Clinical trial NCT05061693
Conditions: Prurigo Nodularis
Keywords: Prurigo nodularis PN INCB054707 chronic pruritus
Sponsor: Incyte Corporation
Start date: 2021-11-04; Completion date: 2024-02-28
Enrollment: 146 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of INCB054707 in participants with prurigo nodularis over a 16-week double-blind placebo-controlled treatment period, followed by a 24 -week single blind extension period.

Detailed description:

Arms: arm 1: Participants will receive INCB054707 Dose A for 16 weeks (Period 1), followed by INCB054707 Dose B (responders) or by INCB054707 Dose C (partial or nonresponders) for 24 weeks (Period 2). arm 2: Participants will receive INCB054707 Dose B for 16 weeks (Period 1), followed by INCB054707 Dose B (responders) or by INCB054707 Dose C (partial or nonresponders) for 24 weeks (Period 2). arm 3: Participants will receive INCB054707 Dose C for 16 weeks (Period 1), followed by INCB054707 Dose B (responders) or by INCB054707 Dose C (partial or nonresponders) for 24 weeks (Period 2). arm 4: Participants will receive placebo for 16 weeks (Period 1), followed by INCB054707 Dose B (responders) or by INCB054707 Dose C (partial or nonresponders) for 24 weeks (Period 2).
Interventions: intervention 1: INCB054707 intervention 2: Placebo
Intervention descriptions: intervention 1: Oral; Tablet intervention 2: Oral; Tablet

Protocol documents:
Prot_000.pdf: 
Official Title:    A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study 
of the Efficacy and Safety of INCB054707 in Participants With Prurigo 
Nodularis
NCT Number: 
 NCT05061693 
Document Date: 
Clinical Study Protocol Amendment 2: 06-May-2022


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Clinical Study Protocol 
TITLE PAGE 
INCB 54707-206 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Ranging Study of the Efficacy and Safety of INCB054707 in 
Participants With Prurigo Nodularis 
Product: 
INCB054707 
IND Number: 
137,156 
Phase of Study: 
Phase 2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
20 APR 2021 
Amendment 1: 
12 JUL 2021 
Amendment 2: 
06 MAY 2022 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 54707-206 Protocol Amendment 2 (dated 06 MAY 2022) and agree to 
conduct the study as outlined.  I agree to maintain the confidentiality of all information received 
or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
2. 
INTRODUCTION ......................................................................................................19 
2.1. 
INCB054707 ...............................................................................................................19 
2.2. 
Prurigo Nodularis ........................................................................................................19 
2.3. 
Study Rationale ...........................................................................................................20 
2.3.1. 
Scientific Rationale for Study Design ........................................................................21 
2.3.2. 
Justification for Dose ..................................................................................................21 
2.3.3. 
Justification for Placebo .............................................................................................22 
2.4. 
Benefit/Risk Assessment ............................................................................................22 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................24 
4. 
STUDY DESIGN .......................................................................................................25 
4.1. 
Overall Design ............................................................................................................25 
4.2. 
Overall Study Duration ...............................................................................................25 
4.3. 
Study Termination ......................................................................................................26 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................31 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................31 
5.4. 
Screen Failures ............................................................................................................32 
5.5. 
Replacement of Participants .......................................................................................32 
5.6. 
Data Monitoring Committee .......................................................................................32 
6. 
STUDY TREATMENT ..............................................................................................33 
6.1. 
Study Treatment Administered ...................................................................................33 
6.2. 
Preparation, Handling, and Accountability ................................................................35 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................36 
6.4. 
Study Treatment Compliance .....................................................................................36 


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6.5. 
Dose Modifications .....................................................................................................36 
6.5.1. 
Criteria and Procedures for Dose Interruptions of Study Drug ..................................36 
6.5.2. 
Criteria for Permanent Discontinuation of Study Drug ..............................................39 
6.6. 
Concomitant Medications and Procedures .................................................................39 
6.6.1. 
Permitted Medications and Procedures ......................................................................39 
6.6.2. 
Restricted Medications and Procedures ......................................................................40 
6.6.3. 
Prohibited Medications and Procedures .....................................................................40 
6.6.4. 
Rescue Therapy ..........................................................................................................41 
6.7. 
Treatment After the End of the Study .........................................................................41 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................41 
7.1. 
Discontinuation of Study Treatment ...........................................................................41 
7.1.1. 
Reasons for Discontinuation .......................................................................................41 
7.1.2. 
Discontinuation Procedures ........................................................................................42 
7.2. 
Participant Withdrawal From the Study .....................................................................43 
7.3. 
Lost to Follow-Up.......................................................................................................43 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................43 
8.1. 
Administrative and General Procedures .....................................................................43 
8.1.1. 
Informed Consent Process ..........................................................................................43 
8.1.2. 
Screening Procedures ..................................................................................................44 
8.1.3. 
Interactive Response Technology Procedure ..............................................................45 
8.1.4. 
Distribution of Reminder Cards and/or Diaries ..........................................................45 
8.1.5. 
Demography and Medical History ..............................................................................45 
8.1.5.1. 
Demographics and General Medical History .............................................................45 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................45 
8.2. 
Efficacy Assessments .................................................................................................45 
8.2.1. 
Health Economics .......................................................................................................45 
8.2.2. 
Investigator's Global Assessment ...............................................................................46 
 
46 
 
46 
 
46 
8.3. 
Patient-Reported Outcomes ........................................................................................46 
8.3.1. 
eDiary .........................................................................................................................47 


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8.3.1.1. 
Itch NRS .....................................................................................................................47 
 
47 
 
47 
 
47 
 
48 
 
48 
 
48 
 
49 
 
49 
8.4. 
Safety Assessments .....................................................................................................49 
8.4.1. 
Adverse Events ...........................................................................................................49 
8.4.2. 
Physical Examinations ................................................................................................50 
8.4.3. 
Vital Signs ..................................................................................................................50 
8.4.4. 
Electrocardiograms .....................................................................................................51 
8.4.5. 
Laboratory Assessments .............................................................................................51 
8.4.5.1. 
Pregnancy Testing ......................................................................................................54 
8.4.5.2. 
Serology ......................................................................................................................54 
8.4.5.3. 
Tuberculosis Screening ...............................................................................................54 
 
55 
 
55 
 
56 
 
56 
8.7. 
Unscheduled Visits .....................................................................................................56 
8.8. 
End of Treatment and/or Early Termination ..............................................................56 
8.9. 
Follow-Up ...................................................................................................................57 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................57 
9.1. 
Definition of Adverse Event .......................................................................................57 
9.2. 
Definition of Serious Adverse Event ..........................................................................58 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........59 
9.4. 
Reporting of Serious Adverse Events .........................................................................61 
9.5. 
Events of Clinical Interest ..........................................................................................62 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................63 


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9.7. 
Pregnancy ...................................................................................................................63 
9.8. 
Warnings and Precautions ..........................................................................................64 
9.9. 
Product Complaints ....................................................................................................64 
9.10. 
Treatment of Overdose ...............................................................................................64 
10. 
STATISTICS ..............................................................................................................64 
10.1. 
Sample Size Determination ........................................................................................64 
10.2. 
Populations for Analysis .............................................................................................64 
10.3. 
Level of Significance ..................................................................................................65 
10.4. 
Statistical Analyses .....................................................................................................65 
10.4.1. 
Primary Analysis ........................................................................................................65 
10.4.2. 
Secondary Analysis ....................................................................................................66 
10.4.3. 
Safety Analyses ..........................................................................................................66 
 
66 
 
67 
 
67 
 
67 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................67 
11.1. 
Investigator Responsibilities .......................................................................................67 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................68 
11.2. 
Data Management .......................................................................................................68 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................70 
11.4. 
Financial Disclosure ...................................................................................................71 
11.5. 
Publication Policy .......................................................................................................71 
11.6. 
Study and Site Closure................................................................................................72 
12. 
REFERENCES ...........................................................................................................73 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................75 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................77 
APPENDIX C. LIST OF STRONG/MODERATE SYSTEMIC CYP3A4 
INHIBITORS AND STRONG SYSTEMIC CYP3A4 INDUCERS..........................80 
APPENDIX D. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
INCB054707 ...............................................................................................................81 


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APPENDIX E. MANAGEMENT OF POTENTIAL HY'S LAW CASES ................................82 
APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................86 
 
LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................11 
Table 2: 
Key Study Design Elements .......................................................................................12 
Table 3: 
Schedule of Activities for the Placebo-Controlled Period ..........................................14 
Table 4: 
Schedule of Activities for the Extension Period .........................................................17 
 
23 
Table 6: 
Objectives and Endpoints ...........................................................................................24 
Table 7: 
Exclusionary Laboratory Values ................................................................................30 
Table 8: 
Study Drug Information ..............................................................................................34 
Table 9: 
Guidelines for Interruption, Restart, and Discontinuation of Study Drug 
Based on Platelet Count ..............................................................................................37 
Table 10: Guidelines for Interruption, Restart, and Discontinuation of Study Drug ..................37 
Table 11: Investigator's Global Assessment ...............................................................................46 
Table 12: Required Laboratory Analytes ....................................................................................53 
Table 13: Populations for Analysis .............................................................................................65 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................13 
Figure 2: 
Role of JAK1 in Prurigo Nodularis ............................................................................21 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
ALT 
alanine transaminase 
ALP 
alkaline phosphatase 
ANC 
absolute neutrophil count 
anti-HBc 
anti–hepatitis B core 
AST 
aspartate transaminase 
 
 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
 
 
COVID-19 
coronavirus disease 2019 
CSR 
Clinical Study Report 
 
 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
 
 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDiary 
electronic diary 
EOS 
end of study 
EOT 
end of treatment 
 
 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
 
 


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Abbreviations and 
Special Terms 
Definition 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HCVAb 
hepatitis C virus antibody 
Hgb 
hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HS 
hidradenitis suppurativa 
hsCRP 
high-sensitivity C-reactive protein 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ID 
identification 
IEC 
independent ethics committee 
IGA 
Investigator's Global Assessment 
IGA-TS 
Investigator's Global Assessment Treatment Success (IGA score of 0 or 1 with 
≥ 2-grade improvement from baseline) 
IgE 
Immunoglobulin E 
IL 
interleukin 
INR 
international normalized ratio 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent-to-treat 
JAK 
Janus kinase 
ka 
absorption rate constant 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
numerical rating scale 
 
 
PD 
pharmacodynamic 
PDE-4 
phosphodiesterase-4 


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Abbreviations and 
Special Terms 
Definition 
 
 
PHL 
potential Hy's law 
PK 
pharmacokinetic 
PN 
prurigo nodularis 
PPD 
purified protein derivative 
PT 
prothrombin time 
Q/F 
apparent intercompartmental clearance 
QALY 
quality-adjusted life year 
QD 
once daily 
QFT-GIT 
QuantiFERON-TB Gold In-Tube test 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
schedules of activities 
SOP 
standard operating procedure 
STAT 
signal transducer and activator of transcription 
 
 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
Th 
T-helper 
 
 
 
 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
VAS 
visual analog scale 
 
 
 
 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 
 
 


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy 
and Safety of INCB054707 in Participants With Prurigo Nodularis 
Protocol Number:  INCB 54707-206 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of 
INCB054707 in PN. 
Proportion of participants achieving ≥ 4-point improvement in 
Itch NRS score at Week 16. 
Secondary 
To further assess the treatment 
effects of INCB054707. 
• Proportion of participants achieving IGA-TS (IGA score of 0 
or 1 with a ≥ 2-grade improvement from baseline) at 
Week 16. 
• Time to ≥ 4-point improvement from baseline in Itch NRS 
score. 
To evaluate the safety and 
tolerability of INCB054707. 
The type, frequency, and severity of AEs, including the results 
of physical examinations, and evaluation of vital signs, ECGs, 
and laboratory data. 
Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table. 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 2 
Clinical Indication 
Treatment of patients with PN 
Population 
Male and female participants 18 to 
 years of age who have had a clinical 
diagnosis of PN for at least 3 months, received prior treatment for PN, and 
have a total of ≥ 20  pruriginous lesions in ≥ 2 different body regions, an IGA 
score ≥ 3, and an Itch NRS score ≥ 5. 
Number of 
Participants 
Approximately 140 participants will be randomized 1:1:1:1 to 1 of 4 treatment 
groups (35 participants per group). 
Study Design 
This is a randomized, double-blind, placebo-controlled study with a 
single-blind extension period.  The dose of INCB054707 in the extension 
period will be based on efficacy response (Itch NRS and IGA) at Week 16. 
Estimated Duration 
of Study 
Participation 
Participants will participate for up to 48 weeks, including up to 4 weeks for 
screening, up to 40 weeks of treatment (16 weeks in the placebo-controlled 
period and 24 weeks in the extension period), and 4 weeks for safety 
follow-up. 
DMC 
Yes (internal) 
Coordinating 
Principal 
Investigator 
Shawn G. Kwatra, MD 
Treatment Groups and Duration: 
On Day 1, eligible participants will be equally randomized to 1 of 4 treatment groups 
(INCB054707 15 mg QD, 45 mg QD, or 75 mg QD or placebo; see Figure 1) and stratified by 
IGA score (3 vs 4).  Participants will receive blinded study drug through Week 16. 
The use of rescue medications should be delayed, if possible, for at least 8 weeks after the first 
dose of study drug. However, the use of rescue medications are allowable at any time during the 
study in participants who have substantial worsening of PN from baseline (as determined by the 
investigator).  Rescue therapy should be provided commensurate with symptom severity.  
Protocol-permitted rescue therapies are presented in Section 6.6.4.  Participants receiving a 
prohibited medication (see Section 6.6.3) as rescue therapy must be withdrawn from study drug. 
Based on the IGA and Itch NRS responses at Week 16, participants will receive either 
INCB054707 
 or 
 QD for an additional 24 weeks in the extension period.  The 
investigator will be aware of the dose in the extension period; the participant will remain blinded 
to the dose received in the extension period. 
 
 
 
 
 
 
. 


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Figure 1 presents the study design schema.  The SoA for the placebo-controlled and extension 
periods are presented in Table 3 and Table 4, respectively.  Adherence to the study design 
requirements, including those specified in the SoA, is essential and required for study conduct. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the outline of potential mitigation 
strategies described in Appendix B. 
Figure 1: 
Study Design Schema 
 
 


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Table 3: 
Schedule of Activities for the Placebo-Controlled Period 
Visit Day (Range) 
Screening 
Placebo-Controlled Treatment 
Notes 
Days 
−28 to −1 
Day 1 
(Baseline) 
Week 2 
Remote 
(± 3 d) 
Week 4 
(± 3 d)  
Week 6 
Remote 
(± 3 d) 
Week 8 
(± 3 d) 
Week 12 
(± 3 d) 
Week 16/ 
EOT1 
(± 3 d) 
Week 16 assessments must be 
complete before a participant can 
continue in the extension period. 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
Section 8.1.1 
Inclusion/exclusion criteria 
review 
X 
X 
 
 
 
 
 
 
Section 5 
Demography and medical 
history 
X 
 
 
 
 
 
 
 
General and disease-specific medical 
history. 
Section 8.1.5 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.6 
Contact IRT 
X 
X 
 
X 
 
X 
X 
X 
Section 8.1.3 
Randomization 
 
X 
 
 
 
 
 
 
 
Dispense study drug 
 
X 
 
X 
 
X 
X 
X 
 
Study drug administered at site 
 
X 
 
X 
 
 
 
X 
 
Collect study drug and review 
study drug compliance 
 
 
 
X 
 
X 
X 
X 
 
Distribute reminder card 
 
X 
 
X 
 
X 
X 
X 
 
Assess eDiary compliance 
 
X 
X 
X 
X 
X 
X 
X 
 
Follow-up phone call (eDiary 
compliance)  
X 
 
 
 
 
 
 
 
Section 8.3.1  
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE is noted, relevant body 
systems should be physically 
examined. 
Section 8.4.1 
Comprehensive physical 
examination 
X 
X 
 
 
 
 
 
X 
Section 8.4.2  
Height 
 
X 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
X 
 
Vital signs 
X 
X 
 
X 
 
X 
X 
X 
Section 8.4.3  
12-lead ECG 
X 
 
 
 
 
 
 
X 
Section 8.4.4  


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Table 3: 
Schedule of Activities for the Placebo-Controlled Period (Continued) 
Visit Day (Range) 
Screening 
Placebo-Controlled Treatment 
Notes 
Days 
−28 to −1 
Day 1 
(Baseline) 
Week 2 
Remote 
(± 3 d) 
Week 4 
(± 3 d)  
Week 6 
Remote 
(± 3 d) 
Week 8 
(± 3 d) 
Week 12 
(± 3 d) 
Week 16/ 
EOT1 
(± 3 d) 
Week 16 assessments must be 
complete before a participant can 
continue in the extension period. 
Efficacy assessments 
IGA 
X 
X 
 
X 
 
X 
X 
X 
Section 8.2.2 
Patient-reported outcomes (Note:  Should be conducted before any other assessments) 
 
Itch NRS 
Diary is completed each evening from screening through the last dose of study drug. 
Section 8.3.1.1 
Laboratory assessments  
TB screening 
X 
 
 
 
 
 
 
 
Table 12 
Serology 
X 
 
 
 
 
 
 
 
Table 12 
Chemistry assessments 
X 
X 
X 
X 
X 
X 
X 
X 
Table 12 
Hematology assessments 
X 
X 
X 
X 
X 
X 
X 
X 
FSH 
X 
 
 
 
 
 
 
 
Women of nonchildbearing potential.  
Table 12 
Serum pregnancy test 
X 
 
 
 
 
 
 
X* 
*WOCBP only. 
Table 12 
Urine pregnancy test 
 
X 
 
X 
 
X 
X 
 
WOCBP only.  Positive urine test to 
be confirmed by serum test. 
Table 12 
Coagulation 
X 
 
 
 
 
X 
 
X 
Table 12 


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Table 3: 
Schedule of Activities for the Placebo-Controlled Period (Continued) 
Visit Day (Range) 
Screening 
Placebo-Controlled Treatment 
Notes 
Days 
−28 to −1 
Day 1 
(Baseline) 
Week 2 
Remote 
(± 3 d) 
Week 4 
(± 3 d)  
Week 6 
Remote 
(± 3 d) 
Week 8 
(± 3 d) 
Week 12 
(± 3 d) 
Week 16/ 
EOT1 
(± 3 d) 
Week 16 assessments must be 
complete before a participant can 
continue in the extension period. 
Laboratory assessments (continued) 
Lipid panel 
 
X 
 
 
 
X 
 
X 
Table 12 
Thyroid function 
X 
 
 
 
 
 
 
X 
Table 12 
Urinalysis 
X 
 
 
 
 
X 
 
X 
Table 12 


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Table 4: 
Schedule of Activities for the Extension Period 
Visit Day (Range) 
Extension Treatment 
Safety 
Follow-up 
Notes 
Week 18 
Remote 
(± 3 d) 
Week 20 
(± 3 d) 
Week 22 
Remote 
(± 3 d)  
Week 24 
(± 3 d) 
Week 28 
(± 3 d) 
Week 32 
(± 3 d) 
Week 36 
(± 3 d) 
Week 40/ 
EOT2 
(± 3 d) 
28 Days 
(+ 7 d) 
After Last 
Dose 
 
Administrative procedures 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.6  
Contact IRT 
 
X 
 
X 
X 
X 
X 
X 
 
Section 8.1.3  
Distribute reminder card 
 
X 
 
X 
X 
X 
X 
X 
 
 
Dispense study drug 
 
X 
 
X 
X 
X 
X 
 
 
 
Collect study drug and 
review study drug 
compliance 
 
X 
 
X 
X 
X 
X 
X 
 
 
Assess eDiary 
compliance 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE is noted, relevant 
body systems should be 
physically examined.  
Section 8.4.1  
Comprehensive physical 
examination 
 
 
 
 
 
 
 
X 
 
Section 8.4.2 
Weight 
 
 
 
 
X 
 
 
X 
 
 
Vital signs 
 
X 
 
X 
X 
X 
X 
X 
X 
Section 8.4.3  
12-lead ECG 
 
 
 
 
 
 
 
X 
 
Section 8.4.4  
Efficacy assessments 
IGA 
 
X 
 
X 
X 
X 
X 
X 
X 
Section 8.2.2  
Patient-reported outcomes (Note:  Should be conducted before any other assessments) 
 
Itch NRS 
Diary is completed each evening from screening through the last dose of study drug. 
 
