Conditions: Chronic Graft-versus-host Disease
Keywords: Graft-versus-host-disease itacitinib Janus kinase inhibitor corticosteroids
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 155
Healthy volunteers: no

Brief summary:
The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Detailed description:

Arms:
arm 1: itacitinib administered in combination with corticosteroids. arm 2: itacitinib administered in combination with corticosteroids or corticosteroids alone. arm 3: itacitinib or placebo administered in combination with corticosteroids

Interventions: intervention 1: Itacitinib intervention 2: Placebo intervention 3: Methylprednisolone intervention 4: Prednisone
Intervention descriptions: intervention 1: In Part 1dose determination participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 1 expansion, participants will receive either itacitinib administered orally either once daily or twice a day or corticosteroid alone based on the assigned treatment regimen according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1 expansion. intervention 2: In Part 2, participants will receive matching placebo. intervention 3: Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease. intervention 4: Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.

Protocol document:
Prot_000.pdf: 
NCT Number: 
Document Date: 
GRAVITAS-309:  A Phase 2/3 Study of Itacitinib and Corticosteroids 
as Initial Treatment for Chronic Graft-Versus-Host Disease 
NCT03584516
Protocol Amendment Version 8: 30 September 2021
Official Title: 


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TITLE PAGE 
Clinical Study Protocol 
INCB 39110-309 
GRAVITAS-309:  A Phase 2/3 Study of Itacitinib and 
Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host 
Disease 
Product: 
Itacitinib 
IND Number: 
113,428 
EudraCT Number: 
2018-001606-29 
Phase of Study: 
2/3 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Steering Committee: 
Chair:  
, MD 
 
 
Co-chair: 
, MD, MS 
 
Original Protocol (Version 0): 
30 APR 2018 
Amendment (Version) 1: 
16 AUG 2018 
Amendment (Version) 2: 
02 NOV 2018 
Amendment (Version) 3: 
30 NOV 2018 
Amendment (Version) 4: 
07 JUN 2019 
Amendment (Version) 5: 
30 AUG 2019 
Amendment (Version) 6: 
16 DEC 2019 
Amendment (Version) 7: 
03 APR 2020 
Amendment (Version) 8: 
30 SEP 2021 
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 39110-309 Protocol Amendment 8 (Version 8 dated 30 SEP 2021) 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 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................9 
1. 
PROTOCOL SUMMARY ..........................................................................................12 
2. 
INTRODUCTION ......................................................................................................20 
2.1. 
Chronic GVHD Background ......................................................................................20 
2.2. 
Itacitinib Background .................................................................................................20 
2.3. 
Study Rationale ...........................................................................................................21 
2.3.1. 
Scientific Rationale for Study Design ........................................................................21 
2.3.2. 
Justification for Dose ..................................................................................................21 
2.3.2.1. 
Preliminary Results From Part 1.................................................................................22 
2.3.2.2. 
Rationale for Part 1 Expansion ...................................................................................23 
2.3.2.3. 
Preliminary Results for Part 1 Expansion ...................................................................24 
2.3.2.4. 
Dose Modifications for Concomitant Medications .....................................................24 
2.3.2.5. 
Dose Rationale for Organ Impairment .......................................................................26 
2.4. 
Benefit/Risk Assessment ............................................................................................26 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................27 
4. 
STUDY DESIGN .......................................................................................................30 
4.1. 
Overall Design ............................................................................................................30 
4.1.1. 
Part 1 ...........................................................................................................................30 
4.1.2. 
Part 1 Expansion .........................................................................................................30 
4.1.3. 
Part 2 ...........................................................................................................................31 
4.2. 
Overall Study Duration ...............................................................................................32 
4.3. 
Study Termination ......................................................................................................32 
5. 
STUDY POPULATION .............................................................................................33 
5.1. 
Inclusion Criteria ........................................................................................................33 
5.2. 
Exclusion Criteria .......................................................................................................34 
5.3. 
Lifestyle Considerations .............................................................................................35 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................35 
5.3.2. 
Activity .......................................................................................................................35 
5.4. 
Screen Failures ............................................................................................................35 


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5.5. 
Replacement of Participants .......................................................................................36 
6. 
STUDY TREATMENT ..............................................................................................36 
6.1. 
Study Treatments Administered .................................................................................36 
6.1.1. 
Itacitinib/Placebo ........................................................................................................36 
6.1.1.1. 
Preparation, Handling, and Accountability of Itacitinib .............................................37 
6.1.1.2. 
Study Treatment Compliance .....................................................................................38 
6.1.1.3. 
Dose-Limiting Toxicity Assessment ..........................................................................38 
6.1.1.4. 
Determination of the Part 2 Dose ...............................................................................39 
6.1.1.5. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................39 
6.1.1.6. 
Tapering of Itacitinib or Placebo and Treatment Duration .........................................43 
6.1.2. 
Corticosteroids ............................................................................................................44 
6.1.2.1. 
Methylprednisolone ....................................................................................................44 
6.1.2.2. 
Prednisone ...................................................................................................................45 
6.1.2.3. 
Corticosteroid Tapering ..............................................................................................45 
6.1.2.4. 
Management of Corticosteroids During cGVHD Flare ..............................................45 
6.1.3. 
Prophylactic and Supportive Care Medications .........................................................46 
6.2. 
Measures to Minimize Bias:  Randomization and Blinding .......................................46 
6.3. 
Concomitant Medications and Procedures .................................................................46 
6.3.1. 
Permitted Medications and Procedures ......................................................................47 
6.3.2. 
Restricted Medications and Procedures ......................................................................47 
6.3.3. 
Prohibited Medications and Procedures .....................................................................47 
6.4. 
Treatment After the End of the Study .........................................................................48 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................48 
7.1. 
Discontinuation of Study Treatment ...........................................................................48 
7.1.1. 
Reasons for Discontinuation .......................................................................................48 
7.1.2. 
Discontinuation Procedures ........................................................................................49 
7.2. 
Participant Withdrawal From the Study .....................................................................49 
7.3. 
Lost to Follow-Up.......................................................................................................50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................50 
8.1. 
Administrative and General Procedures .....................................................................50 
8.1.1. 
Informed Consent Process ..........................................................................................50 


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8.1.2. 
Screening Procedures ..................................................................................................51 
8.1.3. 
Interactive Voice Response System Procedures .........................................................52 
8.1.4. 
Distribution of Reminder Cards ..................................................................................52 
8.1.5. 
Demography and Medical History ..............................................................................52 
8.1.5.1. 
Demographics and General Medical History .............................................................52 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................52 
8.2. 
Efficacy Assessments .................................................................................................52 
8.2.1. 
Chronic GVHD Staging at Screening .........................................................................52 
8.2.2. 
Chronic GVHD Response Assessment .......................................................................53 
8.2.3. 
Hematologic Disease Relapse Monitoring .................................................................54 
8.2.4. 
Patient-Reported Outcomes ........................................................................................54 
8.3. 
Safety Assessments .....................................................................................................54 
8.3.1. 
Adverse Events ...........................................................................................................54 
8.3.2. 
Physical Examinations ................................................................................................55 
8.3.3. 
Vital Signs ..................................................................................................................55 
8.3.4. 
Karnofsky Performance Status ...................................................................................55 
8.3.5. 
Infection Monitoring ...................................................................................................56 
8.3.6. 
Graft Failure and Chimerism Monitoring ...................................................................56 
8.3.7. 
Electrocardiograms .....................................................................................................57 
8.3.8. 
Laboratory Assessments .............................................................................................57 
8.3.8.1. 
Hematology .................................................................................................................58 
8.3.8.2. 
Serum Chemistry ........................................................................................................58 
8.3.8.3. 
Pregnancy Testing ......................................................................................................59 
8.3.8.4. 
Hepatitis Screening .....................................................................................................59 
8.3.8.5. 
HIV Screening ............................................................................................................59 
8.4. 
Pharmacokinetic Assessments ....................................................................................59 
8.4.1. 
Blood Sample Collection ............................................................................................59 
8.4.2. 
Pharmacokinetic Analysis ..........................................................................................60 
 
60 
8.6. 
Unscheduled Visits .....................................................................................................61 
8.7. 
End of Treatment ........................................................................................................61 
8.8. 
Follow-Up ...................................................................................................................61 
8.8.1. 
Safety Follow-Up ........................................................................................................61 


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8.8.2. 
Post-Treatment GVHD Follow-Up .............................................................................61 
8.8.3. 
Survival Follow-Up ....................................................................................................62 
8.9. 
Data Monitoring Committee .......................................................................................62 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................63 
9.1. 
Definition of Adverse Event .......................................................................................63 
9.2. 
Definition of Serious Adverse Event ..........................................................................64 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........65 
9.4. 
Reporting of Serious Adverse Events .........................................................................67 
9.5. 
Adverse Events of Special Interest .............................................................................68 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................68 
9.7. 
Pregnancy ...................................................................................................................69 
9.8. 
Warnings and Precautions ..........................................................................................69 
9.9. 
Product Complaints ....................................................................................................69 
9.10. 
Treatment of Overdose ...............................................................................................70 
10. 
STATISTICS ..............................................................................................................71 
10.1. 
Sample Size Determination ........................................................................................71 
10.1.1. 
Part 1 ...........................................................................................................................71 
10.1.2. 
Part 1 Expansion .........................................................................................................71 
10.1.3. 
Part 2 ...........................................................................................................................72 
10.2. 
Populations for Analysis .............................................................................................72 
10.3. 
Level of Significance ..................................................................................................73 
10.4. 
Statistical Analyses .....................................................................................................73 
10.4.1. 
Primary Analysis ........................................................................................................73 
10.4.1.1. 
Part 1 and Safety Run-In for Part 1 Expansion ...........................................................73 
10.4.1.2. 
Part 2 ...........................................................................................................................74 
10.4.2. 
Secondary Analysis ....................................................................................................74 
10.4.2.1. 
Part 1 ...........................................................................................................................74 
10.4.2.2. 
Part 1 Expansion .........................................................................................................74 
10.4.2.3. 
Part 2 ...........................................................................................................................75 
10.4.3. 
Safety Analyses ..........................................................................................................76 
10.4.4. 
Pharmacokinetic Analyses ..........................................................................................77 
 
77 


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10.5. 
Interim Analysis ..........................................................................................................77 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................78 
11.1. 
Investigator Responsibilities .......................................................................................78 
11.2. 
Data Management .......................................................................................................79 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................80 
11.4. 
Financial Disclosure ...................................................................................................81 
11.5. 
Publication Policy .......................................................................................................81 
11.6. 
Study and Site Closure................................................................................................82 
12. 
REFERENCES ...........................................................................................................83 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................85 
APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING STUDY 
DRUG (ITACITINIB OR PLACEBO) ......................................................................87 
APPENDIX C. DIAGNOSIS AND STAGING OF CHRONIC GVHD (NIH 
CRITERIA) .................................................................................................................88 
APPENDIX D. STAGING OF CHRONIC GVHD (NIH CRITERIA) ......................................91 
APPENDIX E. RESPONSE ASSESSMENT FOR CHRONIC GVHD 
(NIH CRITERIA) .......................................................................................................95 
APPENDIX F. PATIENT GLOBAL IMPRESSION OF CHANGE AND PATIENT 
GLOBAL IMPRESSION OF SEVERITY .................................................................99 
APPENDIX G. DISEASE RISK INDEX .................................................................................100 
APPENDIX H. PROTOCOL AMENDMENT SUMMARY OF CHANGES .........................102 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints, Part 1 and Part 1 Expansion .............................................12 
Table 2: 
Objectives and Endpoints, Part 2 ................................................................................13 
Table 3: 
Key Study Design Elements .......................................................................................14 
Table 4: 
Schedule of Activities .................................................................................................17 
Table 5: 
Preliminary PK Parameters From Part 1 and Part 1 Expansion by Dose, 
Strong CYP3A Inhibitor Coadministration Status, and Day ......................................25 
Table 6: 
Objectives and Endpoints, Part 1 and Part 1 Expansion .............................................27 
Table 7: 
Objectives and Endpoints, Part 2 ................................................................................29 
Table 8: 
Treatment Groups and Dose Levels and Schedules ...................................................31 
Table 9: 
Study Treatment Information, Part 1 ..........................................................................36 
Table 10: Study Treatment Information, Part 1 Expansion ........................................................37 
Table 11: Study Treatment Information, Part 2 ..........................................................................37 
Table 12: Definitions of Dose-Limiting Toxicity .......................................................................39 
Table 13: Itacitinib Dose Reductions for Part 1..........................................................................40 
Table 14: Itacitinib Dose Reductions for Part 1 Expansion ........................................................40 
Table 15: Itacitinib/Placebo Dose Modification Guidelines .......................................................41 
Table 16: Corticosteroid Treatment Details, Parts 1/1 Expansion and 2 ....................................44 
Table 17: Corticosteroid Tapering Guidelines ............................................................................45 
Table 18: Organ Assessments .....................................................................................................53 
Table 19: Postbaseline Response Evaluations ............................................................................53 
Table 20: Karnofsky Performance Status Scale ..........................................................................56 
Table 21: Clinical Laboratory Analytes ......................................................................................58 
Table 22: Pharmacokinetic Sampling for Part 1, Part 1 Expansion, and Participants 1 
Through 70 in Part 2 ...................................................................................................60 
Table 23: Bayesian Posterior Probability to Demonstrate That There is a Clinically 
Meaningful Difference 
Between Any Itacitinib Group and the 
Corticosteroids-Only Group .......................................................................................71 
Table 24: Populations for Analysis .............................................................................................72 
Table 25: Toxicity Stopping Boundaries ....................................................................................73 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................15 
Figure 2: 
Treatment Phase, Post-Treatment, and Survival Follow-Up ......................................16 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
aGVHD 
acute graft-versus-host disease 
ALL 
acute lymphoblastic leukemia 
allo-HCT 
allogeneic hematopoietic stem cell transplantation 
AML 
acute myeloid leukemia 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC0-24 
Area under the plasma or serum concentration-time curve from time = 0 to 
time = 24 hours 
AUC0-t 
area under the plasma or serum concentration-time curve from time = 0 to the 
last measurable concentration at time = t 
BID 
twice daily 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
cGVHD 
chronic graft-versus-host disease 
CI 
confidence interval 
Cl/F 
apparent oral dose clearance 
CLL 
chronic lymphocytic leukemia 
Cmax 
maximum observed concentration 
CMH 
Cochran-Mantel-Haenszel 
CML 
chronic myelogenous leukemia 
CMV 
cytomegalovirus 
Cmin 
minimum observed plasma or serum concentration over the dose interval 
CNI 
calcineurin inhibitor 
CR 
complete response  
Ctau 
trough concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLI 
donor lymphocyte infusion 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee  
DNA 
deoxyribonucleic acid 
DoR 
duration of response 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 


