day 1 and who 
agrees to take appropriate precautions to avoid pregnancy (with at least 99% 
certainty) from screening through safety follow-up.  Permitted methods that are at 
least 99% effective in preventing pregnancy (see Appendix A) should be 
communicated to the subject and their understanding confirmed. 
c. Man who agrees to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through safety follow-up.  Permitted methods that 
are at least 99% effective in preventing pregnancy (see Appendix A) should be 
communicated to the subject and their understanding confirmed. 
8. Ability to comprehend and willingness to sign an informed consent form (ICF). 
3.2. 
Subject Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Subjects with evidence of acute acute or chronic infections. 
2. Use of topical treatments for AD (other than bland emollients) within 2 weeks of 
baseline. 
3. Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable 
corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 
4 weeks or 5 half-lives of baseline (whichever is longer). 
4. Subjects with other dermatologic disease besides AD whose presence or treatments could 
complicate the assessment of disease (eg, psoriasis). 
5. Subjects with a history of other diseases besides dermatologic disorders (eg, other 
autoimmune diseases) taking treatments that could complicate assessments. 
6. Subjects with cytopenias at screening, defined as: 
a. Leukocytes < 3.0 × 109/L. 
b. Neutrophils < lower limit of normal. 
c. Hemoglobin < 10 g/dL. 
d. Lymphocytes < 0.8 × 109/L.  
e. Platelets < 100 × 109/L. 
7. Subjects with severely impaired liver function (Child-Pugh Class C) or end-stage renal 
disease on dialysis or at least 1 of the following: 
a. Serum creatinine > 1.5 mg/dL. 
b. Alanine aminotransferase or AST ≥ 1.5 × upper limit of normal (ULN). 


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8. Subjects taking potent systemic CYP3A4 inhibitors or fluconazole within 2 weeks or 
5 half-lives, whichever is longer, before the baseline visit (topical agents with limited 
systemic availability are permitted, see Appendix C). 
9. Subjects who have previously received JAK inhibitors, systemic or topical (eg, 
ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib). 
10. Women who were pregnant or breastfeeding within 4 months before screening. 
11. Current or recent history (< 30 days before screening and/or < 45 days before 
randomization) of a clinically meaningful bacterial, fungal, parasitic, or mycobacterial 
infection. 
12. Positive serology test results for hepatitis B surface antigen or core antibody, or for 
hepatitis C virus antibody with detectable hepatitis C RNA at screening or human 
immunodeficiency virus (HIV) antibody. 
13. Current clinically meaningful viral infection (eg, eczema herpeticum). 
14. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute 
myocardial infarction within 6 months from Day 1 of study drug administration, New 
York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring 
therapy  or uncontrolled hypertension (blood pressure > 150/90 mmHg) unless approved 
by medical monitor/sponsor. 
15. 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 subject's ability 
to comply with the administration schedule and study assessments. 
16. 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. 
17. Use of any prohibited medications (see Section 5.6.3) within 14 days or 5 half-lives 
(whichever is longer) of the baseline visit. 
18. Donation of blood within 6 weeks before screening or of plasma within 2 weeks before 
screening and unwillingness to forego further blood product donation during the study. 
19. Receipt of blood products within 2 months before screening. 
20. Subjects with a history of malignancy, except for the following adequately treated, 
nonmetastatic malignancies:  basal cell skin cancer not involving the lesions being treated 
with study medication, squamous cell carcinomas of the skin not involving the lesions 
being treated with study medication, or in situ cervical cancer. 
21. Subjects who anticipate receiving a live or live-attenuated vaccination from screening 
through the final follow-up visit. 
22. Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the 
administration schedule and study evaluations. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is a randomized, vehicle- and active (triamcinolone 0.1% cream)-controlled study in 
subjects with mild to moderate AD.  The study is double-blinded for vehicle, INCB018424 
doses, and active control.  Approximately 300 subjects will be randomized 1:1:1:1:1:1 to 
INCB018424 1.5% BID, INCB018424 1.5% QD, INCB018424 0.5% QD, INCB018424 0.15% 
QD, vehicle BID, and active control (triamcinolone 0.1% cream BID) and stratified by EASI 
score (≤ 7 and > 7).  Subjects receiving QD regimens will apply vehicle at the evening 
application.  Subjects will receive blinded study drug for 8 weeks.  Subjects randomized to QD 
regimens will apply vehicle for the evening application.  Subjects randomized to triamcinolone 
will apply triamcinolone 0.1% cream BID for 4 weeks and vehicle cream for 4 weeks to not 
exceed the allowable triamcinolone application duration (Figure 2). 
At Week 8, subjects who meet criteria (compliant with the Protocol and no safety concerns) will 
be offered open-label treatment with INCB018424 1.5% cream BID for 4 weeks. 
Through Week 8, subjects should continue to treat areas identified for treatment at baseline even 
if the area begins to improve.  After Week 8, areas which were treated before Week 8 that are no 
longer symptomatic are not required to be treated. 
Subjects will have follow-up assessments 1 month after the last application of study drug. 
Study drug (INCB018424 cream, vehicle, or triamcinolone) may not be applied to the face or 
intertriginous areas.  The face and intertriginous areas may be treated with hydrocortisone 2.5% 
cream during the study.  Assessments of BSA should be based on treated areas (excluding the 
face and intertriginous areas that cannot be treated with study drug). 
Subjects who develop additional areas of AD after the initiation of treatment may treat these 
additional areas (except the face and intertriginous areas) as long as the total treated BSA does 
not exceed 20% and there are no safety concerns regarding the additional application of study 
drug. 
Subjects may continue to use bland emollients that do not contain urea or ceramides during the 
study.  If bland emollients are used, the type of cream and amount of application should remain 
consistent for the duration of the study. 
An interim analysis will be conducted when at least half of the randomized subjects reach 
Week 4.  These data will be assessed by an unblinded team at the sponsor who does not have 
direct contact with the study sites. 
Sites and the sponsor are blinded to study drug; however, some personnel at Incyte (without 
direct contact with sites) will be unblinded. 


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Figure 2: 
Study Design 
 
4.2. 
Measures Taken to Avoid Bias 
The study is randomized and double-blinded with a vehicle and active comparator (triamcinolone 
0.1% cream).  A designated site staff member will be assigned to dispense and collect study 
drug, as well as instruct and assist with application of study drug during the clinic visits.  This 
person should not have study responsibilities that involve either efficacy or safety assessments.  
Returned study drug should be collected before other study assessments being performed.  Study 
drug should be dispensed at the end of the visit by the same designated staff, after other visit 
assessments have been completed.  When the study drug is dispensed at the study visit, the 
morning dose of study drug for that visit should be applied.  The subject should be counseled at 
this time regarding questions about dose or method of application. 
4.3. 
Number of Subjects 
The study will randomize approximately 300 subjects in a ratio of 1:1:1:1:1:1.  Subjects who 
discontinue will not be replaced. 
4.4. 
Duration of Treatment and Subject Participation 
The total duration of participation will be up to 20 weeks, including up to 4 weeks for screening, 
8 weeks of double-blind treatment, 4 weeks of optional open-label treatment, and 4 weeks of 
safety follow-up. 
4.5. 
Overall Study Duration 
The study begins when the first subject signs the ICF.  The end of the study will occur when all 
subjects have discontinued study drug and have completed applicable follow-up assessments or 
been lost to follow-up. 


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4.6. 
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 institutional review board 
(IRB)/independent ethics committee (IEC) in writing of the study's completion or early 
termination, send a copy of the notification to the sponsor or sponsor's designee, and retain 
1 copy for the site study regulatory file. 
The sponsor may terminate the study electively or if required by regulatory decision.  If the study 
is terminated prematurely, the sponsor will notify the investigators, the IRBs and IECs, and 
regulatory bodies of the decision and reason for termination of the study.   
5. 
TREATMENT 
5.1. 
Treatment Assignment 
5.1.1. 
Subject Numbering and Treatment Assignment 
All subject numbers will be 6 digits; the first 3 digits will be the site number, and the last 3 digits will 
be the subject's number.  This subject number will be maintained throughout the study and will not 
be reassigned.  Subjects who withdraw consent or discontinue from the study after being assigned a 
subject number will retain their initial number. 
The study will utilize an interactive response technology (IRT) for management of study enrollment.  
The system will assign the subject study number, track subject visits, randomize according to the 
defined parameters, track study drug, and maintain the blind.  Site staff will contact the IRT after 
screening is completed to enroll the subject and to allocate the subject to treatment assignment and 
obtain the initial study drug assignment.  The investigator or designee will select the appropriate kit 
from their stock that corresponds to the information provided by the IRT and dispense the study drug 
to the subject.  All subsequent dispensing of study drug should follow this process.  Full details will 
be provided in the IRT manual.  
5.1.2. 
Randomization and Blinding 
For subjects who have met all study inclusion criteria and none of the exclusion criteria, the IRT 
should be contacted at baseline to obtain the study drug assignment. 
The IRT system will set minimum entry criteria for an IGA score of 2 or 3, a BSA 3% to 20%, and 
will stratify the treatment groups based on baseline EASI score of ≤ 7 and > 7.  If 1 or both of the 
limits are reached, the IRT will stop assigning randomization numbers to that group, and no 
additional subjects will be enrolled in that group.  Subjects, investigators, and the sponsor will 
remain blinded to each subject's treatment assignment throughout the study (with the exception 
of the unblinded team that will assess the results of interim analysis).  Emergency unblinding 
will occur if an AE requires the investigator to be made aware of the subject's treatment 
assignment (see emergency unblinding procedures in Section 8.4 and refer to the Study 
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5.2. 
INCB018424 Cream, Matching Vehicle, or Active Comparator 
5.2.1. 
Description and Administration 
INCB018424 1.5% cream, INCB018424 0.5% cream, INCB018424 0.15% cream, vehicle 
cream, or triamcinolone acetonide 0.1% cream will be applied topically as a thin film to the 
affected areas (except the face and intertriginous areas) in the morning and in the evening at least 
1 hour before bedtime, with applications at least 8 hours apart.  Application instructions will be 
provided at study visits and via a diary card given to the subjects.  Application instructions will 
state that the cream is for dermatological use only and not for ophthalmic use.  If sunscreen, 
makeup, or other cream has been applied to the areas to be treated, subjects should wash the 
treatment areas with mild soap and water and pat dry before application of study drug.  If used, 
topical anti-infectives or other topical treatments should be avoided for at least 1 hour before and 
after application of study drug to an area.  Subjects should be cautioned to avoid excessive 
exposure to either natural or artificial sunlight (including tanning booths, sun lamps, etc) and, 
when outdoors, should be advised to wear loose-fitting clothing that protects the treated area 
from the sun as well as apply sunscreen (see Section 5.6.1 for permitted sunscreens).  
Immediately after application of study drug, subjects are to wash hands thoroughly with soap and 
warm water. 
Vehicle cream is matching in appearance to the INCB018424 creams, except that it does not 
contain active drug.  Subjects receiving QD regimens of INCB018424 cream will receive vehicle 
cream at the evening application.  Triamcinolone acetonide 0.1% cream is in a different vehicle.  
Vehicle cream and triamcinolone 0.1% cream are to be applied in the same manner as 
INCB018424 cream. 
The prescribed dose of study drug is to be determined by weighing a tube before and after the 
subject applies a thin film of study drug to the affected areas.  For each 1% of BSA (palm with 
fingers) to be treated with study drug, approximately 2 inches (5 cm) of study drug may be used.  
Subjects will be advised to apply cream as a thin film to the affected areas and limit use to no 
more than 1 tube per application.   
For all study visits where applicable, study drug should be applied at the visit to verify proper 
dispensing and application by the subject. 
5.2.2. 
Supply, Packaging, and Labeling 
INCB018424 drug product will be provided as INCB018424 1.5%, 0.5%, and 0.15% cream, or 
vehicle 1.5% (w/w free base equivalent) of INCB018424 phosphate cream.  INCB018424 cream 
(all doses), INCB018424 vehicle cream, and triamcinolone 0.1% cream and will be packaged as 
15 grams per tube.  Tubes will include labeling for morning or evening application. 
Tubes will include labeling in the local language and will comply with the legal requirements of 
each country. 
5.2.3. 
Storage 
The INCB018424 drug product and vehicle cream should be stored between 15°C and 30°C 
(59°F and 86°F). 


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5.3. 
Treatment Compliance 
Compliance will be assessed for frequency of administration and total amount of application of 
study drug by reviewing the subject diaries and by weighing the study drug tubes.  Subjects will 
also be questioned regarding study drug application technique, missing doses, and use of any 
additional topical or systemic prescriptions of other products or over-the-counter products.  
Starting at the Day 1 visit and each visit thereafter, a diary will be given to each subject in order 
to record use of the study drug.  The completed diary will be collected during each visit.  
Qualified clinical staff will review the subjects' entries for compliance.  Subjects who are 
noncompliant with study drug (defined as < 80% or > 120% compliant based on expected 
application regimen and weight of study drug tubes) will have their administration instructions 
reinforced by the investigator or a qualified designee.  Subjects 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 treatment portion of the study.  Subjects who are 


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noncompliant on more than 1 occasion will be reinstructed by the investigator or a qualified 
designee, and the sponsor should be consulted by the investigator for instruction on the proper 
handling of the subject. 
5.4. 
Treatment Interruptions and Adjustments 
5.4.1. 
Dose Modifications 
Subjects who have additional areas of AD develop after the initiation of treatment may treat 
these additional areas (except the face and intertriginous areas) as long as the total treated BSA 
does not exceed 20%, amount of study drug applied does not exceed 1 tube per application, and 
there are no safety concerns regarding the additional application of study drug.  After Week 8, 
areas that were treated before Week 8 that are no longer symptomatic are not required to be 
treated. 
5.4.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or laboratory abnormalities that may have an unclear relationship to study drug.  Except in cases 
of emergency, it is recommended that the investigator consult with the sponsor medical monitor 
(or other representative of the sponsor) before temporarily interrupting study drug.  Additionally, 
the investigator must obtain approval from the sponsor before restarting study drug that was 
temporarily interrupted because of an AE or laboratory abnormality. 
Individual subjects may have administration interrupted at the discretion of the investigator, in 
consultation with the sponsor, for AEs or laboratory abnormalities until these have resolved.  
Subjects MUST have administration interrupted in the following situations: 
• The subject develops a Grade 2 increase in ALT (> 3 × ULN) or AST (> 3 × ULN), 
or a Grade 2 decrease in ANC (< 1.5 × 109/L) or platelets (< 75 × 109/L), or a Grade 3 
decrease in absolute lymphocyte count (< 0.5 × 109/L).  Laboratory abnormalities 
should be confirmed with repeat testing within 48 hours whenever possible and STAT 
delivery of the laboratory results requested. 
• The subject develops a Grade 3 or higher laboratory abnormality, with the exceptions 
of lipase (in which case a Grade 4, > 5 × ULN, results in discontinuation of study 
medication) or any asymptomatic triglyceride, cholesterol, or amylase elevations.  
Laboratory abnormalities should be confirmed with repeat testing within a medically 
indicated timeframe, based upon the investigator's judgment and in collaboration with 
the sponsor's medical monitor, and STAT delivery of the laboratory results requested. 
• The subject had a Grade 3 or 4 drug-related AE as determined by the investigator. 
5.4.3. 
Criteria for Permanent Discontinuation of Study Drug 
Subjects who have administration interrupted based on above criteria will be followed until the 
parameters return to the normal range or to baseline values.  Laboratory evaluations can be 
repeated as frequently as daily.  A subject who has had their dose interrupted based on these 
criteria may resume administration with study drug at a later time if the subject no longer meets 
the criteria for interrupting the dose with the sponsor's approval in consultation with the 