Section 8.3.1.1  


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Table 4: 
Schedule of Activities for the Extension Period (Continued) 
Visit Day (Range) 
Extension Treatment 
Safety 
Follow-up 
Notes 
Week 18 
Remote 
(± 3 d) 
Week 20 
(± 3 d) 
Week 22 
Remote 
(± 3 d)  
Week 24 
(± 3 d) 
Week 28 
(± 3 d) 
Week 32 
(± 3 d) 
Week 36 
(± 3 d) 
Week 40/ 
EOT2 
(± 3 d) 
28 Days 
(+ 7 d) 
After Last 
Dose 
 
Laboratory assessments 
Chemistry assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table 12 
Hematology assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancy test 
 
 
 
 
 
 
 
 
X 
WOCBP only.   
Table 12 
Urine pregnancy test 
 
X 
 
X 
X 
X 
X 
X 
 
WOCBP only.  Positive 
urine test to be confirmed 
by serum test.   
Table 12 
Coagulation 
 
 
 
X 
 
 
 
X 
 
Table 12 
Lipid panel 
 
 
 
X 
 
 
 
X 
 
Table 12 
Thyroid function 
 
 
 
 
 
 
 
X 
 
Table 12 
Urinalysis 
 
 
 
X 
 
 
 
X 
 
Table 12 
 


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2. 
INTRODUCTION 
2.1. 
INCB054707 
INCB054707 is an oral JAK inhibitor with selectivity for JAK1 that is currently under 
development for the treatment of patients with HS and vitiligo.  Proinflammatory cytokines are 
strongly implicated in the pathogenesis of several dermatologic diseases, such as HS, atopic 
dermatitis, plaque psoriasis, vitiligo, and PN.  Additionally, JAKs mediate extracellular signals 
from a number of relevant proinflammatory cytokines and growth factors upregulated in those 
disease states.  Further, a Phase 2 study of INCB054707 in participants with HS (NCT03607487) 
demonstrated proof of concept by showing a decrease in abscess and inflammatory nodules, as 
well as improvements in skin pain and quality of life.  This supports the investigation of 
INCB054707 in a Phase 2 dose-ranging study in participants with PN. 
2.2. 
Prurigo Nodularis 
Prurigo nodularis is a chronic skin disorder affecting primarily older adults and is characterized 
by firm, dome-shaped, intensely pruritic nodules ranging in size from a few millimeters to 
several centimeters.  The nodules are often symmetrically distributed on the extensor surfaces of 
the arms and legs and on the trunk.  The itch generally precedes the nodules and is thought to be 
neurogenic; however, the underlying cause of the itch is not known.  In a subset of patients with 
chronic pruritus, PN occurs as a result of continuous scratching.  Typically, the upper back is 
spared, as this is an area that patients cannot reach to scratch 
 
Prurigo nodularis has an estimated prevalence of 72 per 100,000 persons in the US, based on 
people with health insurance (Huang et al 2020).  Reports vary on whether it occurs more 
frequently in women versus men (Huang et al 2020) or occurs equally in men and women 
(Elmariah et al 2021, Pereira et al 2018).  People with black skin are substantially more likely to 
have PN than people with white skin (McColl et al 2021).  In particular, 1 study found that 
African American patients were 3.4 times more likely to have PN than White patients (Boozalis 
et al 2018). 
Quality of life can be substantially and negatively impacted by PN (Kwatra 2020), in particular, 
sleep disturbance, impact on job performance, and avoidance of social activities (Todberg 
et al 2020).  In addition, the burden of systemic comorbidities in PN often exceeds that of other 
inflammatory skin disorders (ie, atopic dermatitis or psoriasis).  Prurigo nodularis is associated 
with increased rates of mental health (specifically anxiety and depression) and endocrine, 
cardiovascular, and renal disorders as well as HIV infection and malignancy (Dazzi et al 2011, 
Huang et al 2020, Kowalski et al 2019).  Approximately half of all patients with PN report a 
history of atopic dermatitis (Iking et al 2013). 
Pharmacologic therapy with first-generation sedating antihistamines (eg, hydroxyzine, 
diphenhydramine) administered at bedtime may be useful in controlling nocturnal pruritus.  
Both selective serotonin reuptake inhibitors and tricyclic antidepressants are also used for the 
treatment of chronic pruritus, especially when a component of depression is present 
 


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Superpotent topical corticosteroids are considered first-line therapy (Williams et al 2020).  
Patients with widespread disease may be treated with phototherapy (Kowalski et al 2019).  
Patients with recalcitrant PN may be given systemic treatments including systemic 
immunosuppressants, thalidomide, lenalidomide, and anticonvulsants (Tsianakas et al 2016).  
These treatments are associated with potential significant toxicity, and their efficacy in patients 
with recalcitrant PN has not been established 
. 
2.3. 
Study Rationale 
Inflammatory cells, including T cells, eosinophils, and mast cells, are increased in patients with 
PN and secrete neurotrophins that promote neurogenic inflammation (Kwatra 2020, Perez 
et al 1993).  Central to the pathogenesis of PN is a robust inflammatory response and intense itch 
caused by mediators such as IL-31, tryptase, eosinophil cationic protein, histamine, 
prostaglandins, and neuropeptides (Almeida et al 2004, Zeidler et al 2018). 
The role of Th1 and Th2 cytokines in the pathogenesis of PN has been evaluated by examining 
the cytokine signatures in the epidermis in 22 cases of PN, using STAT 1, 3, and 6 (Fukushi 
et al 2011).  In 19 of the 22 cases of PN, the entire epidermis stained with anti-pSTAT 6, a 
marker for the Th2 cytokines IL-4, IL-5, and IL-13.  Only 8 cases showed scattered staining with 
anti-pSTAT 1, a marker for the Th1 cytokines interferon gamma and IL-27.  
 
 
The improvements in itch seen with JAK inhibitors are well known, and INCB054707 should 
provide relief for itch, which is one of the most bothersome symptoms of PN (Wang and 
Kim 2020). 
 
 


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2.3.1. 
Scientific Rationale for Study Design 
This study will examine the efficacy and safety of 3 doses of INCB054707 (15, 45, and 75 mg 
QD) versus placebo as proof of concept and dose ranging.  The placebo-controlled period will be 
16 weeks, and the dose in the extension period will be determined by IGA and Itch NRS 
responses at Week 16.  
 
 
  This design will provide a well-controlled 
assessment of the efficacy of INCB054707 in PN while minimizing the treatment duration for 
participants assigned to placebo.  In addition, it will help determine the possibility of maintaining 
a response at a lower exposure as well as the possibility of a more robust response at a higher 
exposure if the initial dose was not sufficient to elicit a therapeutic response.  Further, the 
24-week extension period will provide an adequate duration to assess the maintenance of the 
response for responders or the potential improvement of response for nonresponders. 
 
 
 
 
 
 
 
 


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2.3.3. 
Justification for Placebo 
The comparison to placebo is relevant to better understand the effect of an oral systemic JAK1 
inhibitor in the treatment of PN.  The use of placebo is justified considering that there are no 
available PN-specific therapies to be used as a comparator and that delaying treatment does not 
pose excessive harm to patients (Millum and Grady 2013).  In addition, participants who have a 
substantial worsening of PN during the placebo-controlled period may receive rescue therapy 
(see Section 6.6.4 for allowed recue therapies).  After the 16-week placebo-controlled period, all 
participants will receive INCB054707 
 or 
 QD for up to 24 weeks in the extension 
period. 
2.4. 
Benefit/Risk Assessment 
INCB054707 has been studied in 2 healthy participant studies (76 participants) and 2 studies in 
participants with HS (45 participants, NCT03569371 and NCT03607487). 
In healthy participants, single doses of INCB054707 up to 405 mg and multiple doses of 
INCB054707 up to 120 mg QD were administered for up to 10 days.  The most common TEAE 
was mild to moderate headache in 31% of participants who received INCB054707 in the 
multiple-dose study; the events were not dose-dependent and resolved spontaneously following 
discontinuation of INCB054707. 
The studies in participants with HS examined QD doses of 15, 30, 60, and 90 mg and placebo for 
up to 8 weeks.  Transient and asymptomatic thrombocytopenia was observed after 4 weeks of 
exposure in 4 of 8 participants who received INCB054707 90 mg QD.  The dose was interrupted 
for a maximum of 2 weeks, and the thrombocytopenia resolved without intervention; participants 
resumed treatment with INCB054707 90 mg QD and completed the study without clinical 
sequelae or re-emergence of thrombocytopenia.  In addition, Hgb levels remained within normal 
limits and were mostly unchanged during the study, and neutrophil counts showed a mild 
dose-dependent decrease within normal limits.  Across the 2 studies, the most common TEAE 
was fatigue, observed in 6 of the 36 participants (17%).  Mild-to-moderate headache was 
observed in 11% of the participants exposed to INCB054707 compared with 22% of the 
participants exposed to placebo.  No serious or fatal TEAEs were reported in the studies; more 
details are provided in the IB. 
Based on the available nonclinical and clinical data, the potential risks to participants are 
summarized in 
  More detailed information about the known and expected benefits and 
risks and reasonably expected AEs of INCB054707 may be found in the IB. 


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INCB054707 is the first JAK inhibitor being studied in a randomized clinical study in 
participants with PN, so the benefit is unknown.  Based on the mechanism of action of 
INCB054707, it is expected that participants will see a reduction in itch as well as improvement 
in PN lesions (see Section 2.3.1). 
 
 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 6 presents the objectives and endpoints. 
Table 6: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of 
INCB054707 in PN. 
Proportion of participants achieving ≥ 4-point improvement in Itch 
NRS score at Week 16. 
Secondary 
To further assess the treatment effects 
of INCB054707. 
• Proportion of participants achieving IGA-TS (IGA score of 0 or 1 
with a ≥ 2-grade improvement from baseline) at Week 16. 
• Time to ≥ 4-point improvement from baseline in Itch NRS score. 
To evaluate the safety and tolerability 
of INCB054707. 
The type, frequency, and severity of AEs, including the results of 
physical examinations, and evaluation of vital signs, ECGs, and 
laboratory data. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study has a 16-week, randomized, double-blind, dose-ranging, placebo-controlled period 
and a 24-week, single-blind extension period.  The study will include approximately 140 men 
and women 18 to 
 years of age who have had a clinical diagnosis of PN for at least 3 months, 
received prior treatment for PN, and have a total of ≥ 20 pruriginous lesions in ≥ 2 different body 
regions, an IGA score ≥ 3, and an Itch NRS score ≥ 5.  
After signing the ICF, screening assessments may be completed over a period of up to 28 days.  
On Day 1, eligible participants will be equally randomized to 1 of 4 treatment groups 
(INCB054707 15 mg QD, 45 mg QD, or 75 mg QD or placebo; see Figure 1) and stratified by 
IGA score (3 vs 4).  Participants will receive blinded study drug through Week 16. 
The use of rescue medications should be delayed, if possible, for at least 8 weeks after the first 
dose of study drug. However, the use of rescue medications are allowable at any time during the 
study in participants who have substantial worsening of PN from baseline (as determined by the 
investigator).  Rescue therapy should be provided commensurate with symptom severity.  
Protocol-permitted rescue therapies are presented in Section 6.6.4.  Participants receiving a 
prohibited medication (see Section 6.6.3) as rescue therapy must be withdrawn from study drug. 
Based on the IGA and Itch NRS responses at Week 16, participants will receive either 
INCB054707 
 or 
 QD for an additional 24 weeks in the extension period.  The 
investigator will be aware of the dose in the extension period; the participant will remain blinded 
to the dose received in the extension period. 
• 
 
 
 
• 
 
 
After the last dose of study drug, participants will be followed for safety, with a safety visit 
performed at least 28 days after the last dose of study drug. 
Figure 1 presents the study design schema.  The SoA for the placebo-controlled and extension 
periods are presented in Table 3 and Table 4, respectively.  Adherence to the study design 
requirements, including those specified in the SoA, is essential and required for study conduct. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study 
(including AE and laboratory assessments), requiring the outline of potential mitigation 
strategies described in Appendix B.  Participants do not need to stop treatment in the study to 
receive a COVID-19 vaccine. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF.  The end of the study is defined 
as the date of the last visit of the last participant in the study or the last scheduled procedure for 
the last participant in the study globally. 


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It is estimated that an individual will participate for approximately 11 months, including up to 
28 days for screening, up to 40 weeks of treatment (including the placebo-controlled and 
extension periods, as long as participants are receiving benefit and have not met any criteria for 
study withdrawal), and 28 (+ 7) days for follow-up after the last dose of study drug.   
A participant is considered to have completed the study if he/she has completed both the 
placebo-controlled and the extension periods of the study.  The study is considered completed 
when the last participant's last visit has occurred. 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the IRB/IEC of the study's 
completion or early termination in writing, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively if, for example, required by regulatory decision 
or upon advice of the DMC.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and the regulatory bodies of the decision and reason for 
termination of the study. 
5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for the study. 
2. Men and women 18 to
years of age. 
3. Clinical diagnosis of PN for at least 3 months before screening. 
Note:  Diagnosis may be based on investigator assessment and study participant 
interview. 
4. Inadequate response or intolerant to ongoing or prior PN therapy. 
Note:  Previous PN therapy may include any treatment (including over-the-counter 
products) intended to treat PN symptoms. 
5. ≥ 20 pruriginous lesions at screening and Day 1. 
Note:  Pruriginous lesions may include nodules, papules, plaques, umbilicated ulcers, or 
ulcers. 


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6. Pruriginous lesions on ≥ 2 different body regions at screening and Day 1. 
Note:  Pruriginous lesions may include nodules, papules, plaques, umbilicated ulcers, or 
ulcers. 
7. IGA score ≥ 3 at screening and Day 1. 
8. Pruritus as defined by the following: 
a. Screening:  Itch NRS score ≥ 5 based on recall for the week preceding screening. 
b. Day 1:  Average Itch NRS ≥ 5 for the week before Day 1.  Note:  Participants must 
have at least 4 nonmissing Itch NRS daily scores out of the 7 days before Day 1 to 
calculate an average and be randomized. 
9. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children from screening through 90 days (a 
spermatogenesis cycle) after the last dose of study drug and must refrain from 
donating sperm during this period.  Permitted methods in preventing pregnancy (see 
Appendix A) should be communicated to the participants and their understanding 
confirmed. 
b. Female participants who are not of childbearing potential or, if of childbearing 
potential, must have a negative pregnancy test at screening (serum) and before the 
first dose on Day 1 (urine).  Women of childbearing potential must agree to take 
appropriate precautions to avoid pregnancy from screening through 30 days 
(1 menstrual cycle) after the last dose of study drug and must refrain from donating 
oocytes during this period.  Permitted methods in preventing pregnancy (see 
Appendix A) should be communicated to the participants and their understanding 
confirmed. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Have chronic pruritus due to a condition other than PN (eg, such as scabies, insect bite, 
lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid 
papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous 
disease, excoriation syndrome, cholestatic liver disease, chronic kidney disease). 
2. Have neuropathic and psychogenic pruritus such as but not limited to notalgia 
paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or 
delusional parasitosis. 
3. Current use of a medication known to cause pruritus. 
4. Have concurrent conditions and history of other diseases as follows: 
a. Thrombocytopenia, coagulopathy, platelet dysfunction, or history of thrombotic 
events. 
b. Any other concomitant skin disorder (eg, generalized erythroderma such as 
Netherton' syndrome), pigmentation, or extensive scarring that in the opinion of the 


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investigator may interfere with the evaluation of PN lesions or assessments of 
efficacy or compromise participant safety. 
c. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, 
antiparasitics, antiprotozoals, or antifungals within 2 weeks before the Day 1 visit. 
d. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes 
zoster, chickenpox, clinically infected atopic dermatitis, impetigo) within 1 week 
before the Day 1 visit. 
e. Current herpes zoster infection, a history of disseminated herpes simplex, or a history 
of herpes zoster. 
f. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, 
Wiskott-Aldrich syndrome). 
g. History of malignancy, including melanoma, lymphoma, and leukemia within 5 years 
before Day 1, other than a successfully treated nonmetastatic cutaneous squamous 
cell carcinoma, basal cell carcinoma, or localized carcinoma in situ of the cervix. 
h. Albinism. 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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17. Evidence of HBV or HCV infection or risk of reactivation.  Participants cannot be 
positive for HBsAg, anti–hepatitis B core antibody, or HCV antibody; participants also 
cannot be positive for HBV DNA or HCV RNA in case these reflexive assessments are 
required to be performed. 
Note 1:  Participants with no prior history of HBV infection who have been vaccinated 
against HBV and who have a positive antibody (hepatitis B surface antibody) against 
HBsAg as the only evidence of prior exposure may participate in the study. 
Note 2:  Participants with a history of HCV infection who are antibody positive and have 
successfully completed treated > 12 weeks before screening, and have no detectable HCV 
RNA, are allowed in the study. 
18. Known HIV infection.   


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19. Evidence of active or latent or inadequately treated infection with Mycobacterium 
tuberculosis (ie, TB), as defined by the following: 
a. A positive QFT-GIT or positive Mantoux/PPD tuberculin skin test performed at or 
within the 12 weeks prior to Day 1 is exclusionary; a negative test is required for 
eligibility unless other criteria as described here are applicable.  It is recommended 
that participants with a history of Bacille Calmette-Guérin vaccination be tested with 
the QFT-GIT, because the Mantoux/PPD tuberculin skin test may be positive due to 
vaccination.  A QFT-GIT or Mantoux/PPD tuberculin skin test is not required if the 
participant has previously received a documented adequate course of therapy for 
either latent or active TB infection. 
b. A history of either untreated or inadequately treated latent or active TB infection. 
c. If a participant has previously received an adequate course of therapy for either latent 
TB infection (9 months of isoniazid in a locale where rates of primary multidrug TB 
resistance are < 5% or an acceptable alternative regimen) or active TB infection (an 
acceptable multidrug regimen), neither a QFT-GIT nor a Mantoux/PPD tuberculin 
skin test is needed, but a chest x-ray(s) or other appropriate diagnostic image, 
performed within 3 months of Day 1, is required.  To be considered eligible for the 
study, the x-ray(s) must be negative for active TB infection as determined by a 
qualified radiologist.  Documentation of adequate treatment for TB and negative chest 
x-ray(s) results must be obtained prior to Day 1. 
d. A participant who is currently being treated for active or latent TB infection is to be 
excluded. 
20. Pregnant or lactating participants or those considering pregnancy. 
21. History of alcoholism or drug addiction within 1 year before screening or current alcohol 
or drug use that, in the opinion of the investigator, will interfere with the participant's 
ability to comply with the administration schedule and study assessments. 
22. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits; 
pose a significant risk to the participant; or interfere with interpretation of study data. 
23. Planned or expected major surgery within the timelines of study duration. 
24. Concurrent enrollment in another clinical study. 
5.3. 
Lifestyle Considerations 
Participants are not allowed to use tanning beds during the study.  
5.3.1. 
Meals and Dietary Restrictions 
Participants must abstain from consumption of grapefruit or grapefruit juice (pomelos, exotic 
citrus fruits, grapefruit hybrids, or fruit juices) and of Seville oranges from 14 days before the 
start of study drug until after the final dose of study drug. 
Participants must abstain from consumption of dietary supplements containing St John's wort 
(Hypericum perforatum) from 14 days before the start of study drug until after the final dose of 
study drug. 


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5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study drug. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error.  Additionally, a participant who fails screening may 
repeat the screening process 1 time if the investigator believes that there has been a change in 
eligibility status.  Participants who rescreen must reconsent and be assigned a new participant 
number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 
5.6. 
Data Monitoring Committee 
This study will use an internal DMC to monitor safety.  There will be 1 planned DMC review 
after randomization of the initial approximately 40 participants in the study and their respective 
completion of the Week 16 visit.  The DMC will meet for at least 1 additional review at a time to 
be determined after the first review meeting.  The DMC members will be blinded to participants' 
treatment assignment for the initial safety review; however, the DMC members may request 
unblinding at any time. 
The members of the DMC will not be involved with the study in any other way.  The DMC 
charter will describe the composition, responsibilities, governance (including the roles and 
responsibilities of the various members, the sponsor, and protocol team), and requirements for 
and proper documentation of DMC meetings (reports, minutes, and recommendations). 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
Table 8 presents the study drug information. 
Participants will record study drug administration in a daily diary.  Further information regarding 
study drug administration is provided in Appendix D. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix B.  Participants do 
not need to interrupt study drug to receive the COVID-19 vaccine.


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Table 8: 
Study Drug Information 
 
Placebo-Controlled Period, Double-Blind  
(16 Weeks) 
Extension Period, Single-Blind 
(24 Weeks) 
 
Study Treatment 1 
Study Treatment 2 
Study Treatment – Extension  
Study treatment name: 
INCB054707 
Matching placebo 
INCB054707 
Mechanism of action: 
JAK inhibitor 
Not applicable 
JAK inhibitor 
Dosage formulation: 
Tablet, oral 
Tablet, oral 
Tablet, oral 
Unit dose strength(s) 
/dosage level(s): 
• 15 mg = INCB054707 
 
 and  placebo tablets 
• 45 mg = INCB054707 
 
 and  placebo tablets 
• 75 mg =  INCB054707 
 
 
• Placebo =  placebo tablets 
• 
 =  INCB054707 
 
tablets and  placebo tablets 
• 
 = INCB054707 
 
tablets 
Administration 
instructions: 
INCB054707 or matching placebo will be taken orally QD, preferably in 
the morning, with a full glass of water, without regard to food. 
Note:  Dose will be administered at the study site at the Week 4 and 
Week 16 visits.  Participants will withhold self-administration on the days 
of those visits. 
INCB054707 will be taken orally 
QD, preferably in the morning, 
with a full glass of water, without 
regard to food. 
Packaging and labeling: 
 
INCB054707 will be provided as 
 tablets; placebo tablets will match the INCB054707 tablets in smell, 
taste, and appearance.  Tablets will be packaged in blister cards. 
Each container will be labeled as required per country requirement. 
Storage: 
 
Status of treatment in 
participating countries: 
Investigational 
 


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6.2. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records).  Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document the following: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including tablet counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol (see 
Appendix D).  The investigator will also maintain records adequately documenting that the 
participants were provided the specified study drug.  These records should include dates, 
quantities, and any available batch or serial numbers or unique code numbers assigned to the 
investigational product and study participants. 
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 SOPs.  If 
local procedures mandate on-site destruction of the investigational supply, the site should (where 
local procedures allow) maintain the investigational supply until the study monitor inspects the 
accountability records in order to evaluate compliance and accuracy of accountability by the 
investigative site.  At sites where the study drug is destroyed before monitor inspection, the 
monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Pharmacy Manual. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix B. 