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Abbreviations and 
Special Terms 
Definition 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOT 
end of treatment  
EQ-5D-3L 
EuroQol EQ-5D 3 level version 
FDA 
Food and Drug Administration 
FEV1% 
forced expiratory volume in 1 second as a percentage of predicted 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GVHD 
graft-versus-host disease 
HBc 
hepatitis B core 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
IB 
Investigator’s Brochure 
ICF 
informed consent form  
ICH 
International Council on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IFN 
interferon 
IL 
interleukin 
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
IVRS 
interactive voice response system 
JAK 
Janus kinase 
ka 
absorption rate 
KPS 
Karnofsky Performance Status 
LFT 
liver chemistry test 
LSS 
Lee Chronic Graft-Versus-Host Disease Symptom Scale 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPN 
myeloproliferative neoplasm 
MR 
malignancy relapse 
NCI 
National Cancer Institute 
NIH 
National Institute of Health 


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Abbreviations and 
Special Terms 
Definition 
NHL 
non-Hodgkin lymphoma 
NRM 
nonrelapse mortality 
OMRS 
Oral Mucosa Rating Scale 
ORR 
overall response rate 
OS 
overall survival 
PBPK 
physiologically based pharmacokinetic 
PCR 
polymerase chain reaction 
PD 
progressive disease  
PFT 
pulmonary function test 
PGIC 
Patient Global Impression of Change 
PGIS 
Patient Global Impression of Severity 
PK 
pharmacokinetic 
PML 
progressive multifocal leukoencephalopathy 
PO 
orally 
PR 
partial response 
QD 
once daily 
QOD 
every other day 
QOL-SF-36 v2 
Quality-of-Life Questionnaire 36-Item Short Form Survey version 2 
RAEB 
refractory anemia with excess blasts 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
STAT 
signal transducer and activator of transcription 
TEAE 
treatment-emergent adverse event, AEs reported for the first time or worsening 
of a pre-existing event after first dose of study treatment 
Tmax 
time to maximum concentration 
TNF 
tumor necrosis factor 
TYK 
tyrosine kinase 
ULN 
upper limit of normal 
V/F 
volume of distribution after oral administration 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  GRAVITAS-309:  A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial 
Treatment for Chronic Graft-Versus-Host Disease 
Protocol Number:  INCB 39110-309 
Objectives and Endpoints:  Table 1 and Table 2 present the objectives and endpoints in 
Parts 1/1 expansion and 2, respectively. 
Table 1: 
Objectives and Endpoints, Part 1 and Part 1 Expansion 
Objectives 
Endpoints 
Primary 
To identify an appropriate dose of itacitinib in 
combination with corticosteroids as initial 
treatment for moderate or severe cGVHD. 
Part 1:  DLT data through Day 28 and additional data from 
clinical safety and laboratory assessments. 
Part 1 expansion:  Incidence and severity of adverse events, 
across treatment cohorts. 
Key Secondary (for Part 1 Expansion) 
To evaluate preliminary activity across treatment 
cohorts with respect to response rate at Month 3 
and Month 6. 
Response rate at Month 3 and Month 6, defined as the 
proportion of participants who demonstrate a CR or PR at 
each timepoint. 
Secondary 
To evaluate the PK of itacitinib when 
administered in combination with corticosteroids 
in the study population. 
Cmax, Cmin, Tmax, AUC0-t, and Cl/F. 
To estimate efficacy outcomes for each treatment 
cohort. 
Part 1:  Response rate at Month 3, 6, and 12. 
Part 1 expansion:  Response rate at Month 12. 
Response rate is defined as the proportion of participants 
who demonstrate either a CR or PR at each timepoint. 
Time to response, defined as the interval between 
randomization and first response. 
DoR, defined as the interval between first response and 
cGVHD progression, death, or initiation of new systemic 
cGVHD therapy. 
OS, defined as the interval between the date of 
randomization and the date of death due to any cause. 
NRM, defined as the proportion of participants who died due 
to causes other than a relapse of their primary hematologic 
disease. 
Proportion of participants with ≥ 50% reduction in daily 
corticosteroid dose at Day 180. 
Proportion of participants successfully tapered off all 
corticosteroids at Day 180. 
Relapse rate of malignant and nonmalignant hematologic 
diseases, defined as the proportion of participants whose 
underlying disease relapses. 
Time to primary hematologic disease relapse, defined as the 
interval between the date of randomization and the date of 
relapse. 


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Table 2: 
Objectives and Endpoints, Part 2 
Objectives 
Endpoints 
Primary 
To compare the efficacy of itacitinib versus placebo in 
combination with corticosteroids as initial treatment for 
moderate or severe cGVHD. 
Response rate at Month 6, defined as the proportion of 
participants demonstrating a CR or PR at Month 6. 
Secondary 
To compare changes in health-related quality of life. 
Changes in symptom scores using the LSS, 
QOL-SF-36 v2, EQ-5D-3L, PGIC, and PGIS. 
To compare additional efficacy outcomes between 
treatment groups. 
Response rate at Month 3 and 12, defined as the 
proportion of participants who demonstrate either a CR 
or PR at each timepoint. 
DoR, defined as the interval between first response and 
cGVHD progression, death, or initiation of new 
systemic cGVHD therapy. 
OS, defined as the interval between the date of 
randomization and the date of death due to any cause. 
NRM, defined as the proportion of participants who 
died due to causes other than a relapse of their primary 
hematologic disease. 
Proportion of participants with ≥ 50% reduction in 
daily corticosteroid dose at Day 180. 
Proportion of participants successfully tapered off all 
corticosteroids at Day 180. 
Relapse rate of malignant and nonmalignant 
hematologic diseases, defined as the proportion of 
participants whose underlying disease relapses. 
Time to primary hematologic disease relapse, defined 
as the interval between the date of randomization and 
the date of relapse. 
To evaluate the PK of itacitinib in combination with 
corticosteroids in 1L cGVHD. 
Cmin in all participants; Cmax, Tmax, AUC0-t, and Cl/F, 
data permitting. 
To evaluate the safety and tolerability of study 
treatment across the 2 treatment cohorts. 
Data from clinical safety assessments (eg, AEs, 
infections) will be listed and tabulated. 
Overall Design: 
Table 3 presents the key study design elements. 


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Table 3: 
Key Study Design Elements 
Study Phase 
Phase 2/3 
Clinical Indication 
Chronic graft-versus-host disease 
Population 
Males and females who are at least 18 years of age who have not previously 
received systemic treatment for moderate or severe cGVHD. 
Number of 
Participants 
Approximately 401 participants will be enrolled in this study.   
In Part 1, approximately 20 participants will be randomized 1:1 to 1 of 
2 treatment groups (10 participants per group).   
In Part 1 expansion, approximately 140 patients will be randomized 1:1 to 1 of 
4 treatment groups (35 participants per group, including those from Part 1 
meeting the criteria). 
In Part 2, approximately 246 participants will be randomized 1:1 to 1 of 
2 treatment groups (123 participants per group). 
Study Design 
Part 1 and Part 1 expansion:  randomized, open-label 
Part 2:  randomized, double-blind, placebo-controlled 
Estimated Duration 
of Study 
Participation 
It is estimated that an individual participant may participate for as long as 
38 months, which includes the following:   
• up to 28 days for screening. 
• continuous treatment until treatment withdrawal criteria are met or for a 
maximum of 36 months. 
• a minimum of 30 days for safety follow-up. 
• post-treatment cGVHD follow-up for participants who completed 
itacitinib/placebo taper after initial response (CR or PR) or discontinued 
early for reasons other than cGVHD progression and with no requirement for 
new systemic cGVHD therapy (for a maximum of 24 months from Day 1). 
• participants will be followed for survival until the participant dies or 
withdraws consent. 
Treatment Groups and Duration: 
Part 1 is a run-in that will employ a randomized, open-label, parallel-cohort design to assess the 
safety and tolerability of itacitinib in combination with corticosteroids (Figure 1).  A total of 
20 participants with moderate or severe cGVHD will be randomized 1:1 to itacitinib 200 mg QD 
plus corticosteroids or 300 mg QD plus corticosteroids.   
Part 1 expansion is a Phase 2 with an initial safety run-in that will employ a randomized, 
open-label, parallel-cohort design to assess the safety and preliminary efficacy of itacitinib in 
combination with corticosteroids compared with corticosteroids monotherapy and select the 
appropriate dosing/schedule of itacitinib for Part 2 (Figure 2).  A total of 140 participants 
(including those from Part 1) with moderate or severe cGVHD will be randomized 1:1 to 1 of 
4 treatment groups that are itacitinib 300 mg QD plus corticosteroids (Treatment Group A), 
itacitinib 400 mg QD plus corticosteroids (Treatment Group B), itacitinib 300 mg BID plus 
corticosteroids (Treatment Group C) or corticosteroids monotherapy (Treatment Group D).  
Treatment Group C was discontinued as of Amendment 8.  Randomization will be stratified by 


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cGVHD risk status (moderate vs severe).  Treatment Groups B and C will have an initial safety 
run-in of 10 participants each to determine safety and tolerability of the dose before expanding. 
Itacitinib treatment will continue until treatment failure (cGVHD progression, death, or initiation 
of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent and for a 
maximum of 36 months. 
Part 2 will employ a randomized, double-blind, placebo-controlled design in order to assess the 
efficacy of itacitinib in combination with corticosteroids using the dose determined to be safe 
and tolerable in the Part 1 expansion (Figure 1 and Figure 2).  Randomization will be stratified 
by cGVHD risk status (moderate vs severe).  Participants randomized to the placebo group will 
be permitted to cross over to the experimental group after completion of the primary analysis as 
appropriate.  All participants will be followed for survival after completion of study treatment. 
Figure 1: 
Study Design Schema 
 
Note: Treatment Group C discontinued as of SEP 2021. 


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Figure 2: 
Treatment Phase, Post-Treatment, and Survival Follow-Up 
 
Adherence to the study design requirements, including those specified in the schedule of 
activities (Table 4), is essential and required for study conduct. 


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Table 4: 
Schedule of Activities 
Visit Day (Range) 
Screening 
Treatment 
Follow-Up 
Notes 
Safety 
GVHDa 
Survival 
Day -28 
to -1 
D1 D7 D14 D21 
D28/56/84/ 
112/140/168 D180 
D196+ 
(Q28D/Q8W)b 
EOT 
Last Dose 
+ 30 days 
Q28D/ 
Q8Wc  
Q8W 
From 
EOT 
Visit Window 
 
 
± 3 days 
± 7 days 
+ 5 days 
± 7 days ± 14 days  
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
X 
X 
X 
X 
 
 
 
Randomize using IVRS 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Contact IVRS/dispense 
study drug 
 
X 
 
 
 
X 
 
X 
X 
 
 
 
 
Administer study drug 
 
X 
 
 
 
 
Hold treatment on clinic visit 
days until blood draws 
complete 
Administer corticosteroids 
 
X 
 
 
 
 
 
Distribute reminder cards 
 
X 
 
 
 
 
 
Monitor study drug 
compliance 
 
X 
X 
 
 
 
 
Monitor corticosteroid use 
 
X 
X 
 
 
 
 
Safety assessments 
AE assessments 
X 
X 
X 
X 
 
 
 
Physical exam/vitals/weight 
X 
X 
X 
X 
X* 
 
*Only weight 
KPS 
X 
X 
X 
X 
 
 
 
Infection monitoring 
X 
X* 
X* 
X* 
 
 
*As clinically indicated 
 
Graft failure/chimerism* 
Xd 
X* 
X* 
X* 
X* 
 
*As clinically indicated  
12-lead ECG 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Efficacy assessments 
cGVHD diagnosis and 
staging 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
cGVHD response 
 
Xf 
 
X 
 
X 
X 
X 
X 
Xa 
Xa 
 
 


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Table 4: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening 
Treatment 
Follow-Up 
Notes 
Safety 
GVHDa 
Survival 
Day -28 
to -1 
D1 D7 D14 D21 
D28/56/84/ 
112/140/168 D180 
D196+ 
(Q28D/Q8W)b EOT 
Last Dose 
+ 30 days 
Q28D/ 
Q8Wc  
Q8W 
From 
EOT 
Visit Window 
 
 
± 3 days 
± 7 days 
+ 5 days 
± 7 days ± 14 days  
FEV1% (from PFTs) 
X 
Xg 
 
 
 
X* 
X 
X** 
X 
X 
X** 
 
*Day 168 FEV1% may be 
omitted. 
**Q8W starting at Day 196 
up to 1 year (ie, Days 252, 
308, and 364) then Q16 
weeks.  Day 196 may be 
omitted. 
Disease/malignancy relapse 
X 
X* 
*As clinically indicated. 
LSS 
 
Xh 
 
 
 
X 
X 
X 
X 
 
 
 
Part 2 only. 
QOL-SF-36 v2 
 
Xh 
 
 
 
X* 
X 
X** 
X 
 
 
 
Part 2 only. 
* Day 168 may be omitted. 
**Day 196 may be omitted. 
EQ-5D-3L 
 
Xh 
 
 
 
X* 
X 
X** 
X 
 
 
 
PGIC 
 
 
 
 
 
X* 
X 
X** 
X 
 
 
 
PGIS 
 
Xh 
 
 
 
X* 
X 
X** 
X 
 
 
 
New cGVHD therapy data 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Survival assessment 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Laboratory assessments 
Hematology 
X 
Xh  
X 
X 
X 
X 
X 
Q28D 
X 
X 
 
 
 
Serum chemistry 
X 
Xh 
X 
X 
X 
X 
X* 
Q28D 
X 
X 
X* 
 
*Total bilirubin, ALT, and 
ALP. Direct and indirect 
bilirubin also required for 
participants with elevated 
total bilirubin. 
Lipid panel 
X 
Xh 
X 
X 
X 
X 
 
X 
X 
X 
 
 
 
Serum pregnancy testing 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Serum or urine pregnancy 
testing 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
Hepatitis screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK sampling (Part 1 and 
Part 1 expansion) 
 
X 
X 
 
 
X 
 
 
 
 
 
 
D1/7/28 only 
(predose, 1, 2, 5 h) 
*Treatment Group D in 
Part 1 expansion does not 
require PK sampling. 