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investigator.  Subjects who meet withdrawal criteria (see Section 5.5.1) during study drug 
interruption will be withdrawn from the study and may not resume administration. 
5.5. 
Withdrawal of Subjects From Study Treatment 
5.5.1. 
Withdrawal Criteria 
Subjects must be withdrawn from study treatment for the following reasons: 
• The subject becomes pregnant. 
• Consent is withdrawn.   
• Further participation would be injurious to the subject's health or well-being, in the 
investigator's medical judgment. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A subject may be discontinued from study treatment as follows: 
• If, during the course of the study, a subject is found not to have met eligibility 
criteria, then the medical monitor, in collaboration with the investigator, will 
determine whether the subject should be withdrawn from the study. 
• Subjects who are noncompliant with study drug (defined as < 80% or > 120% 
compliant based on tube weight) will have the administration instructions reinforced 
by the investigator or a qualified designee.  After reinforcement, subjects who again 
fail to meet < 80% or > 120% compliance benchmarks in a subsequent visit will be 
considered for withdrawal from the study.  In such cases, the sponsor should be 
consulted by the investigator for instruction on the proper handling of the subject 
before withdrawal. 
• If a subject is noncompliant with study procedures in the investigator's opinion, the 
sponsor should be consulted for instruction on handling the subject. 
5.5.2. 
Withdrawal Procedures 
In the event that the decision is made to permanently discontinue the study drug, the subject will 
be withdrawn from the study and the end-of-treatment (EOT) visit should be conducted.  
Reasonable efforts should be made to have the subject return for a follow-up visit.  These visits 
are described in Section 6.  The last date of the last dose of study drug and the reason for subject 
withdrawal will be recorded in the electronic case report form (eCRF). 
If a subject is withdrawn from the study: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal must be documented in the subject's medical record and 
in the eCRF. 
• The EOT visit should be performed. 


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• The date of the EOT visit should be recorded in the IRT. 
• Subjects 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 subject 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, subjects will have the option of discontinuing study drug but continuing 
in the follow-up period of the study for safety/efficacy assessments. 
5.6. 
Concomitant Medications 
All concomitant medications and treatments must be recorded in the eCRF and ideally should 
remain stable through the end of the treatment portion of the study.  All prior medications for AD 
and any medications received up to 30 days before randomization will be recorded in the eCRF.  
Concomitant treatments and/or procedures that are required to manage a subject's medical 
condition during the study will also be recorded in the eCRF. 


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6. 
STUDY ASSESSMENTS 
All study assessments will be performed as indicated in the schedule of assessments (Table 2), 
and all laboratory assessments will be performed as indicated in Table 3.


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Table 2: 
Schedule of Assessments 
Evaluation 
Protocol 
Section 
Screening 
Treatment 
EOT 
Follow-Up 
Day -28 
to -1 
Baseline 
Day 1 
Week 2 
Day 14 
± 3 Days 
Week 4 
Day 28 
± 3 Days 
Week 8 
Day 56 
± 7 Days 
Week 10 
Day 70 
± 3 Days 
Week 12 
Day 84 
± 7 Days 
30 ± 7 Days 
After Last 
Dose 
Administrative procedures 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
Contact IRT 
7.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inclusion/exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
 
Demography and medical history 
7.3 
X 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
7.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug and diary card 
7.10.1 
 
X 
X 
X 
X 
X 
 
 
 
Apply study drug 
5.2 
 
X 
X 
X 
X 
X 
 
 
 
Collect study drug tubes and review diary cards 
7.10.1 
 
 
X 
X 
X 
X 
X 
X 
 
Assess compliance 
5.3 
 
 
X 
X 
X 
X 
X 
X 
 
Safety procedures/assessments 
Comprehensive physical examination (height 
and weight at screening only) 
7.5.2.1 
X 
 
 
 
 
 
 
 
X 
Targeted physical examination 
7.5.2.2 
 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
7.5.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and chemistry assessments 
7.5.5 
X 
X 
X 
X 
X 
X 
X 
X 
 
Free T4 and thyroid stimulating hormone 
 
X 
 
 
 
 
 
 
 
 
Urinalysis 
7.5.5.3 
X 
 
 
 
 
 
 
 
 
Pregnancy testa 
7.5.5.4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serology 
7.5.5.5 
X 
 
 
 
 
 
 
 
 
12-lead ECG 
7.5.4 
X 
 
 
 
 
 
 
 
 
Assess AEs 
7.5.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Efficacy assessments 
EASI scoring 
7.6.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BSA treated w/study drug (4 regions and overall) 
7.6.5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA 
7.6.2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Photography 
7.6.6 
 
X 
 
X 
 
 
 
 
 
Itch Numerical Rating Scale 
7.6.4 
Diary is completed each evening from screening through the last dose of study drug. 
 
 
a All women will have a serum pregnancy test conducted at the screening visit and urine pregnancy tests conducted at all other visits (including baseline). 


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Table 3: 
Clinical Laboratory Assessments 
Serum Chemistries 
Hematology 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphorus 
Potassium 
Sodium 
Total bilirubin 
Total serum protein 
Hematocrit 
Hemoglobin 
Mean corpuscular volume 
Platelet count 
Red blood cell count 
Reticulocyte count 
White blood cell count 
White blood cell differential  (5 part): 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Other 
Serology 
Urinalysis 
Urine pregnancy test (at site) 
Serum pregnancy test 
Free T4 
TSH 
Hepatitis B surface antigen 
Hepatitis B core antibody 
Hepatitis B core IgM antibody 
Hepatitis C virus antibody 
HCV-RNA (only performed if antibody positive) 
HIV antibody 
HCV-RNA = hepatitis C virus ribonucleic acid; IgM = immunoglobulin M; TSH = thyroid-stimulating hormone. 
6.1. 
Screening 
Screening is the interval between the signing of the ICF and the day that the subject is enrolled in 
the study.  Informed consent must be obtained before performing any study-specific procedures.  
Assessments that are required to demonstrate eligibility may be performed over the course of 
1 or more days during screening. 
Results from the screening evaluations will be reviewed to confirm subject eligibility before 
randomization or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error.  Additionally, a subject who fails screening may repeat the screening process 1 time if 
the investigator believes that there has been a change in eligibility status (eg, following recovery 
from an infection). 


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6.2. 
Baseline 
The results from the screening evaluations will be reviewed to determine whether the subject 
continues to meet the eligibility requirements as specified in the Protocol. 
Subjects who have signed the ICF and meet all the entry criteria (see Section 3) may be enrolled 
or randomized in the study on Day 1. 
6.3. 
Treatment 
Subjects who meet all of the study inclusion criteria and none of the exclusion criteria will return 
to the study site on Day 1 of administration.  Dates for subsequent study visits will be determined 
based on this day and should occur within the visit windows outlined in the schedule of 
assessments (Table 2). 
The treatment period begins when the subject receives their first dose of study drug, which will 
be administered in the clinic.  The amount of study medication to be obtained from the pharmacy 
is determined by the BSA to be treated.  On Day 1, the prescribed dose is to be determined by 
weighing a tube before and after the subject applies a thin film of study drug to the affected 
areas.  For each 1% of BSA (palm with fingers) to be treated with study drug, approximately 
2 inches (5 cm) of study drug may be used.  Subjects will be advised to limit use to no more than 
1 tube per application.  Tubes of INCB018424 cream, triamcinolone 0.1% cream, or vehicle 
cream will be dispensed to subjects with detailed application instructions.  The face and 
intertriginous areas may be treated with hydrocortisone 2.5% cream throughout the study. 
For all study visits, subjects should apply the morning dose of study drug in the clinic to assess 
understanding of dispensing and application.  A designated site staff member will be assigned to 
dispense and collect study drug, as well as instruct and assist with application of study drug 
during the clinic visits.  This person should not have study responsibilities that involve either 
efficacy or safety assessments.  Returned study drug should be collected before other study 
assessments being performed.  Study drug should be dispensed at the end of the visit by the same 
designated staff, after other visit assessments have been completed.  The subject should be 
counseled at this time regarding questions about dose or method of application. 
Subjects who are noncompliant with study drug (defined as < 80% or > 120% compliant based 
on tube weight) will have the administration instructions reinforced by the investigator or a 
qualified designee.  After reinforcement, subjects who again fail to meet < 80% or > 120% 
compliance benchmarks in a subsequent visit will be considered for withdrawal from the study.  
In such cases, the sponsor should be consulted by the investigator for instruction on the proper 
handling of the subject before withdrawal. 
6.4. 
End of Treatment/Early Termination 
If a decision is made that the subject will permanently discontinue study drug, then the EOT visit 
should be conducted.  If the EOT visit coincides with a regular study visit, then the EOT 
evaluations will supersede those of that scheduled visit, and the data should be entered in the 
EOT page in the eCRF.  If this decision does not coincide with a regular visit, reasonable efforts 
should be made to have the subject return to the site to have the EOT procedures completed. 


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6.5. 
Follow-Up 
After the EOT visit (Weeks 8 or 12, or early termination), subjects will have follow-up 
assessments 1 month later to monitor for durability of effect (relapse rate), AEs, medication 
history, vital signs, and clinical assessments.  If prohibited treatment for AD is started, an earlier 
follow-up visit may be performed.  A final and thus end-of-study visit should be performed 
ideally no earlier than 30 days after the last dose of study drug.  Adverse events and SAEs must 
be reported up until at least 30 days after the last dose of study drug, the date of the follow-up 
visit, or until toxicities resolve, return to baseline, or are deemed irreversible, whichever is 
longer.  If needed, a follow-up phone call will be conducted to determine any AEs or SAEs 
during the 30 days after the last dose of study drug.  Reasonable efforts should be made to have 
the subject return for the follow-up visit and report any AEs that may occur during follow-up. 
6.6. 
Unscheduled Visits 
Unscheduled study visits may occur at any time medically warranted.  Any assessments 
performed at those visits should be recorded in the eCRF.   
If the subject develops new areas of AD, treatment of the new areas may begin after 
documenting of the new EASI score and photography of the new or expanding areas.  This may 
occur at an unscheduled visit. 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained from the study subject before conducting any 
study-specific procedures using an ICF approved by the local IRB/IEC that contains all elements 
required by ICH E6 and describes the nature, scope, and possible consequences of the study in a 
form understandable to the study subject.  Local and institutional guidelines for ICF content and 
administration must be followed; the original signed ICF must be retained by the investigator, 
and a copy of the signed ICF must be provided to the study subject.  The informed consent 
process for each subject must be documented in writing within the subject source documentation. 
7.2. 
Interactive Response Technology Procedure 
The IRT will be contacted to obtain a subject ID number when a subject enters screening.  Upon 
determining that the subject 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 to 
update the study drug supply.  Full details will be provided in the IRT manual. 
7.3. 
Demography and Medical History 
7.3.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening. 


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7.3.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and medication history will be collected at screening. 
7.4. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine subject 
eligibility.  All concomitant medications and measures must be recorded in the eCRF, and any 
medication received or procedure performed within 30 days before randomization and up to the 
end of study will be recorded in the eCRF.  The medication record will be maintained after 
signing the ICF to document concomitant medications, including any changes to the dose or 
regimen.  Concomitant medications include any prescription, over-the-counter, or natural/herbal 
preparations taken or administered during the study period.  Concomitant treatments and/or 
procedures that are required to manage a subject's medical condition during the study will also be 
recorded in the eCRF. 
7.5. 
Safety Assessments 
7.5.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs the ICF.  Subjects will be 
instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, subjects will be asked general, 
nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and eCRFs regardless of the assumption of a causal 
relationship with the study drug.  The definition, reporting, and recording requirements for AEs 
are described in Section 8. 
7.5.2. 
Physical Examinations 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits. 
Clinically notable abnormalities that are considered clinically significant in the judgement of the 
investigator are to be reported as AEs. 
7.5.2.1. 
Comprehensive Physical Examination 
The comprehensive physical examination will include height and body weight (at screening 
only) and assessment of the following organ or body systems:  skin; head, eyes, ears, nose, and 
throat; thyroid; lungs; cardiovascular system; abdomen (liver, spleen); extremities; and lymph 
nodes; as well as a brief neurological examination. 
7.5.2.2. 
Targeted Physical Examination 
The targeted physical examination will be a symptom-directed evaluation.  The targeted physical 
examination will include assessment of the body systems or organs, as indicated by subject 
symptoms, AEs, or other findings. 


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7.5.3. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the subject in the sitting position after 5 minutes of 
rest.  Clinically notable abnormalities that are considered clinically significant in the judgment of 
the investigator are to be reported as AEs. 
7.5.4. 
Electrocardiograms 
All 12-lead ECG will be performed with the subject in a recumbent or semirecumbent position 
after 5 minutes of rest. 
The 12-lead ECGs will be interpreted by the investigator at the site to be used for immediate 
subject management.  The decision to include or exclude a subject or withdraw a subject from 
the study based on an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of 
the investigator, in consultation with the sponsor's medical monitor, as appropriate.  Clinically 
notable abnormalities that are considered clinically significant in the judgment of the investigator 
are to be reported as AEs. 
7.5.5. 
Laboratory Assessments 
Clinical laboratory tests will be performed using a central laboratory.  A detailed description of 
the procedures for sampling, handling, storage, and shipment of the central laboratory samples 
and all material such as test tubes and labels is provided in the central Laboratory Manual.  If 
unscheduled local laboratory tests are performed, and if those results lead to a dose modification, 
delay, or dose interruption, or if any additional non-Protocol–required test is performed because 
of an AE, then those results and the normal reference ranges for those analytes must be 
documented in the eCRF.  Otherwise, unscheduled local laboratory test results need not be 
entered in the eCRF. 
Additional analytes may be requested based on emerging data, if indicated for safety of study 
subjects.  In addition, some subjects may receive additional assessments as medically indicated; 
results of nonrequired tests may also be entered in the eCRF. 
7.5.5.1. 
Chemistry 
A panel of standard serum chemistries will be analyzed at times shown in Table 2.  A list of 
required analytes is found in Table 3.  All serum chemistries will be performed from blood 
samples collected without respect to food intake (ie, nonfasted). 
7.5.5.2. 
Hematology 
Hematology tests will be performed at each study visit indicated in Table 2.  A list of required 
analytes for scheduled visits is provided in Table 3. 
7.5.5.3. 
Urinalysis 
Urinalysis will be performed at screening indicated in Table 2. 