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6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT system 
(see Section 8.1.3).  Participant randomization will be stratified based on IGA score on Day 1 
(3 vs 4).  Once a randomization number has been assigned, it must not be reassigned.  Full 
details will be provided in the IRT Study Reference Manual. 
Study drug will be dispensed at study visits summarized in the SoA (see Table 3 and Table 4). 
Returned study drug should not be redispensed to participants. 
Participants, investigators, and the sponsor will remain blinded to each participant's treatment 
assignment during the placebo-controlled period.  The participant will remain blinded to the dose 
of INCB054707 during the extension period.  Emergency unblinding will occur if an AE requires 
the investigator to be made aware of the participant's treatment assignment (see emergency 
unblinding procedures in Section 9.6 and refer to the IRT Manual). 
6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with study drug will be monitored by the study site based on the drug accountability 
and reported in the eCRF.  Participants will be instructed to bring all unused study drug with 
them to study visits in order for site personnel to conduct tablet counts to assess study drug 
accountability.  
Participants' compliance must be within 
, assessed at each study visit.  If outside of 
this range, it will be considered a protocol deviation.  Participants consistently noncompliant 
with the study drug may be withdrawn from the study.  The decision on withdrawal will be made 
by the investigator after consultation with the sponsor, and relevant correspondence will be 
archived in the site study file. 
6.5. 
Dose Modifications 
No dose modifications will be allowed during the placebo-controlled or extension periods.  
 
 
In some circumstances, it may be necessary to temporarily interrupt treatment with study drug as 
a result of AEs or laboratory abnormalities that have an unclear relationship to the study drug. 
 
 
 
 
 
 
 


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6.5.2. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest. 
Table 9 and Table 10 provide specifics on further reasons for permanent discontinuation of study 
drug. 
If a participant has worsening of PN and is given a prohibited medication (see Section 6.6.3) for 
disease control, they must be permanently discontinued from the study.  Permitted medications 
to control PN are noted in Section 6.6.4. 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
medication or procedure received up to 12 weeks before baseline through 30 days after the last 
dose of study drug will be recorded in the eCRF.  Any addition, deletion, or change in the dose 
of these medications will also be recorded. 
Other relevant medications or procedures received more than 12 weeks before the first dose of 
study drug may be recorded in the eCRF at the discretion of the investigator or at the request of 
the sponsor based on emerging events during the study. 
Concomitant medications administered more than 30 days after the last dose of study drug for 
treatment of SAEs should be reported until the SAE is no longer being followed (see 
Section 8.9). 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.6.1. 
Permitted Medications and Procedures 
• Use of bland emollients and sunscreen agents is permitted.  
• Concomitant oral vitamins, herbal supplements, and other skin products should be 
approved by the investigator and ideally should remain stable during the study. 
• Use of corticosteroid inhalers and intranasal sprays is permitted. 
• Use of oral nonsedating antihistamines for conditions other than PN is permitted. 
• Low-dose acetylsalicylic acid (≤ 100 mg QD) is permitted for the purpose of 
cardiovascular prophylaxis at the discretion of the investigator. 
• A stable dose of gabapentin or pregabalin for a condition other than PN or for PN if 
on a stable dose for ≥ 6 months before screening is permitted. 
Medications and procedures not mentioned as restricted or prohibited will be by default allowed. 


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6.6.2. 
Restricted Medications and Procedures 
The following are permitted during the study under specified conditions: 
• Use of oral corticosteroids for ≤ 7 days, if deemed acceptable by the investigator and 
the sponsor, is allowed for nondermatologic conditions (eg, asthma exacerbation, 
bronchitis). 
• Permitted rescue therapies as described in Section 6.6.4. 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.6.4. 
Rescue Therapy 
The initiation of non–study drug therapy to treat worsening of pruritus or PN lesions, or flare of 
previously inactive skin disease, is strongly discouraged throughout the placebo-controlled 
period.  If deemed to be medically necessary by the investigator, rescue treatments for PN noted 
below may be added to the study drug after Week 4: 
• Sedating antihistamine 
• Low- or medium-potency topical corticosteroid (Grades 4-7, Ference and Last 2009) 
• Topical calcineurin inhibitor 
• Topical PDE-4 inhibitor 
If rescue medication is to be added, the efficacy and safety assessments for the visit should be 
completed before the start of rescue therapy. 
The use of rescue medications should be delayed, if possible, for at least 8 weeks after the first 
dose of study drug.  However, the use of rescue medications are allowable at any time during the 
study in participants who have substantial worsening of PN from baseline (as determined by the 
investigator).  The date and time of rescue medication administration as well as the name and 
dose regimen of the rescue medication must be recorded in the eCRF. 
The participant may remain on study drug, unless the rescue therapy is a prohibited medication 
or procedure (see Section 6.6.3). 
6.7. 
Treatment After the End of the Study 
Upon completion of the 40 weeks of treatment, participants will not be provided additional 
treatment within this study. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant becomes pregnant. 
• Consent is withdrawn.   
Note:  Consent withdrawn means that the participant has explicitly indicated that 
he/she does not want to be followed any longer; in this case no further data, except 
data in the public domain, may be solicited from or collected on the participant.  
Participants may choose to discontinue study treatment and remain in the study to be 
followed for progression and survival. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 


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• Unacceptable toxicity as noted in Section 6.5. 
• Had worsening disease and received a prohibited medication as noted in 
Section 6.6.3. 
• The participant received rescue therapy that is noted as a prohibited medication or 
procedure (see Section 6.6.3). 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's opinion, the sponsor should be consulted for instruction on handling 
the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit.  These visits are described in Table 3 and Table 4.  The last date of the last dose 
of study drug and the reason for discontinuation of study drug will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The EOT visit should be performed and date recorded. 
• The status of the participant should be updated to EOT in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments. 


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7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons.  When a participant is withdrawn from the study, the EOT visit 
procedures should be performed; if possible, the safety follow-up visit should also be conducted 
within 28 (+ 7) days of the last dose of study drug. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records.  If the 
participant withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
See Table 3 and Table 4 for data to be collected at the time of study withdrawal and follow-up 
and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 


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− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the countries in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection laws.  The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
• Participants who are rescreened are required to sign a new ICF. 
8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is randomized in the 
study (Day 1).  Screening may not exceed 28 days.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
randomization and the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the result to be 
in error.  For screening assessments that are repeated, the most recent available result before 
randomization will be used to determine eligibility. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 


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8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact the IRT to obtain the 
participant ID number during screening.  Upon determining that the participant is eligible for 
randomization, the IRT will be contacted to randomize the participant and obtain the treatment 
assignment.  Additionally, the IRT will be contacted at each regular study visit to dispense 
medication to the participant and to update the study drug supply.  Additional details are 
provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and/or Diaries 
Participants will be provided with a reminder card at each visit.  The reminder card will indicate 
the date/time of the next visit 
 
 
  
Participants will be instructed on the use of the drug administration diary.  
 
 
  Daily study drug administration will be 
recorded in the diary and verified by the study investigator/designee at study visits as shown in 
Table 3 and Table 4. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, Fitzpatrick scale score, 
nicotine use, medical and surgical history, and current illnesses.  Medical history will include 
relevant medical or surgical treatment that is considered to be clinically significant by the 
investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history will be collected at screening.  Details 
regarding the participant's PN, including date of diagnosis, relevant disease characteristics, and 
prior treatments, including systemic treatments, phototherapy, and surgical procedures, will be 
collected at screening.  A medical or surgical history of other conditions related to PN or relevant 
to the conduct of this clinical trial will also be collected at screening. 
8.2. 
Efficacy Assessments 
8.2.1. 
Health Economics 
Not applicable. 


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8.2.2. 
Investigator's Global Assessment 
The IGA for chronic prurigo considers the number of pruriginous lesions, which includes 
papules, nodules, plaques, umbilicated ulcers and ulcers, and uses them as an overall severity 
rating on a scale of 0 to 4 (Zeidler et al 2021) as noted in Table 11, and will be performed at the 
visits noted in the SoA (see Table 3 and Table 4). 
The IGA-TS is defined as an IGA score of 0 or 1 with a ≥ 2-grade improvement from baseline. 
Table 11: 
Investigator's Global Assessment 
Grade 
Severity 
Description 
0 
Clear 
No pruriginous lesions (0 lesions) 
1 
Almost clear 
Rare palpable pruriginous lesions (approximately 1-5 lesions) 
2 
Mild 
Few palpable pruriginous lesions (approximately 6-19 lesions) 
3 
Moderate 
Many palpable pruriginous lesions (approximately 20-100 lesions) 
4 
Severe 
Abundant palpable pruriginous lesions (over 100 lesions) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
8.3. 
Patient-Reported Outcomes 
For all patient-reported outcome assessments conducted at the study site, in order to avoid bias in 
the participants' responses to the questionnaires, assessments should be completed before any 


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other evaluations or study procedures on the day of the study visit and prior to treatment-related 
discussions with the investigator or study site staff. 
8.3.1. 
eDiary 
Participants will be issued a handheld device (eDiary).  Each participant will be instructed to 
complete the diary each evening beginning on the day of screening through Week 40 or 
treatment discontinuation.  Compliance with the eDiary will be assessed electronically at the 
visits noted in the SoA (see Table 3 and Table 4).  If the participant is not completing the eDiary 
frequently enough, the site staff will be informed so compliance can be addressed in a timely 
manner. 
Study sites will contact participants 1 week before the baseline visit to confirm compliance with 
eDiary assessments to ensure information is available to allow randomization if appropriate. 
8.3.1.1. 
Itch NRS 
Each evening, the participant will assess their worst level of itch during the past 24 hours on a 
scale of 0 to 10. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 


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. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
8.4. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (see Table 3 and Table 4).  
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study, 
requiring the outline of potential mitigation strategies described in Appendix B. 
8.4.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study drug.  Adverse events for randomized participants that begin 
or worsen after informed consent should be recorded on the Adverse Events Form in the eCRF 
regardless of the assumption of a causal relationship with the study drug.  Conditions that were 
already present at the time of informed consent should be recorded on the Medical History Form 
in the eCRF.  Adverse events (including laboratory abnormalities that constitute AEs) should be 
described using a diagnosis whenever possible rather than by individual underlying signs and 
symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 


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qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up on AEs that are serious, 
considered related to the study drug/procedures, or caused the participant to discontinue the 
study drug.  Care will be taken not to introduce bias when detecting AEs and/or SAEs.  
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
If an AE is noted, a targeted physical examination should be conducted as indicated by the 
symptoms reported by the participant or other findings (eg, laboratory abnormalities).  
Abnormalities that are considered clinically significant in the judgment of the investigator (or 
designee) are to be reported as AEs. 
All SAEs will be reported to the sponsor or designee within 24 hours.  The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Adverse events will also be assessed remotely, via a phone/video call conducted by the study 
site, for visits at Weeks 2, 6, 18, and 22 (see Table 3 and Table 4). 
8.4.2. 
Physical Examinations 
A comprehensive physical examination should be conducted at the visits noted in the SoA (see 
Table 3 and Table 4).  The comprehensive physical examination will include assessment(s) of 
the following organ or body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief 
neurological examination. 
Height will be assessed on Day 1.  Body weight will be assessed on Day 1 and at Weeks 16, 28, 
and 40 or at the EOT visit if the participant discontinues study drug. 
As noted in Section 8.4.1, a targeted physical examination should be conducted as indicated by 
the symptoms reported by the participant or other findings (eg, laboratory abnormalities).  
Abnormalities that are considered clinically significant in the judgment of the investigator (or 
designee) are to be reported as AEs.  
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, a physician assistant, or an advanced registered nurse practitioner, as local law 
permits. 
8.4.3. 
Vital Signs 
Abnormal vital sign results identified after the first dose of study drug constitute an AE if they 
are considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug. 


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Vital sign measurements (to be taken before blood collection for laboratory tests) include blood 
pressure, pulse, respiratory rate, and body temperature and will be collected at the visits noted in 
the SoA (see Table 3 and Table 4).  If vital signs cannot be taken before blood collection for 
laboratory tests, there must be a minimum of 30 minutes from the completion of the blood 
collection procedures to the beginning of the vital signs collection.  Blood pressure and pulse 
will be taken with the participant in the recumbent, semirecumbent, or sitting position after 
5 minutes of rest.   
8.4.4. 
Electrocardiograms 
Single 12-lead ECGs will be obtained as outlined in the SoA (see Table 3 and Table 4) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals; if necessary, calculation of such parameters is also acceptable if the ECG machine does 
not perform it automatically.  All 12-lead ECGs will be performed with the participant in a 
recumbent or semirecumbent position after 5 minutes of rest.  Prolonged QTcF values of 
≥ 450 milliseconds are to be confirmed by performing 2 additional ECGs (within the next 
5 minutes) and averaging the results to determine the averaged value. 
Additional 12-lead ECGs may be performed at other visits as deemed clinically necessary.  
Electrocardiograms will be interpreted by the investigator at the site or designee, and the results 
will be used for immediate management of the participant's care.  The decision to include or 
exclude a participant or withdraw a participant 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.  Any abnormalities that are considered clinically 
significant in the judgment of the investigator are to be reported as AEs.  ECGs should be 
performed in line with local standards and results reported in the eCRF. 
8.4.5. 
Laboratory Assessments 
See Table 12 for the list of clinical laboratory tests to be performed, and Table 3 and Table 4 for 
the laboratory assessment visit schedule.  A central laboratory will perform all clinical laboratory 
assessments for safety (ie, blood chemistries, hematology assessments, coagulation tests, 
endocrine function, and urinalysis).  
 
  Additional testing may be required by the investigator or sponsor 
based on emerging safety data.  All Protocol-required laboratory assessments must be conducted 
in accordance with the Laboratory Manual and Table 3 and Table 4. 
To reduce the burden of frequent on-site visits, Weeks 2, 6, 18, and 22 are planned as remote 
visits (see Table 3 and Table 4).  The study site will contact the participant via video/phone call 
and blood samples will be collected via home nursing.  Should the participant prefer to attend the 
visit on-site, this will not be considered a protocol deviation. 
In case of COVID-19–related conditions, the sites may adopt remote participant management in 
addition to the visits listed above.  Further details are provided in Appendix B. 
Information regarding collection, processing, and shipping of samples for laboratory assessment 
is provided in the Laboratory Manual. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 


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participant's condition.  All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 30 (+ 7) days after the last dose of study 
drug should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
If screening laboratory assessments are performed more than 32 days before Day 1, then the tests 
must be repeated and eligibility confirmed before study drug administration on Day 1. 
Laboratory sample collection on Day 1 must be performed before study drug administration.  
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF.  


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Table 12: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology  
Urinalysis  
Serology / Infection 
Pregnancy Testing 
• Albumin 
• ALP 
• ALT 
• AST 
• Bicarbonate or CO2 
• Blood urea nitrogen or urea 
• Calcium 
• Chloride 
• Creatine kinase 
• Creatinine 
• eGFR 
• Glucose 
• GGT 
• Lactate dehydrogenase 
• Phosphate 
• Potassium 
• Sodium 
• Total bilirubin 
• Direct bilirubin (if total 
bilirubin is elevated above 
1.5 × ULN) 
• Total protein 
Complete blood count, 
including: 
• Hgb 
• Mean corpuscular volume 
• Hematocrit 
• Platelet count 
• Mean platelet volume  
• In samples with 
abnormalities in platelet 
count or size distribution 
(as indicated by an 
automated analyzer), a 
blood film should be 
examined. 
• Red blood cell count 
• Red blood cell distribution 
width (RDW) 
• WBC count 
Differential count (% and 
absolute values), including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
• Color and appearance 
• pH and specific 
gravity 
• Bilirubin 
• Glucose 
• Ketones 
• Leukocyte esterase 
• Nitrite 
• Occult blood 
• Protein 
• Microscopic 
evaluation (in case of 
abnormal urinalysis 
results) 
• HBsAg* 
• HBsAb 
• HBcAb* 
• HCVAb* 
• HIV 
• QuantiFERON-TB 
Gold test  
 
*Note:  If either HBsAg 
or HBcAb is positive, a 
reflexive HBV DNA 
must be obtained.  If 
HCVAb is positive, a 
reflexive HCV RNA 
must be obtained. 
Women of nonchildbearing 
potential will have FSH tested at 
screening. 
Women of childbearing potential 
will require the following: 
• Serum pregnancy test at 
screening, the Week 16 visit, 
and the safety follow-up visit. 
• Urine pregnancy test at all 
other in-clinic visits and as 
medically indicated or per 
country or institutional 
requirements. 
Pregnancy tests (serum or urine) 
should be repeated if required by 
local regulations. 
 
Lipid Panel 
Coagulation 
Thyroid Function Markers 
• Total cholesterol 
• Triglycerides 
• LDL 
• HDL 
 
Note:  Fasting is not 
required. 
• PT 
• INR 
• TSH 
• Free T4 
Inflammation Markers 
• hsCRP 
• IgE 
GGT = gamma-glutamyl transferase; HBsAb = hepatitis B surface antibody; HDL = high-density lipoprotein cholesterol; LDL = low-density lipoprotein cholesterol; 
T4 = thyroxine; TSH = thyroid-stimulating hormone. 
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data or to rule out a diagnosis.  
Note:  Alternative tests (ie, CO2 or CO2 Combining Power or HCO3) are also allowed as per regional standard of care. 
 


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8.4.5.1. 
Pregnancy Testing 
At screening, women of nonchildbearing potential will have an FSH assessment.  Women of 
nonchildbearing potential are defined as surgically sterile with a hysterectomy and/or bilateral 
oophorectomy OR postmenopausal, defined as amenorrhea ≥ 12 months prior to screening. 
Women of childbearing potential will have serum and urine pregnancy testing performed 
throughout the study as outlined in the SoA (see Table 3 and Table 4), as medically indicated 
(eg, in case of loss of menstrual cycle, when pregnancy is suspected), or per country-specific 
requirement.   
If a urine pregnancy test is positive, the result should be confirmed with a serum pregnancy test.  
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.7 for reporting 
requirements. 
8.4.5.2. 
Serology 
Hepatitis B and C and HIV screening assessments will be performed at the screening visit to rule 
out infection; required analytes are shown in Table 12.  Generally, hepatitis and HIV tests should 
be performed early in the screening process due to the length of time needed to obtain the results.  
Additional tests may be performed if clinically indicated. 
Eligibility criteria for participants with a history of HCV infection should generally require 
participants to have completed curative antiviral treatment and require HCV viral quantitative 
RNA below the limit of quantification 12 weeks after the end of HCV therapy.  A patient who is 
HCVAb positive but HCV RNA negative due to prior treatment or natural resolution should be 
eligible.  Discussion with the sponsor is required. 
Reactivation of HBV can occur in chronic carriers of HBV infection (HBsAg-positive, 
undetectable or low HBV DNA, and normal ALT) who are not on HBV therapy or in individuals 
who have serologic evidence of a resolved prior HBV infection (ie, HBsAg-negative and 
anti-HBc–positive).  While HBsAg-negative, anti-HBc–positive patients are at lower risk of 
HBV reactivation compared with HBsAg-positive patients, risk of HBV reactivation should be 
considered in all participants.  Discussion with the sponsor is required. 
Participants with no prior history of HBV infection who have been vaccinated against HBV and 
who have a positive antibody against HBsAg as the only evidence of prior exposure may 
participate in the study. 
8.4.5.3. 
Tuberculosis Screening 
At the time of screening, all participants will undergo TB screening.  Depending on the TB status 
of the participant, different assessments may be performed. 
The QFT-GIT is the preferred testing method.  If the QFT-GIT cannot be performed, or if the 
results cannot be determined by the reference laboratory to be either positive or negative (eg, 
indeterminate), then participants may be screened using the PPD tuberculin skin test (Mantoux 


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method; see Note 1) with approval of the medical monitor (or designee).  The QFT-GIT is an 
indirect test for Mycobacterium tuberculosis infection (including disease) and is intended for use 
in conjunction with risk assessment, radiography (see Note 2), and other medical and diagnostic 
evaluations. 
It is recommended that participants with a history of Bacille Calmette-Guérin vaccination be 
tested with the QFT-GIT, because the Mantoux/PPD tuberculin skin test may be positive due to 
vaccination.   
A QFT-GIT or Mantoux/PPD tuberculin skin test is not required if the participant has previously 
received a documented adequate course of therapy for either latent TB infection (eg, 9 months of 
isoniazid in a locale where rates of primary multidrug TB resistance are < 5% or an acceptable 
alternative regimen) or active TB infection (an acceptable multidrug regimen).  In such cases, a 
chest x-ray(s) or other appropriate diagnostic image, performed within 3 months of Day 1, is 
required (see Note 2).  To be considered eligible for the study, the x-ray(s) must be negative for 
active TB infection as determined by a qualified radiologist (see Note 2).  Documentation of 
adequate treatment for TB and negative chest x-ray(s) results must be obtained prior to Day 1.  
Note 1:  If the QFT-GIT cannot be performed, or if the results cannot be determined to be 
positive or negative (eg, indeterminate), then participants may be screened using the PPD 
tuberculin test (Mantoux method), with the approval of the medical monitor (or designee). 
Participants must have the PPD test administered and evaluated by a health care professional 
48 to 72 hours later in order to be eligible for the study, unless performed and documented within 
the past 3 months.  The test should be performed according to local standards with induration of 
< 5 mm required for inclusion. 
Note 2:  At the discretion of the investigator or medical monitor (or designee), participants may 
be required to have a chest x-ray (posterior-anterior and lateral views) or other appropriate 
diagnostic image (ie, computed tomography or magnetic resonance imaging) taken at screening, 
or previously taken within 3 months prior to Study Day 1, and read by a qualified radiologist to 
potentially distinguish between latent and active TB.  Documentation of adequate treatment for 
TB and negative chest x-ray(s) results must be obtained prior to Day 1. 