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Table 4: 
Schedule of Activities (Continued) 
Visit Day (Range) 
Screening 
Treatment 
Follow-Up 
Notes 
Safety 
GVHDa 
Survival 
Day -28 
to -1 
D1 D7 D14 D21 
D28/56/84/ 
112/140/168 D180 
D196+ 
(Q28D/Q8W)b EOT 
Last Dose 
+ 30 days 
Q28D/ 
Q8Wc  
Q8W 
From 
EOT 
Visit Window 
 
 
± 3 days 
± 7 days 
+ 5 days 
± 7 days ± 14 days  
PK sampling (Part 2) 
 
X 
X 
 
 
X 
 
 
 
 
 
 
Participant 1-70:  D1/7/28 
(predose, 1, 2, 5 h). 
Participant 71-246:  D7/28 
(predose only). 
a Only for participants who completed itacitinib/placebo taper after an initial response (CR or PR) or discontinue early for reasons other than cGVHD disease progression and with 
no requirement for new cGVHD therapy (for a maximum of 24 months from Day 1). 
b Every 28 days (± 7 days) up to 1 year (D364) from Day 1 and then every8 weeks (± 7 days), with the exception of hematology and serum chemistry, which will be performed 
every 28 days during the entire treatment period. 
c Every 28 days (± 7 days) up to 1 year (D364) from Day 1 and then every 8 weeks (± 7 days) up to 2 years from Day 1. 
d Chimerism testing can be performed on Day 1 before study drug administration.  Results are not required for randomization and treatment. 
e Chronic GVHD staging (see criteria in Appendix C) performed at screening will be used for eligibility assessment and stratification purposes 
f Chronic GVHD organ score and overall severity score 0 to 10 (see criteria in Appendix E) will be performed on Day 1, and this will be the baseline for cGVHD response 
assessment during treatment and post-treatment follow-up. 
g FEV1% performed within 7 days of Day 1 can be used for cGVHD response assessment if bronchiolitis obliterans was not diagnosed at screening. 
h May be performed within 7 days of Day 1.  If liver cGVHD is diagnosed at screening, total bilirubin, ALT, and ALP should be repeated on Day 1. 
 


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2. 
INTRODUCTION 
2.1. 
Chronic GVHD Background 
Allogeneic hematopoietic stem cell transplantation is an effective immunotherapy for patients 
with blood-related malignancies and hematologic disorders.  More than 32,000 allo-HCTs are 
performed each year worldwide, primarily for the treatment of hematologic malignancies 
(Niederwieser et al 2016).  Acute GVHD (aGVHD) and cGVHD remain major contributors to 
transplantation-related deaths and are the most significant barrier to successful allo-HCT.  
GVHD pathogenesis is driven by a number of risk factors, including donor/recipient HLA 
mismatch, increased age (donor or recipient), sex, intensity of the pretransplant conditioning 
regimen, and donor source (Jagasia et al 2012, Flowers et al 2011).  In short, donor-derived 
immune cells recognize the transplant recipient as foreign, which leads to an inflammatory 
cascade and proliferation of immune effector cells.  Left uncontrolled, these processes can lead 
to extensive tissue damage and potential organ failure in the transplant recipient (Holtan 
et al 2014). 
The prevalence and severity of cGVHD, occurring in 30% to 70% of allo-HCT patients (Lee and 
Flowers 2008) has increased over the past 2 decades due to several factors, including the 
increased use of mobilized peripheral blood stem cell grafts (containing higher numbers of donor 
T-cells than BM), advanced age of transplant recipients rising from 55 to 75 years due to 
development of better tolerated reduced intensity conditioning, and improvements in survival 
during the first months after allo-HCT.  Chronic GVHD is classified into mild, moderate, and 
severe categories based on the degree of organ involvement according to NIH Consensus 
Criteria; approximately 50% of patients diagnosed with cGVHD have disease present in 3 or 
more organ systems (Jagasia et al 2015).  Standard initial treatment of moderate and severe 
cGVHD includes systemic corticosteroids at a prednisone dose ranging between 0.5 to 1 mg/kg 
per day and may also include cyclosporine, tacrolimus, or sirolimus.  Prolonged exposure to high 
doses of corticosteroids has been associated with a number of significant AEs, requiring 
clinicians to initiate a corticosteroid taper once responses are observed.  Approximately half of 
cGVHD patients are able to discontinue corticosteroids within the first 7 years of treatment; 
10% require prolonged treatment beyond 7 years, and the remaining 40% develop MR or die due 
to non–relapse-related causes within the first 7 years (Martin et al 2015). 
2.2. 
Itacitinib Background 
Itacitinib adipate is a novel, potent, and selective inhibitor of the JAK family of protein tyrosine 
kinases with selectivity for JAK1.  Itacitinib is an investigational product that is proposed for 
development for treatment of MPNs, including MF; inflammatory diseases, including 
rheumatoid arthritis and psoriasis; GVHD; solid tumors; and B-cell malignancies.  Janus kinases 
play an important role in signal transduction following cytokine and growth factor binding to 
their receptors.  Aberrant production of cytokines and growth factors has been associated with 
MPNs and a number of chronic inflammatory conditions, and JAK1 has been shown to cooperate 
with other JAKs to mediate the signaling of a number of inflammatory cytokines.  Therefore, 
JAK inhibitors represent potential therapeutic agents for these disease states.  Additional 
information can be found in the IB. 


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2.3. 
Study Rationale 
2.3.1. 
Scientific Rationale for Study Design 
The scientific rationale for evaluating itacitinib in moderate or severe cGVHD patients is based 
on current knowledge of cGVHD pathogenesis.  Tissue damage and inflammation characterized 
by proinflammatory cytokine release is observed following allo-HCT; these cytokines, along 
with luminal damage-associated molecular patterns and pathogen-associated molecular patterns, 
drive the activation of host APCs.  Activated host APCs then present host antigens to donor 
immune cells, leading to an adverse cycle of donor T-cell proliferation, expansion of T-effector 
cells, and additional inflammatory cytokine production.  Cytokine dysregulation has also been 
implicated through observations that high levels of IL-1β, IFNγ, and TNF-α are associated with 
more severe cGVHD (Socié and Ritz 2014).  Until recently, cGVHD was believed to be a 
Th2-mediated disease, but recent findings also implicate Tc/Th17, particularly in cGVHD 
presenting with sclerodermatous skin and oral mucosa features.  Nonetheless, the mechanism(s) 
by which IL-17 and other proinflammatory cytokines coproduced by Tc17/Th17 contribute to the 
pathogenesis of cGVHD are not well-understood and require further research (MacDonald et al 
2017). 
Overall response rate at Month 6 was chosen as a primary endpoint for Part 2 in order to evaluate 
durability of response; longer term outcomes will also be assessed to better understand the 
relationships between baseline disease status, patient-reported outcomes, and response.  A 
placebo-controlled design implemented in Part 2 will aid in distinguishing the effects of itacitinib 
versus concomitant background treatment once the appropriate dose and schedule is confirmed in 
Part 1 expansion (Martin et al 2015). 
The study patient population is composed of patients with various hematologic diseases and 
expected to be heterogeneous for individual primary disease and allo-HCT characteristics.  
Exploratory subgroup analysis will be performed, as described in Section 10.4. 
2.3.2. 
Justification for Dose 
In a Phase 1 study (INCB 39110-108) that assessed the safety and tolerability of itacitinib in 
combination with corticosteroids, 30 aGVHD participants were randomized to 1 of 2 treatment 
cohorts (200 mg cohort, n = 14; 300 mg cohort, n = 16).  One participant was randomized to the 
300 mg cohort but withdrew from the study before starting treatment.  The Day 28 ORR in 
first-line aGVHD participants in both treatment cohorts was 83.3%; for participants with 
steroid-refractory aGVHD, the ORR at Day 28 was 64.7% (200 mg cohort, 62.5%; 300 mg 
cohort, 66.7%).  One DLT of Grade 3 thrombocytopenia was reported in 1 participant with 
pre-existing thrombocytopenia who was randomized to the 300 mg cohort.  Adverse events 
reported in greater than 20% of all participants include diarrhea, hypokalemia, peripheral edema, 
hyperglycemia, abdominal pain, hypophosphatemia, fatigue, headache, hypomagnesemia, and 
sepsis.  Thrombocytopenia and platelet count decreased were observed in 24.2% and 20.7% of 
participants, respectively, with a higher proportion of these events occurring in the 300 mg 
cohort, although a higher incidence of pre-existing thrombocytopenia was also observed in this 
group.  Among both dose groups (200 mg and 300 mg QD), itacitinib was generally 
well-tolerated with an AE profile as expected given previous experience in other populations, 
underlying disease, and/or concomitant therapy.  


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Doses of 200 mg QD and 300 mg QD were originally supported based on literature data.  In a 
study evaluating ruxolitinib, a JAK1/2 inhibitor, in patients with steroid refractory acute GVHD 
(n = 54), the ORR was 81.5% (Zeiser et al 2015).  In this study, ruxolitinib was given at doses of 
5 to 10 mg BID in most patients.  Average inhibition of IL-6 stimulated phosphorylation of 
STAT3, a measure of JAK inhibition, over the dosing interval, following 5 mg BID or 10 mg 
BID was 21.5% and 31.6%, respectively.  Based on a PK/pharmacodynamics model for itacitinib 
using the same biomarker, the predicted average JAK inhibition over the dosing interval after 
100 mg QD, 200 mg QD, and 300 mg QD dosing was 18.0%, 26.9%, and 41.1%, 
respectively.  Given the historical data with ruxolitinib in GVHD patients and the 
PK/pharmacodynamics data for itacitinib, starting doses of 200 mg QD and 300 mg QD were 
chosen, as 100 mg QD is expected to result in JAK inhibition below what has previously been 
shown to be effective. 
Based on collected data in the GVHD indication, doses of 200 mg and 300 mg QD result in 
systemic JAK1 inhibition that may have therapeutic benefit and are generally well-tolerated in 
GVHD patients.  Therefore, doses of 200 mg QD and 300 mg QD are being explored in Part 1 of 
this study. 
2.3.2.1. 
Preliminary Results From Part 1 
Preliminary data from Part 1 was reviewed by an independent DMC.  At the data cutoff date for 
the DMC review (20 SEP 2019), 21 participants had been enrolled in the study in the 200 mg 
QD dose cohort (n = 11) or 300 mg QD dose cohort (n = 10); of them, 20 participants (10 in each 
dose cohort) had completed 28 days on study at that timepoint.  The median duration of exposure 
was 50 days (range:  5-246 days) in the 200 mg dose cohort and 70 days (range:  29-200 days) in 
the 300 mg dose cohort. 
The most common TEAEs were thrombocytopenia/platelet count decrease reported in 9 of 
21 participants (43%), including 4 of 11 participants (36%) in the 200 mg dose cohort and 5 of 
10 participants (50%) in the 300 mg dose cohort.  The most commonly reported nonhematologic 
TEAEs were muscular weakness (24%), CMV infection, diarrhea, fatigue, headache, pyrexia, 
and blood creatinine increased (19% each).  The frequency of these events were generally 
consistent across dose cohorts.  A total of 5 participants (3 in the 200 mg dose cohort and 2 in the 
300 mg dose cohort) experienced an AE that led to itacitinib interruption, specifically, platelet 
count decrease (2 participants) and febrile neutropenia, pneumonia, sinusitis, and hyperkalemia 
(1 participant each).  TEAEs that required itacitinib dose reduction were reported in 
4 participants (2 participants in each dose cohort) and was thrombocytopenia/platelet count 
decrease in all cases, associated with microangiopathy in 1 participant.  One participant in the 
200 mg dose cohort discontinued itacitinib due to Grade 3 thrombocytopenia. 
Dose-limiting toxicities as assessed by investigator were Grade 3 hyperkalemia in 1 participant 
with pre-existing hyperkalemia at baseline enrolled in the 200 mg dose cohort and Grade 4 
thrombocytopenia in 1 participant enrolled in the 300 mg dose cohort. 
Pharmacokinetics of itacitinib were evaluated using plasma samples collected predose and at 1, 
2, and 5 hours postdose on Days 1, 7, and 28.  Based on preliminary data, itacitinib displayed 
dose-dependent exposure.  Maximal exposure occurred 2 to 3 hours postdose across doses and 
PK sampling days.  Exposures were increased in participants on potent CYP3A4 inhibitors 
(mainly posaconazole) compared to those who were not, 1.6 to 2.9× increase across both doses.  


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This is similar to the magnitude of increase in exposure observed in aGVHD patients when 
comparing patients concomitantly on a potent inhibitor (mainly posaconazole) to those who were 
not (1.7-2.9×; DMB-18.60.1). 
The DMC recommended that 300 mg QD be chosen as the Part 2 dose of itacitinib as no 
differences emerged between the doses with respect to toxicity. 
2.3.2.2. 
Rationale for Part 1 Expansion 
Additional dosing regimens of itacitinib were selected for evaluation in combination with 
corticosteroids in an expansion to Part 1 of the study based on the following rationale: 
• Study INCB39110-301 was a randomized, double-blind, placebo-controlled Phase 3 
study evaluating itacitinib or placebo, in combination with corticosteroids, as a 
first-line treatment for participants with aGVHD. A total of 439 participants were 
randomized 1:1 to receive either itacitinib or placebo.  The primary endpoint was 
ORR at Day 28, and the key secondary endpoint was nonrelapse mortality at Month 
6.  Although there was a higher ORR for itacitinib versus placebo (74.0% vs 66.4%, 
respectively), the result was not statistically significant (p = 0.08), and there was no 
difference in nonrelapse mortality (approximately 18% in both arms).  There was a 
trend favoring itacitinib with regards to the rate of complete response (53% vs 41%, 
respectively); however, this was an unplanned, exploratory sensitivity analysis.  The 
safety profile observed in GRAVITAS-301 was consistent with that observed in 
previously reported studies of itacitinib in combination with corticosteroids, and no 
new safety signals were identified.  A preliminary exposure/response analysis 
demonstrated a statistically significant relationship between steady-state exposure and 
Day 28 ORR with response rates in participants in the upper tertile of exposure (ie, 
AUC > ~6500 nM∙h) predicted to be > 90%. 
• Preliminary exposure data from 21 participants enrolled in Part 1 of the current study 
showed that the majority (14/21) of participants had AUC ≤ 10,000 nM∙h.  
Participants with relatively high exposures (AUCτ > 20,000 nM∙h) experienced 
Grade 3/4 AEs, mainly thrombocytopenia, that were manageable with dose reductions 
and/or discontinuations. 
• At a dose of itacitinib of 400 mg QD, the predicted AUC in participants with chronic 
GVHD is approximately 20,000 nM∙h.  At a dosing/schedule of itacitinib of 300 mg 
BID, the Cmax is predicted to be comparable with the observed value of 300 mg QD, 
with a higher daily AUC and trough approximately 3 times higher with BID dosing 
compared with QD; supporting more sustained inhibition of the target throughout the 
dosing interval.  
• Itacitinib doses as high as 400 mg BID and 600 mg QD have been studied in other 
patient populations, for example, rheumatoid arthritis, plaque psoriasis, and 
myelofibrosis and were well-tolerated with manageable AEs (additional information 
can be found in the IB). 
Considering the dose range and the corresponding safety profile across patients with acute and 
chronic GVHD and other autoimmune and oncology populations, doses of 400 mg QD and 
300 mg BID were selected for further evaluation in an expansion to Part 1 of the 