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7.5.5.4. 
Pregnancy Testing 
Pregnancy testing will be performed on all female subjects as noted in the schedules of 
assessments (Table 2).  Serum pregnancy test will be obtained at screening.  A urine pregnancy 
test will be obtained all other visits.  A positive urine pregnancy test should be confirmed by a 
serum pregnancy test. 
7.5.5.5. 
Serology 
Subjects will be tested for hepatitis and HIV as shown in Table 3.  Serology will be conducted 
during the screening period.  This thorough hepatitis testing is being obtained to better interpret 
any abnormalities in liver function tests that may develop during the course of the study; 
therefore, it is not mandatory that results of all tests be available before enrollment (Day 1) if 
clinical evaluation and medical history provide no reason to suspect ongoing active or subclinical 
hepatitis infection. 
7.6. 
Efficacy Assessments 
7.6.1. 
Eczema Area and Severity Index Score 
Atopic dermatitis will be assessed using the EASI scoring system (Appendix B), which is a 
validated disease measurement for clinical studies (Hanifin et al 2001).  The severity strata for 
the EASI are as follows:  0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 
21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe (Leshem et al 2015). 
7.6.2. 
Investigator's Global Assessment 
The grades for the IGA are shown in Table 4. 
Table 4: 
Investigator's Global Assessment 
Grade 
Severity 
Status 
0 
Clear 
No inflammatory signs of AD 
1 
Almost clear 
Just perceptible erythema and just perceptible papulation/infiltration 
2 
Mild disease 
Mild erythema and mild papulation/infiltration 
3 
Moderate disease 
Moderate erythema and moderate papulation/infiltration 
4 
Severe disease 
Severe erythema and severe papulation/infiltration 
5 
Very severe disease 
Severe erythema and severe papulation/infiltration with oozing/crusting 


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7.6.4. 
Itch Numerical Rating Scale 
The Itch NRS is a daily patient-reported measure (24-hour recall) of itch intensity.  Subjects will 
be asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) 
to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. 
Subjects will be issued a hand-held device (eDiary) on which to record itch severity.  The subject 
will be instructed to complete the eDiary each night beginning on the day of screening through 
treatment discontinuation.  Subjects will bring the device to the study site at each study visit so 
that the device charging can be verified and accumulated data can be downloaded, as applicable.  
The device will then be returned to the subject for continued use each night.  The subject will 
return the device and the docking station for the final time at the EOT visit so that the data can be 
archived.  Detailed directions for the administration of the eDiary will be provided in the Study 
Reference Manual. 
7.6.6. 
Photography 
For each visit with photography (baseline and Week 4), photographs of the areas of AD 
 
 will be obtained. 


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7.10. 
Other Study Procedures 
7.10.1. 
Distribution of Subject Diaries 
Starting at the Day 1 visit and each visit thereafter, a diary will be given to each subject in order 
to record use of the study product.  The completed diary will be collected during the subject's 
visit.  Qualified clinical staff will review the subjects' entries for compliance.  Subjects who are 
noncompliant with either their study drug (defined as < 80% or > 120% compliant based on 
prescribed application regimen and weight of study drug tubes) will have their administration 
instructions reinforced by the investigator or a qualified designee.  Subjects 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 treatment phase of the study. 


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8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions 
For the purposes of this Protocol, an AE is defined as any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug related, that occurs 
after a subject provides informed consent.  Abnormal laboratory values or test results occurring 
after informed consent constitute AEs only if they induce clinical signs or symptoms, are 
considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
8.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 30 days after the last dose of study drug.  Adverse 
events (including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible rather than by individual underlying signs and symptoms.  When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
The severity of AEs will be assessed using CTCAE v4.03 Grades 1 through 4.  The CTCAE 
v4.03 severity of Grade 5 will not be used; AEs resulting in death will be graded accordingly 
using Grades 1 through 4 and have the outcome noted as fatal.  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: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention 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 intervention indicated. 
The occurrence of AEs should be sought by nondirective questioning of the subject during the 
screening process after signing the ICF and at each visit during the study.  Adverse events may 
also be detected when they are volunteered by the subject during the screening process or 
between visits, or through physical examination, laboratory test, or other assessments.  To the 
extent possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 4). 
• Whether there is at least a reasonable possibility that the AE is related to the study 
treatment:  suspected (yes) or not suspected (no). 


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• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, 
recovering/resolving, recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per SAE definition provided in Section 8.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements (see Section 8.3.2). 
All AEs should be treated appropriately.  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event form and the treatment should 
be specified on the Prior/Concomitant Medications or Procedures and Non-Drug Therapy form 
in the eCRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves.  For example, 
2 separate AEs will be reported if a subject has Grade 1 diarrhea, meeting the definition of an AE 
that lasts for 3 days before worsening to a Grade 3 severity.  The Grade 1 event will be reported 
as an AE with a start date equal to the day the event met the Grade 1 AE definition and a stop 
date equal to the day that the event increased in severity from Grade 1 to Grade 3.  The Grade 3 
event will also be reported as an AE, with the start date equal to the day the event changed in 
intensity from Grade 1 to Grade 3 and a stop date equal to the day that the event either changed 
severity again or resolved. 
8.2. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug) should be recorded on the Adverse Event form in the eCRF.  Whenever possible, a 
diagnosis rather than a symptom should be provided (eg, "anemia" instead of "low hemoglobin").  
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or an adequate explanation of the abnormality is found.  When an abnormal 
laboratory test result corresponds to a sign or symptom of a previously reported AE, it is not 
necessary to separately record the laboratory test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 (severe) AE does not automatically indicate an SAE unless it meets the definition 
of serious, as defined in Section 8.3.1.  A dose modification for the laboratory abnormality may 
be required (see Section 5.4) and should not contribute to the designation of a laboratory test 
abnormality as an SAE. 


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8.3. 
Serious Adverse Events 
8.3.1. 
Definitions 
An SAE is defined as an event that meets at least 1 of the following criteria: 
• Is fatal or life-threatening. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− A routine treatment or monitoring of the studied indication not associated with 
any deterioration in condition. 
− An elective surgery or preplanned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since signing the 
ICF. 
− A treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE and not resulting in hospital admission. 
− Any social reasons and respite care, in the absence of any deterioration in the 
subject's general condition. 
• Results in persistent or significant disability, incapacity, or a substantial disruption of 
a person's ability to conduct normal life functions. 
• Constitutes a congenital anomaly or birth defect. 
• Is considered to be an important medical event or a medically significant 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 subject or may require medical or surgical intervention to prevent 
1 of the outcomes listed above. 
8.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drug(s) or study 
procedure or disease progression), occurring after the subject has signed the ICF through the last 
study visit (or 30 days after the last dose of study drug, whichever is later) must be reported to 
the sponsor (or designee) within 24 hours of learning of its occurrence, unless otherwise 
specified by the Protocol.  Any SAEs occurring more than 30 days after the last dose of study 
drug should be reported to the sponsor or its designee only if the investigator suspects a causal 
relationship to the study drug.   
Information about all SAEs is collected and recorded on the Adverse Event form of the eCRF.  
The investigator must assess and record the causal relationship of each SAE to the study 
treatment.  
The investigator must also complete the Incyte Serious Adverse Event Report Form, in English, 
and send the completed and signed form to the sponsor or designee within 24 hours of becoming 
aware of the SAE.  The investigator must provide a causality assessment, that is, assess whether 
there is at least a reasonable possibility that the SAE is related to the study treatment:  suspected 


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(yes) or not suspected (no).  Refer to the Incyte Reference Guide for Completing the Serious 
Adverse Event Report Form. 
The contact information of the sponsor's study-specific representatives is listed in the 
investigator manual provided to each site.  The original copy of the SAE Report Form and the 
confirmation sheet must be kept at the study site. 
Investigational site personnel must report any new information regarding the SAE within 
24 hours of becoming aware of the information in the same manner that the initial SAE Report 
Form was sent.  Follow-up information is recorded on an amended or new SAE Report Form, 
with an indication that it is follow-up to the previously reported SAE and the date of the original 
report.  The follow-up report should include information that was not provided on the previous 
SAE Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or subject 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. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification (IN) to inform all investigators involved in any 
study with the same drug that this SAE has been reported.  Suspected Unexpected Serious 
Adverse Reactions (SUSARs) will be collected and reported to the competent authorities and 
relevant ethics committees in accordance with Directive 2001/20/EC, or as per national 
regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
The procedure for emergency unblinding is provided in the study reference manual.  This option 
may be used ONLY if the subject's well-being requires the investigator to be aware of the 
subject's treatment assignment. 
The investigator should make every effort to contact the sponsor's (or its designee's) clinical 
research physician or medical monitor before unblinding a subject's treatment assignment; 
however, this is not mandatory.  If a subject's treatment assignment is unblinded, the sponsor or 
its designee must be notified immediately by telephone. 
If an investigator, site personnel performing assessments, or subject is unblinded, the subject 
must be withdrawn from the study treatment.  In cases where there are ethical reasons to have the 
subject remain in the study, the investigator must obtain specific approval from the sponsor's (or 
its designee's) clinical research physician or medical monitor for the subject to continue in the 
study. 


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8.5. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a subject during maternal or paternal exposure to study drug, 
the following procedures should be followed in order to ensure subject safety: 
• The study drug must be discontinued immediately (female subjects only; see 
Section 5.4 for the maximum permitted duration of study drug interruption). 
• 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 and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up should be conducted for each pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy form 
and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up information 
should be recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the 
first well-baby visit or the duration specified in local regulations, whichever is later.  Refer to the 
Incyte Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy must be recorded on the SAE report form and 
submitted to the sponsor or designee. 
8.6. 
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 Investigator's Brochure (IB).  Additional safety 
information collected between IB updates will be communicated in the form of Investigator 
Notifications (INs).  Any important new safety information should be discussed with the subject 
during the study, as necessary.  If new significant risks are identified, they will be added to the 
ICF. 
8.7. 
Data Monitoring Committee 
No external data monitoring committee will be used; however, an internal data monitoring 
committee will examine the interim analysis. 
8.8. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 


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The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be reported as described in Section 8.1.2 of this Protocol. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9. 
STATISTICS 
9.1. 
Study Populations 
The intent-to-treat (ITT) population includes all randomized subjects.  Treatment groups for this 
population will be defined according to the treatment assignment at randomization. 
The per protocol population includes randomized subjects who are considered to be sufficiently 
compliant with the Protocol. 
The safety evaluable population includes all subjects who applied at least 1 dose of study drug.  
Treatment groups for this population will be determined according to the actual treatment the 
subject received on Day 1. 
9.2. 
Selection of Sample Size 
The assumptions in Table 5 were used for the percentage change from baseline in EASI scores at 
Week 4. 
Table 5: 
Assumed Percentage Change From Baseline in EASI at Week 4 
Treatment 
Percentage Change 
Vehicle 
30% 
Triamcinolone 0.1% (active control) 
50% 
INCB018424 1.5% BID 
75% 
INCB018424 1.5% QD 
65% 
INCB018424 0.5% QD 
50% 
INCB018424 0.15% QD 
30% 
The standard deviation was assumed to be 0.13 (13%).  These assumptions were based on the 
review of a historical clinical study in AD (Beck et al 2014). 
In order to provide a large safety database and to provided adequate power for efficacy variables, 
the total sample size for the study is 300 subjects randomized in a 1:1:1:1:1:1 ratio (stratified by 
baseline EASI score) to INCB018424 1.5% BID, INCB018424 1.5% QD, INCB018424 0.5% 
QD, INCB018424 0.15% QD, triamcinolone (active control), and vehicle.  


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9.2.1. 
Graphical Procedure 
A graphical procedure with gatekeeping testing strategy for the primary and key secondary 
analyses will be implemented.  A family of 7 elementary hypotheses, corresponding to treatment 
comparison between each active dose group to vehicle or triamcinolone is evaluated in Figure 3 
based on the percentage change from baseline to Week 4 of EASI score. 
The primary endpoint will test the superiority of INCB018424 1.5% BID compared with vehicle.  
The key secondary endpoint has 2 branches.  Branch 1 will test whether: 
• INCB018424 1.5% BID is noninferior to triamcinolone (active control) 
• INCB018424 1.5% QD is noninferior to triamcinolone (active control) 
• INCB018424 1.5% BID is superior to triamcinolone (active control) 
• INCB018424 1.5% QD is superior to triamcinolone (active control) 
Branch 2 will test whether: 
• INCB018424 1.5% QD is superior to vehicle 
• INCB018424 0.5% QD is superior to vehicle 
Figure 3: 
Illustration of the Statistical Treatment Comparisons  
 
AC = active control; s = superiority; ni = noninferiority; V = vehicle. 
9.2.1.1. 
Primary Analysis 
The primary alternative hypothesis (superiority of INCB018424 1.5% BID compared with 
vehicle) will be tested at a 2-sided α = 0.05 level.  The test on the primary endpoint will be used 


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as a gatekeeper for 6 statistical tests on secondary endpoints that will be grouped into 2 parallel 
branches (see Figure 3).  The first branch (Branch 1) includes tests of INCB018424 versus 
triamcinolone.  The second branch (Branch 2) includes tests of INCB018424 versus vehicle, as 
visualized in Figure 3.  The initial allocation of the overall significance level to Branch 1 and 
Branch 2 is three-fifths and two-fifths, respectively.  The weights of the level to be passed on if 
1 hypothesis is rejected are specified in Figure 3. 
9.2.1.2. 
Secondary Analysis 
9.2.1.2.1. Tests in Branch 1 
• Step 1:  The first alternative hypothesis (noninferiority of INCB018424 1.5% BID 
compared with triamcinolone) will be tested at a 2-sided α = 0.03 level if the primary 
test is significant.  If the first alternative hypothesis is established, then hypotheses in 
Step 2 will be tested at an overall error rate of 0.03. 
• Step 2:  If Step 1 is established, then a superiority test of INCB018424 1.5% BID 
compared with triamcinolone and noninferiority test of INCB018424 1.5% QD 
compared with triamcinolone will be carried out using the Bonferroni-Holm 
procedure at an overall 2-sided α = 0.03 level.   
• Step 3:  If both of the null hypotheses in Step 2 are rejected, then a superiority test of 
INCB018424 1.5% QD compared with triamcinolone will be carried out at a 2-sided 
α = 0.03 level. 
If all 4 tests in Branch 1 are significant, then the overall level (α = 0.03) of Branch 1 will be 
reallocated to Branch 2, and the first alternative hypothesis in Branch 2 will be tested with start 
level of 2-sided 0.05.  If 1 or more of the tests in Branch 1 is nonsignificant, there will be no 
level reallocated from Branch 1 to Branch 2, and the first alternative hypothesis in Branch 2 will 
be tested with start level of 2-sided 0.02. 
9.2.1.2.2. Tests in Branch 2 
• Alternative hypotheses (superiority of INCB018424 1.5% QD and 0.5% QD 
compared with vehicle) will be tested in sequence using the alpha level decided in the 
previous steps.  
If 1 or more of the 4 tests in Branch 1 is nonsignificant, but all tests in Branch 2 are significant, 
then the alpha level will be reallocated to Branch 1, and Branch 1 will reopen with a start level of 
0.05. 
9.2.2. 
Noninferiority Margin 
In the historical study (Beck et al 2014), the difference of percentage change from baseline to 
Day 29 in EASI scores between active control (placebo and glucocorticoids) and placebo was 
27.1% with the derived lower limit of 95% confidence interval (CI) 16.4%.  Therefore, 
27% constitutes the minimum expected benefit of triamcinolone (active control) over vehicle.  
Given that the result is based on 2 studies with small sample sizes, the margin is chosen to 
be -10%, which is between a half of the lower 95% CI (-8%) and 50% of the minimum 
effect (-13.5%).    