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8.7. 
Unscheduled Visits 
Unscheduled visits may occur at any time at the investigator's (or designee's) discretion and 
appropriate clinical and laboratory tests may be performed as clinically indicated. 
If there is a potential clinically significant abnormality in hematology or chemistry assessments 
(particularly in platelet count) during the study, an unscheduled visit within the following week 
should occur to repeat laboratory assessments (further details are provided in Table 9 and 
Table 10).  The investigator must inform and consult the sponsor (or designee) regarding any 
hematologic abnormality. 
8.8. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues study drug, whether the participant is terminating 
the study early or the participant has completed the study, the appropriate EOT visit should be 
conducted (EOT1 or EOT2).  If the EOT visit coincides with a regular study visit, the EOT 
evaluations corresponding with the study period will supersede those of that scheduled visit, and 
the data should be entered in the appropriate EOT visit in the eCRF.  The participant should be 
encouraged to return for the follow-up visit (EOS). 


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8.9. 
Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit (EOS), which should occur approximately 30 days after the EOT visit (or after the last dose 
of study drug if the EOT visit was not performed).  Adverse events and SAEs must be reported 
up until 1) at least 30 days after the last dose of study drug or 2) until toxicities resolve, return to 
baseline, or are deemed irreversible, whichever is longer.  Reasonable efforts should be made to 
have the participant return for the follow-up visit and report any AEs that may occur during this 
period.  In exceptional cases when the participant cannot return to the site for the safety 
follow-up visit, the participant should be contacted by telephone/video call for assessment of 
AEs and SAEs and the site should properly document the contact. 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug-related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. 
Additional Guidance for Events Meeting the Adverse Event Definition 
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to progression of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug.  Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low Hgb, platelet count decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study drug (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease progression," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy assessments. 


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• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent.  The procedure should also be 
reported in the eCRF.  If the condition was present before entering the study, then it should be 
captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 
9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs.  This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) is not considered an SAE. 
d. Results in persistent or significant disability/incapacity 
• The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions.  This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle), that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 


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e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
An important medical event is an event that may not result in death, be immediately life-threatening, or 
require hospitalization but may be considered serious when, based on appropriate medical judgment, 
the event may jeopardize the participant and may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definition.  Examples of such events include new invasive or 
malignant cancers; intensive treatment in an emergency department or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization; or development of 
drug dependency or drug abuse.  Secondary malignancies should always be considered SAEs. 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF.  AEs/SAEs should be reported for randomized participants, but 
only SAEs need to be reported for screen failure participants.  For randomized participants, 
conditions that were present at the time informed consent was given should be recorded on the 
Medical History Form in the eCRF.  For detailed information, refer to the eCRF guidelines. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Event Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested.  In this 
case, all participant identifiers, with the exception of the participant number, will be redacted by the 
site staff on the copies of the medical records before submission.  These records can be submitted to 
Incyte Pharmacovigilance by email/fax per the contact information listed in the Study Reference 
Manual or as per SAE completing guidelines. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information.  Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE.  When a clear diagnosis cannot be identified, each sign or 
symptom should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine the following: 
• The severity grade (CTCAE v5.0 Grade 1 to 5).  See below for further instructions on the assessment 
of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug:  suspected 
(yes) or not suspected (no).  See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 


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• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures, and 
Non-Drug Therapy). 
Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB or Product Information for study drug, or 
marketed products, respectively, in making his/her assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report.  However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements.  Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and 
submit the updated causality assessment. 


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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• Once an AE is detected, it should be followed in the AE eCRFs until it has resolved or until it is 
judged to be permanent; assessment should be made at each visit (or more frequently if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology. 
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance (via the AE and SAE eCRFs in the EDC) until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours of receipt of the information. 
See Appendix E for the management of PHL cases. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug, study procedures), all SAEs 
occurring after the participant has signed the ICF through the last safety visit or at least 30 days 
after the last dose of study drug must be reported to the sponsor (or designee) immediately, 
without undue delay but not later than within 24 hours of obtaining knowledge of its occurrence 
unless otherwise specified by the Protocol.  The investigator will submit any updated SAE data 
to the sponsor (or designee) immediately, without undue delay but not later than within 24 hours 
of it being available.  
Investigators are not obligated to actively seek SAE information after the safety follow-up visit 
or 30 days after the last dose of study drug.  If the investigator learns of any SAE, including 
death, at any time during this period, and he/she considers the event to be reasonably related to 
the study drug or study participation, then the investigator must notify the sponsor (or designee) 
within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the IB for the study drug (new occurrence) and is 
thought to be related to the study drug, the sponsor or its designee may urgently require further 


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information from the investigator for expedited reporting to health authorities.  The sponsor or its 
designee may need to issue an Investigator Notification to inform all investigators involved in 
any study with the same drug that this SAE has been reported.  Suspected unexpected serious 
adverse reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC or as per national regulatory requirements 
in participating countries. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation.  The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event and Serious Adverse 
Event Forms in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAE via the EDC 
system (primary method) or by completing the Serious Adverse Event Report Form in English (only 
if the EDC system is not available).  The contact information for Incyte Pharmacovigilance by 
email/fax is listed in the Study Reference Manual or as per the Incyte Reference Guide for 
Completing the Serious Adverse Event Report Form. 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours, refer to the Incyte Reference 
Guide for Completing the Serious Adverse Report Form.  Once the EDC system is functional, the 
SAE report should be retrospectively added to the EDC system and follow-up should be completed 
through the EDC.  The original copy of the Serious Adverse Event Report Form and the email or 
facsimile confirmation sheet must be kept at the study site (refer to the Incyte Reference Guide for 
Completing the Serious Adverse Event Report Form or Study Reference Manual for details and for 
the email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system.  The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation).  Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs. 
9.5. 
Events of Clinical Interest 
Not applicable. 


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9.6. 
Emergency Unblinding of Treatment Assignment 
In case of a medical emergency, for a participant's safety management, the procedure for 
emergency unblinding is provided to the investigator in the IRT Manual.  If a participant's 
treatment assignment is unblinded, the sponsor or its designee should be notified immediately for 
awareness. 
If an investigator, the site personnel performing assessments, or a participant is unblinded, then 
the participant must discontinue study drug unless there are ethical reasons to have the 
participant remain on the study treatment.  In these cases, the investigator must obtain specific 
approval from the sponsor's (or its designee's) medical monitor for the participant to continue in 
the study. 
9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only; see 
Section 7.1 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 are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form or Study Reference Manual. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or its designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 


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9.8. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9.10. 
Treatment of Overdose 
There has been no clinical experience with overdose of INCB054707.  Treatment of overdose 
should consist of general supportive measures. 
10. 
STATISTICS 
10.1. 
Sample Size Determination 
In order to provide a safety database and adequate power for efficacy analysis, the total sample 
size for the study is 140 participants randomized in a 1:1:1:1 ratio to INCB054707 15 mg, 
45 mg, or 75 mg or placebo groups.  The sample size calculation is based on Fisher exact test for 
the statistical comparison on the primary efficacy endpoint, proportion of participants achieving 
≥ 4-point improvement in Itch NRS score at Week 16.  Based on the result from a Phase 2 trial 
of nemolizumab (Ständer et al 2020), the response rate is assumed to be 50% for the 
INCB054707 45 mg or 75 mg groups and 15% for the placebo group.  Using a 2-sided alpha of 
0.05, 35 participants per group will have 85% power to detect such a difference between either 
1 of the 3 active treatment groups and the placebo group. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 13. 


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Table 13: 
Populations for Analysis 
Population 
Description 
ITT 
The ITT population includes all randomized participants.  Treatment groups for 
this population will be defined according to the treatment assignment at 
randomization. 
Safety 
The safety population includes all participants who received at least 1 dose of 
study drug.  Treatment groups for this population will be determined according to 
the actual treatment the participant received on Day 1. 
10.3. 
Level of Significance 
The overall significance level for efficacy analysis will be 0.05 for 2-sided tests. 
10.4. 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the participant 
populations to be included in the analyses and procedures for accounting for missing, unused, 
and spurious data.  This section is a summary of the planned statistical analyses of the primary 
and secondary endpoints. 
10.4.1. 
Primary Analysis 
The primary analysis will be based on the ITT population.  The primary alternative hypothesis 
(superiority of the INCB054707 groups compared with the placebo group for the proportion of 
participants achieving ≥ 4-point improvement in Itch NRS score at Week 16) will be tested using 
exact logistic regression (Mehta and Patel 1995).  This model will include the treatment groups 
and stratification factor.  The unadjusted p-values between each of the INCB054707 groups and 
the placebo group will be compared with the prespecified significance level.  Odds ratio and 
corresponding 95% CI will be provided as well.  All nonresponders in the placebo-controlled 
period, as well as all participants who are missing postbaseline values, will be defined as 
nonresponders for the nonresponder imputation analysis.  All participants who receive rescue 
therapy during the placebo-controlled period will be imputed as nonresponders. 


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The endpoint of different active doses versus placebo will be tested in a fixed sequence from 
high to low (75 mg, 45 mg, and 15 mg) at 2 sided α = 0.5 level.  The lower dose will be tested 
only if the statistical hypothesis associated with the higher dose is rejected. 
10.4.2. 
Secondary Analysis 
The secondary efficacy analyses will be conducted on the ITT population.  All secondary 
efficacy variables will be summarized using descriptive statistics.  For the binary endpoint, 
proportion of participants achieving IGA-TS (IGA score of 0 or 1 with a ≥ 2-grade improvement 
from baseline) at Week 16, summary statistics will include sample size, frequency, and 
percentages.  For the time-to-event endpoint, time to ≥ 4-point improvement from baseline in 
Itch NRS score, Kaplan-Meier curves will be presented by treatment groups.  The number of 
participants, number of events, and number of censoring events will be summarized by treatment 
groups.  The Kaplan-Meier estimate of median time will be presented with its 95% CI.  The 
95% CI will be calculated using the method by Brookmeyer and Crowley (1982). 
10.4.3. 
Safety Analyses 
The safety analyses will be conducted on the safety population.  A TEAE is any AE either 
reported for the first time or worsening of a pre-existing event after first dose of study drug up to 
30 days after the last dose of study drug.  Analysis of AEs will be limited to TEAEs, but data 
listings will include all AEs regardless of their timing to study drug administration.  Adverse 
events will be tabulated by the MedDRA preferred term and system organ class.  Severity of AEs 
will be based on the National Cancer Institute CTCAE v5.0 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, then the AE will be considered treatment-related.  The incidence of AEs 
and treatment-related AEs will be tabulated.  
The clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned.  Laboratory test values outside the normal range will be assessed for 
severity based on the normal ranges for the clinical reference laboratory.  The incidence of 
abnormal laboratory values and shift tables relative to baseline will be tabulated.  Descriptive 
statistics and mean change from baseline will be determined for vital signs (blood pressure, 
pulse, respiratory rate, and body temperature) at each assessment time.  Descriptive statistics and 
mean change from baseline will be determined for each ECG parameter at each assessment time. 
 
 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both Health Authorities 
and IRB/IEC before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 


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− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study.  As part of his or her responsibilities, the coordinating principal investigator will review 
the final CSR.  Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system.  The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF.  The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements.  Other data outside the EDC system required in the study conduct 
of the Protocol such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors and, as designated by the sponsor, will have their own data flow 
management plans, study charters, 
, as applicable. 


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The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 
The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
, diary data), 
or as otherwise specified in the Protocol. 
• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants.  Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete.  Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail).  Source data are in general all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source data are contained in source 
documents (original records or certified copies).  
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed and 
available at the investigator's site.  Examples of source documents are original 
documents, data, and records (eg, hospital records, electronic hospital records, 
clinical and office charts, laboratory notes, memoranda, participants' diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being 
accurate copies, microfiches, photographic negatives, microfilm or magnetic 
media, x-rays, participants' files, and e-records/records kept at the pharmacy, at 


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the laboratories and at medico-technical departments involved in the clinical 
trial).   
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, 
depending on the study.  Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, or copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor.  
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 


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Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations require 
otherwise.  No records may be destroyed during the retention period without the written approval 
of the sponsor.  No records may be transferred to another location or party without written 
notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation (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. 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 


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11.6. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
Almeida TA, Rojo J, Nieto PM, et al. Tachykinins and tachykinin receptors: structure and 
activity relationships. Curr Med Chem 2004;11:2045-2081. 
Andrassy KM. Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and 
Management of Chronic Kidney Disease'. Kidney Int. 2013;84:622-623. 
Boozalis E, Tang O, Patel S, et al. Ethnic differences and comorbidities of 909 prurigo nodularis 
patients. J Am Acad Dermatol 2018;79:714-719. 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
 
 
 
 
 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Dazzi C, Erma D, Piccinno R, Veraldi S, Caccialanza M. Psychological factors involved in 
prurigo nodularis: a pilot study. J Dermatolog Treat 2011;22:211-214. 
Elmariah S, Kim B, Berger T, et al. Practical approaches for diagnosis and management of 
prurigo nodularis: United States expert panel consensus. J Am Acad Dermatol 2021;84:747-760.  
Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physician 2009;79:135-140. 
 
 
Fukushi S, Yamasaki K, Aiba S. Nuclear localization of activated STAT6 and STAT3 in 
epidermis of prurigo nodularis. Br J Dermatol 2011;165:990-996. 
 
 
 
 
 
Huang AH, Canner JK, Khanna R, Kang S, Kwatra SG. Real-world prevalence of prurigo 
nodularis and burden of associated diseases. J Invest Dermatol 2020;140:480-483. 
 
 
Iking A, Grundmann S, Chatzigeorgakidis E, Phan NQ, Klein D, Ständer S. Prurigo as a 
symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 
patients. J Eur Acad Dermatol Venereol 2013;27:550-557. 
INCB054707 Investigator's Brochure. Wilmington, DE: Incyte Corporation. 


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Kowalski EH, Kneiber D, Valdenbran M, Patel U, Amber KT. Treatment-resistant prurigo 
nodularis: challenges and solutions. Clin Cosmet Investig Dermatol 2019;12:163-172. 
Kwatra SG. Breaking the itch-scratch cycle in prurigo nodularis. N Engl J Med 
2020;382:757-758. 
McColl M, Boozalis E, Aguh C, et al. Pruritus in black skin: unique molecular characteristics 
and clinical features. J Natl Med Assoc 2021;113:30-38. 
Mehta CR, Patel NR. Exact logistic regression: theory and examples. Stat Med 
1995;14:2143-2160. 
Millum J, Grady C. The ethics of placebo-controlled trials: methodological justifications. 
Contemp Clin Trials 2013;36:510-514. 
Pereira MP, Steinke S, Zeidler C, et al. European academy of dermatology and venereology 
European prurigo project: expert consensus on the definition, classification and terminology of 
chronic prurigo. J Eur Acad Dermatol Venereol 2018;32:1059-1065. 
Perez GL, Peters MS, Reda AM, Butterfield JH, Peterson EA, Leiferman KM. Mast cells, 
neutrophils, and eosinophils in prurigo nodularis. Arch Dermatol 1993;129:861-865. 
 
 
 
 
Ständer S, Yosipovitch G, Legat FJ, et al. Trial of nemolizumab in moderate-to-severe prurigo 
nodularis. N Engl J Med 2020;382:706-716. 
Todberg T, Zachariae C, Skov L. Treatment and burden of disease in a cohort of patients with 
prurigo nodularis: a survey-based study. Acta Derm Venereol 2020;100:adv00119.  
Tsianakas A, Zeidler C, Ständer S. Prurigo nodularis management. Curr Probl Dermatol 
2016;50:94-101. 
Wang F, Kim BS. Itch: a paradigm of neuroimmune crosstalk. Immunity 2020;52:753-766. 
  
Williams KA, Huang AH, Belzberg M, Kwatra SG.  Prurigo nodularis: pathogenesis and 
management. J Am Acad Dermatol 2020;83:1567-1575. 
Zeidler C, Pereira MP, Augustin M, Spellman M, Ständer S. Investigator's global assessment of 
chronic prurigo: a new instrument for use in clinical trials. Acta Derm Venereol 2021;101:1-5. 
Zeidler C, Yosipovitch G, Ständer S. Prurigo nodularis and its management. Dermatol Clin 
2018;35:189-197. 
 
 


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


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 that can achieve a failure rate of 
< 1% per year when used consistently and correctly are considered as highly effective birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation.d 
− oral 
− intravaginal  
− transdermal  
• Progestogen-only hormonal contraception associated with inhibition of ovulationd  
− oral 
− injectable 
− implantablee 
• Intrauterine devicee 
• Intrauterine hormone-releasing systeme 
• Bilateral tubal occlusione 
• Vasectomized partnere,f 
• Sexual abstinencec  
HRT = hormone replacement therapy. 
a Documentation can come from the site personnel's review of the participant's medical records, medical examination, or medical 
history interview. 
b If the male participant has a partner with childbearing potential, the partner should also use contraceptives. 
c In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment.  The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the 
participant. 
d Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may reduce the 
efficacy of the contraception method.  In this case, 2 methods of contraception should be used. 
e Contraception methods that in the context of this guidance are considered to have low user dependency. 
f Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success. 
Source:  Clinical Trials Facilitation and Coordination Group 2020. 


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APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical trials.  The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the investigational 
product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical trial, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the trial.  Because of this risk and 
in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines: 
In addition to the remote visits already specified in the Protocol, the evolving situation of the 
pandemic may require further travel restrictions and isolation requirements, or the investigator's 
benefit/risk assessment may determine it to be unsafe for participants to attend study visits at the 
investigational site.  In such cases, the site staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video calls).  At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed.  Periodic on-site visits 
should be conducted whenever feasible, in addition to the mandatory on-site visits 
outlined below. 
• No efficacy assessments can be performed via telemedicine (video call, phone call, or 
via photography). 
• Laboratory sampling:  in order to support investigator oversight of participant safety 
and disease management, off-site laboratory sampling (in accordance with the SoA, 
see Table 3 and Table 4) may be allowed in 1 of 2 ways:  
− Use of home nursing services  
− Instruction of the participant to undergo some laboratory tests at a local (nearby) 
hospital laboratory or facility closer to the participant's residence rather than at the 
investigational site.  In this case, the study physician will provide the participant 
with the list of parameters to be checked.  These tests should be performed at 
certified laboratories and copies of results provided to the site. 


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Mandatory On-Site Visits: 
The visits outlined below must be performed in person in order to capture the investigator's 
efficacy assessments and the patient-reported outcomes, even if the date that the participant 
eventually comes into the clinic deviates from the visit window.  
No efficacy assessments can be performed via telemedicine (video call, phone call, or 
photography). 
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic.  Further instructions 
will be provided if needed. 
During the placebo-controlled period, the following visits must be performed in person: 
• Screening 
• Day 1 (Baseline) 
• Week 4 visit 
• Week 16 visit 
During the extension period, the following visits must be performed in person: 
• Week 24 visit 
• Week 40 visit 
Investigational Medicinal Product Dispensation and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug via shipment 
to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study drug 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant.   
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Trial Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the site monitor will continue to employ off-site monitoring practices such as routine 
communication methods (eg, phone calls, e-mails, video visits) with the sites to get information 
on trial progress, participant status, and information on issue resolution.  The study monitor may 
remotely review data entered into the EDC for accuracy and completeness.  If allowed by local 
regulations, remote source data verification may be implemented with agreement of the principal 
investigator and institution, as applicable. 


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If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes and the operation cannot be postponed, it may be performed by a 
pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training.  The study drug can be returned to the sponsor by the hospital pharmacy directly or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Other Considerations  
If necessary, direct contracts can be established with third-party local physicians to conduct 
activities related to the clinical management of participants for whom the investigator is 
responsible and maintains oversight.  In such situations, the investigator is required to provide 
the local physician with a delegation letter listing all delegated activities.  The sponsor, through 
the study investigator or institution, will reimburse the local physician for the tests/procedures 
conducted outside of the standard of care. 
• In case of need, participants may refer to the local health care provider.  Participants will 
be requested to obtain certified copies of the source data at the local health facility with 
the outcome of the contact and provide those to the investigator for appropriate oversight.  
The investigator/delegate will be requested to enter any relevant information into the 
EDC. 
• Should COVID-19–related restrictions be localized and have an effect on a limited 
number of sites, the affected sites may utilize direct contracting of third parties to support 
continuous study conduct (eg, home nursing services, couriers, etc). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [nearby] laboratory tests). 