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study (additional dose cohorts of 35 participants each).  The original cohort of 300 mg QD will 
also be expanded to provide a more robust safety and efficacy assessment of this dose level; 
Part 1 expansion will also include 1 cohort of corticosteroids as single-agent for a contemporary 
comparison of the safety and efficacy of each combination cohort.  Data from Part 1 expansion 
will guide dose selection for Part 2 of the study. 
Itacitinib doses should be adjusted to maintain a consistent exposure with concomitant use of a 
strong CYP3A inhibitor; see Section 6.1.1.5 for more information. 
2.3.2.3. 
Preliminary Results for Part 1 Expansion 
Preliminary data from the Part 1 expansion was reviewed ad hoc by an independent DMC.  At 
the data cutoff date for the ad hoc DMC review (09 JUL 2021), 107 participants had been 
enrolled in the Part 1 expansion portion of the study in the 300 mg QD dose cohort (Treatment 
Group A; n = 32), 400 mg QD dose cohort (Treatment Group B; n = 25), 300 mg BID dose 
cohort (Treatment Group C; n = 24), and corticosteroid monotherapy dose cohort (Treatment 
Group D; n = 26).  The median duration of exposure was 83 days (range:  2-579 days) across the 
itacitinib treatment groups.  At the time of the data cutoff, 62 participants remained on treatment 
across the 4 treatment groups. 
Malignancy relapse was the most frequent reason for discontinuation in Treatment Group C 
(itacitinib 300 mg BID in combination with corticosteroids). Although no interim analysis was 
planned, and the number of participants was small, with 4 confirmed relapses reported in this 
cohort versus 1 relapse in each of the 300 mg QD and 400 mg QD cohorts and no relapse in the 
corticosteroids alone cohort, the sponsor had decided, following the DMC recommendation, to 
discontinue the itacitinib 300 mg BID study arm. 
2.3.2.4. 
Dose Modifications for Concomitant Medications 
Observed data from Study INCB 39110-108 suggest that there is an approximate 2-fold increase 
in exposure when itacitinib is coadministered with a potent CYP3A4 inhibitor (posaconazole in 
the majority of cases; DMB-18.60.1).  This was further supported by preliminary data from 
Study INCB 39110-301, in which the magnitude of increase in itacitinib exposure with 
coadministration of strong CYP3A inhibitors (ie, posaconazole or voriconazole) was 1.65- to 
2.55-fold (DMB-20.35.1).  However, preliminary PK data from Part 1 and the Part 1 expansion 
in this current study in participants with cGVHD demonstrated a larger impact of the strong 
CYP3A inhibitors than observed in the aGVHD population.  From Table 5, it can be seen that the 
current dose reductions did not normalize the exposure within a given treatment arm.  For 
example, a dose reduction to 300 mg QD with concomitant administration of a strong CYP3A 
inhibitor resulted in a geometric mean AUC0-24 that was still 2.4 to 2.9 times greater than that of 
the 400 mg QD dose administered without a strong CYP3A inhibitor.  Similarly, a dose reduction 
to 200 mg QD with a strong CYP3A inhibitor resulted in an exposure 2.3 to 2.4 times that of the 
300 mg QD dose alone.  From Table 5, however, a dose of 200 mg QD with a strong CYP3A 
inhibitor has an exposure that approximates that of 400 mg QD alone.  In this patient population 
(ie, cGVHD), a greater dose reduction is recommended when coadministering itacitinib with a 
strong CYP3A inhibitor; 400 mg QD to 200 mg QD or 300 mg QD to 100 mg QD.  More 
detailed dosing information is provided in Table 13 and Table 14. 


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Table 5: 
Preliminary PK Parameters From Part 1 and Part 1 Expansion by Dose, Strong CYP3A Inhibitor 
Coadministration Status, and Day 
Day 
200 mg QD 
300 mg QD 
400 mg QD 
200 mg BID 
300 mg BID 
No 
Yes 
No 
Yes 
No 
Yes 
No 
Yes 
No 
Yes 
AUC0-24 
7 
4230 (2370), 
3720 [6] 
14,800 
(10,800), 
11,400 [16] 
5850 (3980), 
4680 [15] 
29,500 
(14,300), 
25,500 [11] 
10,200 
(5250), 8800 
[13] 
23,700 
(28,700), 
13,600 [3] 
— 
38,200 
(24,600), 
32,600 [8] 
14,880 
(10,280), 
12,120 [9] 
— 
28 
6300 (4230), 
5220 [6] 
15,100 
(7630), 
13,300 [15] 
6670 (3730), 
5690 [10] 
29,900 
(17,200), 
21,200 [12] 
10,300 
(5690), 8880 
[10] 
— 
— 
40,800 
(34,200), 
32,000 [4] 
19,020 
(11,260), 
16,740 [7] 
— 
Cmax 
7 
610 (348), 
538 [6] 
1600 (934), 
1360 [16] 
821 (511), 
673 [15] 
3370 (927), 
3240 [11] 
1750 (1440), 
1340 [13] 
2910 (3130), 
1940 [3] 
— 
2320 (1050), 
2160 [8] 
1510 (875), 
1280 [9] 
— 
28 
833 (391), 
754 [6] 
1710 (633), 
1580 [15] 
1060 (509), 
939 [10] 
3480 (1780), 
2390 [12] 
1490 (714), 
1310 [10] 
- 
— 
2910 (2230), 
2370 [4] 
1830 (919), 
1660 [7] 
— 
Ctau 
7 
127 (279), 
24.2 [6] 
218 (501), 
87.4 [16] 
58.3 (124), 
20.8 [15] 
245 (201), 
153 [11] 
99.8 (178), 
43.2 [13] 
99.7 (146), 
39.9 [3] 
— 
1170 (1040), 
718 [8] 
258 (395), 
114 [9] 
— 
28 
86.8 (134), 
31.0 [6] 
133 (165), 
81.0 [15] 
22.2 (27.1), 
15.0 [10] 
237 (312), 
139 [12] 
51.0 (60.9), 
29.9 [10] 
— 
— 
916 (887), 
622 [4] 
297 (303), 
205 [7] 
— 
Note:  No and yes represent without and with strong CYP3A inhibitor coadministration, respectively. 
Note:  Data presented as mean (SD), geometric mean [n]. 


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The solubility of itacitinib is > 1.10 mg/mL (and therefore > 200 mg/250 mL or 300 mg/250 mL) 
at pH values up to 4.3.  In most cases of treatment with gastric acid–reducing agents, the target 
pH is approximately 4, and in those situations, there should not be any significant impact on the 
absorption of itacitinib.  The lack of impact of gastric pH–modifying agents was supported 
through graphical analysis and modeling of observed data along with PBPK modeling.  No dose 
modification of itacitinib is recommended in participants concomitantly taking gastric pH 
modifying agents. 
2.3.2.5. 
Dose Rationale for Organ Impairment 
A  population PK model in participants with aGVHD indicates that mild hepatic impairment has 
no impact on the PK of itacitinib.  Therefore, no dose modification is recommended in 
participants with mild hepatic impairment in cGVHD.  Data are insufficient to evaluate the 
impact of moderate or severe hepatic impairment using a modeling approach.  Given the limited 
data in patients with moderate to severe hepatic impairment, while acknowledging several 
participants from Study INCB 39110-108 did have severe hepatic impairment with no significant 
impact on itacitinib PK, no dose modification is recommended in participants with moderate 
hepatic impairment.  Participants with hepatic impairment not due to cGVHD (ie, those with 
persistent total bilirubin > 2 mg/dL) are excluded.  Participants with hepatic impairment due to 
cGVHD may potentially benefit from study treatment, with improvement of their liver function.  
The benefit from treatment could outweigh the risk; therefore, participants with hepatic 
impairment due to cGVHD may be enrolled in the study under close monitoring for response to 
treatment and liver function improvement. 
The population PK model indicates that there is also no impact of mild or moderate renal 
impairment on the PK of itacitinib.  Therefore, no dose adjustment is recommended in 
participants with mild or moderate renal impairment.  Participants with severe renal impairment, 
that is, creatinine clearance ≤ 30 mL/min, are excluded from the study. 
Pharmacokinetics data from Part 1 of this study will be analyzed and used to refine the starting 
dose in Part 2.  
2.4. 
Benefit/Risk Assessment 
The potential benefit for itacitinib in moderate to severe cGVHD patients is based on available 
preclinical data demonstrating inhibition of the JAK/STAT pathway implicated in the previously 
described pathogenesis of cGVHD. 
Risks to study participants may be minimized by compliance with the eligibility criteria and 
study procedures as well as close clinical monitoring and adherence to dose modification 
guidelines for toxicity.  Risks related to myelosuppression and bleeding should be further 
managed in accordance to standard institutional practices for administration of hematopoietic 
growth factors and transfusion support.  Risks related to infections should be managed through 
continued prophylaxis and prompt identification and treatment. 
Progressive multifocal leukoencephalopathy (PML) is a rare complication in allo-HCT 
recipients.  Actions to minimize the risk of PML in cGVHD participants will follow standard 
allo-HCT guidelines, including close monitoring of any clinical signs of progressive focal 


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neurological symptoms, with prompt diagnostic work-up and treatment.  Any case of PML 
should be reported as per the process described in Section 9.4. 
Recent animal studies of itacitinib in rats showed development of benign tumors in the thyroid of 
rats, called follicular adenomas, and hibernomas. Follicular adenomas are benign lesions 
consisting of a type of cells in the thyroid gland called follicular cells. In humans, hibernomas 
are rare, benign tumors consisting of brown fat tissue. The relevance of these animal findings to 
humans is unclear.  Among participants who received itacitinib in clinical trials, there was no 
case of thyroid tumor reported thus far. 
Treatment Group C (itacitinib 300 mg BID in combination with corticosteroids) was 
discontinued in this study after review of preliminary data due to a potential safety issue of 
increased malignancy relapse.  Although no interim analysis was planned and the number of 
participants is small, with 4 confirmed relapses reported in this cohort versus 1 relapse in each of 
the 300 mg QD and 400 mg QD cohorts and no relapse in the corticosteroids alone cohort), the 
sponsor had decided to discontinue the itacitinib 300 mg BID study arm. 
There may be unforeseen and potentially serious risks with itacitinib.  More detailed information 
about the known and expected benefits and risks and reasonably expected AEs of itacitinib may 
be found in the IB. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 6 and Table 7 present the objectives and endpoints in Parts 1/1 expansion and 2, 
respectively. 
Table 6: 
Objectives and Endpoints, Part 1 and Part 1 Expansion 
Objectives 
Endpoints 
Primary  
To identify an appropriate dose of itacitinib in 
combination with corticosteroids as initial 
treatment for moderate or severe cGVHD. 
Part 1:  DLT data through Day 28 and additional 
data from clinical safety and laboratory 
assessments. 
Part 1 expansion:  Incidence and severity of 
adverse events, across treatment cohorts. 
Key Secondary (for Part 1 Expansion) 
To evaluate preliminary activity across treatment 
cohorts with respect to response rate at Month 3 
and Month 6. 
Response rate at Month 3 and Month 6, defined as 
the proportion of participants who demonstrate a 
CR or PR at each timepoint. 


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Table 6: 
Objectives and Endpoints, Part 1 and Part 1 Expansion (Continued) 
Objectives 
Endpoints 
Secondary 
To evaluate the PK of itacitinib when 
administered in combination with corticosteroids 
in the study population. 
Cmax, Cmin, Tmax, AUC0-t, and Cl/F. 
To estimate efficacy outcomes for each treatment 
cohort. 
Part 1:  Response rate at Month 3, 6, and 12. 
Part 1 expansion:  Response rate at Month 12. 
Response rate is defined as the proportion of 
participants who demonstrate either a CR or PR at 
each timepoint. 
Time to response, defined as the interval between 
randomization and first response. 
DoR, defined as the interval between first 
response and cGVHD progression, death, or 
initiation of new systemic cGVHD therapy. 
OS, defined as the interval between the date of 
randomization and the date of death due to any 
cause. 
NRM, defined as the proportion of participants 
who died due to causes other than a relapse of 
their primary hematologic disease. 
Proportion of participants with ≥ 50% reduction 
in daily corticosteroid dose at Day 180. 
Proportion of participants successfully tapered off 
all corticosteroids at Day 180. 
Relapse rate of malignant and nonmalignant 
hematologic diseases, defined as the proportion of 
participants whose underlying disease relapses. 
Time to primary hematologic disease relapse, 
defined as the interval between the date of 
randomization and the date of relapse. 