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Noninferiority analysis will be performed between each of the active treatment groups and 
triamcinolone. 
9.2.3. 
Power Analysis 
Given the assumptions specified in Table 5, a simulation following the graphical procedure was 
performed and showed that a sample size of 50 subjects in each group would yield a power of 
> 99% to test the superiority of the each of the active treatment group (INCB018424 1.5% BID, 
INCB018424 1.5% QD, and INCB018424 0.5% QD) to the vehicle group with a 2-sample t test.   
Assuming no true difference between the active treatment group and triamcinolone with respect 
to percentage change from baseline in EASI scores and an SD of 13%, the simulation showed 
that the sample size of 50 in each group would yield a power of > 99% to declare that the active 
treatment changes in INCB018424 1.5% BID and INCB018424 1.5% QD are noninferior to 
triamcinolone (ie, that the lower limit of the 2-sided 95% CI of INCB018424 minus 
triamcinolone is greater than or equal to the noninferiority margin of -10%).  The sample size 
will also provide at least 95% power to test the superiority of each of the active treatment groups 
of INCB018424 1.5% BID and INCB018424 1.5% QD to the triamcinolone group. 
9.3. 
Level of Significance 
A graphical procedure with a gatekeeping testing strategy for the primary and key secondary 
analyses will be implemented to control the overall Type I error rate at a 2-sided alpha level 
of 0.05.  The underlying procedure is derived using the methodology developed in Bretz et al 
(2009).  This method will guarantee a strong control of the family-wise error rate.  
Simulations results are provided to illustrate Type I error control for the graphical procedure.  
The Type I error rates, provided in Appendix E, Table E.2, are strongly controlled in all 
scenarios.   
9.4. 
Statistical Analyses 
9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Efficacy Measures for Primary and Secondary Endpoints 
9.4.1.1.1. Eczema Area and Severity Index–50 
Eczema Area and Severity Index score is specified in Section 7.6.  The categorical variable 
EASI-50 will be equal to 1 if the percentage improvement from baseline in EASI scores is 50 or 
greater and 0 if less than 50.  This definition is introduced for the purpose of identifying subjects 
who respond to the treatment (1 - responder, 0 - nonresponder). 
9.4.1.1.2. Investigator's Global Assessment Response 
Investigator's Global Assessment response is defined as an IGA score of 0 or 1 who have an 
improvement of ≥ 2 points from baseline. 


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9.4.1.1.3. Itch Numerical Rating Scale  
The Itch NRS score is a single-question assessment tool with a scale of 0 to 10, with 0 being 'no 
itch' and 10 being 'worst itch imaginable.'  The average itch NRS score will be measured overall, 
for the previous week, and for the previous 24 hours.  
9.4.1.2. 
Primary Efficacy Analyses 
Comparisons between INCB018424 1.5% BID and vehicle based on percentage change from 
baseline in EASI scores at Week 4 will be performed with a fixed-effect ANOVA model using 
last observations carrying forward in the ITT. 
The ANOVA model will include the fixed effects of treatment and randomization stratification 
factor.  If there are no data after the date of randomization, then the endpoint will be considered 
missing and will not be included in analysis. 
Supportive analyses for the primary endpoint include a similar ANOVA approach in the per 
protocol population. 
9.4.1.3. 
Secondary Efficacy Analyses 
Secondary efficacy analyses will be conducted in the ITT population.   
The key secondary endpoints will be analyzed using the similar ANOVA as specified in the 
primary analysis.  The graphic approach will be used to control family-wise error rate.  Tests for 
noninferiority between 2 treatment groups will be performed using the least square mean 
estimate of the percentage change in EASI at 4 weeks.  Noninferiority will be established if the 
lower limit of a 2-sided CI for the difference (INCB018424 minus active control) is higher than 
or equal to -10%.  There will be no adjustment for multiple comparisons for secondary endpoints 
besides key secondary endpoints. 
Mean, change from baseline, and percentage change from baseline of EASI scores at other visits 
besides Week 4 will be summarized using descriptive statistics.  Itch NRS score daily, 
 
 will be summarized and analyzed in a similar fashion.  
An Emax model will be fit for assessment of the dose response and provide estimates of the 
maximum and minimum response levels, ED50 (the concentration where the response is the 
midpoint between the maximum and minimum), and the slope parameter. 


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The categorical endpoints, percentage of subjects with IGA response and subjects achieving an 
EASI-50 response, will be summarized and may be analyzed by Cochran-Mantel-Haenszel test 
with stratification factor of randomization. 
The Kaplan-Meier product limit method will be used to estimate time–to–EASI-50 response.  
Treatment comparisons may be performed using the log-rank test stratified by randomization 
stratification factor, if applicable.  
9.4.1.4. 
Other Efficacy Analyses 
Other efficacy variables will be summarized and analyzed using similar methods as described for 
the primary and secondary endpoints.  
9.4.2. 
Safety Analyses 
9.4.2.1. 
Adverse Events 
A treatment-emergent AE (TEAE) is any AE either reported for the first time or worsening of a 
pre-existing event after first dose of study drug.  Analysis of AEs will be limited to TEAEs, but 
data listings will include all AEs regardless of their timing to study drug administration.  Adverse 
events will be tabulated by the MedDRA preferred term and system organ class.  Severity of AEs 
will be based on the National Cancer Institute CTCAE v4.03 using Grades 1 through 4. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, then the AE will be considered treatment-related.  The incidence of AEs 
and treatment-related AEs will be tabulated. 
9.4.2.2. 
Clinical Laboratory Tests 
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. 
Laboratory data will be classified into Grades 1 through 4 using CTCAE v4.03.  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of subjects with worst postbaseline CTCAE grade (regardless 
of baseline value).  Each subject will be counted only for the worst grade observed 
postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 
9.4.2.3. 
Vital Signs 
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. 


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9.4.2.4. 
Twelve-Lead Electrocardiograms  
Subjects exhibiting clinically notable ECG abnormalities will be listed. 
9.5. 
Analyses for the Data Monitoring Committee 
There will be no external Data Monitoring Committee.  Sites will remain blinded to study drug, 
but some personnel at Incyte without direct contact with sites may be unblinded.  
9.6. 
Interim Analysis 
An interim analysis will be performed when at least half of the randomized or more subjects 
reach Week 4.  Details will be specified in the Statistical Analysis Plan. 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
10.1. 
Investigator Responsibilities 
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as defined in 
Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP consolidated guidelines; and 
local regulatory requirements as applicable to the study locations. 
The investigator will be responsible for: 
• 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 
subject 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 subjects. 


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− 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. 
• Obtaining informed consent and ensuring that the study subjects' questions have been 
answered and the subjects fully understand study procedures: 
− 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 subject.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to subject records. 
• Obtaining approval from the IRB/IEC before the start of the study and for any 
changes to the clinical study Protocol, important Protocol deviations, routine updates, 
and safety information in accordance with institutional requirements and local law. 
− The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements 
and with the policies and procedures established by the IRB/IEC. 
• 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 subjects who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 


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10.2. 
Accountability, Handling, and Disposal of Study Drug 
The investigator is responsible for drug accountability of INCB018424 phosphate cream, 
INCB018424 vehicle cream, and triamcinolone at the study site; however, some of the drug 
accountability duties may be assigned to an appropriate pharmacist or other designee.  Inventory 
and accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Subject use of the study drug including tube counts from each supply dispensed. 
• Return of study drug to the investigator or designee by subjects. 
The investigational product as well as triamcinolone must be used only in accordance with the 
Protocol.  The investigator will also maintain records adequately documenting that the subjects 
were provided the specified study drug.  These records should include dates, quantities, and any 
available batch or serial numbers or unique code numbers assigned to the investigational product 
and study subjects. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
10.3. 
Data Management 
Data management will be performed in a validated database via an Electronic Data Capture 
(EDC) system.  All data entry, verification, and validation will be performed in accordance with 
the current standard operating procedures of the Data Management Department at the sponsor or 
its designee.  The database will be authorized for lock once all defined procedures are completed. 
The investigator will be provided with access to an EDC system so that an eCRF can be 
completed for each subject.  Entries made in the eCRF must be verifiable against source 
documents; if updates to the database are not possible, any discrepancies should be explained 
and documented.  The investigator will be responsible for reviewing all data and eCRF entries, 
and will sign and date the designated forms in each subject's eCRF, verifying that the 
information is true and correct.  The investigator is responsible for the review and approval of all 
query responses. 
Protocol deviations will be identified and recorded in the Protocol Deviation form of the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 


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is appropriately documented, reported, and resolved in a timely manner in accordance with the 
plan's requirements. 
10.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
Subject names will not be supplied to the sponsor or its designee, if applicable.  Only the subject 
number and subject's initials (subject's initials will only be recorded if allowable by local 
regulations) will be recorded in the eCRF, where permitted; if the subject's name appears on any 
other document (eg, laboratory report), it must be obliterated on the copy of the document to be 
supplied to the sponsor or its designee.  Study findings stored on a computer will be stored in 
accordance with local data protection laws.  The subjects will be informed that representatives of 
the sponsor or its designee, IRB or IEC, or regulatory authorities may inspect their medical 
records to verify the information collected, and that all personal information made available for 
inspection will be handled in strictest confidence and in accordance with local data protection 
laws. 
10.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 Code of Federal Regulations (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 subjects, including the spouse and each dependent child of the clinical investigator or 
subinvestigator.  These requirements apply to both US and foreign clinical investigators 
conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 


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10.6. 
Publication Policy 
By signing the study Protocol, the investigator and his or her institution agree that the results of 
the study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  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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11. 
REFERENCES 
Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe 
atopic dermatitis. N Engl J Med 2014;371:130-139. 
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med 2009;28:586-604. 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 15, 2014. http://www.hma.eu/ctfg.html. Accessed 
May 26, 2016. 
Ellis CN, Drake LA, Prendergast MM, et al. Cost of atopic dermatitis and eczema in the United 
States. J Am Acad Dermatol 2002;46:361-370. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis.  Acta Derm Venereol Suppl 
(Stockh) 1980;92:44-47. 
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. "The eczema area and 
severity index (EASI): assessment of reliability in atopic dermatitis." Exp Dermatol 
2001;10:11-18. 
Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of 
the prevalence and impact of skin conditions. J Invest Dermatol 2014;134:1527-1534. 
INCB018424 Phosphate Cream Investigator's Brochure (IB). Wilmington, DE: Incyte 
Corporation. 
Kim BS. Atopic dermatitis. 2015. http://emedicine.medscape.com/article/1049085-overview. 
Accessed May 26, 2016. 
Kim BS, Wang K, Siracusa MC, et al. Basophils promote innate lymphoid cell responses in 
inflamed skin. J Immunol 2014;193:3717-3725. 
Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score 
tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol 
2015;172:1353-1357. 
Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus 
kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 2015;73:395-399. 
Poulin Y, Bissonnette R, Papp K, et al. Efficacy and safety of topical Janus kinase inhibitor 
tofacitinib in the treatment of atopic dermatitis: results of a Phase 2a randomized clinical trial. 
Presented at: 24th European Academy of Dermatology and Venereology Congress; 
October 7-11, 2015; Copenhagen, Denmark. 
Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other 
variables: a US population-based study. J Allergy Clin Immunol 2013;132:1132-1138. 
Spergel JM. Epidemiology of atopic dermatitis and atopic march in children. Immunol Allergy 
Clin North Am 2010;30:269-280. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method provided of avoiding pregnancy that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source:  CTFG 2014. 