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APPENDIX C. LIST OF STRONG/MODERATE SYSTEMIC CYP3A4 
INHIBITORS AND STRONG SYSTEMIC CYP3A4 
INDUCERS 
Strong and Moderate Systemic CYP3A4 Inhibitors 
Strong Systemic CYP3A4 Inducers 
• 
Erythromycin  
• 
Troleandomycin, Clarithromycin, Telithromycin   
• 
Ciprofloxacin  
• 
Ketoconazole, Fluconazole, Itraconazole, 
Voriconazole, Posaconazole 
• 
Nefazodone  
• 
Diltiazem 
• 
Mibefradil  
• 
Verapamil  
• 
Aprepitant, Casopitant  
• 
Grapefruit/grapefruit juice 
• 
Seville oranges 
• 
Indinavir, Atazanavir, Nelfinavir, Ritonavir, 
Saquinavir, Boceprevir, Danoprevir, Elvitegravir, 
Lopinavir, Paritaprevir, Saquinavir, Telaprevir, 
Tipranavir, Ombitasvir, Cobicistat 
• 
Idelalisib 
• 
Conivaptan 
• 
Crizotinib 
• 
Cyclosporine 
• 
Dronedarone 
• 
Fluvoxamine 
• 
Imatinib 
• 
Tofisopam 
 
• 
Rifampicin/rifampin  
• 
St John's wort 
• 
Phenytoin 
• 
Apalutamide 
• 
Carbamazepine 
• 
Bosentan 
• 
Efavirenz 
• 
Etravirine 
• 
Enzalutamide 
• 
Mitotane 
• 
Phenobarbital 
• 
Primidone 
Note:  Updated lists of CYP3A4 inhibitors/inducers can be found at Food and Drug Administration.  Drug 
Development and Drug Interactions:  Table of Substrates, Inhibitors and Inducers.  Available at: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-
inhibitors-and-inducers. 


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APPENDIX D. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
INCB054707 
The participant must be instructed in the handling of study drug as follows: 
• Store study drug at room temperature (15°C-30°C/59°F-86°F). 
• Keep study drug in a safe place and out of reach of children. 
• Only remove the number of tablets needed at the time of administration. 
• Do not remove doses in advance of the next scheduled administration. 
• Make every effort to take doses on schedule. 
• Report any missed doses/lost tablets. 
• Take study drug, preferably in the morning, with a full glass of water, without regard 
to food.  Withhold drug self-administration for visits when the dose will be taken at 
the study site. 
• If vomiting occurs after taking study drug, do not take another dose.  If vomiting is 
persistent, contact the study site. 
• Bring all used and unused study drug kits to the study site at each visit. 
• If a dose is missed within the morning period, it is acceptable to take the dose within 
the same day (afternoon or evening).  The next scheduled dose should occur at the 
usual time in the morning, unless required otherwise. 


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APPENDIX E. MANAGEMENT OF POTENTIAL HY'S LAW CASES 
INTRODUCTION 
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry.  The investigator is responsible for determining whether a participant meets PHL 
criteria at any point during the study. 
The investigator participates, in conjunction with Incyte clinical project and pharmacovigilance 
representatives, in the review and assessment of cases fulfilling PHL criteria to ascertain whether 
there is an alternative explanation for the elevations in liver biochemistry other than 
drug-induced liver injury caused by the study drug. 
The investigator fulfills requirements for the recording of data pertaining to PHL or Hy's law 
cases and AE/SAE reporting according to the outcome of the review and assessment in line with 
standard safety reporting processes. 
DEFINITIONS 
For the purpose of this process, definitions are as follows: 
Potential Hy's Law 
An increase in AST or ALT > 3 × ULN and total bilirubin > 2 × ULN at any point during the 
study.  The elevations do not have to be at the same time or within a specified timeframe. 
Hy's Law 
An increase in AST or ALT ≥ 3 × ULN and total bilirubin > 2 × ULN, where no other reason can 
be found to explain the combination of increases (eg, elevated serum ALP indicating cholestasis, 
viral hepatitis, another drug). 
ACTIONS REQUIRED IN CASES OF AST OR ALT > 3 × ULN OR TOTAL BILIRUBIN 
≥ 2 × ULN 
Identification and Determination of Potential Hy's Law 
To identify cases of AST or ALT > 3 × ULN or total bilirubin > 2 × ULN and consequently 
determine whether the participant meets PHL criteria, please follow the instructions below: 
• Review the laboratory report and if a participant has AST or ALT > 3 × ULN OR 
total bilirubin > 2 × ULN at any visit: 
− Determine without delay whether the participant meets PHL criteria by reviewing 
laboratory reports from all previous visits. 
− Enter the laboratory data into the laboratory eCRF as soon as possible. 


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Potential Hy's Law Criteria Not Met 
If the participant has NOT had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any 
point in the study (the elevations do not have to be at the same time or within a specified 
timeframe), irrespective of ALP, please follow the instruction below: 
• Perform follow-up on subsequent laboratory results according to the guidance 
provided in Section 6.5. 
Potential Hy's Law Criteria Met 
If the participant has had AST or ALT ≥ 3 × ULN AND total bilirubin > 2 × ULN at any point in 
the study (the elevations do not have to be at the same time or within a specified timeframe), 
irrespective of ALP, please follow the instruction below: 
• Have the participant interrupt study drug. 
• Notify the Incyte study team without delay. 
− The investigator, or designee, should contact the medical monitor to discuss and 
agree upon an approach for the study participant's follow-up and the continuous 
review of data. 
• Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as medically indicated. 
• Investigate the etiology of the event and perform any relevant diagnostic 
investigations as discussed with the medical monitor. 
• Enter the laboratory data into the laboratory CRF as soon as possible. 
• If at any time (in consultation with the medical monitor) the PHL case meets serious 
criteria, report it as an SAE using standard reporting procedures. 
REVIEW AND ASSESSMENT 
No later than 3 weeks after the biochemistry abnormality is initially detected and the criteria for 
PHL are met, the medical monitor, Incyte pharmacovigilance physician, and investigator will 
discuss and review available data and agree on whether there is an alternative explanation for the 
elevations in liver biochemistry other than drug-induced liver injury caused by the study drug.  
Participant matter experts will be included in the review as appropriate. 
Evaluation of Alternative Causes 
In order to gather additional clinical information to seek other possible causes of the observed 
liver test abnormalities, the following alternative etiologies should be considered, including but 
not limited to: 
• Active viral hepatitis 
• Alcoholic and autoimmune hepatitis 


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• Hepatobiliary disorders 
− Biliary tract disease, such as migration of gallstones or intrahepatic lesions, more 
often causes cholestatic injury initially and should be investigated with 
gallbladder and ductal imaging studies, especially if ALP is increased.  Malignant 
interruption of the biliary tract also should be considered. 
• Concomitant treatment 
• Other causes such as systemic infections (eg, bacterial, fungal, viral), nonalcoholic 
steatohepatitis, and cardiovascular diseases 
Actions After Review and Assessment 
According to outcome of the review and assessment, please follow the instructions below: 
If there is an agreed alternative explanation for the AST or ALT and total bilirubin elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for an SAE. 
• If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF if possible. 
• If the alternative explanation is an AE/SAE, record the AE/SAE in the eCRF 
accordingly and follow the standard study processes. 
• Have the participant resume study drug as per Protocol guidelines. 
If it is agreed that there is no explanation that would explain the AST or ALT and total bilirubin 
elevations: 
• Have the participant permanently discontinue study drug and perform end-of-
treatment procedures. 
• Report an SAE (report term "Hy's Law"). 
− The 'medically important' serious criterion should be used if no other serious 
criteria apply. 
− As there is no alternative explanation for the Hy's law case, a causality assessment 
of related should be assigned. 
• If there is an unavoidable delay of over 3 weeks in obtaining the information 
necessary to assess whether or not the case meets the criteria for a Hy's law case, then 
it is assumed that there is no alternative explanation until such time as an informed 
decision can be made.  Report an SAE (report term "Potential Hy's Law") applying 
serious criteria and causality assessment as per above. 


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ACTIONS REQUIRED FOR REPEAT EPISODES OF AST OR ALT > 3 × ULN AND/OR 
TOTAL BILIRUBIN > 2 × ULN 
The requirement to conduct follow-up, review, and assessment of a repeat occurrence(s) of PHL 
is based on the nature of the alternative cause identified for the previous occurrence. 
If the alternative cause for the previous occurrence of PHL was not chronic or progressing 
malignant disease, please follow the process for PHL review and assessment as described in this 
appendix. 
If the alternative cause for the previous occurrence of PHL was chronic or progressing malignant 
disease, please follow the instructions below: 
• Determine whether there has been a significant change* in the participant's condition. 
− If there is no significant change, no action is required. 
− If there is a significant change, follow the process described for PHL review and 
assessment as described in this appendix. 
* A 'significant' change in the participant's condition refers to a clinically relevant change in ALT, AST, or total 
bilirubin, or associated symptoms.  The determination of whether there has been a significant change will be at the 
discretion of the investigator; this may be in consultation with the medical monitor if there is any uncertainty. 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
12 JUL 2021 
Amendment 2 
06 MAY 2022 
Amendment 2 (06 MAY 2022)  
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to remove the interim analysis, modify exclusion 
criteria associated with estimated glomerular filtration rate; to add clarification on the types of 
PN lesions being assessed; and to add clarification on the management of creatine kinase 
elevations. Additional changes are summarized below. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; Figure 1:  
Study Design Schema ); Section 4.1, Overall Design; Section 5.1, Inclusion Criteria 
(Criteria #5 and #6); Section 8.2.2 Investigator’s Global Assessment (Table 11:  
Investigator's Global Assessment) 
Description of change:  Revised wording from nodule to pruriginous lesion to be in line 
with chronic prurigo IGA. 
Rationale for change:  To clarify that different types of pruriginous lesions are 
considered for this study 
2. Section 1, Protocol Summary (Treatment Groups and Duration); Section 4.1, 
Overall Design; Section 6.5.2, Criteria for Permanent Discontinuation of Study 
Drug; Section 6.6.4, Rescue Therapy; Section 7.1.1, Reason for Discontinuation 
Description of change:  Revised wording to indicate the use of rescue medication is 
allowable at any time during the study in participants who have substantial worsening of 
PN from baseline, but should be delayed if possible for at least 8 weeks after the first 
dose of study drug. 
Rationale for change:  To clarify that administration of rescue therapy before Week 4 
does not lead to discontinuation from study treatment. 
3. Section 1, Protocol Summary (Table 3:  Schedule of Activities for the 
Placebo-Controlled Period) 
Description of change:  Added a weight assessment to the screening visit. 
Rational for change:  Weight is required for calculating the estimated glomerular 
filtration rate. 
4. Section 5.1, Inclusion Criteria (Criterion #3) 
Description of change:  Added a note that diagnosis may be based on investigator 
assessment and study participant interview. 
Rationale for change:  To clarify that clinical diagnosis of PN may be based on 
investigator assessment and participant interview. 


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5. Section 5.1, Inclusion Criteria (Criterion #4) 
Description of change:  Added a note to include over-the-counter products for PN 
therapy. 
Rationale for change:  To clarify that over-the-counter products are acceptable. 
6. Section 5.1, Inclusion Criteria (Criteria #5 and #6); Section 8.2.2 Investigator’s 
Global Assessment 
Description of change:  Added that pruriginous lesions may include nodules, papules, 
plaques, umbilicated ulcers, or ulcers. 
Rationale for change:  To align with current literature and to clarify assessments to be 
used. 
7. Section 5.2, Exclusion Criteria (Criterion #13) 
Description of change:  Revised prior treatment with a JAK inhibitor to include a history 
of treatment failure (as assessed by the investigator through study participant interview) 
for PN or any other inflammatory condition with any systemic or topical JAK or TYK2 
inhibitor (eg, abrocitinib, baricitinib, brepocitinib, deucravacitinib, filgotinib, lestaurtinib, 
pacritinib, ruxolitinib, tofacitinib, upadacitinib). 
Rationale for change:  To clarify the previously failed treatments that exclude 
participation in the study. 
8. Section 5.2, Exclusion Criteria (Table 7:  Exclusionary Laboratory Values 
[Criterion j]) 
Description of change:  Modified estimated glomerular filtration rate from ≤ 70 mL/min 
based on Cockcroft-Gault formula to ≤ 45mL/min. 
Rationale for change:  To align the exclusionary criteria with chronic kidney disease 
guidelines (Andrassy 2013). 
9. Section 5.2, Exclusion Criteria (Table 7:  Exclusionary Laboratory Values 
[Criteria l and m]) 
Description of change:  Added a note to the exclusion criteria laboratory values for PT 
and INR that the investigator may determine if the result is acceptable based on clinical 
assessment. 
Rationale for change:  To allow the investigator to consider participation by clinical 
assessment in addition to the PT and/or INR values. 
10. Section 6.5.1 Criteria and Procedures for Dose Interruptions of Study Drug 
(Table 10:  Guidelines for Interruption, Restart, and Discontinuation of Study 
Drug) 
Description of change:  Added guidance to describe management of creatine kinase 
elevations. 
Rationale for change:  To clarify how creatine kinase elevations should be managed by 
investigators. 


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11. Section 8.4.5, Laboratory Assessments (Table 12:  Required Laboratory Analytes) 
Description of change:  Added the analysis of eGFR under Blood Chemistries. 
Rationale for change:  To monitor in line with chronic kidney disease guidelines 
(Andrassy 2013). 
12. Section 10.3, Level of Significance; Section 10.4.1, Primary Analysis 
Description of change:  Updated the level of significance wording and revised the 
2 sided α = 0.049 level to 2 sided α = 0.5 in alignment with removal of the interim 
analysis section. 
Rationale for change:  To align with removal of the interim analysis. 
13. Section 10.5, Interim Analysis 
Description of change:  Removed interim analysis. 
Rationale for change:  An interim analysis is not needed due to emerging safety and 
efficacy data for INCB054707 in other indications. 
14. Incorporation of administrative changes:  Other minor administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1 (12 JUL 2021) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to change the inclusion criteria associated with 
minimum number of nodules, to include a substudy for itch and sleep monitoring assessment, 
and to revise the interim analysis.  Additional changes are summarized below. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema); Section 4.1, Overall Design; Section 5.1, Inclusion 
Criteria 
Description of change:  Changed the inclusion criteria for minimum number of nodules 
from 10 to 20. 
Rationale for change:  To align the minimum nodule count with the range listed in the 
description of Grade 3 in Table 11. 
2. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements) 
Description of change:  Added the name for the coordinating principal investigator. 
Rationale for change:  To update the coordinating principal investigator field in the 
table. 
3. Section 1, Protocol Summary (Table 3:  Schedule of Activities for the 
Placebo-Controlled Period 
Description of change:  
 
Rationale for change:  
 
 
4. Section 1, Protocol Summary (Table 3:  Schedule of Activities for the 
Placebo-Controlled Period 
Description of change:  Added Follow-up phone call (eDiary compliance) to the table. 
Rationale for change:  To coincide with the text in Section 8.3.1 of the Protocol. 
5. Section 3, Objectives and Endpoints (Table 6:  Objectives and Endpoints) 
Description of change:  
 
 
Rationale for change:  
 
 


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6. Section 5.2, Exclusion Criteria (Table 7:  Exclusionary Laboratory Values) 
Description of change:  Removed "Conjugated (direct) bilirubin" and ≥ 1.2 × ULN from 
Exclusion Criterion 16g. 
Rationale for change:  To clarify that Exclusion Criterion 16g is only applicable to total 
bilirubin.  
7. Section 6.5.1, Criteria and Procedures for Dose Interruptions of Study Drug 
(Table 10:  Guidelines for Interruption, Restart, and Discontinuation of Study 
Drug) 
Description of change:  Added clarification for the number of times the study drug can 
be interrupted/restarted due to ALT and/or AST > 3.0 x ULN. 
Rationale for change:  To clarify that the study drug can only be interrupted/restarted up 
to 2 times. 
8. Section 8.2.2, Investigator's Global Assessment (Table 11:  Investigator's Global 
Assessment) 
Description of change:  Included appropriate literature reference and added description 
to Table 11 for each of the IGA grades. 
Rationale for change:  To properly describe each of the IGA grades. 
9. 
 
Description of change:  
 
 
Rationale for change:  
. 
10. Section 8.3.1.1, Itch NRS; 
 
Description of change:  Clarified that the correct NRS ranges from 0 to 10. 
Rationale for change:  To correct the NRS range. 
11. 
 
  
 
  
 
 
12. Section 1, Protocol Summary (Table 3:  Schedule of Activities for the 
Placebo-Controlled Period; Table 4:  Schedule of Activities for the Extension 
Period); Section 8.4.5, Laboratory Assessments (Table 12:  Required Laboratory 
Analytes) 
Description of change:  
 
Rationale for change:  
 
 


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13. Section 10.3, Level of Significance 
Description of change:  Updated to include alpha spending and to show allocation of 
significance level for dose-response signal testing for interim and primary analyses. 
Rationale for change:  To align with updates made to Section 10.5. 
14. Section 10.4.1, Primary Analysis 
Description of change:  Updated significance level for 2-sided test. 
Rationale for change:  To align with updates made to Section 10.3 and Section 10.5. 
15. Section 10.5, Interim Analysis 
Description of change:  Updated number of participants required to perform interim 
analysis and added a 2-sided test for the presence of a dose-response signal. 
Rationale for change:  To allow for efficacy testing during interim analysis. 
16. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-013854 v5.0
Signature Page for VV-CLIN-013854 v5.0
Approval
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Approval
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Approval
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Signature Page for VV-CLIN-013854 v5.0
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Approval
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 Biostatistics
Approval
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Approval
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SAP_001.pdf: 
Official Title:    A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study 
of the Efficacy and Safety of Povorcitinib in Participants with Prurigo 
Nodularis
NCT Number: 
 NCT05061693 
Document Date: 
Statistical Analysis Plan Amendment 1: 15-Jun-2023


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TITLE PAGE 
Statistical Analysis Plan 
INCB 54707-206 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Ranging Study of the Efficacy and Safety of Povorcitinib in 
Participants with Prurigo Nodularis
IND Number: 
137,156 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 2 dated 06 MAY 2022 
CRF Approval Date: 
13 MAR 2023 
SAP Version: 
Amendment 1 
SAP Author: 
 
Date of Plan: 
15 JUN 2023 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................9 
2.1. 
Protocol and Case Report Form Version ......................................................................9 
2.2. 
Study Objectives and Endpoints ...................................................................................9 
3. 
STUDY DESIGN .......................................................................................................11 
3.1. 
Randomization ............................................................................................................12 
3.2. 
Control of Type I Error ...............................................................................................12 
3.3. 
Sample Size Considerations .......................................................................................13 
3.4. 
Schedule of Assessments ............................................................................................13 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................14 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................14 
4.1.1. 
Day 1 ...........................................................................................................................14 
4.1.2. 
Study Day ...................................................................................................................14 
4.1.3. 
Baseline Value ............................................................................................................15 
4.1.4. 
Handling of Missing and Incomplete Dates ...............................................................16 
4.2. 
Variable Definitions ....................................................................................................16 
4.2.1. 
Body Mass Index ........................................................................................................16 
4.2.2. 
Prior and Concomitant Medication .............................................................................16 
5. 
STATISTICAL METHODOLOGY ...........................................................................18 
5.1. 
General Methodology .................................................................................................18 
5.2. 
Treatment Groups .......................................................................................................18 
5.3. 
Analysis Populations ..................................................................................................19 
5.3.1. 
All-Randomized Population .......................................................................................19 
5.3.2. 
Intent-to-Treat Population ..........................................................................................19 
5.3.3. 
Safety Population ........................................................................................................19 
5.3.4. 
Extension Evaluable Population .................................................................................19 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................20 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................20 


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6.1.1. 
Demographics and Baseline Characteristics ...............................................................20 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................20 
6.1.3. 
Medical History ..........................................................................................................21 
6.2. 
Disposition of Participant ...........................................................................................21 
6.3. 
Protocol Deviations ....................................................................................................22 
6.4. 
Exposure .....................................................................................................................22 
6.5. 
Study Drug Compliance .............................................................................................23 
6.6. 
Prior and Concomitant Medication .............................................................................23 
7. 
EFFICACY .................................................................................................................24 
7.1. 
General Considerations ...............................................................................................24 
7.2. 
Efficacy Parameters ....................................................................................................24 
7.2.1. 
Investigator's Global Assessment ...............................................................................24 
 
24 
 
25 
7.2.4. 
Patient-Reported Outcomes ........................................................................................25 
7.2.4.1. 
Itch Numerical Rating Scale .......................................................................................25 
 
26 
 
26 
 
27 
 
28 
 
28 
 
29 
 
31 
 
33 
7.3. 
Efficacy Hypotheses ...................................................................................................34 
7.4. 
Analysis of the Primary Efficacy Parameter ..............................................................34 
7.4.1. 
Primary Efficacy Analysis ..........................................................................................34 
7.4.2. 
Subgroup Analyses for Primary Endpoint ..................................................................34 
7.4.3. 
Sensitivity and Supportive Analyses for Primary Endpoint .......................................35 
7.5. 
Analysis of the Secondary Efficacy Parameters .........................................................35 
 