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Table 7: 
Objectives and Endpoints, Part 2 
Objectives 
Endpoints 
Primary 
To compare the efficacy of itacitinib versus 
placebo in combination with corticosteroids as 
initial treatment for moderate or severe cGVHD. 
Response rate at Month 6, defined as the 
proportion of participants demonstrating a CR or 
PR at Month 6. 
Secondary 
To compare changes in health-related quality of 
life. 
Changes in symptom scores using the LSS, 
QOL-SF-36 v2, EQ-5D-3L, PGIC, and PGIS. 
To compare additional efficacy outcomes between 
treatment groups. 
Response rate at Month 3 and 12, defined as the 
proportion of participants who demonstrate either 
a CR or PR at each timepoint. 
DoR, defined as the interval between first 
response and cGVHD progression, death, or 
initiation of new systemic cGVHD therapy. 
OS, defined as the interval between the date of 
randomization and the date of death due to any 
cause. 
NRM, defined as the proportion of participants 
who died due to causes other than a relapse of 
their primary hematologic disease. 
Proportion of participants with ≥ 50% reduction in 
daily corticosteroid dose at Day 180. 
Proportion of participants successfully tapered off 
all corticosteroids at Day 180. 
Relapse rate of malignant and nonmalignant 
hematologic diseases, defined as the proportion of 
participants whose underlying disease relapses. 
Time to primary hematologic disease relapse, 
defined as the interval between the date of 
randomization and the date of relapse. 
To evaluate the PK of itacitinib in combination 
with corticosteroids in 1L cGVHD. 
Cmin in all participants; Cmax, Tmax, AUC0-t, and 
Cl/F, data permitting. 
To evaluate the safety and tolerability of study 
treatment across the 2 treatment cohorts. 
Data from clinical safety assessments (eg, AEs, 
infections) will be listed and tabulated. 
 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
GRAVITAS-309 is a 2-part, multicenter Phase 2/3 study that will assess the efficacy and safety 
of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe 
chronic GVHD. 
4.1.1. 
Part 1  
Part 1 is a run-in that will employ a randomized, open-label, parallel-cohort design with the 
primary objective to assess the safety and tolerability of itacitinib in combination with 
corticosteroids in order to identify the appropriate dose of itacitinib in combination with 
corticosteroids as initial treatment for moderate or severe cGVHD.  A total of 20 participants 
with moderate or severe cGVHD will be randomized 1:1 to itacitinib 200 mg QD plus 
corticosteroids or 300 mg QD plus corticosteroids.  Itacitinib treatment will continue until 
treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), 
unacceptable toxicity, or withdrawal of consent.  Participants will remain on study for a total of 
37 months, including study treatment (up to 36 months), safety follow-up (30 days after EOT), 
and post-treatment GVHD follow-up (up to 24 months from Day 1), unless death or withdrawal 
of consent occurs earlier. 
Chronic GVHD staging and grading will be assessed using NIH consensus guidelines (Lee 
et al 2015, Jagasia et al 2015); safety and tolerability will be assessed as per NCI CTCAE v4.03.  
An analysis to determine the dose for further study will be performed once the 20th participant 
completes 28 days of study treatment.  An external DMC will review data from this analysis and 
provide a recommendation on an appropriate dose for Part 2. 
4.1.2. 
Part 1 Expansion 
Part 1 expansion is a Phase 2 with an initial safety run-in that will employ a randomized, 
open-label, parallel-cohort design with the primary objective to assess the safety and preliminary 
efficacy of itacitinib in combination with corticosteroids compared with corticosteroids 
monotherapy and identify the appropriate dosing/schedule of itacitinib in combination with 
corticosteroids as initial treatment for cGVHD for Part 2.  A total of up to 140 participants 
(35 per treatment group) with moderate or severe cGVHD will be randomized 1:1 to 1 of 
4 treatment groups (Table 8), specifically:  itacitinib 300 mg QD plus corticosteroids (Treatment 
Group A), itacitinib 400 mg QD plus corticosteroids (Treatment Group B), itacitinib 300 mg BID 
plus corticosteroids (Treatment Group C) or corticosteroids monotherapy (Treatment Group D). 


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Table 8: 
Treatment Groups and Dose Levels and Schedules 
Treatment Group 
Dose Level and Schedule 
A 
Itacitinib 300 mg QD plus corticosteroids 
B 
Itacitinib 400 mg QD plus corticosteroids 
C 
Itacitinib 300 mg BID plus corticosteroids; may be decreased to 200 mg BID if a 
boundary is reached during safety run.  This treatment group was discontinued due 
to concern of a potential increase in relapse rate.  Participants in this treatment 
group who were ongoing were allowed to reduce to 400 mg QD plus 
corticosteroids. 
D 
Corticosteroids monotherapy. 
Randomization will be stratified by cGVHD risk status (moderate vs severe).  Treatment groups 
B and C will have an initial safety run-in of 10 participants to determine safety and tolerability of 
the dose before expanding (see definition of DLT in Section 6.1.1.3).  Participants enrolled in the 
safety run-in will be monitored continuously using the Bayesian approach (Section 10.4.1.1). 
Treatment Group C was discontinued as of Amendment 8 and participants in that treatment 
group who were ongoing were allowed to reduce to 400 mg QD plus corticosteroids. 
Itacitinib treatment will continue until treatment failure (cGVHD progression, death, or initiation 
of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent.  Participants 
will remain on study for a total of 37 months, including study treatment (up to 36 months), safety 
follow-up (30 days after EOT), and post-treatment GVHD follow-up (up to 24 months from 
Day 1), unless death or withdrawal of consent occurs earlier. 
Chronic GVHD staging and grading will be assessed using NIH consensus guidelines (Lee 
et al 2015, Jagasia et al 2015); safety and tolerability will be assessed as per NCI CTCAE v4.03.  
Telephone conferences with study investigators will be scheduled by the sponsor in order to 
review cohort-specific data and overall safety data, to adjudicate individual high-grade AEs as 
potentially dose-limiting, and to guide other major study decisions. 
An analysis to determine the dose and schedule for Part 2 will be performed once the last 
participant completes at least 3 months of study treatment (see Section 6.1.1.4).  An external 
DMC will review the data from this analysis and provide a recommendation on an appropriate 
dose for Part 2. 
Participants who are randomized to the steroids single-agent cohort may be crossed over once the 
appropriate dosing/schedule for itacitinib for Part 1 was determined provided the participant 
completed 6 months of treatment with corticosteroids alone. 
4.1.3. 
Part 2 
Part 2 will employ a randomized, double-blind, placebo-controlled design in order to assess the 
efficacy of itacitinib in combination with corticosteroids using the dose selected in Part 1 
expansion.  Randomization will be stratified by cGVHD risk status (moderate vs severe).  
Participants randomized to the placebo group will be permitted to cross over to the experimental 
group after completion of the primary analysis as appropriate.  Participants will remain on study 
for a total of 37 months, including the treatment period, safety follow-up, and post-treatment 


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GVHD follow-up, unless confirmed GVHD progression, start of a new GVHD therapy, or 
relapse/recurrence of underlying hematologic disease occurs earlier. 
GVHD staging and grading will be assessed using NIH consensus guidelines (Lee et al 2015, 
Jagasia et al 2015); safety and tolerability will be assessed as per NCI CTCAE v4.03.  
An interim analysis for futility will be performed once 70 participants have completed the 
Day 180 visit; the final analysis will be performed once all participants have completed the 
Day 180 visit.  
 
 
 
 
 
  
4.2. 
Overall Study Duration 
The study begins when the first participant signs the ICF.  A participant is considered to have 
completed the study once all periods of the study are finished or consent is withdrawn.  It is 
estimated that an individual participant may participate for as long as 38 months. 
The primary analysis for Part 1 will occur once the last evaluable participant completes 28 days 
of treatment or experiences a DLT.  In Part 1 expansion, an analysis to determine the dose and 
schedule for Part 2 will be performed once the last participant completes at least 3 months of 
study treatment.  Participants who are still on treatment at the time of this analysis will continue 
to receive study treatment until treatment withdrawal criteria are met (Section 7.1.1).  In Part 2, 
the primary analysis will occur once the last participant enrolled in the study completes all 
required Day 180 assessments.  At the time of the primary analysis, any remaining participants 
may continue to receive study treatment and be assessed as per Protocol for a maximum of 
36 months or until treatment withdrawal/study withdrawal criteria are met.  Participants who are 
randomized to placebo may also be crossed over at the time of the primary analysis as 
appropriate.  The study will end once all randomized participants have reached Month 36 or 
discontinued the study early due to any reason; at this time, the clinical study report will be 
generated. 
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 in writing of the 
study's completion or early termination, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if 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 regulatory bodies of the decision and reason for 
termination of the study. 


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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed when enrolling a participant into the study, 
because they can potentially jeopardize the scientific integrity of the study, regulatory 
acceptability, and/or participant safety.  Therefore, adherence to the criteria as specified in the 
Protocol is essential.  Prospective approval of Protocol deviations to recruitment and enrollment 
criteria, also known as Protocol waivers or exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female, aged 18 years or older inclusive at the time of signing the ICF.  
2. Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria 
(Jagasia et al 2015; Appendix C): 
a. Moderate cGVHD:  At least 1 organ (except lung) with a score of 2, 3 or more organs 
involved with a score of 1 in each organ, or lung score of 1. 
b. Severe cGVHD:  At least 1 organ with a score of 3, or lung score of 2 or 3. 
Note:  Candidates who transition from active aGVHD to cGVHD without tapering off of 
corticosteroids (< 0.25 mg/kg per day methylprednisolone or equivalent) ± CNI are also 
eligible.  
3. Underwent allo-HCT from any donor HLA type (related or unrelated donor with any 
degree of HLA matching) using any graft source (bone marrow, peripheral blood stem 
cells, or cord blood).  Recipients of myeloablative, nonmyeloablative, or reduced 
intensity conditioning are eligible. 
4. KPS score ≥ 60%. 
5. Evidence of myeloid and platelet engraftment, that is, ANC ≥ 1.0 × 109/L and platelet 
count ≥ 50 × 109/L.  Note:  Use of growth factor supplementation and transfusion support 
is allowed during the study; however, transfusion to reach a minimum platelet count for 
inclusion is not allowed within the 7 days before the screening laboratory assessment. 
6. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Men must agree to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through 90 days after the last dose of study 
drug(s)/treatment and must refrain from donating sperm during this period.  Permitted 
methods that are at least 99% effective in preventing pregnancy (see Appendix A) 
should be communicated to the participants and their understanding confirmed.  
b. Women of childbearing potential must have a negative serum pregnancy test at 
screening and before the first dose on Day 1 and must agree to take appropriate 
precautions to avoid pregnancy (with at least 99% certainty) from screening through 
safety follow-up.  Permitted methods that are at least 99% effective in preventing 
pregnancy (see Appendix A) should be communicated to the participants and their 
understanding confirmed. 
c. Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR ≥ 12 months of amenorrhea) are eligible. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Has received more than 1 prior allo-HCT.  Prior autologous HCT is allowed. 
2. Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD. 
3. Has received any other systemic treatment for cGVHD, including ECP.  CNIs initiated 
before randomization may be continued at the same or lower dose; topical/inhaled 
steroids are acceptable. 
4. Prior treatment with a JAK inhibitor within 8 weeks before randomization.  Participants 
who received a JAK inhibitor for aGVHD are eligible only if they achieved CR or PR. 
5. Removed in Amendment 6. 
6. Presence of active uncontrolled bacterial, fungal, parasitic, or viral infection.  Infections 
are considered controlled if appropriate therapy has been initiated and, at the time of 
screening, no signs of infection are present. 
7. Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation 
(ie, positive HBsAg).  Participants with negative HBsAg and positive total HBc antibody 
may be included if HBV DNA is undetectable at the time of screening.  Participants who 
are positive for HCV antibody are eligible only if PCR is negative for HCV RNA.  
Participants whose immune status is unknown or uncertain must have results confirming 
immune status before enrollment.  Prior serology results are acceptable for determining 
eligibility. 
8. Known HIV infection. 
9. Evidence of relapsed primary hematologic disease, or receipt of treatment for relapse 
after the allo-HCT was performed, including DLIs for the treatment of molecular relapse. 
10. Maintenance therapy for the primary hematologic disease started within 4 weeks before 
initiation of study treatment (Day 1) or plans to start maintenance therapy after Day 1. 
11. Corticosteroid therapy at doses > 0.25 mg/kg per day methylprednisolone or equivalent 
for any treatment other than the diagnosis of cGVHD within 7 days of randomization.  
12. Participants on mechanical ventilation or requiring oxygen support or FEV1 < 30%. 
13. History or current diagnosis of cardiac disease indicating significant risk of safety for 
participation in the study, such as uncontrolled or significant cardiac disease, including 
any of the following: 
a. Recent myocardial infarction (within 6 months before randomization). 
b. New York Heart Association Class III or IV congestive heart failure. 
c. Unstable angina (within last 6 months before randomization). 
d. Clinically significant (symptomatic) cardiac arrhythmias (eg, sustained ventricular 
tachycardia, and clinically significant second or third degree AV block without a 
pacemaker). 
e. Uncontrolled hypertension. 


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14. Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive 
disease of the liver (defined as persistent total bilirubin > 2 mg/dL, or abnormalities not 
attributable to GVHD and ongoing organ dysfunction). 
15. Creatinine clearance ≤ 30 mL/min measured or calculated by Cockcroft-Gault equation. 
16. Pregnant or breastfeeding women. 
17. Anticipated need for live (including attenuated) vaccines during the first year of study. 
18. Treatment with an investigational agent, procedure, or device within 30 days of 
randomization, or within 5 half-lives of the investigational product, whichever is longer. 
19. Known allergies, hypersensitivity, or intolerance to any of the study medications, 
excipients, or similar compounds. 
20. Inability or unlikeliness of the participant to comply with the dose schedule and study 
evaluations, in the opinion of the investigator. 
21. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug/treatment and attending required 
study visits; pose a significant risk to the participant; or interfere with interpretation of 
study data.  Clinically significant laboratory abnormalities requiring urgent treatment 
should be resolved before initiation of study treatment. 
22. Inability of the participant (or parent, guardian, or legally authorized representative) to 
comprehend the ICF or unwillingness to sign the ICF. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants should be instructed to refrain from the consumption of pomegranates or 
pomegranate juice, and grapefruit or grapefruit juice, as these are known to inhibit cytochrome 
CYP3A enzymes and may increase exposure to itacitinib. 
5.3.2. 
Activity 
No restrictions are required. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
subsequently not randomized to study treatment. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be in error.   
A participant who fails screening may repeat the screening process 1 time if the investigator 
believes that there has been a change in eligibility status (eg, following recovery from an 
infection).  Participants who rescreen must reconsent and be assigned a new participant number. 