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APPENDIX B. ECZEMA AREA AND SEVERITY INDEX 
The EASI score examines 4 areas of the body and weights them for subjects 8 years of age and 
older as follows: 
Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. 
The percentage of area involved for each of the 4 body regions is weighted as follows:  0 = no 
eruption, 1 = some to < 10%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 
89%, and 6 = 90% to 100%. 
Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema 
(I), excoriations (Ex), and lichenification (L) for an average degree of severity of each sign in 
each region with:  0 = none, 1 = mild, 2 = moderate, and 3= severe, with half-step allowed. 
Body Region 
EASI Score 
Head/Neck (H) 
(E + I + Ex + L) × Area × 0.1 
Upper limbs (UL) 
(E + I + Ex + L) × Area × 0.2 
Trunk (T) 
(E + I + Ex + L) × Area × 0.3 
Lower limbs (LL) 
(E + I + Ex + L) × Area × 0.4 
EASI total 
Sum of the above 4 body region scores 
 


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EASI Score Calculation Tool 
Body Region 
Redness 
 
Thickness 
 
Scratching 
 
Lichenification 
 
Severity 
Score 
 
Area 
Score 
Multiplier 
 
Region 
Score 
Head/neck 
 
+ 
 
+ 
 
+ 
 
= 
 
× 
 
× 0.1 
= 
 
Trunk 
 
+ 
 
+ 
 
+ 
 
= 
 
× 
 
× 0.3 
= 
 
Upper limbs 
 
+ 
 
+ 
 
+ 
 
= 
 
× 
 
× 0.2 
= 
 
Lower limbs 
 
+ 
 
+ 
 
+ 
 
= 
 
× 
 
× 0.4 
= 
 
Add up the 4 regions to calculate the EASI score =  
 


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APPENDIX C. POTENT CYP3A4 INHIBITORS AND FLUCONAZOLE 
In clinical studies with CYP3A4 inhibitors, elevated levels of INCB018424 of approximately 
2-fold have been observed after oral administration.  Additionally, simulations using 
physiologically based pharmacokinetic models suggested that fluconazole (a dual CYP3A4 and 
CYP2C9 inhibitor) increases steady-state ruxolitinib AUC by approximately 1- to 3-fold after 
oral administration.  Thus, these concomitant medications should not be taken by subjects 
beginning 2 weeks or 5 half-lives (whichever is longer) before the first application of study drug 
until the last administration (either Week 24 or Week 48); however, topical use of these agents if 
the systemic bioavailability is low may be permitted on a case by case basis.  The following is a 
list of potent CYP3A4 inhibitors and fluconazole.  The sponsor should be contacted with any 
questions regarding concomitant medications that might be considered potent CYP3A4 inhibitors 
but are not on this list. 
boceprevir 
clarithromycin 
cobicistat 
conivaptan 
danoprevir 
elvitegravir 
fluconazole 
grapefruit juice 
idelalisib 
indinavir 
itraconazole 
ketoconazole 
LCL161 
lopinavir 
mibefradil 
nefazodone 
nelfinavir 
posaconazole 
ritonavir 
saquinavir 
telaprevir 
telithromycin 
tipranavir 
troleandomycin 
voriconazole 


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APPENDIX E. STATISTICAL CONSIDERATIONS 
Type I Error Rates 
Six scenarios are examined for Type I error rates, corresponding to null hypothesis that there is 
no different treatment effect between 1 or more active treatment groups with active control or 
vehicle.   
With 50 subjects per group, normal distributions, with standard deviation of 0.13, and mean 
percentage changes specified in Table E.1 were generated.  For each scenario, 
10,000 replications were run using SAS® 9.2.  Comparisons between each of the active dose to 
active control or vehicle are performed using 2 sample t-tests.  Confidence intervals of the means 
(INCB018424 - active control or vehicle) were created with corresponding alpha level following 
the graphical procedure specified in Section 9.2.  The lower limits of CIs were compared with 
the critical values (0 for superiority, and -10% for noninferiority) for treatment comparisons.  To 
provide conservative estimates, the primary comparison (INCB018424 1.5% BID vs vehicle 
superiority) was excluded from the procedure, that is, only key secondary endpoints were 
evaluated. 
The Type I error rates are provided in Table E.2 under different null hypotheses.  The rates are 
compared with the nominal alpha 2.5%, which showed that the Type I error rates are 
well-controlled in all scenarios (< 2.5%). 
Table E.1: 
Assumed Percentage Change From Baseline of EASI Score at Week 4 for 
Type I Error Rates  
Scenario 
1.5% BID 
1.5% QD 
0.5% QD 
Active Control 
Vehicle 
S1 
40% 
40% 
40% 
50% 
40% 
S2 
50% 
40% 
40% 
50% 
40% 
S3 
60% 
40% 
40% 
50% 
40% 
S4 
40% 
40% 
40% 
50% 
30% 
S5 
50% 
40% 
40% 
50% 
30% 
S6 
60% 
40% 
40% 
50% 
30% 
Table E.2: 
1-Sided Type I Error Rates (%) 
Scenarios 
S1 
S2 
S3 
S4 
S5 
S6 
Reject at least 
1 hypothesis in 
T11, T12, T13, 
T14, or T21 or 
T22 
T12, T13, 
T14, or T21 
or T22 
T13, T14, or 
T21 or T22 
T11, T12, T13, 
or T14 
T12, T13, or 
T14 
T13 or T14 
Type I error rates 
2.44 
2.14 
2.19 
2.34 
1.25 
1.34 
Note:  T11:  To test whether INCB018424 1.5% BID is noninferior to triamcinolone (active control). 
         T12:  To test whether INCB018424 1.5% BID is superior to triamcinolone (active control). 
         T13:  To test whether INCB018424 1.5% QD is noninferior to triamcinolone (active control). 
         T14:  To test whether INCB018424 1.5% QD is superior to vehicle. 
         T21:  To test whether INCB018424 1.5% QD is superior to vehicle. 
         T22:  To test whether INCB018424 0.5% QD is superior to vehicle. 
S1 to S6 are defined in Table E.1. 



SAP_001.pdf: 
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INCB 18424-206 Statistical Analysis Plan 
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CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
INCB018424 PHOSPHATE CREAM 
INCB 18424-206/NCT03011892   
A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and 
Triamcinolone 0.1% Cream-Controlled Study to Evaluate the 
Safety and Efficacy of INCB018424 Phosphate Cream Applied 
Topically to Adults With Atopic Dermatitis 
IND Number: 
77,101 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
15 SEP 2016 
CRF Approval Date: 
06 FEB 2017 
SAP Version: 
Original 
SAP Author: 
, Biostatistics 
Date of Plan: 
27 APR 2017 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................7 
2.1. 
Protocol and Case Report Form Version ......................................................................7 
2.2. 
Study Objectives ...........................................................................................................7 
2.2.1. 
Primary Objective .........................................................................................................7 
2.2.2. 
Secondary Objectives ...................................................................................................7 
2.2.2.1. 
Key Secondary Objective .............................................................................................7 
2.2.2.2. 
Other Secondary Objective ...........................................................................................7 
 
8 
2.3. 
Study Endpoints ............................................................................................................8 
2.3.1. 
Primary Endpoint ..........................................................................................................8 
2.3.2. 
Secondary Endpoints ....................................................................................................8 
2.3.2.1. 
Key Secondary Endpoints .............................................................................................8 
2.3.2.2. 
Other Secondary Endpoints ..........................................................................................8 
 
9 
3. 
STUDY DESIGN .......................................................................................................10 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................10 
3.2.1. 
Primary Analysis ........................................................................................................12 
3.2.2. 
Secondary Analysis ....................................................................................................12 
3.2.2.1. 
Tests in Branch 1 ........................................................................................................12 
3.2.2.2. 
Tests in Branch 2 ........................................................................................................12 
3.2.3. 
Noninferiority Margin ................................................................................................13 
3.3. 
Sample Size Considerations .......................................................................................13 
3.4. 
Schedule of Assessments ............................................................................................13 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................13 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................13 
4.1.1. 
Definitions for Day 1, Baseline, and the Last Available Value ..................................13 
4.1.2. 
Study Day ...................................................................................................................14 
4.2. 
Variable Definitions ....................................................................................................15 


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4.2.1. 
Age ..............................................................................................................................15 
4.2.2. 
Body Mass Index ........................................................................................................15 
4.2.3. 
Prior and Concomitant Medication .............................................................................15 
5. 
STATISTICAL METHODOLOGY ...........................................................................16 
5.1. 
General Methodology .................................................................................................16 
5.2. 
Treatment Groups .......................................................................................................16 
5.3. 
Analysis Populations ..................................................................................................17 
5.3.1. 
Double-Blind Period ...................................................................................................17 
5.3.1.1. 
Intent-to-Treat Population ..........................................................................................17 
5.3.1.2. 
Per-Protocol Population ..............................................................................................17 
5.3.1.3. 
Safety Population ........................................................................................................17 
 
17 
5.3.2. 
Open-Label Period ......................................................................................................17 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................18 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............18 
6.2. 
Disposition of Subjects ...............................................................................................18 
6.3. 
Protocol Deviations and Violations ............................................................................19 
6.4. 
Exposure .....................................................................................................................19 
6.5. 
Study Drug Compliance .............................................................................................19 
6.6. 
Medical History ..........................................................................................................20 
6.7. 
Prior and Concomitant Medication .............................................................................20 
7. 
EFFICACY .................................................................................................................20 
7.1. 
General Considerations ...............................................................................................20 
7.1.1. 
Handling of Dropouts or Missing Data ......................................................................20 
7.2. 
Efficacy Measures ......................................................................................................21 
7.2.1. 
Primary Efficacy Measures .........................................................................................21 
7.2.2. 
Other Efficacy Measures ............................................................................................22 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................24 
7.3.1. 
Primary Efficacy Analysis ..........................................................................................24 
7.3.2. 
Subgroup Analyses .....................................................................................................24 
7.3.3. 
Sensitivity and Supportive Analyses for Primary Endpoint .......................................24 
7.4. 
Analysis of the Secondary 
 Efficacy Parameters ..............................25 


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7.4.1. 
Efficacy Analysis for Key Secondary Endpoints .......................................................25 
7.4.2. 
Efficacy Analysis for Other Secondary Endpoints .....................................................25 
 
26 
 
26 
8. 
SAFETY AND TOLERABILITY ..............................................................................27 
8.1. 
General Considerations ...............................................................................................27 
8.2. 
Adverse Events ...........................................................................................................27 
8.2.1. 
Adverse Event Definitions ..........................................................................................27 
8.2.2. 
Adverse Event Summaries ..........................................................................................28 
8.3. 
Clinical Laboratory Tests ...........................................................................................29 
8.3.1. 
Laboratory Value Definitions .....................................................................................29 
8.3.2. 
Laboratory Value Summaries .....................................................................................30 
8.4. 
Vital Signs ..................................................................................................................30 
9. 
INTERIM ANALYSES ..............................................................................................31 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................31 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................31 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................31 
11. 
REFERENCES ...........................................................................................................32 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................33 
 
LIST OF TABLES 
Table 1: 
Definition of Day 1, Baseline, and Last Available Value ..........................................14 
Table 2: 
Duration of Treatment ................................................................................................19 
Table 3: 
EASI Score Calculation ..............................................................................................21 
 
23 
Table 5: 
Allocation of Treatment-Emergent Adverse Events to Study Period .........................27 
Table 6: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................30 
Table 7: 
Statistical Analysis Plan Versions ..............................................................................31 
 
LIST OF FIGURES 
Figure 1: 
Illustration of the Statistical Treatment Comparisons ................................................11 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AD 
atopic dermatitis 
AE 
adverse event 
ANOVA 
analysis of variance 
BMI 
body mass index 
BID 
twice daily 
 
 
CI 
confidence interval 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events  
DB 
double blind 
DBP 
diastolic blood pressure 
EASI 
Eczema Area and Severity Index  
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FWER 
family-wise error rate 
IGA 
Investigator's Global Assessment 
IND 
Investigational New Drug 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities  
MMRM 
mixed-model repeated measures 
NCI 
National Cancer Institute  
NRI 
nonresponder imputation analysis 
NRS 
Numerical Rating Scale 
PD 
pharmacodynamics 
PI 
percentage improvement 
 
 
PP 
per protocol 
PT 
preferred term 
QD 
once daily 
 
  
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 


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Abbreviation 
Term 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
This is a randomized, vehicle- and active (triamcinolone 0.1% cream)-controlled study in 
subjects with mild to moderate AD.  The study is double-blinded for vehicle, INCB018424 
doses, and active control.  Subjects will receive blinded study drug for 8 weeks followed by 
4 weeks of optional open-label treatment with INCB018424 1.5% cream BID for subjects who 
meet Protocol-defined criteria.  Section 1 of the Protocol provides a detailed description of the 
investigational product, target patient population, rationale for doses to be examined, and 
potential risks and benefits of treatment with INCB018424 cream.  The purpose of this SAP is to 
define the methodology for analyzing and summarizing the data collected during the conduct of 
Study INCB 18424-206.  The scope of this plan includes the interim and final analyses that are 
planned and will be executed by the Department of Biostatistics or designee 
 
 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 18424-206 Protocol dated 15 SEP 2016, Administrative Change 1 
dated 10 JAN 2017, Administrative Change 2 dated 28 MAR 2017, and Administrative Change 3 
dated 19 APR 2017, and eCRFs approved 06 FEB 2017.  Unless superseded by an amendment, 
this SAP will be effective for all subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objective 
• To establish the efficacy of each dose of INCB018424 cream QD or BID in subjects 
with AD compared with vehicle cream BID.  
2.2.2. 
Secondary Objectives 
2.2.2.1. 
Key Secondary Objective 
• To establish the efficacy of each dose of INCB018424 cream QD or BID in subjects 
with AD compared with triamcinolone 0.1% cream BID. 
2.2.2.2. 
Other Secondary Objective 
• To evaluate the safety and tolerability of INCB018424 cream when applied QD or 
BID to subjects with AD. 


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2.3. 
Study Endpoints 
2.3.1. 
Primary Endpoint 
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with 1.5% INCB018424 cream BID compared with subjects treated with vehicle 
cream BID.  
2.3.2. 
Secondary Endpoints 
2.3.2.1. 
Key Secondary Endpoints 
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with INCB018424 compared with subjects treated with vehicle cream BID.  
• Mean percentage change from baseline in EASI score at Week 4 in subjects treated 
with INCB018424 compared with subjects treated with triamcinolone 0.1% cream 
BID.  
2.3.2.2. 
Other Secondary Endpoints 
• Mean percentage change from baseline in EASI score at Week 2 and Week 8. 
• Proportion of subjects who achieve a ≥ 50% improvement from baseline in EASI 
(EASI-50) at Weeks 2, 4, and 8.  
• Assessment of dose response based on percentage change from baseline in EASI 
score at Week 4. 
• Time to achieve EASI-50. 
• Proportion of subjects achieving an IGA score of 0 to 1 who have an improvement of 
≥ 2 points from baseline at Weeks 2, 4, and 8. 
• Mean change from baseline in the Itch NRS score at Weeks 2, 4, and 8. 
• Safety and tolerability assessed by monitoring the frequency, duration, and severity of 
AEs; performing physical examinations; collecting vital signs; and collecting 
laboratory data for hematology, serum chemistry, and urinalysis. 


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3. 
STUDY DESIGN 
This is a randomized, vehicle- and active (triamcinolone 0.1% cream)-controlled study in 
subjects with mild to moderate AD.  The study is double-blinded for vehicle, INCB018424 
doses, and active control.  Approximately 300 subjects will be randomized 1:1:1:1:1:1 
(approximately 50 subjects each) to treatment with INCB018424 1.5% BID, INCB018424 1.5% 
QD, INCB018424 0.5% QD, INCB018424 0.15% QD, vehicle BID, and active control 
(triamcinolone 0.1% cream) BID and stratified by EASI score (≤ 7 and > 7).  Subjects will 
receive blinded study drug for 8 weeks.  Subjects randomized to QD regimens will apply vehicle 
for the evening application.  Subjects randomized to triamcinolone will apply triamcinolone 
0.1% cream BID for 4 weeks and vehicle cream for 4 weeks to not exceed the allowable 
triamcinolone application duration. 
After the DB period, a 4-week period of open-label treatment with INCB018424 1.5% cream 
BID will be offered to subjects who meet Protocol-defined criteria.  Subjects will have follow-up 
assessments 1 month after the last application of study drug.  The total duration of participation 
will be up to 20 weeks, including up to 4 weeks for screening, 8 weeks of DB treatment, 4 weeks 
of optional open-label treatment, and 4 weeks of safety follow-up. 
3.1. 
Randomization 
In the treatment period, approximately 300 subjects will be randomized 1:1:1:1:1:1 to the 
6 treatment groups.  Subjects will be stratified at randomization based on baseline EASI score of 
≤ 7 or > 7. 
3.2. 
Control of Type I Error 
For the primary endpoint and key secondary endpoints, the overall 2-sided Type I error rate is 
0.05. 
A graphical procedure with a gatekeeping testing strategy for the primary and key secondary 
analyses, as specified in Protocol Section 9.2.1, will be implemented to control the overall Type I 
error rate.  The underlying procedure is derived using the methodology developed in Bretz et al 
(2009).  This method will guarantee a strong control of the FWER.   
A family of 7 elementary hypotheses, corresponding to treatment comparisons between active 
dose groups and vehicle (or triamcinolone) is evaluated in Figure 1 based on the percentage 
change from baseline to Week 4 EASI score. 