35 
 
35 
 
36 


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37 
 
37 
 
37 
9. 
SAFETY AND TOLERABILITY ..............................................................................37 
9.1. 
General Considerations ...............................................................................................37 
9.2. 
Adverse Events ...........................................................................................................37 
9.2.1. 
Adverse Event Definitions ..........................................................................................37 
9.2.2. 
Adverse Event Summaries ..........................................................................................38 
9.3. 
Clinical Laboratory Tests ...........................................................................................39 
9.3.1. 
Laboratory Value Definitions .....................................................................................39 
9.3.2. 
Laboratory Value Summaries .....................................................................................39 
9.3.3. 
Potentially Clinically Important Laboratory Values ...................................................40 
9.3.4. 
Potential Drug-Induced Liver Injury Events ..............................................................41 
9.4. 
Vital Signs ..................................................................................................................42 
9.5. 
Electrocardiograms .....................................................................................................42 
10. 
INTERIM ANALYSES ..............................................................................................43 
10.1. 
Overview of Interim Analyses ....................................................................................43 
10.2. 
Data Cutoff for Interim Analysis ................................................................................43 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................44 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................44 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................44 
11.2.1. 
Amendment 1 ..............................................................................................................44 
12. 
REFERENCES ...........................................................................................................45 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................47 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................9 
Table 2: 
Definition of Day 1 .....................................................................................................14 
Table 3: 
Definitions of Baseline ...............................................................................................15 
Table 4: 
Definition of First and Last Dose Date .......................................................................22 
Table 5: 
Investigator's Global Assessment ...............................................................................24 
Table 6: 
Criteria for Potentially Clinically Important Laboratory Values ................................40 
Table 7: 
Normal Ranges for Vital Sign Values ........................................................................42 
Table 8: 
Normal Ranges for Electrocardiogram Intervals ........................................................42 
Table 9: 
Statistical Analysis Plan Versions ..............................................................................44 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................12 
 
29 
 
30 
 
30 
 
31 
 
32 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
BMI 
body mass index 
bpm 
beats per minute 
Cavg,ss 
average concentration of study drug at steady state 
CI 
confidence interval  
 
 
 
 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
 
 
CTCAE 
Common Terminology Criteria for Adverse Events 
DILI 
Drug-Induced Liver Injury 
 
 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
 
 
 
 
Ext-Ev 
Extension Evaluable 
 
 
H1; H2 
null hypothesis; alternate hypothesis 
 
 
HDL 
high-density lipoprotein 
ICF 
informed consent form 
IGA  
Investigator's Global Assessment 
IGA-TS 
Investigator's Global Assessment Treatment Success  
ITT 
intent-to-treat 
 
 
LDL 
low-density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRI 
nonresponder imputation 
NRS 
numerical rating scale 


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Abbreviations and 
Special Terms 
Definition 
 
 
PC 
placebo-controlled 
 
 
  
 
 
 
PN 
prurigo nodularis 
 
 
PT 
preferred term  
 
 
QALYs 
quality-adjusted life years 
QD 
once daily 
QTcB 
Bazett's corrected QT interval 
QTcF 
Fridericia's corrected QT interval 
SAP  
Statistical Analysis Plan  
SAE 
serious adverse event 
SI 
International System of Units 
SMA 
smooth moving average 
SOC 
system organ class 
 
 
TEAE 
treatment-emergent adverse event  
 
 
 
 
ULN 
upper limit of normal 
 
 
 
  
WHO 
World Health Organization 
 
 
 


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1. 
INTRODUCTION 
This is a Phase 2, multicenter, randomized, parallel-group, placebo-controlled, double-blind, 
dose-ranging study to evaluate the efficacy and safety of povorcitinib (15, 45, and 75 mg QD) in 
participants with PN over a 16-week treatment period, followed by a 24-week single-blind 
extension period (
 or 
 QD). Each participant's dose of povorcitinib in the extension 
period will be based on their efficacy response (Itch NRS and IGA) at Week 16. A safety 
follow-up visit will be conducted approximately 4 weeks after the last dose of study drug.  
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 54707-206 Protocol. 
 
 
 
 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 54707-206 Protocol Amendment 2 dated 06 MAY 2022 and CRFs 
approved 13 MAR 2023. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol Amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To establish the efficacy of 
povorcitinib in PN. 
Proportion of participants achieving ≥ 4-point improvement in Itch 
NRS score at Week 16. 
Secondary 
To further assess the 
treatment effects of 
povorcitinib. 
• Proportion of participants achieving IGA-TS (IGA score of 0 or 1 
with a ≥ 2-grade improvement from baseline) at Week 16. 
• Time to ≥ 4-point improvement from baseline in Itch NRS score. 
To evaluate the safety and 
tolerability of povorcitinib. 
The type, frequency, and severity of AEs, including the results of 
physical examinations, and evaluation of vital signs, ECGs, and 
laboratory data. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
 


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3. 
STUDY DESIGN 
This is a Phase 2, multicenter, randomized, parallel-group, placebo-controlled, double-blind, 
dose-ranging study to evaluate the efficacy and safety of povorcitinib (15, 45, and 75 mg QD) 
over a 16-week double-blind PC period followed by a 24-week single-blind extension period 
(
 or 
 QD). The study will enroll approximately 140 men and women aged 18 to 
 years 
who have had a clinical diagnosis of PN for at least 3 months, received prior treatment for PN, 
and have a total of ≥ 20 pruriginous lesions in ≥ 2 different body regions, an IGA score ≥ 3, and 
an Itch NRS score ≥ 5. 
Participants will be screened for up to 28 days before the first dose of study drug. On Day 1, 
eligible participants will be equally randomized to 1 of 4 treatment groups (ie, povorcitinib 
15, 45, or 75 mg QD or placebo) and stratified by IGA score (3 vs 4). 
The use of rescue medications should be delayed, if possible, for at least 8 weeks after the first 
dose of study drug; however, the use of rescue medications is allowable at any time during the 
study in participants who have substantial worsening of PN from baseline (as determined by the 
investigator). Rescue therapy should be provided commensurate with symptom severity. 
Participants receiving a prohibited medication as rescue therapy must be withdrawn from study 
drug. 
Based on individual IGA and Itch NRS responses at Week 16, participants will receive either 
povorcitinib 
 or 
 QD for an additional 24 weeks (extension period). The investigator will 
know the dose administered during the extension period; however, the participant will remain 
blinded to the dose they receive. For the extension period, participants will be grouped based on 
the outcome from the PC period: 
 
 
 
 
 
After the last dose of study drug, participants will be followed for safety. A safety visit will 
occur at least 28 days following the last dose of study drug. 
Figure 1 depicts the study schema. 


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Figure 1: 
Study Design Schema 
 
The primary analysis will occur after the primary database lock, when all participants have 
completed or discontinued from the PC, double-blind treatment period. The sponsor will be 
unblinded at the time of primary analysis. 
The final analysis will occur when all participants have completed or withdrawn from the study. 
3.1. 
Randomization 
Approximately 140 participants will be randomized 1:1:1:1 (ie, placebo or povorcitinib 15, 45, or 
75 mg) with approximately 35 participants per group. 
Participant randomization will be stratified based on IGA score on Day 1 (3 vs 4). 
3.2. 
Control of Type I Error 
The overall significance level for efficacy analysis will be 0.05 for 2-sided tests. 
A set of hypotheses corresponding to the treatment comparisons between povorcitinib 15, 45, or 
75 mg and placebo will be tested in fixed sequential: 
• H1: Povorcitinib 75 mg is not equal to placebo in achieving ≥ 4-point improvement in 
Itch NRS score at Week 16 
• H2: Povorcitinib 45 mg is not equal to placebo in achieving ≥ 4-point improvement in 
Itch NRS score at Week 16 
• H3: Povorcitinib 15 mg is not equal to placebo in achieving ≥ 4-point improvement in 
Itch NRS score at Week 16 
Hypothesis 2 will only be tested if H1 is rejected; testing for H3 will be implemented only if H1 
and H2 are rejected. 


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3.3. 
Sample Size Considerations 
In order to provide a safety database and adequate power for efficacy analysis, the total sample 
size for the study is 140 participants randomized in a 1:1:1:1 ratio to povorcitinib 15, 45, or 
75 mg or placebo groups and stratified by IGA score on Day 1 (3 vs 4). The sample size 
calculation is based on Fisher's exact test for the statistical comparison on the primary efficacy 
endpoint, ie, the proportion of participants achieving ≥ 4-point improvement in Itch NRS at 
Week 16. Based on the results from a Phase 2 trial of nemolizumab (Stander et al 2020), the 
response rate is assumed to be 50% for the povorcitinib 45 and 75 mg groups and 15% for the 
placebo group. Using a 2-sided alpha of 0.05, 35 participants per group will have 85% power to 
detect such a difference between either one of the 3 active treatment groups and the placebo 
group. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 2 dated 06 MAY 2022 for a full description of all study 
procedures and assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug (povorcitinib) or placebo is administered to 
participants. The treatment groups are described in Table 2 for each period, as well as in 
Section 5.2. 
Table 2: 
Definition of Day 1 
Treatment Period 
Treatment Group 
Day 1 
PC period 
(Up to Week 16) 
Placebo 
Povorcitinib 15 mg 
Povorcitinib 45 mg 
Povorcitinib 75 mg 
The day of the first dose of study drug 
(povorcitinib or placebo) administered to 
participants in the PC period. 
Extension period 
(Week 16 through Week 40) 
Week 16 responder:  
Placebo to povorcitinib
 mg 
Povorcitinib 15 to
Povorcitinib
Povorcitinib
to
 
Week 16 nonresponder: 
Placebo to povorcitinib
Povorcitinib 15 to
Povorcitinib
o
Povorcitinib
The day of the first dose of study drug 
(povorcitinib 
 or 
 mg) administered to 
participants in the extension period. 
Overall period 
(Up to Week 40)  
Povorcitinib 45 mg 
Povorcitinib 75 mg 
Note: These groups consist of 
participants who took only 
povorcitinib 45 or 75 mg 
during the study. 
The day of the first dose of study drug 
(povorcitinib 45 or 75 mg) administered to 
participants in the PC period. 
For randomized participants not treated with any study drug, Day 1 is defined as the day of 
randomization. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of –1 indicates 1 day before Day 1. 


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4.1.3. 
Baseline Value 
For efficacy and safety evaluations in the PC period, baseline is the last nonmissing 
measurement obtained before or on the first administration of povorcitinib or placebo in the PC 
period. 
• For randomized participants not treated with any study drug, baseline is defined as the 
last nonmissing assessment before or on the day of randomization for all parameters. 
Note that for participants who entered the extension period, baseline is defined as follows: 
• For efficacy evaluation in the extension period, baseline is the last nonmissing 
measurement obtained before the first administration of povorcitinib or placebo in the 
PC period (hereafter referred to as PC baseline). 
• For safety evaluation in the extension period, baseline is the last nonmissing 
measurement obtained before the first administration of study drug in the extension 
period (hereafter referred to as extension baseline). 
When scheduled assessments and unscheduled assessments occur on the same day and the time 
of the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first 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. 
Table 3 provides an outline of baseline definitions for efficacy and safety evaluation in each 
period. 
Table 3: 
Definitions of Baseline 
Treatment Period 
Treatment Group 
For Efficacy Evaluation For Safety Evaluation 
PC period 
(Up to Week 16) 
Placebo 
Povorcitinib 15 mg 
Povorcitinib 45 mg 
Povorcitinib 75 mg 
PC baseline 
PC baseline 
Extension period 
(Week 16 through Week 40) 
Week 16 responder:  
Placebo to povorcitinib 
 
Povorcitinib 15 to 
Povorcitinib
Povorcitinib
to
 
Week 16 nonresponder: 
Placebo to povorcitinib
Povorcitinib 15 to
Povorcitinib 
o
Povorcitinib
PC baseline 
Extension baseline 


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Table 3: 
Definitions of Baseline (Continued) 
Treatment Period 
Treatment Group 
For Efficacy Evaluation For Safety Evaluation 
Overall period 
(Up to Week 40)  
Povorcitinib 45 mg 
Povorcitinib 75 mg 
Note: These groups consist of 
participants who took only 
povorcitinib 45 or 75 mg 
during the study. 
Not applicable 
PC baseline 
4.1.4. 
Handling of Missing and Incomplete Dates 
In general, values for missing dates will not be handled unless methods for handling missing 
dates are specified in this section or relevant sections. The original reported dates collected on 
the eCRF should be used in all relevant listings. The following rules will be used for handling 
partial dates for analyses requiring dates. 
When calculating the time since diagnosis of PN, a partial PN diagnosis date will be handled as 
follows in the calculation: 
• If only the day is missing, then the first day of the month will be used. 
• If both the month and day are missing, then 01 JAN of the year will be used. 
• If the diagnosis date is completely missing, then the time since diagnosis will not be 
calculated. 
When the date of the last dose in a specific period is used in deriving variables, such as duration 
of treatment or TEAE flag, a missing or partial date of the last dose will be handled as follows: 
• If only the day is missing, then the earlier date of the last day of the month or the date 
that the participant discontinued treatment will be used. 
• If both the month and day are missing, then the earlier date of 31 DEC of the year or 
the date that the participant discontinued treatment will be used.  
• Otherwise, the date that the participant discontinued treatment will be used as the date 
of the last dose. 
4.2. 
Variable Definitions 
The following variable will only be calculated if not reported on the eCRF. 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
Body mass index (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
povorcitinib or placebo in the PC period. 


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For the PC period, concomitant medication is defined as any nonstudy medication that is started 
accordingly: 
• Before the date of first administration of povorcitinib or placebo in the PC period and 
is ongoing or ends on/after the date of first study drug administration in the PC 
period, OR 
• On/after the date of first administration of povorcitinib or placebo in the PC period, 
and before the date of first administration of povorcitinib in the extension period for 
participants who enter the extension period. 
For the extension period, concomitant medication is defined as any nonstudy medication that is 
started accordingly: 
• Before the date of first administration of povorcitinib in the extension period and is 
ongoing throughout the study or ends on/after the date of first study drug 
administration in the extension period, OR 
• On/after the date of first administration of povorcitinib in the extension period. 
For the overall period, concomitant medication is defined as any nonstudy medication that is 
started accordingly: 
• Before the date of first administration of povorcitinib in the PC period and is ongoing 
throughout the study or ends on/after the date of first study drug administration in the 
PC period, OR 
• On/after the date of first administration of povorcitinib in the PC period. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of povorcitinib or placebo in the PC period. In the listing, it will be 
indicated whether a medication is only prior, only concomitant, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9.1 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 participants in each category. 
5.2. 
Treatment Groups 
This is a randomized, double-blind, placebo-controlled, dose-ranging study followed by a 
single-blind extension period. Table summaries, unless otherwise indicated, will present data by 
treatment group. The results will be summarized and presented separately for the PC period, the 
extension period, and overall period (for safety only) unless otherwise specified. 
For the PC period, the treatment groups will be placebo and povorcitinib 15, 45, and 75 mg. 
For the extension period, participants will be grouped into 2 cohorts (Week 16 responders and 
Week 16 nonresponders); these 2 cohorts will then be separated into the following subgroups, 
per the treatments they received during the PC and extension periods: 
• Week 16 responders:  
− Placebo to povorcitinib 
 
− Povorcitinib 15 to
− Povorcitinib
− Povorcitinib
to 
 
• Week 16 nonresponders: 
− Placebo to povorcitinib 
 
− Povorcitinib 15 to 
 
− Povorcitinib
to 
 
− Povorcitinib 
 
Safety results will be summarized and presented by the following treatment groups who took 
same dose across study: 
• Povorcitinib 45 mg will consist of participants who took only 45 mg during the 
overall period (including participants who received at least 1 dose of 
 during 
both the PC and extension periods, and participants who received at least 1 dose of 
45 mg during the PC period and discontinued during the PC period). 
• Povorcitinib 75 mg will consist of participants who took only 75 mg during the 
overall period (including participants who received at least 1 dose of 
 during 
both the PC and extension periods, and participants who received at least 1 dose of 
75 mg during the PC period and discontinued during the PC period). 


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5.3. 
Analysis Populations 
5.3.1. 
All-Randomized Population 
The all-randomized population will include all participants who were randomly assigned to 
receive placebo or povorcitinib. 
5.3.2. 
Intent-to-Treat Population 
All participants who were randomized will constitute the ITT population. Treatment groups for 
this population will be defined according to the treatment assignment at the time of 
randomization regardless of the actual study treatment the participant might apply during their 
participation in the PC period. 
The ITT population will be used for the summary of demographics, baseline characteristics, 
participant disposition, and analyses of all efficacy data in the PC period and the overall period. 
5.3.3. 
Safety Population 
The safety population will include all participants who received at least 1 dose of povorcitinib or 
placebo during the PC period. Treatment groups for this population will be determined according 
to the actual treatment the participant receives on Day 1 in the PC period regardless of assigned 
study drug treatment. 
All safety analyses for the PC period and the overall period will be conducted using the safety 
population. 
5.3.4. 
Extension Evaluable Population 
All analyses for the extension period will be conducted with the extension evaluable population, 
which includes all participants who received at least 1 dose of povorcitinib during the extension 
period. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION  
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
The demographics, baseline characteristics, and disease history will be summarized by treatment 
groups and overall. 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics will be summarized for the ITT and the extension evaluable 
populations: age; age group (< 65 and ≥ 65 years); sex; race; ethnicity; weight; height; BMI; and 
BMI category (< 25 kg/m2, ≥ 25 to < 30 kg/m2, ≥ 30 to < 40 kg/m2, ≥ 40 to < 50 kg/m2, and 
≥ 50 kg/m2). 
The following demographic will be summarized for the ITT population only: tobacco use 
(never used, current user, or former user). 
6.1.2. 
Baseline Disease Characteristics and Disease History 
The following baseline disease characteristics and disease history will be summarized for all 
participants in the ITT population, including, but not limited to: 
• Disease duration (years) 
• Fitzpatrick scale skin type (Type I/II/III/IV/V/VI)  
• PN family history 
• Prior therapy for PN (yes/no) 
• Prior therapeutic response (complete, good, limited improvement, lack of efficacy) 
• Selected comorbidities 
 
 
 
 
 
 
• Baseline IGA score 
• Baseline Itch NRS score (See Section 7.2.4.1) 
 
 
 
 
 
 
 
 


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Note: Disease duration (years) will be calculated as follows: 
Disease duration (years) = (date of randomization – date of initial PN diagnosis + 1) / 365.25. 
6.1.3. 
Medical History 
For participants in the ITT population, medical history will be summarized by assigned treatment 
group. This summation will include the number and percentage of participants with medical 
history for each body system/system organ class as documented on the eCRF. 
6.2. 
Disposition of Participant 
The number of participants enrolled by country and/or site will be provided by treatment group 
and overall. 
The following categories will be summarized by treatment group and overall for the 
ITT population in the PC period: 
• Number (%) of participants who were randomized 
• Number (%) of participants who were treated in the double-blind PC period 
• Number (%) of participants who completed treatment in the PC period through 
Week 16 
• Number (%) of participants who discontinued treatment with a primary reason for 
discontinuation in the PC period 
• Number (%) of participants who withdrew from the study with a primary reason for 
withdrawal in the PC period  
• Number (%) of participants who withdrew from study due to COVID-19 in the 
PC period 
The following categories will be summarized by treatment group and overall for the extension 
evaluable population in the extension period: 
• Number (%) of participants who were treated in the extension period 
• Number (%) of participants who completed treatment in the extension period  
• Number (%) of participants who discontinued the study treatment with a primary 
reason for discontinuation in the extension period 
• Number (%) of participants who completed the study  
• Number (%) of participants who withdrew from the study with a primary reason for 
withdrawal in the extension period  
• Number (%) of participants who withdrew from study due to COVID-19 in the 
extension period 


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6.3. 
Protocol Deviations 
Protocol deviations recorded will be summarized and listed for the ITT and extension evaluable 
populations, as well as the individual protocol deviations indicated on the eCRF. 
6.4. 
Exposure 
For participants in the safety population in the PC period and the extension evaluable population 
in the extension period, as well as for participants who only took povorcitinib 45 or 75 mg during 
the overall period, the exposure to the study drug will be descriptively summarized by treatment 
group as follows: 
• Duration of treatment with povorcitinib (days): Date of last dose of study drug in 
the specific period – date of first dose of study drug in the specific period + 1. 
Note that the date of first and last dose of the study drug in each period are defined in Table 4. 
Table 4: 
Definition of First and Last Dose Date  
Treatment Period 
Treatment Group 
First Dose Date 
Last Dose Date 
PC period 
Placebo 
Povorcitinib 15 mg 
Povorcitinib 45 mg 
Povorcitinib 75 mg 
Date of first dose of 
study drug 
administration in the 
PC period 
Date of last dose of study 
drug administration in the 
PC period 
Extension period 
Week 16 responders: 
Placebo to povorcitinib 
 
Povorcitinib 15 to
Povorcitinib
Povorcitinib
o
 
Week 16 nonresponders: 
Placebo to povorcitinib 
Povorcitinib 15 to
Povorcitinib 
o
Povorcitinib 
 
Date of first dose of 
study drug 
administration in the 
extension period 
Date of last dose of study 
drug administration in the 
extension period 
Overall period  
Povorcitinib 45 mg 
Povorcitinib 75 mg 
 