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5.5. 
Replacement of Participants 
In Part 1 and safety run-in for Part 1 expansion (for Treatment Group B and Treatment Group C), 
any participant who withdraws from treatment before the completion of the 28-day observation 
period for any reason other than a DLT (eg, not evaluable for DLT) may be replaced to ensure a 
minimum number of evaluable participants. 
Participants in Part 2 will not be replaced.  
6. 
STUDY TREATMENT 
6.1. 
Study Treatments Administered 
Once eligibility is confirmed, participants will be randomized to an assigned study treatment 
arm, will begin the treatment period on Day 1, and will continue on study treatment until 
discontinuation criteria are met.   
6.1.1. 
Itacitinib/Placebo 
Itacitinib 100 mg (free base equivalent) sustained-release tablets contain the active ingredient, 
hypromellose, microcrystalline cellulose, lactose monohydrate, and magnesium stearate.  
Placebo tablets developed to match the itacitinib 100 mg sustained-release tablets are similar in 
appearance to active drug product tablets with regard to color, size, and shape and contain 
hypromellose, microcrystalline cellulose, and magnesium stearate. 
Details regarding the agents that will be used as study treatment in Part 1, Part 1 expansion, and 
Part 2 of this study are provided in Table 9, Table 10, and Table 11, respectively.  
Table 9: 
Study Treatment Information, Part 1 
 
Study Treatment 
Study treatment name: 
Itacitinib 
Dosage formulation: 
Sustained-release tablets 
Unit dose strength(s)/dosage level(s): 
200 or 300 mg QD; 2 or 3 × 100 mg tablets 
Route of administration:  
PO 
Administration instructions: 
200 mg group:  take 2 × 100 mg tablets QD 
300 mg group:  take 3 × 100 mg tablets QD 
Itacitinib may be taken without regard to food except on 
PK days.  See Section 8.4. 
Packaging and labeling: 
Itacitinib will be provided in high-density polyethylene 
bottles.  Each bottle will be labeled as required per 
country requirement. 
Storage: 
Ambient conditions (15°C to 30°C, or 59°F to 86°F) 


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Table 10: 
Study Treatment Information, Part 1 Expansion 
 
Study Treatment 
Study treatment name: 
Itacitinib 
Dosage formulation: 
Sustained-release tablets 
Unit dose strength(s)/dosage level(s): 
300 or 400 mg QD; 3 or 4 × 100 mg tablets 
Route of administration:  
PO 
Administration instructions: 
TG A:  300 mg QD:  take 3 × 100 mg tablets QD 
TG B:  400 mg QD:  take 4 × 100 mg tablets QD 
TG C:  300 mg BID:  take 3 × 100 mg tablets BID.  
Participants remaining on study after discontinuation of 
TG C will follow the 400 mg QD administration 
instructions. 
Itacitinib may be taken without regard to food except on 
PK days.  See Section 8.4. 
Packaging and labeling: 
Itacitinib will be provided in high-density polyethylene 
bottles.  Each bottle will be labeled as required per 
country requirement. 
Storage: 
Ambient conditions (15°C to 30°C, or 59°F to 86°F) 
Table 11: 
Study Treatment Information, Part 2 
 
Study Treatment 
Study treatment name: 
Itacitinib/placebo 
Dosage formulation: 
Sustained-release tablets/NA 
Unit dose strength(s)/dosage level(s): 
To be determined in Part 1 expansion 
Route of administration:  
PO 
Administration instructions: 
Depending on dose selected in Part 1 expansion, 
participants will take 3 or 4 × 100 mg tablets QD or 
3 × 100 mg tablets BID. 
Itacitinib may be taken without regard to food except on 
PK days.  See Section 8.4. 
Packaging and labeling: 
Itacitinib will be provided in high-density polyethylene 
bottles.  Each bottle will be labeled as required per 
country requirement. 
Storage: 
Ambient conditions (15°C to 30°C, or 59°F to 86°F) 
6.1.1.1. 
Preparation, Handling, and Accountability of Itacitinib 
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. 


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Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatment must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records).  Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document: 
• Delivery of study drug(s) to the study site. 
• Inventory of study drug(s) at the site. 
• Participant use of the study drug(s) including pill counts from each supply dispensed. 
• Return of study drug(s) to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the participants were provided the 
specified study drug.  These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the investigational product and study 
participants. 
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 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. 
Participant handling instructions can be found in Appendix B. 
6.1.1.2. 
Study Treatment Compliance 
Compliance with all study treatment 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 treatment will be calculated by the sponsor based on the drug 
accountability documented by the site staff and monitored by the sponsor/designee (tablet 
counts). 
6.1.1.3. 
Dose-Limiting Toxicity Assessment 
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities in Table 12 with 
onset up to and including Day 28, except those with a clear alternative explanation.  All DLTs 
will be assessed for severity by the investigator using CTCAE v4.03 criteria.  Participants who 
receive at least 21 of 28 doses of study drug at the level assigned or have a DLT will be 


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considered evaluable for determining tolerability of the dose.  Participants who do not achieve 
this duration of exposure and do not have a DLT will be replaced for purposes of toxicity 
identification.  CYP3A inhibitors may be used during the DLT assessment window (ie, first 
28 days of study treatment) with appropriate dose reductions for itacitinib, according to Table 13 
and Table 14. 
Individual dose reductions may be made based on events observed at any time during treatment 
with study drug.  
Table 12: 
Definitions of Dose-Limiting Toxicity 
Toxicity 
Definition 
Nonhematologic 
• Any ≥ Grade 3 nonhematologic toxicity that can be reasonably attributed to study 
treatment.  ≥ Grade 3 nonhematologic clinical findings that may be related to underlying 
GVHD (eg, nausea, vomiting, diarrhea, rash, dry eye) will not be considered as DLTs. 
• Any ≥ Grade 3 clinical chemistry laboratory abnormalities that are considered clinically 
significant and related to study treatment.  Transient laboratory abnormalities not 
associated with clinically significant signs and symptoms, manageable with adequate 
medical care, and not leading to hospitalization will not be considered as DLTs. 
Hematologic 
• Grade 4 neutropenia lasting more than 7 days or a ≥ 90% decrease in ANC from baseline 
that can reasonably be attributed to study treatment. 
• Platelet count < 10 × 109/L related to study treatment that does not recover to at least 
20 × 109/L after 2 weeks with no requirement for platelet transfusion in the preceding 
3 days. 
6.1.1.4. 
Determination of the Part 2 Dose 
An analysis to determine the dose and schedule for further study will be performed once the last 
participant completes at least 3 months of study treatment.   
The overall safety profile and preliminary activity observed in each dose cohort will be taken 
into consideration when determining the Part 2 dose of itacitinib in combination with 
corticosteroids. 
The key secondary endpoints, Month 3 and Month 6 response rates, will be summarized 
descriptively for each treatment groups to support the determination of the dose and schedule for 
the Part 2 dose of itacitinib.  Descriptive summary of other secondary endpoints will also be 
taken into consideration for the determination. 
An external DMC will review the data from this analysis and provide a recommendation on an 
appropriate dose for Part 2. 
6.1.1.5. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug  
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment. 
Treatment with itacitinib/placebo may be delayed up to 3 weeks (21 days) to allow for resolution 
of toxicity.  Participants may resume treatment if no medical condition or other circumstance 
exists that, in the opinion of the investigator, would make the participant unsuitable for further 
participation in the study.  The treating investigator should contact the sponsor to discuss the 


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case of any participant whose treatment has been delayed for more than 21 days before restarting 
treatment with itacitinib/placebo. 
Because participants may enter the study with extensive pretreatment conditions and/or 
compromised bone marrow function, dose reduction recommendations provided in Table 15 are 
provided as guidelines.  Individual decisions regarding dose modifications should be made using 
clinical judgment and an individual benefit/risk assessment taking into account relatedness of the 
AE to the study treatment and the participant's underlying condition.  Adverse events that have a 
clear alternative explanation, or transient (≤ 72 hours) abnormal laboratory values without 
associated clinically significant signs or symptoms, may be exempt from dose modification rules.  
The sponsor's medical monitor may be consulted for advice. 
Participants receiving itacitinib may have their dose reduced and, if necessary, a second dose 
reduction may be considered, following the dose reduction schema in Table 13 and Table 14 
below.  Participants who are unable to tolerate itacitinib at a dose of 100 mg QD should be 
withdrawn from study treatment. 
Table 13: 
Itacitinib Dose Reductions for Part 1 
Part 1  
Cohort 
Starting Dose 
First Dose Reduction 
Second Dose Reduction 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
200 mg QD 
200 mg QD 
100 mg QD 
100 mg QD 
Discontinue 
Not 
applicable 
Not 
applicable 
300 mg QD 
300 mg QD 
200 mg QD 
200 mg QD 
100 mg QD 
100 mg QD 
Discontinue 
Table 14: 
Itacitinib Dose Reductions for Part 1 Expansion 
Part 1 Expansion 
Treatment Group 
Starting Dose 
First Dose Reduction 
Second Dose Reduction 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
A – No 
sCYP3A4 
B – With 
sCYP3A4 
Treatment Group A 
300 mg QD 
100 mg QD 
200 mg QD 
Discontinue 
100 mg QD 
Discontinue 
Treatment Group B  
400 mg QD 
200 mg QD 
300 mg QD 
100 mg QD 
200 mg QD 
Discontinue 
Treatment Group C: 
Discontinued as of 
SEP 2021 
300 mg BID 200 mg BID 200 mg BID 100 mg BID 100 mg BID 
100 mg QD 
sCYP3A4 = strong CYP3A4 (ie, posaconazole, itraconazole, voriconazole, ketoconazole, mibefradil, 
clarithromycin). 


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Table 15: 
Itacitinib/Placebo Dose Modification Guidelines 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
AST and/or ALT > 3.0 × ULN that 
occurs in the presence of GVHD 
response and cannot be attributed to new 
liver GVHD or concomitant therapy. 
1) Interrupt for up to 21 days until the toxicity has resolved to 
≤ Grade 1.  Exceptions require sponsor approval.  Monitor AST/ALT 
on a weekly basis. 
2) Restart at previous dose.  If assessed as related to itacitinib/placebo, 
restart at next lower dose and monitor as clinically indicated. 
AST and/or ALT > 3.0 × ULN that 
occurs in participants with liver GVHD 
and cannot be attributed to worsening of 
liver GVHD or concomitant therapy. 
• Repeat assessment within 7 days.  If elevation persists: 
-  Reduce dose by 1 dose level.  For participants receiving 300 mg 
QD or higher, a second dose reduction may be considered. 
- Resume previous dose if AST and/or ALT ≤ 3.0 × ULN. 
Total bilirubin elevations that occur in 
the presence of GVHD response that 
cannot be attributed to new liver 
GVHD or concomitant therapy. 
Total bilirubin 3.0-5.0 × ULN: 
- 
Reduce dose by 1 dose level and repeat assessment within 
7 days.  If elevation persists: 
- 
Interrupt until bilirubin ≤ 1.5 × ULN.  For participants 
receiving 300 mg QD or higher, a second dose reduction may be 
considered. 
- 
Monitor LFTs weekly or more frequently as appropriate 
- 
Resume previous dose if resolved in 14 days; if > 14 days, 
maintain reduced dose. 
Total bilirubin > 5.0-10.0 × ULN: 
- 
Interrupt and repeat assessment within 7 days.  If elevation 
persists: 
- 
Keep interruption until bilirubin ≤ 1.5 × ULN.  For participants 
receiving 300 mg QD or higher, a second dose reduction may be 
considered. 
- 
Monitor LFTs weekly or more frequently as appropriate. 
- 
Resume previous dose if resolved in 14 days; if > 14 days, 
resume at reduced dose. 
Total bilirubin > 10.0 × ULN: 
- 
Interrupt and repeat assessment within 7 days.  If elevation 
persists: 
- 
Keep interruption until bilirubin ≤ 1.5 × ULN.  For participants 
receiving 300 mg QD or higher, a second dose reduction may be 
considered. 
- 
Monitor LFTs weekly or more frequently as appropriate. 
- 
Resume at reduced dose if resolved in 14 days; if > 14 days, 
discontinue treatment and monitor as appropriate. 
Total bilirubin elevations that occur in 
participants with Stage 1/2 liver GVHD 
that cannot be attributed to worsening 
liver GVHD or concomitant therapy. 
Total bilirubin > 3.0 × ULN:  
• Repeat assessment within 7 days.  If elevation persists: 
- Reduce dose by 1 dose level.  For participants receiving 300 mg QD 
or higher, a second dose reduction may be considered. 
- Resume previous dose if bilirubin ≤ 3.0 × ULN. 


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Table 15: 
Itacitinib/Placebo Dose Modification Guidelines (Continued) 
ADVERSE EVENT 
ACTION TAKEN 
Hematology 
ANC < 0.5 × 109/L, suspected as 
unrelated to study drug (eg, GVHD, 
active cytomegalovirus viremia). 
• Reduce dose by 1 dose level. 
• Monitor ANC count as clinically indicated.  For participants receiving 
300 mg QD or higher, a second dose reduction may be considered. 
• Resume previous dose if ANC count is ≥ 0.5 × 109/L for more than 
7 days. 
ANC < 0.5 × 109/L, suspected as 
related to study drug. 
• Interrupt for up to 21 days. 
• Monitor ANC count as clinically indicated. 
• Resume at a reduced dose if ANC count is ≥ 0.5 × 109/L for more than 
7 days.  If the ANC count remains at ≥ 0.5 × 109/L for more than 
7 days after resuming treatment at a lower dose, the previous dose may 
be resumed. 
Platelet count < 10 × 109/L, suspected 
as unrelated to study drug or 
 
Platelet count < 20 × 109/L to 
10 × 109/L, suspected as related to 
study drug. 
• Reduce dose by 1 dose level until platelet count has improved to 
≥ 20 × 109/L 
• Monitor platelet count as clinically indicated.  For participants 
receiving 300 mg QD or higher, a second dose reduction may be 
considered. 
• Resume at previous dose if platelet count improves to ≥ 20 × 109/L in 
≤ 7 days. 
• Maintain at reduced dose if platelet count improves to ≥ 20 × 109/L in 
> 7 days.  If the platelet count then remains stable and continuously 
≥ 20 × 109/L for > 14 days, the previous dose may be resumed. 
Platelet count < 10 × 109/L, suspected 
as related to study drug. 
• Interrupt for up to 21 days. 
• Monitor platelet count as clinically indicated. 
• Resume at a reduced dose if platelet count has sustained improvement 
to ≥ 20 × 109/L for more than 7 days.  If the platelet count remains 
stable for an additional 7 days (sustained improvement to ≥ 20 × 109/L 
for > 14 consecutive days), the previous dose may be resumed. 
Other toxicities 
Any Grade 1 or Grade 2 toxicity. 
• Continue treatment and manage the toxicity. 
• Monitor as clinically indicated. 
Any Grade 3 toxicity, if clinically 
significant and not manageable by 
supportive care. 
• Interrupt up to 21 days until toxicity resolves to ≤ Grade 1. 
• Restart at same dose; if assessed as related to itacitinib/placebo, 
restart at next lower dose and monitor as clinically indicated. 
Any recurrent Grade 3 toxicity at 
100 mg QD dose. 
• Discontinue study treatment; follow-up per Protocol.  Exceptions 
require sponsor approval. 
Any other Grade 4 toxicity. 
• Discontinue study treatment; follow-up per Protocol.  
 Exceptions require sponsor approval. 
• For Grade 4 laboratory abnormalities not associated with 
signs/symptoms and that are transient and manageable with adequate 
medical care, decision to resume study drug at reduced dose may be 
made per investigator judgment based on individual benefit/risk.  
Medical monitor may be consulted for advice. 