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Figure 1: 
Illustration of the Statistical Treatment Comparisons 
 
AC = active control; s = superiority; ni = noninferiority; V = vehicle. 
Note:  Active control (triamcinolone 0.1% cream) BID for 4 weeks followed by vehicle cream BID for 4 weeks. 
The primary endpoint will test the superiority of INCB018424 1.5% BID compared with vehicle.  
The key secondary endpoint has 2 branches.  Branch 1 will test whether: 
• INCB018424 1.5% BID is noninferior to triamcinolone (active control) 
• INCB018424 1.5% QD is noninferior to triamcinolone (active control) 
• INCB018424 1.5% BID is superior to triamcinolone (active control) 
• INCB018424 1.5% QD is superior to triamcinolone (active control) 
Branch 2 will test whether: 
• INCB018424 1.5% QD is superior to vehicle 
• INCB018424 0.5% QD is superior to vehicle 


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3.2.1. 
Primary Analysis 
The primary alternative hypothesis (superiority of INCB018424 1.5% BID compared with 
vehicle) will be tested at a 2-sided α = 0.05 level.  The test on the primary endpoint will be used 
as a gatekeeper for 6 statistical tests on secondary endpoints that will be grouped into 2 parallel 
branches (see Figure 1).  The first branch (Branch 1) includes tests of INCB018424 versus the 
active control (triamcinolone).  The second branch (Branch 2) includes tests of INCB018424 
versus vehicle.  The initial allocation of the overall significance level to Branch 1 and Branch 2 
is 3/5 and 2/5, respectively.  The weights of the level to be passed on if 1 hypothesis is rejected 
are specified in Figure 1. 
3.2.2. 
Secondary Analysis 
3.2.2.1. 
Tests in Branch 1 
• Step 1:  The first alternative hypothesis (noninferiority of INCB018424 1.5% BID 
compared with triamcinolone) will be tested at a 2-sided α = 0.03 level if the primary 
test is significant.  If the first alternative hypothesis is established, then hypotheses in 
Step 2 will be tested at an overall error rate of 0.03.  
• Step 2:  If Step 1 is established, then a superiority test of INCB018424 1.5% BID 
compared with triamcinolone and noninferiority test of INCB018424 1.5% QD 
compared with triamcinolone will be carried out using the Bonferroni-Holm 
procedure at an overall 2-sided α = 0.03 level.  
• Step 3:  If both of the null hypotheses in Step 2 are rejected, then a superiority test of 
INCB018424 1.5% QD compared with triamcinolone will be carried out at a 2-sided 
α = 0.03 level.  
If all 4 tests in Branch 1 are significant, then the overall level (α = 0.03) of Branch 1 will be 
reallocated to Branch 2, and the first alternative hypothesis in Branch 2 will be tested with start 
level of 2-sided 0.05.  If 1 or more of the tests in Branch 1 is nonsignificant, there will be no 
level reallocated from Branch 1 to Branch 2, and the first alternative hypothesis in Branch 2 will 
be tested with start level of 2-sided α = 0.02.  
3.2.2.2. 
Tests in Branch 2 
• Alternative hypotheses (superiority of INCB018424 1.5% QD and 0.5% QD 
compared with vehicle) will be tested in sequence using the alpha level decided in 
previous steps.  
If 1 or more of the 4 tests in Branch 1 is nonsignificant, but all tests in Branch 2 are significant, 
then the alpha level will be reallocated to Branch 1, and Branch 1 will reopen with a start level of 
2-sided α = 0.05.  


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3.2.3. 
Noninferiority Margin 
In a historical study (Beck et al 2014), the difference of percentage change from baseline to 
Day 29 in EASI scores between active control (placebo and glucocorticoids) and placebo was 
27.1% with the derived lower limit of 95% CI 16.4%.  Therefore, 27% constitutes the minimum 
expected benefit of triamcinolone (active control) over vehicle.  Given that the result is based on 
2 studies with small sample sizes, the margin is chosen to be -10%, which is between a half of 
the lower 95% CI (-8%) and 50% of the minimum effect (-13.5%).  
Noninferiority analysis will be performed between each of the active treatment groups and 
triamcinolone. 
3.3. 
Sample Size Considerations 
In order to provide a large safety database and to provided adequate power for efficacy variables, 
the total sample size for the study is 300 subjects randomized at a 1:1:1:1:1:1 ratio (stratified by 
baseline EASI score) to treatment with INCB018424 1.5% BID, INCB018424 1.5% QD, 
INCB018424 0.5% QD, INCB018424 0.15% QD, triamcinolone (active control), and vehicle.  
3.4. 
Schedule of Assessments 
Refer to Protocol dated 15 SEP 2016 for a full description of all study procedures and assessment 
schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Definitions for Day 1, Baseline, and the Last Available Value 
Day 1, baseline, and last available value for the DB period and the open-label period are defined 
in Table 1.  


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Table 1: 
Definition of Day 1, Baseline, and Last Available Value 
Study 
Period 
Treatment 
Group 
Day 1 
Baseline 
Last Available Value 
DB period 
INCB018424 
cream 
1.5% BID 
1.5% QD 
0.5% QD 
0.15% QD 
Vehicle 
triamcinolone 
Date of first 
application or date 
of randomization 
for subjects 
randomized but 
not treated in the 
DB period  
The last nonmissing 
measurement 
obtained on or before 
the day of the first 
dose. 
The last nonmissing 
measurement obtained 
after the first dose, and 
within 30 days after the 
last dose in the DB period 
or before the first dose in 
the extension period, 
whichever is earlier. 
Open-label 
period 
INCB018424 
cream 
1.5% BID 
Date of first 
application in DB 
period 
The last nonmissing 
measurement 
obtained on or before 
the day of the first 
dose in DB period  
The last nonmissing 
measurement obtained 
after the first dose and 
within 30 days after the 
last dose. 
INCB018424 
cream 
1.5% QD 
0.5% QD 
0.15% QD 
Vehicle 
triamcinolone 
Date of first 
application in 
open-label period  
The last nonmissing 
measurement 
obtained on or before 
the day of the first 
dose in the open-label 
period 
The last nonmissing 
measurement obtained 
after the first dose in 
open-label period and 
within 30 days after the 
last dose. 
When scheduled assessments and unscheduled assessments occur on the same day and time of 
the assessment or when the first dose is not available, use the following convention to determine 
the baseline value: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.2. 
Study Day 
Study Day 1 is used to calculate the study day for mapping scheduled visits.  Study Day 1 is the 
date of the first dose of INCB018424 cream, vehicle, or triamcinolone cream in the DB treatment 
period. 
If a visit/reporting date is on or after Study Day 1, then the study day at the visit/reporting date 
will be calculated as 
Study Day # = (Visit/Reporting Date – Study Day 1 date + 1).  


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If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as  
Study Day # = (Visit/Reporting Date – Study Day 1 date).  
A study day of -1 indicates 1 day before Study Day 1. 
4.2. 
Variable Definitions 
4.2.1. 
Age 
Subject age will be calculated as the integer part of the number of years from date of birth to the 
date of signing the informed consent form, using the following formula: 
Age = integer part of (date of informed consent – date of birth + 1) / 365.25 
4.2.2. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.3. 
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 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; Version 9 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, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of subjects in each category. 
During the DB period, the safety population will be used for all safety analyses, and the ITT 
population will be used for all efficacy analyses.  
 
Interim analyses are planned for this Protocol as defined in Section 9.  
5.2. 
Treatment Groups 
This is a study in subjects with AD, with a DB, randomized, and vehicle- and active 
(triamcinolone 0.1% cream)-controlled treatment period followed by an optional open-label 
treatment period.  Data will be summarized based on the treatment regimen that was initially 
assigned or that subjects received during the DB period.  
• DB period versus open-label period: 
− INCB018424  1.5% BID 
− INCB018424  1.5% QD 
− INCB018424  0.5% QD 
− INCB018424  0.15% QD 
− TAC*  
− Vehicle BID 
*Active control (triamcinolone 0.1% cream) BID for 4 weeks followed by vehicle 
cream BID for 4 weeks. 
Table summaries, unless otherwise indicated, will present data by treatment group.  The results 
will be summarized and presented separately for the DB period and open-label period. 


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5.3. 
Analysis Populations 
5.3.1. 
Double-Blind Period 
5.3.1.1. 
Intent-to-Treat Population 
All subjects who are randomized to the study constitute the ITT population in the DB period.  
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 subject might receive during 
study participation.  This population will be used for analyses of all efficacy data in the DB 
Treatment Period. 
5.3.1.2. 
Per-Protocol Population 
Subjects in the ITT population who are considered to be sufficiently compliant with the Protocol 
compose the PP population, which is defined for supportive sensitivity analyses for efficacy 
endpoints in the treatment period.   
5.3.1.3. 
Safety Population 
The safety population in the DB treatment period includes all enrolled subjects who applied at 
least 1 dose of INCB018424 cream, triamcinolone cream, or vehicle cream.  Treatment groups 
for this population will be determined according to the actual treatment the subject received 
regardless of assigned study treatment.  All safety analyses will be conducted using the safety 
population. 
5.3.2. 
Open-Label Period 
All analyses for the open-label period will be conducted with the open-label evaluable 
population, which includes all subjects who applied at least 1 dose of INCB018424 1.5% cream 
during the open-label period. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
The following demographic variables will be summarized for the ITT population in the DB 
period, and open-label evaluable population in the open-label period:  age, sex, race, ethnicity, 
weight, height, BMI. 
The following baseline disease characteristics will be summarized for the ITT population: 
• Months since first onset of AD 
• Prior history of asthma (No/Yes) 
• Prior allergies (food, environmental) (No/Yes) 
• History of contact dermatitis (No/Yes) 
• Common complications of AD 
• Prior treatments for AD 
• Months since onset of current AD 
• Prior therapy for AD given in the past 30 days (No/Yes) 
• Total BSA involvement in current AD episode 
• Facial involvement (No/Yes) 
• Number of AD episodes/flare-ups over the last 12 months 
6.2. 
Disposition of Subjects 
The number and percentage of subjects who were treated, randomized, and completed the DB 
treatment period through Week 4 and Week 8; were treated in open-label period; completed the 
open-label period; discontinued from the study or study treatment during the DB period; and 
discontinued from the study during the open-label period with a primary reason for 
discontinuation will be summarized for the ITT population in the DB period and open-label 
evaluable population in open-label period. 


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6.3. 
Protocol Deviations and Violations 
Protocol deviations and violations recorded in the eCRF will be presented in the subject data 
listings. 
6.4. 
Exposure 
For subjects in the safety population in the DB period and in the open-label evaluable population 
in the open-label period, descriptive statistics will be provided by treatment group for duration of 
treatment, average daily dose, and total dose.  Duration of treatment with INCB018424 cream, 
vehicle cream, or triamcinolone cream is defined as the number of days from Day 1 to the last 
record (defined in Table 2) of INCB018424 cream, vehicle cream, or triamcinolone cream 
application. 
Table 2: 
Duration of Treatment 
Study Period 
Treatment Group 
Day 1 
Last Record 
DB period 
All treatment 
groups 
Date of first application in the DB 
period  
Date of last record in the DB 
period 
Open-label 
period 
INCB018424 cream 
1.5% BID 
Date of first application in the DB 
Period  
Date of last record in the 
open-label period 
INCB018424 cream 
1.5% QD 
0.5% QD 
0.15% QD 
Vehicle 
triamcinolone 
Date of first application in the 
open-label period  
Date of last record in the 
open-label period 
6.5. 
Study Drug Compliance 
Overall compliance (%) for the application of INCB018424 cream, vehicle cream, or 
triamcinolone cream (4 weeks) followed by vehicle cream (4 weeks) will be calculated for all 
subjects in the safety (DB period) and open-label evaluable (open-label period) populations as 
follows: 
Overall compliance (%) = 100 × [total amount dispensed – total amount returned] / [intended 
"dose"] 
• Total amount dispensed is defined as the sum of the weights of tubes dispensed 
before the current visit. 
• Total amount returned is defined as the sum of the weights of the tubes returned 
before and at the current visit. 
• The intended dose will be based on the earliest study day of permanent 
discontinuation of study drug (ie, first AE with action taken = "drug withdrawn" for 
AE discontinuation) or last study drug record in the database.  


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6.6. 
Medical History 
For subjects in the ITT population in the DB period, medical history will be summarized by 
assigned treatment groups.  This summary will include the number and percentage of subjects 
with medical history for each body system/organ class as documented in the eCRF.  
6.7. 
Prior and Concomitant Medication 
For subjects in the safety population in the DB period and the open-label evaluable population in 
the open-label period, prior medications and concomitant medications will be coded using the 
WHO Drug Dictionary and summarized by WHO drug class and WHO drug term.  Results will 
be summarized as number and percentage of subjects with prior and concomitant medications by 
PT and WHO drug class. 
Prior medication information for AD will also be used to identify medication received by 
subjects before enrollment into the study in the treatment periods.  Prior medications for AD will 
be summarized by treatment group as well as listed. 
7. 
EFFICACY 
7.1. 
General Considerations 
For continuous measurements, summary statistics will include sample size, mean, median, 
standard deviation, standard error of the mean, minimum, and maximum.  For all continuous 
variables, both the actual value and change and/or percentage from baseline (if available) will be 
analyzed. 
For categorical measurements, summary statistics will include sample size, frequency, and 
percentages. 
All by-visit analyses will include the follow-up period if the data are available. 
7.1.1. 
Handling of Dropouts or Missing Data 
In general, for continuous endpoints on primary and secondary endpoints, any subject who 
discontinues from the study before the timepoint of interest may have missing data imputed 
using the imputation techniques, such as MMRM under the missing-at-random assumption.  
MMRM model implicitly adjusts for missing data through a variance-covariance structure. 
For response endpoints, all nonresponders, as well as all subjects who discontinue study 
treatment at any time before the timepoint of interest or discontinue from the study for any 
reason, will be defined as nonresponders for the NRI analysis.   
For other endpoints, missing observations will be handled as detailed in the specific sections 
addressing each analysis. 