Note: These groups consist of 
participants who took only 
povorcitinib 45 or 75 mg during 
the study. 
Date of first dose of 
study drug 
administration in the 
PC period 
Date of first dose of study 
drug administration 
during the overall period 


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For participants in the safety population in the PC period and the extension evaluable population 
in the extension period, the average daily dose of povorcitinib and total actual dose of 
povorcitinib administered will be summarized by treatment groups as follows: 
• Average daily dose of povorcitinib (mg/day): Total actual povorcitinib dose taken 
in the specific period (mg) / [duration of treatment with povorcitinib in the specific 
period (days) – number of interrupted days with povorcitinib in the specific period]. 
• Total actual dose of povorcitinib administered (mg): (Total number of tablets 
dispensed in the specific period – total number of tablets returned in the specific 
period) × 15 (mg/tablet) × 𝑝𝑇, 
where  𝑝𝑇 denotes the proportion of povorcitinib among the 5 tablets taken daily 
(ie, 𝑝𝑇= 0 (0/5) for placebo group, 1/5 for povorcitinib 15 mg group, 3/5 for 
povorcitinib 45 mg group, and 5/5 for povorcitinib 75 mg group). 
The total number of tablets dispensed and returned in each period is based on information 
entered on the Drug Accountability eCRF. Should the dispensed drug not be returned, the actual 
dose taken, starting from the dispense date of the unreturned drug, will be imputed by the dose 
taken per the Compliance eCRF. 
6.5. 
Study Drug Compliance 
For participants in the safety and the extension evaluable populations, the overall compliance 
(%) for povorcitinib/placebo will be calculated as follows:  
Compliance (%) = 100 × [total dose actually taken in the specific period] / [total prescribed 
dose in the specific period]. 
The total prescribed dose in the specific period is defined as the sum of the doses prescribed by 
the investigator accounting for dose interruptions during the specific period; this will be 
calculated as follows: 
[Duration of treatment with study drug in the specific period – number of days with dose 
interruptions in the specific period] × 5 (tablets/day). 
The total actual dose taken in a specific period will be calculated as follows: 
Total number of tablets dispensed in the specific period – total number of tablets returned in 
the specific period. 
For more details on the total number of tablets dispensed and returned, see Section 6.4. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
For the ITT population in the PC period, both prior and concomitant medication will be 
summarized by treatment group and overall. For the extension evaluable population in the 
extension period, only concomitant medications will be summarized by treatment group and 
overall. For participants who took only povorcitinib 45 or 75 mg during the overall period, 
concomitant medications will be summarized by treatment group and overall. The number and 
percentage of participants in all populations will be summarized by WHO drug class and 
WHO drug preferred term. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
General Considerations 
All by-visit analyses for the extension evaluable population will include the follow-up period, if 
the data are available or unless otherwise specified. Likewise, unless otherwise stated, the strata 
identified in the randomization process will be used in all efficacy analyses. 
7.2. 
Efficacy Parameters 
7.2.1. 
Investigator's Global Assessment  
The IGA for chronic prurigo considers the number of pruriginous lesions, which includes 
papules, nodules, plaques, umbilicated ulcers and ulcers to rate the overall severity on a scale of 
0 to 4 (Zeidler et al 2021; see Table 5). The nodular rating will be performed at scheduled visits. 
The IGA-TS is defined as an IGA score of 0 or 1 with a ≥ 2-grade improvement from baseline. 
Table 5: 
Investigator's Global Assessment 
Grade 
Severity 
Description 
0 
Clear 
No nodules (0 nodules) 
1 
Almost clear 
Rare palpable pruriginous nodules (approximately 1-5 nodules) 
2 
Mild 
Few palpable pruriginous nodules (approximately 6-19 nodules) 
3 
Moderate 
Many palpable pruriginous nodules (approximately 20-100 nodules) 
4 
Severe 
Abundant palpable pruriginous nodules (over 100 nodules) 
 
 


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7.2.4. 
Patient-Reported Outcomes 
Patient-reported outcomes and quality of life will be assessed using the following tools: 
• Itch NRS (see Section 7.2.4.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.2.4.1. 
Itch Numerical Rating Scale 
Each evening, participants will assess their worst level of itch during the past 24 hours on a scale 
of 0 (no itch) to 10 (worst itch imaginable) via a handheld device (eDiary). 
The baseline Itch NRS score will be determined by averaging the 7 daily Itch NRS scores before 
Day 1 (ie, Day −7 to Day −1). Should ≥ 4 of the 7 days of the daily Itch NRS scores be missing 
prior to Day 1, then the baseline Itch NRS will be set to "missing." 
The by-visit Itch NRS score for postbaseline visits will be determined by averaging the 7 daily 
Itch NRS scores before the visit day. If 4 or more daily Itch NRS scores out of the 7 days before 
the visit day are missing, the Itch NRS at the visit will be set to missing.  
The most appropriate threshold for defining a clinically relevant, in-person response is ≥ 4-point 
reduction relative to baseline (Kimball et al 2016). 


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For time to ≥ 4-point improvement from baseline in Itch NRS score, 3-day smooth moving 
average (SMA) method will be used. For each Day X (X = 2 to two days before the first dose 
date in extension period for participants who entered extension period, or one day before 
discontinuation date for participants who discontinued PC period), a SMA value is calculated as 
the average of daily Itch NRS scores on Day X − 1, Day X, and Day X + 1. If 1 or more daily 
Itch NRS scores out of the 3-day interval are missing, the SMA value for the day will be set to 
missing. The first day achieving ≥ 4-point improvement from baseline in daily Itch NRS score is 
defined as the day with both the value at the day, and its SMA value are ≥ 4-point lower as 
compared to the baseline Itch NRS score defined above. Then the time to ≥ 4-point improvement 
from baseline in Itch NRS score will be calculated as:  
(Date of first day achieving ≥ 4-point improvement from baseline in daily Itch NRS score – 
Day 1 date +1).  
Participants who did not achieve ≥ 4-point improvement from baseline in Itch NRS score during 
the PC period will be censored as follows: 
• Participants who completed the PC treatment period through Week 16 without having 
the event will be censored at one day before the first dose date in extension period, 
and the censored time will be calculated as: (Date of one day before the first dose date 
in extension period – Day 1 date +1) 
• Participants who discontinued during the PC period without having the event will be 
censored at the date of discontinuation in PC period, and the censored time will be 
calculated as: (Date of discontinuation in PC period – Day 1 date +1).  
 
 
 
 


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7.3. 
Efficacy Hypotheses 
The primary hypothesis is that povorcitinib 75 mg is superior to placebo in proportion of 
participants achieving ≥ 4-point improvement in Itch NRS at Week 16. If the response rates of 
achieving ≥ 4-point improvement in Itch NRS at Week 16 in the povorcitinib 75 mg and placebo 
groups are denoted as 𝑝𝑇 and 𝑝𝐶, respectively, then the primary hypotheses of the study are as 
follows:  
• H0 (null hypothesis): 𝑝𝑇= 𝑝𝐶 
• HA (alternative hypothesis): 𝑝𝑇≠𝑝𝐶 
7.4. 
Analysis of the Primary Efficacy Parameter 
The primary efficacy endpoint is the proportion of participants achieving ≥ 4-point improvement 
in Itch NRS at Week 16. 
7.4.1. 
Primary Efficacy Analysis 
The primary efficacy analysis will compare povorcitinib 75 mg versus placebo in the proportion 
of participants achieving ≥ 4-point improvement in Itch NRS score at Week 16 using an exact 
logistic regression (Mehta and Patel 1995) based on the ITT population. This model will include 
the treatment groups (placebo and povorcitinib 15, 45, and 75 mg) and stratification factor 
(Day 1 IGA score [3 or 4]). The unadjusted p-values between each of the povorcitinib groups 
and the placebo group will be compared at 2-sided α = 0.05 in a fixed sequence from high dose 
to low dose (75 mg vs placebo → 45 mg vs placebo → 15 mg vs placebo); the lower dose will be 
tested only if the null hypothesis associated with the higher dose is rejected. The estimated odds 
ratios and corresponding 95% CIs will be provided as well. All observed nonresponders, as well 
as all participants who discontinue study treatment, withdraw from the study for any reason at 
any time before the timepoint of interest (ie, Week 16), or those participants that do not have the 
postbaseline assessment at the timepoint of interest, will be defined as nonresponders for the 
NRI analysis. All participants who receive rescue therapy during the placebo-controlled period 
will be imputed as nonresponders for all subsequent visits after the initiation date of rescue 
therapy. 
The number of participants achieving ≥ 4-point improvement in Itch NRS score at Week 16 and 
the respective rates, as well as the 2-sided 95% exact CIs, which are based on the 
Clopper-Pearson method, will be presented by treatment group. 
7.4.2. 
Subgroup Analyses for Primary Endpoint 
Subgroups will be formed based on the following participant characteristics and baseline 
variables for those participants whose data are available: 
• Age group (< 65 and ≥ 65 years) 
• Gender (male, female) 
• Geographical region 
• Baseline IGA (3 vs 4) 


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The primary efficacy endpoint will be summarized using descriptive statistics based on the 
ITT population for the aforementioned subgroups. 
7.4.3. 
Sensitivity and Supportive Analyses for Primary Endpoint 
Not applicable. 
7.5. 
Analysis of the Secondary Efficacy Parameters 
The secondary efficacy endpoints include the proportion of participants achieving IGA-TS at 
Week 16 and the time it takes to achieve a ≥ 4-point improvement from baseline in the Itch NRS 
score. 
The proportion of participants achieving IGA-TS at Week 16 will be summarized using 
descriptive statistics. The NRI approach will be used to address initiation of rescue medication, 
treatment discontinuation, and missing data. 
For the time to ≥ 4-point improvement from baseline in Itch NRS score during the PC period, 
Kaplan-Meier curves will be presented by treatment groups. The number of participants, number 
of events, and number of censoring events will be summarized by treatment groups. The 
Kaplan-Meier estimate of median time will be presented with its 95% CI. The 95% CI will be 
calculated using the method by Brookmeyer and Crowley (1982). 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
The analyses in this section will be provided for the safety population in the PC period, the 
extension evaluable population in the extension period, and for participants who took only 
povorcitinib 45 or 75 mg during the overall period, unless otherwise specified. 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 preferred terms reported on relatively few 
participants. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the 
first dose of study drug and up to 30 days after the last dose of study drug. Analysis of AEs will 
be limited to TEAEs, but data listings will include all AEs regardless of their timing in relation to 
study drug administration. For purposes of analysis, all AEs will be considered TEAEs unless the 
AE can unequivocally be defined as not treatment-emergent. 


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A TEAE in the PC period is any AE with a start time after the first dose of study drug in the 
PC period and until the end of the safety follow-up, or prior to the first dose in the extension 
period for participants who entered in to the extension period. 
A TEAE in the extension period is any AE with a start time after the first dose of study drug in 
the extension period and until the end of the safety follow-up. 
For participants who took only povorcitinib 45 or 75 mg during overall period, a TEAE is any 
AE with a start time after the first dose of study drug in the PC period and until the end of the 
safety follow-up. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the National Cancer Institute CTCAE v5.0. The CTCAE reporting guidelines and grading 
details are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. In addition, serious TEAEs will also be tabulated. 
9.2.2. 
Adverse Event Summaries 
Adverse events will be summarized by treatment group and povorcitinib dose groups combined 
for the safety population in the PC period, and by treatment group and overall in each cohort (ie, 
Week 16 responders and nonresponders) for the extension evaluable population in the extension 
period, and by treatment group and overall for participants who took only povorcitinib 45 or 
75 mg during the overall period. 
An overall summary of AEs will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any treatment-related TEAEs 
• Number (%) of participants who temporarily interrupted study treatment because of 
TEAEs 
• Number (%) of participants who permanently discontinued study treatment because 
of TEAEs 
• Number (%) of participants who had a fatal TEAE 
• Number (%) of participants who had TEAE requiring concomitant medication 


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The following summaries will be produced by MedDRA term (if 10 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by MedDRA SOC and PT 
• Summary of TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of TEAEs by MedDRA SOC, PT, and maximum severity 
• Summary of TEAEs by MedDRA SOC, PT, and CTCAE grade category 
• Summary of Grade 3 or higher TEAEs by MedDRA SOC and PT 
• Summary of Grade 3 or higher TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of serious TEAEs by MedDRA SOC and PT 
• Summary of serious TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of Grade 3 or higher treatment-related TEAEs by MedDRA SOC and PT 
• Summary of treatment-related serious TEAEs by MedDRA SOC and PT 
• Summary of TEAEs with a fatal outcome by MedDRA SOC and PT 
• Summary of TEAEs leading to dose interruption by MedDRA SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by MedDRA SOC and 
PT 
• Summary of TEAEs requiring concomitant medications by MedDRA SOC and PT 
9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
Laboratory values, change from baseline values, and percent change from baseline values will be 
summarized descriptively by visit, and non-numeric test values will be tabulated when necessary. 
Baseline will be determined according to Section 4.1.3. The last record before administration in 
the highest priority will be considered the baseline record. For baseline laboratory candidates 
with the same date and time in the same priority category, additional rules may be provided after 
consultation with the medical monitor to delineate which value will be defined as baseline. 
9.3.2. 
Laboratory Value Summaries 
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. 


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When there are multiple nonmissing laboratory values for a participant's particular test at a 
scheduled visit, laboratory values have higher priority over local laboratory values. If a tie still 
exists, the laboratory value with the smallest laboratory sequence number will be used in by-visit 
summaries. In addition, boxplots will be provided for creatine kinase, hemoglobin, hematocrit, 
platelet count, high sensitivity C-reactive protein, lymphocyte absolute count, neutrophil 
absolute count, white blood cell count, total cholesterol, HDL, LDL, and HDL/LDL ratio. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low (but never high), normal, high (but never 
low), and both low and high will be calculated for each test. This shift summary will be produced 
for each test. The denominator for the percentage calculation will use the number of participants 
in the baseline category (ie, low, high, normal, missing) as the denominator for the percentage in 
each of the categories during the study. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5. Shift tables will also be presented showing change in CTCAE grade from baseline to 
the worst grade postbaseline. Separate summaries for abnormally high and abnormally low 
laboratory values will be provided when the laboratory parameter has both high and low grading 
criteria. The denominator for the percentage calculation will be the number of participants in the 
baseline category. The number of participants who experienced worsening of laboratory 
abnormalities will be summarized by maximum severity. 
9.3.3. 
Potentially Clinically Important Laboratory Values 
Criteria for potentially clinically important laboratory values are listed in Table 6. The number 
and percentage of participants with postbaseline laboratory values that meet each criterion will 
be summarized at each scheduled visit by treatment group. Participants with potentially clinically 
important laboratory values will also be listed. 
Table 6: 
Criteria for Potentially Clinically Important Laboratory Values 
Laboratory Parameter 
Grade (Criteria) 
Hemoglobin 
Grade 2 (80 to < 100 g/L) 
Grade 3 (< 80 g/L) 
Lymphocytes 
Grade 2 (0.5 to < 0.8 × 109/L) 
Grade 3 (0.2 to < 0.5 × 109/L) 
Grade 4 (< 0.2 × 109/L) 
Neutrophils 
Grade 2 (1.0 to < 1.5 × 109/L) 
Grade 3 (0.5 to < 1.0 × 109/L) 
Grade 4 (< 0.5 × 109/L) 


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Table 6: 
Criteria for Potentially Clinically Important Laboratory Values (Continued) 
Laboratory Parameter 
Grade (Criteria) 
Platelets 
Grade 2 (50 to < 75 × 109/L) 
Grade 3 (25 to < 50 × 109/L) 
Grade 4 (< 25 × 109/L) 
Creatinine 
Grade 2 (> 1.5 to 3 × ULN or > 1.5 to 3 × baseline) 
Grade 3 (> 3 to 6 × ULN or > 3 × baseline) 
Grade 4 (> 6 × ULN) 
Creatine kinase 
Grade 2 (> 2.5 to 5 × ULN) 
Grade 3 (> 5 to 10 × ULN) 
Grade 4 (> 10 × ULN) 
9.3.4. 
Potential Drug-Induced Liver Injury Events 
According to FDA's guidance on Drug-Induced Liver Injury (2009), the criteria for potential 
DILI events include the following: 
• ALT ≥ 3 × ULN 
• ALT ≥ 5 × ULN 
• ALT ≥ 10 × ULN 
• ALT ≥ 20 × ULN 
• AST ≥ 3 × ULN 
• AST ≥ 5 × ULN 
• AST ≥ 10 × ULN 
• AST ≥ 20 × ULN 
• ALT or AST ≥ 3 × ULN 
• ALT or AST ≥ 5 × ULN 
• ALT or AST ≥ 10 × ULN 
• ALT or AST ≥ 20 × ULN 
• Alkaline phosphatase ≥ 1.5 × ULN 
• Total bilirubin ≥ 2 × ULN 
• ALT and/or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN 
Note that combination of values need to be measured on the same day. 
The number and percentage of participants with postbaseline liver specific function test values 
that meet these criteria will be presented at each scheduled visit by treatment group. Participants 
with potential DILI events will also be listed. 


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9.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, temperature, respiratory rate, 
and weight will be summarized descriptively. Baseline will be determined according to 
Section 4.1.3. 
Normal ranges for vital sign values are defined in Table 7. For participants exhibiting vital sign 
abnormalities, the abnormal values will be listed along with their assigned treatment group. Alert 
vital signs are defined as an absolute value outside the defined normal range and percentage 
change greater than 25%. Note that the definition of alert vital signs does not apply for body 
temperature and weight. The abnormal values for participants exhibiting alert vital sign 
abnormalities will be listed. 
Table 7: 
Normal Ranges for Vital Sign Values 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
≤ 155 mmHg 
≥ 85 mmHg 
Diastolic blood pressure 
≤ 100 mmHg 
≥ 40 mmHg 
Pulse 
≤ 100 bpm 
≥ 45 bpm 
Temperature 
≤ 38ºC 
≥ 35.5ºC 
Respiratory rate 
≤ 24 breaths/min 
≥ 8 breaths/min 
9.5. 
Electrocardiograms 
Twelve-lead ECGs, including PR, QT, QRS and QTcF intervals, will be obtained for each 
participant during the study. Values at each scheduled visit, change, and percentage change from 
baseline will be summarized for each ECG parameter. Baseline will be determined as the 
average of all nonmissing values before the first administration of povorcitinib or placebo. 
Normal ranges for ECG values are defined in Table 8. The ECG values will also be considered 
abnormal if the absolute percentage change from baseline is more than 25% (30% for 
QRS interval). Participants exhibiting ECG abnormalities will be listed with study visit and 
assigned treatment group. Abnormal values for participants with alert ECG values, defined as 
both the absolute value and the percentage change from baseline being outside normal ranges, 
will be identified and listed. Outliers of QT and QTcF values, defined as absolute values 
> 450 millisecond, > 500 millisecond, or change from baseline > 30 millisecond, will be 
summarized. 
Table 8: 
Normal Ranges for Electrocardiogram Intervals 
Parameter 
High Threshold 
Low Threshold 
PR 
≤ 220 ms 
≥ 75 ms 
QT 
≤ 500 ms 
≥ 300 ms 
QRS 
≤ 120 ms 
≥ 50 ms 
QTcF 
≤ 450 ms 
≥ 295 ms 


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10. 
INTERIM ANALYSES 
There are no planned, formal interim analyses for this study.  
10.1. 
Overview of Interim Analyses 
No formal interim analysis is planned in this study. 
10.2. 
Data Cutoff for Interim Analysis 
Not applicable. 


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11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 9. 
Table 9: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
03 APR 2023 
Amendment 1 
15 JUN 2023 
11.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
11.2. 
Changes to the Statistical Analysis Plan 
11.2.1. 
Amendment 1 
Updated Section 3 to better align with Section 6.3 of Protocol Amendment 2. In Appendix A, the 
title of Figure 4.2.2.2 was corrected.  


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12. 
REFERENCES 
 
 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982:38:29-41. 
 
 
 
 
 
 
Food and Drug Administration. Guidance for industry: drug-induced liver injury: premarketing 
clinical evaluation. 2009. 
 
 
 
 
 
 
 
Kimball AB, Naegeli AN, Edson-Heredia E, et al. Psychometric properties of the Itch Numeric 
Rating Scale in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 
2016;175:157-162. 
Mehta CR, Patel NR. Exact logistic regression: theory and examples. Stat Med 1995;14:2143-
2160. 
 
 
 
 
Stander S, Yosipovitch G, Legat FJ, et al. Trial of nemolizumab in moderate-to-severe prurigo 
nodularis. N Engl J Med 2020;382:706-716. 


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Zeidler C, Pereira MP, Augustin M, Spellman M, Ständer S. Investigator's global assessment of 
chronic prurigo: a new instrument for use in clinical trials. Acta Derm Venereol 2021;101:1-5. 
 