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6.1.1.6. 
Tapering of Itacitinib or Placebo and Treatment Duration 
Systemic therapy for patients with moderate-to-severe chronic GVHD is generally recommended 
for at least 1 year (Flowers and Martin 2015).  Participants enrolled in this study may continue 
on study treatment for a maximum total treatment duration of 36 months or until criteria for 
treatment discontinuation are met (see Section 7.1.1). 
For participants who achieved CR or PR, the investigators may initiate a taper of 
itacitinib/placebo on or after Day 365 provided that therapeutic doses of systemic corticosteroids 
(ie, > 10 mg/day prednisone or prednisone equivalent) and other systemic immunosuppressive 
therapies have been discontinued for at least 3 months.  For investigators wishing to initiate a 
taper of itacitinib/placebo at an earlier timepoint for participants achieving sustained CR, they 
may start taper between D180 and D365 provided that the participant is still in CR after at least 
3 months off systemic immunosuppressive therapies including corticosteroids. 
Investigators may begin to taper the dose of itacitinib/placebo by 1 dose level (eg, from 400 mg 
QD to 300 mg QD, 300 mg BID to 200 mg BID).  Discontinuation or subsequent tapering 
(eg, from 200 mg QD to 100 mg QD, from 200 mg BID to 100 mg BID) may occur within 28 to 
56 days after the initial taper, as appropriate. 
Participants who complete itacitinib/placebo taper after an initial response (CR or PR) or 
discontinue early for reasons other than GVHD progression and with no requirement for new 
GVHD therapy will enter the safety and post-treatment GVHD follow-up (see Table 4 and 
Section 8.8.2).  
A physiological dose of 6 to 8 mg/day of methylprednisolone (ie, 7.5-10 mg/day of prednisone) 
during itacitinib taper is allowed and will not be considered treatment failure.  Hydrocortisone 
hemisuccinate may be used as physiological maintenance dosing. 
If GVHD signs/symptoms worsen during the taper of itacitinib/placebo (ie, first flare), the dose 
may be escalated by 1 dose level.  If the participant requires addition or initiation of a new 
systemic therapy or experiences subsequent flare, then the participant would be considered as 
having progression of disease and would be withdrawn from study treatment.  A short pulse of 
corticosteroids may be used once, without being considered progression, as long as the dose does 
not exceed the corticosteroid dose on Day 1 and can be tapered to physiological doses of 6 to 
8 mg/day of methylprednisolone (or 7.5-10 mg/day of prednisone) within 6 weeks from starting. 
After completion of an itacitinib/placebo taper, if reappearance or worsening of cGVHD occurs, 
the participant may be treated per institutional practice. 
Participants who do not achieve or maintain a CR or PR at Day 180 who are still receiving 
benefit from itacitinib/placebo per investigator clinical judgment may continue on study 
treatment for a maximum total treatment duration of 36 months. 
If the participant is not receiving benefit from itacitinib/placebo per investigator judgment, the 
participant must discontinue study treatment and be treated per institutional practice.  However, 
if mixed response or stable/unchanged disease is assessed, it is recommended that a new 
systemic therapy be initiated after confirmation at the next scheduled visit, at least 4 weeks later.  
These participants will be followed for survival. 


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6.1.2. 
Corticosteroids 
Systemic corticosteroids (methylprednisolone or prednisone) should be administered as 
background reference therapy at a dose level that is commensurate with institutional guidelines 
based on organ involvement and severity of disease.  Doses are expected to range from 
0.5 mg/kg per day to 1.0 mg/kg per day prednisone (or methylprednisolone equivalent to 
prednisone dose) for moderate to severe disease; questions regarding doses outside this range 
may be discussed with the sponsor medical monitor. Doses of prednisone will be converted to 
methylprednisolone equivalents by multiplying the prednisone dose by 0.80.  Prednisolone may 
also be used (at the same dose as prednisone). 
Details regarding the corticosteroids that will be used in Parts 1/1 expansion and Part 2 of this 
study are provided in Table 16.  
Table 16: 
Corticosteroid Treatment Details, Parts 1/1 Expansion and 2 
 
Study Treatment 
Study treatment name: 
Corticosteroids (methylprednisolone, prednisone) 
Dosage formulation: 
Varies based on form and country-specific requirements 
Unit dose strength(s)/dosage level(s): 
Starting dose 0.5-1.0 mg/kg per day prednisone (or 
methylprednisolone equivalent to prednisone dose); may 
vary based on institutional practice 
Route of administration:  
PO/IV 
Administration instructions: 
Per prescribing information 
Packaging and labeling: 
Varies based on form and country-specific requirements 
Storage: 
Per prescribing information 
6.1.2.1. 
Methylprednisolone 
6.1.2.1.1. Description 
Methylprednisolone sterile powder is an anti-inflammatory glucocorticoid, which contains 
methylprednisolone sodium succinate as the active ingredient.  Methylprednisolone sodium 
succinate, USP, is the sodium succinate ester of methylprednisolone, and it occurs as a white, or 
nearly white, odorless hygroscopic, amorphous solid.  It is very soluble in water and in alcohol; 
it is insoluble in chloroform and is very slightly soluble in acetone. 
6.1.2.1.2. Supply, Packaging, and Labeling 
Investigators are responsible for ensuring that participants receive commercially available 
supplies of methylprednisolone for the duration of the study treatment period.  Incyte may 
provide methylprednisolone where required by applicable law or regulation. 
6.1.2.1.3. Storage 
Methylprednisolone (unreconstituted product or solution) should be stored in accordance with 
local prescribing information. 


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6.1.2.2. 
Prednisone  
6.1.2.2.1. Description 
Prednisone is a white to off-white, odorless, crystalline powder.  Tablets are typically white in 
color and contain lactose monohydrate, magnesium stearate, microcrystalline cellulose, 
pregelatinized starch, and sodium starch glycolate.  Commonly available dose strengths include 
1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg tablets. 
6.1.2.2.2. Supply, Packaging, and Labeling 
Investigators are responsible for ensuring that participants receive commercially available 
supplies of prednisone for the duration of the study treatment period.  Incyte may provide 
prednisone where required by applicable law or regulation. 
6.1.2.2.3. Storage 
Prednisone tablets should be stored in accordance with local prescribing information 
requirements. 
6.1.2.3. 
Corticosteroid Tapering  
Tapering of corticosteroids should be initiated on Day 14 or attempted earlier during the second 
week of starting treatment per the following published recommendations (Flowers and 
Martin 2015).  This guidance applies to all randomized participants (Table 17). 
Table 17: 
Corticosteroid Tapering Guidelines 
Study Day 
Dose, mg/kg Body Weight 
1 
Current QD dose of corticosteroid (eg, 1 mg/kg per day) 
7-14 
Current dose of corticosteroid (eg, 1 mg/kg per day); 
Decrease alternate day dose by 50% (0.5 mg/kg per day) 
28 
Current dose of corticosteroid (1 mg/kg per day); 
Decrease alternate day dose by 50% (0.25 mg/kg per day) 
42 
Current dose of corticosteroid (1 mg/kg), QOD 
56 
Decrease current dose of corticosteroid by 10% every week until off 
Although commercial supplies of corticosteroids will be used, dose changes and interruptions 
will also be documented in the medical record and monitored by the sponsor or its designee.  As 
corticosteroid dose strengths and administration types will vary, compliance with corticosteroids 
will not be calculated. 
6.1.2.4. 
Management of Corticosteroids During cGVHD Flare 
If cGVHD flares during a corticosteroid taper, the dose of corticosteroids may be re-escalated at 
the investigator's discretion and will not be considered treatment failure.  If the flare requires 
addition or initiation of new systemic therapy or re-escalation of prednisone or 
methylprednisolone at a dose exceeding the dose on Day 1, the participant will be considered to 
have experienced treatment failure and must be withdrawn from study treatment.  The use of 


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systemic corticosteroids other than prednisone or methylprednisolone will not be considered 
initiation of new systemic therapy as long as the dose does is not higher than the equivalent 
prednisone dose on Day 1.  This guidance applies to all randomized participants.  
6.1.3. 
Prophylactic and Supportive Care Medications 
Standard cGVHD prophylaxis and treatment medications initiated before randomization 
including CNIs (cyclosporine or tacrolimus), and topical/inhaled corticosteroid therapy may be 
continued per institutional guidelines.  CNIs may be continued at the same dose or may be 
reduced per institutional practice or at a 25% dose reduction per month. 
Patients who undergo allo-HCT are at risk for a variety of infections based on the degree of 
immunosuppression induced by the conditioning regimen before transplant.  As such, it is 
considered routine practice to use antibiotics and anti-infectives as prophylactic therapies 
(Tomblyn et al 2009).  In cases where post-transplant anti-infective prophylaxis measures are 
necessary, ongoing therapy may continue at the investigator's discretion per institutional 
guidelines. 
6.2. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IVRS.  Before the study is 
initiated, the telephone number and call-in directions for the IVRS and/or the login information 
and directions for the IVRS will be provided to each site.  Full details will be provided in the 
IVRS section of the Study Manual. 
Study treatment will be dispensed at the study visits summarized in the schedule of activities 
(Table 4). 
Returned study treatment should not be redispensed to the participants. 
Centralized randomization numbers within each stratum will be created for treatment 
assignment.  Participants will be assigned to study drug cohorts in accordance with the 
randomization schedule.  In Part 1, the participant, the investigator, and the sponsor will be 
aware of each treatment assignment; in Part 2, they will remain blinded to treatment assignment. 
6.3. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
prior medication received up to 28 days before the first dose of study treatment and 30 days after 
the last dose of study treatment, or until the participant begins a new cGVHD therapy, whichever 
occurs first, will be recorded in the eCRF.  Any addition, deletion, or change in the dose of these 
medications will also be recorded. 
Concomitant treatments/procedures that are required to manage a participant's medical condition 
during the study will also be recorded in the eCRF.  The medical monitor should be contacted if 
there are any questions regarding concomitant or prior therapy. 


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6.3.1. 
Permitted Medications and Procedures 
As described in Section 6.1.3, continued use of agents administered as cGVHD prophylaxis, 
including agents used to prevent or treat infections, is permitted. 
Additional supportive care measures (eg, transfusions, use of antiemetics and antimotility agents 
for diarrhea management) are permitted at the investigator's discretion. 
6.3.2. 
Restricted Medications and Procedures 
 The following medications have restrictions on use during the treatment period of the study: 
• Coadministration with potent CYP3A4 inhibitors, as follows: 
− Coadministration with posaconazole, itraconazole, voriconazole, ketoconazole, 
mibefradil, and clarithromycin.  If the participant’s medical condition requires 
treatment with any of these drugs, a dose reduction of itacitinib by 1 dose level as 
displayed in Table 13 and Table 14 should be performed.  
− The sponsor medical monitor may be consulted for advice when CYP3A 
inhibitors are considered. 
• If concomitant administration of an anticoagulant/antiplatelet medication is indicated, 
then caution and enhanced monitoring is required.  The presence and severity of 
thrombocytopenia should be a factor in the choice of anticoagulant and dose.  Use of 
aspirin at doses > 81 mg per day should be avoided.  Use of low-molecular-weight 
heparin is allowed. 
6.3.3. 
Prohibited Medications and Procedures 
The following medications are prohibited during the treatment period of the study:  
• Any concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, 
immunotherapy, biologic therapy) required to treat a suspected malignancy relapse.  
Post-transplant maintenance treatment for the primary hematologic disease can be 
continued for a participant on maintenance therapy at study entry.  Initiation of 
maintenance treatment within the 4 weeks before Day 1 or after Day 1 is not 
permitted. 
• Any secondary GVHD therapy due to insufficient response/progression on study 
treatment.  Use of targeted therapies with anti-GVHD activity, including but not 
limited to TNF-alpha inhibitors and IL-6R inhibitors, are not permitted. 
• Concomitant use of a JAK inhibitor.  
• Initiating therapy with an investigational medication unless otherwise approved by 
the medical monitor.  
• Coadministration with strong CYP3A4 inducers.  The FDA website provides the most 
current list of strong CYP3A4 inducers. 


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6.4. 
Treatment After the End of the Study 
At the time of the primary analysis for Part 1 and Part 2 of the study, provisions will be made to 
ensure participants who are benefitting from study treatment will have continued access to 
itacitinib.  Participants in Part 2 of the study who were randomized to the placebo arm will be 
permitted to cross over to open-label itacitinib as appropriate. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
The decision to discontinue study treatment will not constitute study completion.  In the event 
the decision is made to discontinue study treatment, the treatment period will be considered 
complete, and the follow-up period will begin. 
7.1.1. 
Reasons for Discontinuation 
Participants must be withdrawn from study treatment for the following reasons: 
• GVHD progression or if additional systemic therapy is considered due to lack of 
clinical benefit from study treatment (including corticosteroids at a dose exceeding 
the dose on Day 1). 
• An unacceptable toxicity is observed.  An unacceptable toxicity is defined as an AE 
that is related to study treatment that, in the judgment of the investigator or the 
sponsor's medical monitor, compromises the participant’s ability to continue 
study-specific procedures or is considered to not be in the participant’s best interest. 
• Relapse of primary hematologic disease. 
• The participant becomes pregnant. 
• Consent is withdrawn.   
Note:  Consent withdrawn means that the participant has explicitly indicated that they 
do not want to be followed any longer; in this case, no further data, except data in 
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. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 


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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 participant will be discontinued unless discontinuation would result in a 
risk to the participant, as per the investigator's medical judgment. 
• If a participant is noncompliant with study procedures or study drug/treatment 
administration in the investigator's opinion, the sponsor should be consulted for 
instruction on handling the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit as indicated in Table 4. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal must be documented in the participant's medical record 
and the primary reason for withdrawal must be included in the eCRF. 
• The date of the last dose of study treatment must be recorded in the participant's 
medical record and eCRF.  
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the IVRS. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug/treatment–related toxicities resolve, return to baseline, or are deemed 
irreversible, whichever is longest. 
If the participant discontinues study treatment and 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/survival assessments.   
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If a participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 


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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.  In Germany, according to the German drug law, this clinical 
study should not be conducted in participants incapable of giving informed consent.  
Reference to a legally authorized representative is therefore not applicable in 
Germany. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 


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• 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(s) 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. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date. 
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. 
Procedures conducted as part of the participant's routine clinical management (eg, blood count, 
hepatitis serology) obtained before signing of informed consent may be used for screening or 
baseline purposes provided the procedure meets the Protocol-defined criteria and has been 
performed in the timeframe of the study.  For participants who are randomized in the study, 
information associated with eligibility requirements must be entered into the appropriate eCRF. 
Results from screening visit evaluations will be reviewed by the investigator to confirm 
eligibility before randomization or the administration of study treatment.  Tests with results that 
do not meet eligibility requirements may be repeated once during screening if the investigator 
believes the result to be in error or believes there has been a change in eligibility status (eg, 
following recovery from an infection).  For screening assessments that are repeated, the most 
recent available result before randomization will be used to determine eligibility. Treatment 
should start as soon as possible, but within 2 days after the date of randomization. 
Screening and randomization may occur on the same day provided all assessments have been 
completed and eligibility has been confirmed.  