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7.2. 
Efficacy Measures 
7.2.1. 
Primary Efficacy Measures 
Atopic dermatitis will be assessed using the EASI scoring system, which is a validated disease 
measurement for clinical studies (Hanifin et al 2001).  The severity strata for the EASI are as 
follows:  0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 
50.0 = severe; and 50.1 to 72.0 = very severe (Leshem et al 2015). 
The EASI score (Table 3) examines 4 areas of the body and weights them for subjects 8 years of 
age and older as follows: 
Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. 
The percentage of area involved for each of the 4 body regions is weighted as follows:  0 = no 
eruption, 1 = some to < 10%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 
89%, and 6 = 90% to 100%. 
Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema 
(I), excoriations (Ex), and lichenification (L) for an average degree of severity of each sign in 
each region with:  0 = none, 1 = mild, 2 = moderate, and 3 = severe, with half-step allowed. 
Table 3: 
EASI Score Calculation 
Body Region 
EASI Score 
Head/Neck (H) 
(E + I + Ex + L) × Area score × 0.1 
Upper limbs (UL) 
(E + I + Ex + L) × Area score × 0.2 
Trunk (T) 
(E + I + Ex + L) × Area score × 0.3 
Lower limbs (LL) 
(E + I + Ex + L) × Area score × 0.4 
EASI total 
Sum of the above 4 body region scores 
Missing values will not be imputed.  An EASI total score is calculated as the sum of the 
nonmissing scores and will only be calculated when all subscores are nonmissing.   
The PI in EASI score from baseline will be computed as follows: 
PI = 100 × (baseline EASI score - observed EASI score) / baseline EASI score 
A positive score denotes improvement, and a negative score denotes worsening.  


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7.2.2. 
Other Efficacy Measures 
• EASI-50 
The categorical variable EASI-50 will be equal to 1 for percentage improvement from 
baseline in EASI score of 50% or greater and will be equal to 0 for percentage 
improvement of less than 50%.  This definition is introduced for the purpose of 
identifying subjects who respond to the treatment (1 = responder, 0 = nonresponder).  
• Time to EASI-50 
Time to EASI-50 is defined as the interval between the time of randomization and the 
time of achieving at least 50% improvement in EASI score. 
• Investigator's Global Assessment 
The IGA score is based on a 5-point scale comparing evaluations at postbaseline 
visits to baseline photographs (0, clear; 1, almost clear; 2, mild disease; 3, moderate 
disease; 4, severe disease; 5, very severe disease).  
• Investigator's Global Assessment Responder 
This categorical variable is defined to be equal to 1 (ie, responder) for a subject 
achieving an IGA score of 0 to 1 with an improvement of at least 2 from baseline and 
0 (ie, nonresponder) otherwise.  
• Itch Numerical Rating Scale Score 
The Itch NRS is a once-per-24 hours ("daily") patient-reported measure of itch 
intensity assessed using an 11-point scale (0 = no itch to 10 = worst imaginable itch).  
Subjects will be asked to record their highest (worst) level of itch over the 24-hour 
recall period. 
The Itch NRS score for baseline and postbaseline visits will be determined by 
averaging the 7 daily NRS scores before the actual measurement date (inclusive) at 
the visit.  If 4 or more daily scores are missing (out of the 7), the Itch NRS score at 
the visit will be set to missing. 
The categorical NRS is defined as 0 = None, 1 to 3 = Mild, 4 to 6 = Moderate, and 
7 to 10 = Severe.  


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7.3. 
Analysis of the Primary Efficacy Parameter 
7.3.1. 
Primary Efficacy Analysis 
An MMRM will be fitted for the comparisons between INCB018424 1.5% BID and vehicle 
cream based on percentage change from baseline in EASI scores to Week 2 and Week 4.  The 
MMRM will include the fixed effect of treatment (the 4 dose levels of INCB018424 cream, 
active control, and vehicle cream), the randomization stratification factor (baseline EASI score of 
≤ 7 or > 7), the visit, and treatment by visit interaction.  The variance-covariance matrix of the 
within-subject errors in MMRM will be modeled as unstructured. 
A test for superiority between INCB018424 1.5% BID and vehicle cream will be performed 
using the least squares mean estimate of the percentage change from baseline in EASI at Week 4 
from the MMRM specified above.  Superiority will be established if the p-value of the difference 
(INCB018424 1.5% BID minus vehicle) is less than 0.05. 
The MMRM implicitly adjusts for missing data through a variance-covariance structure. 
7.3.2. 
Subgroup Analyses  
Subgroups will be formed based on the following baseline variables for those subjects whose 
data are available: 
• EASI score (0 to 7 and  > 7 to 72); 
• Baseline facial involvement (No/Yes) 
• Serum IgE (> 200 kU/L, < 200 kU/L) 
7.3.3. 
Sensitivity and Supportive Analyses for Primary Endpoint 
A fixed-effect ANOVA model will also be performed for the comparisons between INCB018424 
1.5% BID and vehicle cream based on percentage change from baseline in EASI scores to 
Week 4.  Missing observations will be imputed by the last observations carrying forward in the 
ITT.  The ANOVA model will include the fixed effects of treatment and randomization 
stratification factor. 
The primary endpoint will be analyzed using the PP population as a sensitivity analysis to the 
ITT population in the DB period. 
If the proportion of subjects with missing values for the primary endpoint is greater than 5% of 
the ITT population, extended models based on missing not at random assumption may be 
conducted for sensitivity analysis in ITT population.  


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7.4. 
Analysis of the Secondary 
 Efficacy Parameters 
Secondary efficacy analyses will be conducted for the ITT population in the DB period. 
7.4.1. 
Efficacy Analysis for Key Secondary Endpoints 
The efficacy analysis for key secondary endpoints includes the 6 comparisons if the primary null 
hypothesis is rejected.  Each comparison will be analyzed using a similar MMRM to that 
specified for the primary analysis.  The graphical approach as specified in Figure 1 will be used 
to control the FWER. 
Four tests for superiority of 1 of the INCB018424 doses to active control or vehicle cream will 
be performed using the least squares mean estimate of the percentage change from baseline in 
EASI at Week 4 from the MMRM model specified above.  Superiority will be established if the 
p-value of the difference (INCB018424 minus the reference group, either active control or 
vehicle) is less than the alpha level determined by the graphical procedure. 
For noninferiority, tests comparing each of 2 INCB018424 treatment groups (1.5% BID and 
1.5% QD) to the active control group will be performed using the least squares mean estimate of 
the percentage change from baseline in EASI at Week 4.  Noninferiority will be established if the 
lower limit of a 2-sided CI for the difference (INCB018424 minus active control) is higher than 
or equal to -10%.  The level of the corresponding CI will be determined by the graphical 
procedure.  In addition, a CI with the usual 95% level will be reported. 
7.4.2. 
Efficacy Analysis for Other Secondary Endpoints 
There will be no adjustment for multiple comparisons for secondary endpoints other than the key 
secondary endpoints. 
Mean, change from baseline, and percentage change from baseline of EASI scores to Week 2, 
Week 4, and Week 8 may be analyzed with the similar MMRM for the primary endpoint.  EASI 
scores at visits other than those covered by the primary and key secondary endpoints will be 
summarized by treatment and visit using descriptive statistics. 
Categorical endpoints, including the percentage of subjects achieving EASI-50 and the 
percentage of IGA responders at postbaseline visits, will be summarized by treatment and visit 
using descriptive statistics and may be analyzed by logistic regression with stratification factor of 
randomization (ie, EASI ≤ 7 or > 7).  All nonresponders in the DB period, as well as all subjects 
who discontinue study treatment at any time before the timepoint of interest, or discontinue from 
the study for any reason, will be defined as nonresponders for the NRI analysis.   
An Emax model will be fit for assessment of the dose-response relationship on percentage change 
from baseline of EASI scores at Week 4, which will provide estimates of the maximum and 
minimum response levels; ED50 (the concentration where the response is the midpoint between 
the maximum and minimum); and the slope parameter.  The 5 dose levels of INCB018424 cream 
in the model fitting will be vehicle, 0.15% QD, 0.5% QD, 1.5% QD, and 1.5% BID (equivalent 
to 3% QD). 


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The Kaplan-Meier product limit method will be used to estimate time to EASI-50.  Treatment 
comparisons may be performed using the log-rank test stratified by randomization stratification 
factor, if applicable. 
Daily Itch NRS scores will be summarized by treatment and visit using descriptive statistics as a 
continuous endpoint.  Itch NRS scores for baseline and Weeks 2, 4, 8, 10, and 12 will be 
determined by averaging the daily NRS for the days from the start to the end of window as 
described in Section 7.2.2.  In addition, daily NRS Itch scores, from Day -7 to Week 4 will be 
summarized by treatment group and presented graphically.  


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8. 
SAFETY AND TOLERABILITY 
8.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the DB period and for 
the open-label evaluable population in the open-label period.  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 subjects.  Unless otherwise 
stated, table summaries will be limited to AEs occurring within 30 days of the last application of 
study treatment or the first application in the open-label period (if available) of the study, 
whichever is earlier.  
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first application of study treatment.  Adverse events will be considered treatment-emergent if 
they first occurred or worsened in severity after the first application of study treatment and on or 
before the date of the last visit of the period.  Maximum severity from previous period(s) will be 
considered as the baseline severity for TEAEs. 
Treatment-emergent AEs will be allocated to the study period (DB or open-label) according to 
the rules specified in Table 5. 
Table 5: 
Allocation of Treatment-Emergent Adverse Events to Study Period 
Study Period 
Treatment 
Group 
First Application Date 
Last Visit 
Identification of 
Maximum Severity 
DB period 
All groups 
Date of first application  Date of last visit in 
DB period  
Maximum severity 
from baseline  
Open-label 
period 
INCB018424 
cream 
1.5% BID 
Date of first application 
in DB period 
Date of last visit in 
open-label period 
Maximum severity 
from baseline  
INCB018424 
cream 
1.5% QD 
0.5% QD 
0.15% QD 
Vehicle 
triamcinolone 
Date of first application 
in the open-label period  
Date of last visit in 
open-label period 
Maximum severity 
from baseline and 
DB period 
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 treatment. 


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Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be described 
and graded using the NCI CTCAE v4.03.  The CTCAE reporting guidelines and grading details 
are available on the Cancer Therapy Evaluation Program website.  
Adverse events will be tabulated by the MedDRA PT and SOC.  A grading (severity) scale is 
provided for each AE term as follows:  (1) mild, (2) moderate, (3) severe. 
The subset of AEs considered by the investigator to be related to study treatment (INCB018424 
cream, vehicle cream, or triamcinolone cream) will be considered to be treatment-related AEs.  If 
the investigator does not specify the relationship of the AE to study medication, the AE will be 
considered to be treatment-related.  The incidence of AEs and treatment-related AEs will be 
tabulated.  In addition, SAEs will be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution.  Unresolved 
missing values 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. 
8.2.2. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include: 
• Number (%) of subjects reporting any TEAEs 
• Number (%) of subjects reporting any treatment-related TEAEs 
• Number (%) of subjects reporting any SAEs 
• Number (%) of subjects reporting any Grade 3 or 4 TEAEs 
• Number (%) of subjects who temporarily interrupted study treatment because of 
TEAEs 
• Number (%) of subjects who permanently discontinued study treatment because of 
TEAEs 
• Number (%) of subjects who had a fatal TEAE 


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The following summaries will be produced by MedDRA term (if 2 or fewer subjects 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 TEAEs by SOC, PT, and maximum severity 
• Summary of treatment-related AEs by SOC and PT 
• Summary of treatment-related AEs by PT in decreasing order of frequency 
• Summary of treatment-related AEs by SOC, PT, and maximum severity 
• Summary of TEAEs leading to death by SOC and PT 
• Summary of treatment-emergent SAEs by SOC and PT 
• Summary of treatment-related SAEs by SOC and PT 
• Summary of TEAEs leading to interruption of study treatment by SOC and PT 
• Summary of TEAEs leading to discontinuation of study treatment by SOC and PT 
• Summary of TEAEs requiring concomitant medications by SOC and PT 
• Summary of treatment-emergent non-SAE by SOC and PT 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
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 nonmissing values collected before the first 
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. 


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8.3.2. 
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 subject's particular test within a visit 
window, the laboratory value with the smallest laboratory sequence number will be used in 
by-visit summaries. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percent change from baseline for vital signs, 
including SBP, DBP, pulse, respiration rate, and body temperature will be summarized 
descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 6.  The abnormal 
values for subjects 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 greater than 25%.  The abnormal values for subjects 
exhibiting alert vital sign abnormalities will be listed. 
Table 6: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
Raw Value 
Percent Change From Baseline 
SBP 
90-150 mmHg 
± 25% 
DBP 
50-90 mmHg 
± 25% 
Pulse 
45-100 beats/min 
± 25% 
Respiration rate 
8-20 breaths/min 
± 25% 
Temperature 
35.5°C-38.0°C 
± 25% 


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9. 
INTERIM ANALYSES 
An interim analysis will be conducted when at least half of the randomized subjects reach 
Week 4.  The interim analysis will not include any testing for futility.  
Sites will remain blinded to study treatment, but some Incyte personnel who do not have direct 
contact with the study sites will be unblinded.  An internal committee at Incyte will be charged 
with evaluating the unblinded interim results based on both efficacy and safety analyses.  
Dose-response relationships may be examined using a dose-response curve and may provide 
information in planning Phase 3 studies.  As there are no plans for stopping early for efficacy, no 
adjustments of alpha or final p-values for repeated testing are necessary.   
For analysis of the primary endpoint, a cutoff for clinical data used in the interim analysis will be 
based on the earliest date that the first 150 subjects complete the Week 4 visit or discontinue the 
study.  All visits occurring on or before this date for these 150 subjects will be included in the 
analysis. 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 7. 
Table 7: 
Statistical Analysis Plan Versions 
SAP Version 
Approval Date 
Original 
27 APR 2017 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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11. 
REFERENCES 
Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe 
atopic dermatitis. N Engl J Med 2014;371:130-139. 
Bretz F, Maurer W, Brannath W, Posch M. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med 2009;28:586-604. 
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and 
severity index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol 
2001;10:11-18. 
Leshem YA, Hajar T, Hanifin JM, Simpson EL. What the Eczema Area and Severity Index score 
tells us about the severity of atopic dermatitis: an interpretability study. Br J Dermatol 
2015;172:1353-1357. 