 


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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. Shells are provided in a separate document for tables that are not in the most current 
Standard Safety Tables. In-text tables are identical in structure and content as appendix tables, 
but follow a Rich Text Format. 
The list of tables, figures, and listings are to be used as guidelines. Modifications of the lists that 
do not otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
1.1 Baseline and Demographics Characteristics 
1.1.1 
Analysis Populations 
All 
X 
1.1.2.x 
Summary of Participant Disposition in the PC Period 
ITT/Ext-Ev 
X 
1.1.3 
Summary of Number of Participants Enrolled by Country and Site 
ITT 
X 
1.1.4.x 
Summary of Protocol Deviations in the PC Period 
ITT/Ext-Ev 
X 
1.2 Demographics and Baseline Characteristics 
1.2.x 
Summary of Demographics and Baseline Characteristics in the PC 
Period 
ITT/Ext-Ev 
X 
1.3 Baseline Disease Characteristics 
1.3.1 
Summary of Baseline Disease Characteristics 
ITT 
X 
1.4 Prior and Concomitant Medication 
1.4.1 
Summary of Prior Medications  
ITT 
X 
1.4.2 
Summary of Concomitant Medications in the PC Period 
ITT/Ext-Ev 
X 
1.5 Others 
1.5 
Summary of General Medical History 
ITT 
X 
Efficacy 
2.1 Primary Efficacy  
ITCH NRS 
2.1.1 
Summary and Analysis of Proportion of Participants Achieving 
≥ 4-Point Improvement in Itch NRS Score by Visit in the PC Period 
ITT 
 
2.1.2 
Summary of Proportion of Participants Achieving ≥ 4-Point 
Improvement in Itch NRS Score by Visit by Age Group in the PC 
Period 
ITT 
 
2.1.3 
Summary of Proportion of Participants Achieving ≥ 4-Point 
Improvement in Itch NRS Score by Visit by Gender in the PC Period 
ITT 
 
2.1.4 
Summary of Proportion of Participants Achieving ≥ 4-Point 
Improvement in Itch NRS Score by Visit by Baseline IGA (3 v 4) in 
the PC Period 
ITT 
 
2.1.5 
Summary of Proportion of Participants Achieving ≥ 4-Point 
Improvement in Itch NRS Score by Visit by Geographical Region in 
the PC Period 
ITT 
 
2.2 Secondary Efficacy  
2.2.1 IGA-TS 
2.2.1.x 
Summary of Proportion of Participants Achieving IGA-TS by Visit 
in the PC Period  
ITT/Ext-Ev 
 


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Table No. 
Title 
Population 
Standard 
2.2.2 ITCH NRS 
2.2.2.1 
Summary of Time to ≥ 4-Point Improvement From Baseline in Itch 
NRS Score in the PC Period 
ITT 
 


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Table No. 
Title 
Population 
Standard 
Safety 
3.1 Dose Exposure 
3.1.1.x 
Summary of Study Drug Exposure in the PC Period  
Safety/Ext-Ev 
X 
3.1.1.3 
Summary of Study Drug Exposure for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg Throughout Study Participation 
(Overall Period) 
Safety 
X 
3.1.2.x 
Summary of Study Drug Compliance in the PC Period 
Safety/Ext-Ev 
X 
3.2 Adverse Events  
3.2.1.x 
Overall Summary of Treatment-Emergent Adverse Events in the PC 
Period 
Safety/Ext-Ev 
X 
3.2.1.3 
Overall Summary of Treatment-Emergent Adverse Events for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 
3.2.2.x 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term in the PC Period 
Safety/Ext-Ev 
X 
3.2.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term for Participants Who Took 
Only Povorcitinib 45 mg or 75 mg During Study Participation 
Safety 
X 
3.2.3.x 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency in the PC Period 
Safety/Ext-Ev 
X 
3.2.3.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency for Participants 
Who Took Only Povorcitinib 45 mg or 75 mg During Study 
Participation 
Safety 
X 
3.2.4.x 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity in the 
PC Period 
Safety/Ext-Ev 
X 
3.2.4.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and Maximum Severity for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.2.5.x 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and CTCAE Grade Category 
in the PC Period 
Safety/Ext-Ev 
X 
3.2.5.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class, Preferred Term, and CTCAE Grade Category 
for Participants Who Took Only Povorcitinib 45 mg or 75 mg 
During Study Participation 
Safety 
X 
3.2.6.x 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term in the PC 
Period 
Safety/Ext-Ev 
X 
3.2.6.3 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 
3.2.7.x 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency in 
the PC Period 
Safety/Ext-Ev 
X 
3.2.7.3 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 
3.2.8.x 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term in the PC Period 
Safety/Ext-Ev 
X 
3.2.8.3 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term for Participants 
Who Took Only Povorcitinib 45 mg or 75 mg During Study 
Participation 
Safety 
X 
3.2.9.x 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency in the 
PC Period 
Safety/Ext-Ev 
X 
3.2.9.3 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation  
Safety 
X 
3.2.10.x 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term in the 
PC Period 
Safety/Ext-Ev 
X 
3.2.10.3 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 
3.2.11.x 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of 
Frequency in the PC Period 
Safety/Ext-Ev 
X 
3.2.11.3 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of 
Frequency for Participants Who Took Only Povorcitinib 45 mg or 75 
mg During Study Participation 
Safety 
X 
3.2.12.x 
Summary of Grade 3 or Higher Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term in the PC Period 
Safety/Ext-Ev 
X 


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Table No. 
Title 
Population 
Standard 
3.2.12.2 
Summary of Grade 3 or Higher Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term in the Extension Period 
Ext-Ev 
X 
3.2.12.3 
Summary of Grade 3 or Higher Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class and 
Preferred Term for Participants Who Took Only Povorcitinib 45 mg 
or 75 mg During Study Participation 
Safety 
X 
3.2.13.x 
Summary of Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred 
Term in the PC Period 
Safety/Ext-Ev 
X 
3.2.13.3 
Summary of Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred 
Term for Participants Who Took Only Povorcitinib 45 mg or 75 mg 
During Study Participation 
Safety 
X 
3.2.14.x 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term in 
the PC Period 
Safety/Ext-Ev 
X 
3.2.14.3 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Study Participation 
Safety 
X 
3.2.15.x 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Interruption by MedDRA System Organ Class and Preferred Term in 
the PC Period 
Safety/Ext-Ev 
X 
3.2.15.3 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
for Participants Who Took Only Povorcitinib 45 mg or 75 mg 
During Study Participation 
Safety 
X 
3.2.16.x 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ Class 
and Preferred Term in the PC Period 
Safety/Ext-Ev 
X 
3.2.16.3 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ Class 
and Preferred Term for Participants Who Took Only Povorcitinib 45 
mg or 75 mg During Study Participation 
Safety 
X 
3.2.17.x 
Summary of Treatment-Emergent Adverse Events Requiring 
Concomitant Medications by MedDRA System Organ Class and 
Preferred Term in the PC Period 
Safety/Ext-Ev 
X 
3.2.17.3 
Summary of Treatment-Emergent Adverse Events Requiring 
Concomitant Medications by MedDRA System Organ Class and 
Preferred Term for Participants Who Took Only Povorcitinib 45 mg 
or 75 mg During Study Participation  
Safety 
X 
3.3 Laboratory 
3.3.1.1.x 
Summary of Laboratory Values in the PC Period - Hematology  
Safety/Ext-Ev 
X 
3.3.1.1.3 
Summary of Laboratory Values for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Study Participation - 
Hematology 
Safety 
X 
3.3.1.2.x 
Summary of Laboratory Values in the PC Period - Chemistry 
Safety/Ext-Ev 
X 
3.3.1.2.3 
Summary of Laboratory Values for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Study Participation - Chemistry 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.3.1.3.x 
Summary of Laboratory Values in the PC Period - Lipid Panel 
Safety/Ext-Ev 
X 
3.3.1.3.3 
Summary of Laboratory Values for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Study Participation - Lipid 
Panel 
Safety 
X 
3.3.1.4.x 
Summary of Laboratory Values in the PC Period - Urinalysis 
Safety/Ext-Ev 
X 
3.3.1.4.3 
Summary of Laboratory Values for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Study Participation - Urinalysis 
Safety 
X 
3.3.1.5.x 
Summary of Laboratory Values in the PC Period - Thyroid Function 
Markers and Inflammation Marker 
Safety/Ext-Ev 
X 
3.3.1.5.3 
Summary of Laboratory Values for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period - Thyroid 
Function Markers and Inflammation Marker 
Safety 
X 
3.3.2.1.x 
Shift Summary of Hematology Laboratory Values - to the Worst 
Abnormal Value in the PC Period  
Safety/Ext-Ev 
X 
3.3.2.1.3 
Shift Summary of Hematology Laboratory Values - to the Worst 
Abnormal Value for Participants Who Took Only Povorcitinib 45 
mg or 75 mg During Overall Period 
Safety 
X 
3.3.2.2.x 
Shift Summary of Chemistry Laboratory Values - to the Worst 
Abnormal Value in the PC Period 
Safety/Ext-Ev 
X 
3.3.2.2.3 
Shift Summary of Chemistry Laboratory Values - to the Worst 
Abnormal Value for Participants Who Took Only Povorcitinib 45 
mg or 75 mg During Overall Period 
Safety 
X 
3.3.2.3.x 
Shift Summary of Lipid Panel Laboratory Values - to the Worst 
Abnormal Value in the PC Period  
Safety/Ext-Ev 
X 
3.3.2.3.3 
Shift Summary of Chemistry Laboratory Values - to the Worst 
Abnormal Value for Participants Who Took Only Povorcitinib 45 
mg or 75 mg During Overall Period 
Safety 
X 
3.3.3.1.x 
Shift Summary of Hematology Laboratory Values in CTCAE Grade 
- to the Worst Grade Abnormal Value in the PC Period  
Safety/Ext-Ev 
X 
3.3.3.1.3 
Shift Summary of Hematology Laboratory Values in CTCAE Grade 
- to the Worst Grade Abnormal for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.3.3.2.x 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade - 
to the Worst Grade Abnormal Value in the PC Period  
Safety/Ext-Ev 
X 
3.3.3.2.3 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade - 
to the Worst Grade Abnormal for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.3.3.3.x 
Shift Summary of Lipid Panel Laboratory Values in CTCAE Grade - 
to the Worst Grade Abnormal Value in the PC Period  
Safety/Ext-Ev 
X 
3.3.3.3.3 
Shift Summary of Lipid Panel Laboratory Values in CTCAE Grade - 
to the Worst Grade Abnormal for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.3.4.x 
Summary of Potential Clinically Important Laboratory Values by 
Visit in the PC Period 
Safety/Ext-Ev 
 
3.3.4.3 
Summary of Potential Clinically Important Laboratory Values by 
Visit for Participants Who Took Only Povorcitinib 45 mg or 75 mg 
During Overall Period 
Safety 
 
3.3.5.x 
Summary of Potential Drug Induced Liver Injury Events by Visit in 
the PC Period 
Safety/Ext-Ev 
 


Incyte Corporation 
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INCB 54707-206 Statistical Analysis Plan Am 1 
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Table No. 
Title 
Population 
Standard 
3.3.5.3 
Summary of Potential Drug Induced Liver Injury Events by Visit for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Overall Period 
Safety 
 
3.4 Vital Signs 
3.4.1.x 
Summary of Systolic Blood Pressure in the PC Period 
Safety/Ext-Ev 
X 
3.4.1.3 
Summary of Systolic Blood Pressure for Participants Who Took 
Only Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.4.2.x 
Summary of Diastolic Blood Pressure in the PC Period 
Safety/Ext-Ev 
X 
3.4.2.3 
Summary of Diastolic Blood Pressure for Participants Who Took 
Only Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.4.3.x 
Summary of Pulse in the PC Period 
Safety/Ext-Ev 
X 
3.4.3.3 
Summary of Pulse for Participants Who Took Only Povorcitinib 45 
mg or 75 mg During Overall Period 
Safety 
X 
3.4.4.x 
Summary of Respiratory Rate in the PC Period 
Safety/Ext-Ev 
X 
3.4.4.3 
Summary of Respiratory for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.4.5.x 
Summary of Body Temperature in the PC Period 
Safety/Ext-Ev 
X 
3.4.5.3 
Summary of Body Temperature for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period 
Safety 
X 
3.5 ECG 
3.5.1.1.x 
Summary of PR Interval (ms) From 12-Lead ECG by Visit in the PC 
Period 
Safety/Ext-Ev 
X 
3.5.1.2.x 
Summary of QRS Interval (ms) From 12-Lead ECG by Visit in the 
PC Period 
Safety/Ext-Ev 
X 
3.5.1.3.x 
Summary of QT Interval (ms) From 12-Lead ECG by Visit in the PC 
Period 
Safety/Ext-Ev 
X 
3.5.1.4.x 
Summary of QTcF Interval (ms) From 12-Lead ECG by Visit in the 
PC Period 
Safety/Ext-Ev 
X 
3.5.1.5.x 
Summary of Heart Rate (bpm) From 12-Lead ECG by Visit in the 
PC Period 
Safety/Ext-Ev 
X 
3.5.1.6.x 
Summary of Outliers of QT and QTcF Interval Values (ms) From 
12-Lead ECG by Visit in the PC Period 
Safety/Ext-Ev 
X 
3.5.1.7.x 
Summary of Clinically Significant ECG Abnormality by Visit in the 
PC Period 
Safety/Ext-Ev 
X 


Incyte Corporation 
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Figures 
Figure No. 
Title 
Population 
4.1 Primary Efficacy 
4.1.1 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit in the PC Period Using Nonresponder Imputation 
ITT 
4.1.2 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit Using Observed Values 
ITT 
4.1.3.1 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit by IGA Score (3 or 4) in the PC Period 
ITT 
4.1.3.2 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit Gender in the PC Period 
ITT 
4.1.3.3 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit Age Group (< 65, ≥ 65 years) in the PC Period 
ITT 
4.1.3.4 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit Geographical Region in the PC Period 
ITT 
4.2 Secondary Efficacy 
4.2.1 IGA-TS 
4.2.1.1 
Proportion of Participants Achieving IGA-TS by Visit in the PC Period 
Using Nonresponder Imputation 
ITT 
4.2.1.2 
Proportion of Participants Achieving IGA-TS by Visit in the Extension 
Period 
Ext-Ev 
4.2.2 ITCH NRS 
4.2.2.1 
Kaplan-Meier Curve of the Time to ≥ 4-Point Improvement in Itch 
NRS Score by Visit in the PC Period 
ITT 
4.2.2.2 
Proportion of Participants Achieving ≥ 4-Point Improvement in Itch 
NRS Score by Visit in the Extension Period  
Ext-Ev 
4.6 Laboratory 
4.6.1.1.1 
Boxplot of Mean (± SE) of Selected Laboratory Values by Visit and 
Treatment Group in the PC Period  
Safety  
4.6.1.1.2 
Boxplot of Mean (± SE) of Change from Baseline in Selected 
Laboratory Values by Visit and Treatment Group in the PC Period 
Safety  
4.6.1.1.3 
Boxplot of Mean (± SE) of Percent Change from Baseline in Selected 
Laboratory Values by Visit and Treatment Group in the PC Period 
Safety  
4.6.1.2.1 
Boxplot of Mean (± SE) of Selected Laboratory Values by Visit and 
Treatment Group in the Extension Period  
Ext-Ev 
4.6.1.2.2 
Boxplot of Mean (± SE) of Change From Baseline in Selected 
Laboratory Values by Visit and Treatment Group in the Extension 
Period 
Ext-Ev 
4.6.1.2.3 
Boxplot of Mean (± SE) of Percent Change From Baseline in Selected 
Laboratory Values by Visit and Treatment Group in the Extension 
Period 
Ext-Ev 
4.6.1.3.1 
Boxplot of Mean (± SE) of Selected Laboratory Values by Visit and 
Treatment Group for Participants Who Took Only Povorcitinib 45 mg 
or 75 mg During Overall Period - Lipid Panel 
Safety  
4.6.1.3.2 
Boxplot of Mean (± SE) of Change From Baseline in Selected 
Laboratory Values by Visit and Treatment Group Period for 
Participants Who Took Only Povorcitinib 45 mg or 75 mg During 
Overall Period - Lipid Panel 
Safety  


Incyte Corporation 
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INCB 54707-206 Statistical Analysis Plan Am 1 
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CONFIDENTIAL 
Figure No. 
Title 
Population 
4.6.1.3.3 
Boxplot of Mean (± SE) of Percent Change from Baseline in Selected 
Laboratory Values by Visit and Treatment Group for Participants Who 
Took Only Povorcitinib 45 mg or 75 mg During Overall Period - Lipid 
Panel 
Safety  
4.6.2.1.1 
Boxplot of Mean (± SE) of Lipid Panel Values by Visit and Treatment 
Group in the PC Period  
Safety  
4.6.2.1.2 
Boxplot of Mean (± SE) of Change from Baseline of Lipid Panel 
Values by Visit and Treatment Group in the PC Period 
Safety  
4.6.2.1.3 
Boxplot of Mean (± SE) of Percent Change from Baseline of Lipid 
Panel Values by Visit and Treatment Group in the PC Period 
Safety  
4.6.2.2.1 
Boxplot of Mean (± SE) of Lipid Panel Values by Visit and Treatment 
Group in the Extension Period  
Ext-Ev 
4.6.2.2.2 
Boxplot of Mean (± SE) of Change From Baseline of Lipid Panel 
Values by Visit and Treatment Group in the Extension Period 
Ext-Ev 
4.6.2.2.3 
Boxplot of Mean (± SE) of Percent Change From Baseline of Lipid 
Panel Values by Visit and Treatment Group in the Extension Period 
Ext-Ev 
4.6.2.3.1 
Boxplot of Mean (± SE) of Lipid Panel Values by Visit and Treatment 
Group for Participants Who Took Only Povorcitinib 45 mg or 75 mg 
During Overall Period - Lipid Panel 
Safety  
4.6.2.3.2 
Boxplot of Mean (± SE) of Change from Baseline in Lipid Panel 
Values by Visit and Treatment Group for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period - Lipid Panel 
Safety  
4.6.2.3.3 
Boxplot of Mean (± SE) of Percent Change from Baseline of Lipid 
Values by Visit and Treatment Group for Participants Who Took Only 
Povorcitinib 45 mg or 75 mg During Overall Period - Lipid Panel 
Safety  
Listings 
Listing No. 
Title 
2.1 Demographic and Baseline Characteristics 
2.1.1.x 
Participant Enrollment and Disposition Status in the PC Period 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2 Protocol Deviations 
2.2.x 
Protocol Deviations in the PC Period 
2.3 Analysis Populations 
2.3 
Analysis Populations 
2.4 Demographic and Baseline Characteristics (including Prior and Concomitant Medications) 
2.4.1 
Demographic and Baseline Characteristics  
2.4.2 
Disease History 
2.4.3 
Prior Therapy for Prurigo Nodularis 
2.4.4 
Medical History  
2.4.5.1 
Prior and Concomitant Medication in the PC Period 
2.4.5.2 
Concomitant Medication in the Extension Period 
2.5 Drug Compliance 
2.5.1.x 
Study Drug Compliance in the PC Period 
2.5.2.x 
Study Drug Administration in PC Period 


Incyte Corporation 
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Listing No. 
Title 
2.6 Efficacy 
2.6.1.x 
Itch NRS Score and ≥ 4-Point Improvement Responses in the PC Period 
2.6.2.x 
IGA Score and IGA-TS Responses in the PC Period 
2.6.3.x 
Itch NRS and IGA Score in the PC Period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.7 Adverse Events 
2.7.1. 
Adverse Events  
2.7.2.x 
Serious Adverse Events in the PC Period 
2.7.3.x 
Grade 3 and Higher Adverse Events in the PC Period 
2.7.4.x 
Fatal Adverse Events in the PC Period 
2.7.5.x 
Treatment-Related Adverse Events in the PC Period 
2.7.6.x 
Adverse Events Leading to Dose Interruption in the PC Period 
2.7.7.x 
Adverse Events Leading to Discontinuation of Study Drug in the PC Period 
2.8 Laboratory Data 
2.7.8.x 
Adverse Events Requiring Concomitant Medications in the PC Period 
2.8.1.1.x 
Clinical Laboratory Values in the PC Period - Hematology 
2.8.1.2.x 
Clinical Laboratory Values in the PC Period - Chemistry 
2.8.1.3.x 
Clinical Laboratory Values in the PC Period - Lipid Panel 
2.8.1.4.x 
Clinical Laboratory Values in the PC Period - Urinalysis 
2.8.1.5.x 
Clinical Laboratory Values in the PC Period - Thyroid Function Markers and Inflammation 
Marker 
2.8.2.1.x 
Abnormal Clinical Laboratory Values in the PC Period - Hematology 
2.8.2.2.x 
Abnormal Clinical Laboratory Values in the PC Period - Chemistry 
2.8.2.3.x 
Abnormal Clinical Laboratory Values in the PC Period - Lipid Panel 
2.8.2.4.x 
Abnormal Clinical Laboratory Values in the PC Period - Thyroid Function Markers and 
Inflammation Marker 
2.8.3.x 
Potentially Clinically Important Laboratory Values in the PC Period 
2.8.4.x 
Potential Drug Induced Liver Injury Events in the PC Period 
2.9 Vital Signs 
2.9.1.x 
Vital Signs in the PC Period 


Incyte Corporation 
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Listing No. 
Title 
2.9.2.x 
Abnormal Vital Sign Values in the PC Period 
2.9.3.x 
Alert Vital Sign Values in the PC Period 
2.10 ECG 
2.10.1 
12-Lead ECG Values 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.3 
Alert 12-Lead ECG Values