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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.  Standard tables will follow the conventions in the Standard Safety Tables initial version.  
In-text tables are identical in structure and content as appendix tables, but follow a Rich Text 
Format. 
The list of tables, figures, and the shells are to be used as a guideline.  Modifications of the list or 
shells that do not otherwise affect the nature of the analysis will not warrant an amendment to the 
SAP. 
Tables for Double-Blind Period 
Table No. 
Title 
Population 
In-Text 
Baseline Demographic and Characteristic 
1.1.1.1 
Analysis Populations 
All 
 
1.1.1.2 
Summary of Subject Disposition 
ITT 
X 
1.1.1.3 
Summary of Number of Subjects Enrolled by Site 
 
1.1.2.1 
Summary of Demographics 
ITT 
X 
1.1.3.1 
Summary of Baseline Characteristics 
ITT 
X 
1.1.3.2 
Summary of Medical History 
ITT 
 
1.1.4.1 
Summary of Prior Medications 
ITT 
 
1.1.4.2 
Summary of Prior Medications for Atopic Dermatitis 
ITT 
X 
1.1.4.3 
Summary of Concomitant Medications 
ITT 
 
1.1.5.1 
Summary of Drug Compliance 
ITT 
 
Efficacy 
EASI 
2.1.1.1 
Summary of EASI Score at Week 4 (Primary Endpoint) 
ITT 
X 
2.1.1.2 
Summary of EASI Score at Week 4  
PP 
X 
2.1.1.3 
Summary and Analysis of EASI Score by Visit from Baseline to Week 8  
ITT 
X 
2.1.1.4 
Summary and Analysis of EASI Score by Visit from Baseline to Week 8 
by Baseline EASI Score ≤ 7 and > 7 
ITT 
X 
2.1.1.5 
Summary and Analysis of EASI Score by Visits from Baseline to Week 8 
by Baseline Face Involvement 
ITT 
X 
EASI Response 
2.1.2.1 
Summary of Subjects Achieving ≥ 50%, ≥ 75%, and ≥ 90% Reduction in 
EASI Score by Visits from Baseline to Week 8 
ITT 
X 
2.1.2.2 
Summary of Subjects Achieving ≥ 50%, ≥ 75%, and ≥ 90% Reduction in 
EASI Score by Visits from Baseline to Week 8 by Baseline EASI Score 
≤ 7 and > 7 
ITT 
 
2.1.2.3 
Summary of Subjects Achieving ≥ 50%, ≥ 75%, and ≥ 90%  Reduction in 
EASI Score by Visits from Baseline to Week 8 by Baseline Face 
Involvement 
ITT 
 
 


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Table No. 
Title 
Population 
In-Text 
IGA 
2.1.3.1 
Summary of IGA Responders by Visit from Baseline to Week 8 
ITT 
X 
2.1.3.2 
Summary of IGA Responders by Visit from Baseline to Week 8 by 
Baseline EASI Score ≤ 7 and > 7 
ITT 
 
2.1.3.3 
Summary of IGA Responders by Visit from Baseline to Week 8 by 
Baseline Face Involvement 
ITT 
 
2.1.3.4 
Shift Summary of IGA at Week 4 
ITT 
X 
2.1.3.5 
Summary of IGA Improvement from Baseline by Visit 
ITT 
 
Itch NRS Score 
2.1.4.1 
Summary of Itch NRS score by Visit from Baseline to Week 8 
ITT 
X 
2.1.4.2 
Summary of Categorical Itch NRS Score by Visit from Baseline to Week 8 
ITT 
 
2.1.4.3 
Shift Summary of Categorical NRS Score at Week 4 
ITT 
X 
Exposure, Adverse Events, Laboratory, and Vital Signs 
3.1.1.1 
Summary of Study Drug Exposure 
Safety 
X 
3.1.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
3.1.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
 
3.1.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency 
Safety 
X 
3.1.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System 
Organ Class, Preferred Term, and Maximum Severity 
Safety 
 
3.1.2.6 
Summary of Treatment-Related Adverse Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
 
3.1.2.7 
Summary of Treatment-Related Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency 
Safety 
 
3.1.2.8 
Summary of Treatment-Related Adverse Events by MedDRA System 
Organ Class, Preferred Term, and Maximum Severity 
Safety 
 
3.1.2.10 
Summary of Treatment-Emergent Adverse Events Leading to Death by 
MedDRA System Organ Class and Preferred Term 
Safety 
 
3.1.2.11 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
X 
3.1.2.12 
Summary of Non-Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
 
3.1.2.13 
Summary of Treatment-Related Serious Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
 
3.1.2.14 
Summary of Treatment-Emergent Adverse Events Leading to Interruption 
of Study Drug by MedDRA System Organ Class and Preferred Term 
Safety 
 
3.1.2.15 
Summary of Treatment-Emergent Adverse Events Leading to Permanent 
Discontinuation of Study Drug by MedDRA System Organ Class and 
Preferred Term 
Safety 
 


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Table No. 
Title 
Population 
In-Text 
3.1.2.16 
Summary of Treatment-Emergent Adverse Events Requiring Concomitant 
Medications by MedDRA System Organ Class and Preferred Term 
Safety 
 
3.1.3.1 
Summary of Laboratory Values - Hematology 
Safety 
 
3.1.3.5 
Summary of Laboratory Values - Chemistry 
Safety 
 
3.1.4.1 
Summary of Systolic Blood Pressure 
Safety 
 
3.1.4.2 
Summary of Diastolic Blood Pressure 
Safety 
 
3.1.4.3 
Summary of Pulse 
Safety 
 
3.1.4.4 
Summary of Body Temperature 
Safety 
 
3.1.4.5 
Summary of Respiration Rate 
Safety 
 
Tables for Open-Label Period 
Table No. 
Title 
Population 
In-Text 
Baseline Demographic and Characteristic 
1.2.1.2 
Summary of Subject Disposition in Open-Label Period 
Open-Label Evaluable 
X 
1.2.4.3 
Summary of Concomitant Medications in Open-Label Period 
Open-Label Evaluable 
 
1.2.5.1 
Summary of Drug Compliance in Open-Label Period 
Open-Label Evaluable 
 
Efficacy 
EASI 
2.2.1.3 
Summary of EASI Score in Open-Label Period 
Open-Label Evaluable 
X 
2.2.1.4 
Summary of EASI Score by Baseline EASI Score ≤ 7 and > 7 in 
Open-Label Period 
Open-Label Evaluable 
 
2.2.1.5 
Summary of EASI Score by Baseline Face Involvement in 
Open-Label Period 
Open-Label Evaluable 
 
EASI Response 
2.2.2.1 
Summary of Subjects Achieving ≥ 50%,  ≥ 75%, and ≥ 90% 
Reduction in EASI Score in Open-Label Period 
Open-Label Evaluable 
X 
2.2.2.2 
Summary of Subjects Achieving ≥ 50%,  ≥ 75%, and ≥ 90% 
Reduction in EASI Score by Baseline EASI Score ≤ 7 and > 7 in 
Open-Label Period 
Open-Label Evaluable 
 
2.2.2.3 
Summary of Subjects Achieving ≥ 50%,  ≥ 75%, and ≥ 90% 
Reduction in EASI Score by Baseline Face Involvement in 
Open-Label Period 
Open-Label Evaluable 
 
IGA 
2.2.3.2 
Summary of IGA Responders by Baseline EASI Score ≤ 7 and 
> 7 in Open-Label Period 
Open-Label Evaluable 
 
2.2.3.3 
Summary of IGA Responders by Baseline Face Involvement in 
Open-Label Period 
Open-Label Evaluable 
 
2.2.3.5 
Summary of IGA Improvement in Open-Label Period 
Open-Label Evaluable 
 
Itch NRS 
2.2.4.1 
Summary of Itch NRS in Open-Label Period 
Open-Label Evaluable 
X 
2.2.4.2 
Summary of Categorical Itch NRS in Open-Label Period 
Open-Label Evaluable 
X 


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Table No. 
Title 
Population 
In-Text 
Exposure, Adverse Events, Laboratory, and Vital Signs 
3.2.1.1 
Summary of Study Drug Exposure in Open-Label Period 
Open-Label Evaluable 
X 
3.2.2.1 
Overall Summary of Treatment-Emergent Adverse Events in 
Open-Label Period 
Open-Label Evaluable 
X 
3.2.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term in Open-Label Period 
Open-Label Evaluable 
 
3.2.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency in Open-Label 
Period 
Open-Label Evaluable 
X 
3.2.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.2.6 
Summary of Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term in Open-Label Period 
Open-Label Evaluable 
 
3.2.2.7 
Summary of Treatment-Related Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency in Open-Label 
Period 
Open-Label Evaluable 
 
3.2.2.8 
Summary of Treatment-Related Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.2.10 
Summary of Treatment-Emergent Adverse Events Leading to 
Death by MedDRA System Organ Class and Preferred Term in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.2.11 
Summary of Treatment-Emergent Serious Adverse Events by 
MedDRA System Organ Class and Preferred Term in 
Open-Label Period 
Open-Label Evaluable 
X 
3.2.2.12 
Summary of Non-Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.2.13 
Summary of Treatment-Related Serious Adverse Events by 
MedDRA System Organ Class and Preferred Term in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.2.14 
Summary of Treatment-Emergent Adverse Events Leading to 
Interruption of Study Drug by MedDRA System Organ Class and 
Preferred Term in Open-Label Period 
Open-Label Evaluable 
 
3.2.2.15 
Summary of Treatment-Emergent Adverse Events Leading to 
Permanent Discontinuation of Study Drug by MedDRA System 
Organ Class and Preferred Term in Open-Label Period 
Open-Label Evaluable 
 
3.2.2.16 
Summary of Treatment-Emergent Adverse Events Requiring 
Concomitant Medications by MedDRA System Organ Class and 
Preferred Term in Open-Label Period 
Open-Label Evaluable 
 
3.2.3.1 
Summary of Laboratory Values - Hematology in Open-Label 
Period 
Open-Label Evaluable 
 
3.2.3.5 
Summary of Laboratory Values - Chemistry in Open-Label 
Period 
Open-Label Evaluable 
 
3.2.3.8 
Shift Summary of Chemistry Values in CTC Grade - To the 
Worst Abnormal Value (Two-Directional CTC Grade) in 
Open-Label Period 
Open-Label Evaluable 
 
3.2.4.1 
Summary of Systolic Blood Pressure in Open-Label Period 
Open-Label Evaluable 
 
3.2.4.2 
Summary of Diastolic Blood Pressure in Open-Label Period 
Open-Label Evaluable 
 
3.2.4.3 
Summary of Pulse in Open-Label Period 
Open-Label Evaluable 
 
3.2.4.4 
Summary of Body Temperature in Open-Label Period 
Open-Label Evaluable 
 
3.2.4.5 
Summary of Respiration Rate in Open-Label Period 
Open-Label Evaluable 
 


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Figures 
Figure No. 
Title 
Double-Blind 
Period 
Open-Label 
Period 
2.x.1.1 
EASI Score by Visit and Treatment Group  
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.1.2 
Mean Change From Baseline in EASI Score by Visit and 
Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.1.3 
Percentage Change From Baseline in EASI Score by Visit 
and Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.1.1.4 
EASI Score by Visit and Treatment Group  
PP 
 
2.1.1.5 
Mean Change From Baseline in EASI Score by Visit and 
Treatment Group 
PP 
 
2.1.1.6 
Percent Change From Baseline in EASI Score by Visit and 
Treatment Group 
PP 
 
2.x.2.1 
Proportion of Subjects with a ≥ 50% Reduction in EASI 
Score by Visit and Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.2.2 
Proportion of Subjects with a ≥ 75% Reduction in EASI 
Score by Visit and Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.2.3 
Proportion of Subjects with a ≥ 90% Reduction in EASI 
Score by Visit and Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.1.2.4 
Kaplan-Meier Curve of the Time to First ≥ 50% 
Improvement From Baseline in EASI Score 
ITT 
 
2.1.2.5 
Kaplan-Meier Curve of the Time to First ≥ 75% 
Improvement From Baseline in EASI Score 
ITT 
 
2.1.2.6 
Kaplan-Meier Curve of the Time to First ≥ 90% 
Improvement From Baseline in EASI Score 
ITT 
 
2.x.3.1 
Proportion of Subjects with IGA Response by Visit and 
Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
 
  
 
 
2.x.4.1 
Itch NRS Score by Visit and Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.4.2 
Mean Change in Itch NRS Score by Visit and Treatment 
Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
2.x.4.3 
Mean Percent Change in Itch NRS Score by Visit and 
Treatment Group 
x = 1 
ITT 
x = 2 
Open-Label Evaluable 
Listings 
Listing No. 
Title 
Baseline Demographic and Characteristic 
1.1.1 
Subject Enrollment and Disposition Status 
1.1.2 
Subject Inclusion and Exclusion Criteria 
1.1.3 
Protocol Deviations 
1.2.1 
Demographic 
1.2.2 
Baseline Characteristics 
1.3 
Medical History 
1.4.1 
Prior and Concomitant Medications 
1.4.2 
Prior and Concomitant Medications for Atopic Dermatitis 
1.5 
Study Drug Compliance 


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Listing No. 
Title 
Efficacy 
2.1.1 
EASI Scores 
2.1.2 
Time to EASI-50 
2.3.1 
IGA Scores 
 
 
2.4 
Itch NRS 
 
 
 
 
 
 
Adverse Events (and Exposure) 
3.1 
Study Drug Administration 
3.2.1 
Adverse Events 
3.2.2 
Adverse Events Leading to Discontinuation 
3.2.3 
Serious Adverse Events 
3.2.4 
Fatal Adverse Events 
3.2.5 
Treatment Related Adverse Events 
3.2.6 
Adverse Events Leading to Interruption of Drug 
3.2.7 
Adverse Events Requiring Concomitant Medications 
Laboratory Data 
3.3.1 
Clinical Laboratory Values - Hematology 
3.3.2 
Clinical Laboratory Values - Serum Chemistry 
3.3.4 
Abnormal Clinical Laboratory Values - Hematology 
3.3.5 
Abnormal Clinical Laboratory Values - Serum Chemistry 
 
 
3.3.7 
Central Laboratory Collection Times 
Vital Signs 
3.4.1 
Vital Signs 
3.4.2 
Abnormal Vital Sign Values 
3.4.3 
Alert Vital Sign Values 
 


Signature Manifest
Document Number: IC-STS-SAP-0088
Revision: 0
Title: INCB 18424-206 SAP Original
All dates and times are in Eastern Standard Time.
APPROVAL: 18424-206 SAP
Approval and Release
Name/Signature
Title
Date
Meaning/Reason
 
27 Apr 2017, 03:18:16 PM
Approved
 & 27 Apr 2017, 03:22:12 PM
Approved
27 Apr 2017, 03:26:51 PM
Approved
 
 
27 Apr 2017, 08:37:19 PM
Approved
Page 1 of 1
Signature Manifest
4/28/2017