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See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Voice Response System Procedures 
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 IVRS to obtain 
the participant ID number during screening.  Upon determining that the participant is eligible for 
randomization, the IVRS will be contacted to obtain the treatment assignment.  The IVRS will 
also be contacted as indicated in Table 4 to update study drug supply.  Additional details are 
provided in the IVRS manual. 
8.1.4. 
Distribution of Reminder Cards  
Participants will be provided with a reminder card as indicated in Table 4.  The reminder card 
will indicate the date/time of the next visit and will also remind the participant that they should 
not take their morning dose of study drug on clinic visit days until after blood draws are 
collected.  The reminder cards for the PK collection visits will have an area to record the date 
and time of the last dose taken and the time of their last meal before the visit. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and a complete medical and medication history will be collected during 
screening by the investigator or qualified designee.  
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history will be collected during screening.  Details 
regarding the participant's primary hematologic disease, including diagnosis, prior therapy, 
disease stage at the time of transplantation, disease risk index (Armand et al 2014, 
Appendix G), and details regarding allo-HCT, prior and current GVHD prophylaxis, history of 
aGVHD, and current cGVHD staging information will be recorded. 
8.2. 
Efficacy Assessments 
8.2.1. 
Chronic GVHD Staging at Screening 
During screening, cGVHD will be staged and classified into mild, moderate, and severe 
categories according to established NIH consensus criteria for diagnosing and staging cGVHD 
(Jagasia et al 2015, Appendix C).  Stratification will be based on cGVHD severity (moderate 
versus severe) assessed at screening. 
The cGVHD staging assessment is a global and organ-specific clinician assessment of symptom 
severity.  This assessment collects individual organ symptom scores (mouth, GI, lungs, eyes, 
joints and fascia, liver, skin, genital tract).  Assessments for all organs must be performed at 
screening. 


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8.2.2. 
Chronic GVHD Response Assessment 
Chronic GVHD organ scoring and the overall severity score 0 to 10 will be assessed on Day 1 
(ie, baseline).  Postbaseline response evaluations will be performed by the treating physician 
according to the detailed schedule in Table 4.  At each postbaseline assessment, each organ must 
be assessed using the same criteria as for baseline, and response should be determined by 
comparing the current organ assessment with the baseline organ assessment on Day 1.  A high 
level summary of organ-specific response assessment criteria as per NIH consensus guideline 
(Lee et al 2015, Appendix E) are listed in Table 18 and Table 19. 
Table 18: 
Organ Assessments 
Organ 
Evaluation 
Criteria 
Skin 
NIH Skin Score, considering %BSA 
involvement and sclerotic features 
Change of Skin score 
Eyes 
NIH Eye score 
Change of Eye score 
Mouth 
NIH Modified OMRS (sum of scores for erythema, 
lichenoid, and ulcers) 
Change of OMRS 
Esophagus 
NIH Esophagus score 
Change in Esophagus score 
Upper GI 
NIH Upper GI score 
Change in Upper GI score 
Lower GI 
NIH Lower GI score 
Change of Lower GI score 
Liver 
Lab results for ALT, ALP, and total bilirubin 
Change in values of lab results 
Lungs 
NIH Lung score and FEV1% 
(in participants using a bronchodilator, the 
post-bronchodilator response should be used for response 
assessment) 
Change in FEV1% 
Joints and fascia 
NIH Joint and Fascia score and P-ROM scores 
Change of Joint and Fascia 
score and P-ROM scores 
Table 19: 
Postbaseline Response Evaluations 
Organ 
Organ Specific Response 
Skin 
CR/not involved 
PR in at least 
1 organ with 
baseline 
involvement 
AND 
no progression 
in any other 
organ (ie, CR, 
PR, unchanged, 
or no 
involvement) 
PR or CR in 1 or 
more organ(s) 
with baseline 
involvement 
AND 
progression in 
1 or more 
organs (incl. 
new occurrence 
in an organ with 
no baseline 
involvement) 
Progression in 
1 or more 
organ(s) with 
baseline 
involvement 
OR 
new occurrence 
in an organ with 
no baseline 
involvement 
AND 
no CR or PR in 
any other organ 
Organ-specific 
response 
‘unchanged’ for 
all organs (incl. 
no involvement) 
Eyes 
Mouth 
Esophagus 
Upper GI 
Lower GI 
Liver 
Lungs 
Joints and fascia 
Overall 
Response 
CR 
PR 
MR 
PD 
Unchanged 


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Participants will be also monitored for occurrence of cGVHD flares, defined as any increase in 
symptoms observed during the tapering of corticosteroids, CNIs, or itacitinib/placebo after an 
initial response (CR or PR).  Any change in treatment to manage the flare must be reported on 
the appropriate eCRF, including changes in corticosteroid dosing, initiation of new systemic 
treatment, or other measures. 
Additional assessments of cGVHD may be performed by the treating investigator as required. 
Details on the initiation of new cGVHD treatment administered during the follow-up period of 
the study must be reported on the appropriate eCRF. 
8.2.3. 
Hematologic Disease Relapse Monitoring 
Participants will be closely monitored for any evidence of underlying disease relapse or 
recurrence at each visit during treatment, EOT, and follow-up periods of the study (as clinically 
indicated).  These evaluations will be conducted in accordance with local institutional practices.  
In this study, molecular relapse of disease requiring therapy will also be considered relapse of 
underlying hematologic disease.  Details on malignant and nonmalignant hematologic disease 
relapse and subsequent management should be collected on the appropriate eCRF.   
8.2.4. 
Patient-Reported Outcomes 
Data from patient-reported changes in health status, symptoms, and well-being will be collected 
during screening, treatment, and EOT.  The following tools will be used to facilitate this 
collection:  
• The LSS consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, 
and psychological). 
• The QOL-SF-36 v2 is 36-item scale that will capture changes in health status during the 
course of treatment.  The SF-36 assesses 8 health concepts related to limitations in 
physical activities, social activities, bodily pain, general mental and physical health, and 
vitality. 
• The EQ-5D-3L is a descriptive classification consisting of 5 dimensions of health:  
mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. 
• The PGIC is 1 question that will capture the overall change in symptoms over the course 
of treatment (Appendix F). 
• The PGIS is 1 question that will capture the overall change in the severity of symptoms 
over the previous week (Appendix F). 
8.3. 
Safety Assessments 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study treatment.  Adverse events that begin or worsen after 
informed consent should be recorded on the Adverse Events Form in the eCRF regardless of the 
assumption of a causal relationship with study treatment(s).  Conditions that were already present 
at the time of informed consent should be recorded on the Medical History Form in the eCRF.  


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Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
considered related to the study treatment/procedures, or that caused the participant to discontinue 
study treatment.  Care will be taken not to introduce bias when detecting AEs and/or SAEs.  
Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?" is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits, or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours.  The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.3.2. 
Physical Examinations 
Physical examinations must be performed by a medically qualified individual, such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits.  Abnormalities identified after the first dose of study treatment constitute an AE if they 
are considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study treatment.  Investigators should pay special attention to 
clinical signs related to previous serious illnesses. 
8.3.3. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, body temperature, and 
weight.  Height will also be measured at screening.  Blood pressure and pulse will be taken with 
the participant in the recumbent, semirecumbent, or sitting position after 5 minutes of rest.  
Abnormal vital sign results identified after the first dose of study treatment constitute an AE if 
they are considered clinically meaningful, induce clinical signs or symptoms, require 
concomitant therapy, or require changes in study treatment. 
8.3.4. 
Karnofsky Performance Status 
KPS score (Table 20) will be assessed at screening, during treatment, EOT, and follow-up as 
indicated in Table 4.  KPS must be assessed by a medically qualified individual and recorded in 
the eCRF. 


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Table 20: 
Karnofsky Performance Status Scale 
Score 
Performance Status 
100 
Normal; no complaints; no evidence of disease. 
90 
Able to carry on normal activity; minor signs or symptoms of disease. 
80 
Normal activity with effort; some signs or symptoms of disease. 
70 
Cares for self; unable to carry on normal activity or to do active work. 
60 
Requires occasional assistance, but is able to care for most of their personal needs. 
50 
Requires considerable assistance and frequent medical care. 
40 
Disabled; requires special care and assistance. 
30 
Severely disabled; hospital admission is indicated although death not imminent. 
20 
Very sick; hospital admission necessary; active supportive treatment necessary. 
10 
Moribund; fatal processes progressing rapidly. 
0 
Dead. 
8.3.5. 
Infection Monitoring 
Monitoring for infection will be performed at screening per institutional practice and will assess 
for the following at a minimum:  CMV, EBV, and hepatitis B/C (see Section 8.3.8.4).  
Participants may be randomized and treated prior to receiving CMV and EBV PCR results in the 
absence of clinical symptoms. 
Additional monitoring should be performed during treatment, EOT, and follow-up if there is 
clinical suspicion of an infection; outcomes should be reported as adverse events as appropriate.  
8.3.6. 
Graft Failure and Chimerism Monitoring 
Participants will be monitored for evidence of graft failure during study treatment and 
post-treatment follow-up.  Monitoring of graft failure will be primarily based on the monitoring 
of blood counts and supported by chimerism studies.  Secondary graft failure will be defined as a 
decrease of ANC < 0.5 × 109/L on at least 3 subsequent laboratory assessments without another 
potential etiology or > 95% recipient cells any time after engraftment with no signs of relapse. 
Donor chimerism after an allo-HCT involves identifying the genetic profiles of the recipient and 
of the donor pre-transplant and then evaluating the ratio of donor to recipient cells in the 
recipient's blood or bone marrow.  Chimerism testing using peripheral blood or bone marrow 
will be performed at the treating investigator's discretion according to local institutional practice 
as indicated in Table 4.  In general, genomic polymorphisms should be assessed via PCR 
analysis of short tandem repeat loci from isolated lymphocytes or myeloid cells.  Fluorescence in 
situ hybridization analysis may also be used in cases with sex-mismatched transplants 
(Matsuda et al 2004). 
If a participant experiences graft failure, any action taken to manage the graft including rapid 
taper of immunosuppression, administration of nonscheduled DLI, stem cell boost, or other 
intervention(s) should be recorded on the appropriate eCRF.   


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8.3.7. 
Electrocardiograms 
A 12-lead ECG will be performed during screening with the participant in a recumbent or 
semirecumbent position after 5 minutes of rest.  The 12-lead ECG will be interpreted by the 
investigator at the site and will be used for immediate management.  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.  
An additional ECG will be performed at the EOT visit. 
Based on findings from a concentration-QTc analysis, a QT effect exceeding the threshold of 
concern (10 msec) can be excluded within the observed range of itacitinib plasma concentrations.  
Therefore, additional ECGs are not required and would only need to be performed at the 
investigator's discretion.  Electrocardiograms that are identified as abnormal and clinically 
meaningful compared with the screening assessment should be reported as AEs. 
8.3.8. 
Laboratory Assessments 
Blood draws for laboratory assessments will occur at study visits indicated in Table 4.  Table 21 
summarizes the clinical laboratory analytes to be assessed.  Blood draws will be completed 
before the participant receives study drug.   
All laboratory assessments will be performed at a local (site) laboratory using institutional best 
practices.  Results and normal reference ranges will be entered into the eCRF.  


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Table 21: 
Clinical Laboratory Analytes 
Serum Chemistries 
Hematology 
Pregnancy Testing 
Albumin 
ALP 
ALT 
AST 
Bicarbonate or CO2 (at 
screening and then as clinically 
indicated) 
Blood urea nitrogen or urea 
Calcium 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin (Direct and 
indirect bilirubin required for 
participants with elevated total 
bilirubin). 
Total protein  
Total cholesterol 
Complete blood count, including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell count 
• White blood cell count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Female participants of childbearing 
potential only require a serum test at 
screening and EOT and a serum or 
urine pregnancy every 28 days. 
Pregnancy tests (serum or urine) 
should be repeated if required by local 
regulations. 
Lipid Panel 
Infection Screening Tests 
Triglycerides 
Cholesterol 
LDL 
HDL 
HIV (if HIV status is unknown) 
Hepatitis B surface antigen 
Hepatitis B surface antibody 
Hepatitis B core antibody 
HCV antibody 
HBV-DNA (if required) 
HCV-RNA (if required) 
CMV-PCR and EBV-PCR 
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety 
data. 
8.3.8.1. 
Hematology 
Hematology assessments, including complete blood count with differential, will be performed at 
a local (site) laboratory using institutional best practices before administration of study drug.  
Results and normal reference ranges will be entered into the eCRF.  
8.3.8.2. 
Serum Chemistry 
All chemistry panel assessments will be performed at a local (site) laboratory from blood 
samples collected using institutional best practices before administration of study drug.  For 
GVHD follow-up assessments on total bilirubin, ALT, and ALP will need to be reported.  Direct 


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and indirect bilirubin are also required for participants with elevated total bilirubin.  Results and 
normal reference ranges will be entered into the eCRF.  
8.3.8.3. 
Pregnancy Testing  
A serum pregnancy test will be required for all women of childbearing potential during screening 
and at the EOT visit.  
Urine or serum pregnancy tests will be conducted locally every 28 days.  If a urine pregnancy 
test is positive, results should be confirmed with a serum pregnancy test.  If the serum pregnancy 
test is negative after a urine test was positive, the investigator will assess the potential 
benefit/risk to the participant and determine whether it is in the participant’s best interest to 
resume study drug and continue participation in the study. 
8.3.8.4. 
Hepatitis Screening  
Participants with active HBV or HCV infection that requires treatment or who are at risk for 
HBV reactivation (ie, positive HBsAg serology) are excluded from the study.  Note: Candidates 
with negative HBsAg and positive total HBc antibody may be included if HBV DNA is 
undetectable at the time of screening.  Candidates positive for HCV antibody are eligible only if 
PCR is negative for HCV RNA. 
Prior test results obtained as part of standard of care before allo-HCT confirming that a 
participant is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, 
surface antibody positive) may be used for purposes of eligibility, and tests do not need to be 
repeated.  Participants with positive antigen serology results must have negative PCR results.   
Participants whose immune status is unknown or uncertain must have results confirming immune 
status before enrollment.  
8.3.8.5. 
HIV Screening  
Participants with an active HIV infection are excluded from the study.  Prior HIV screening 
results obtained as standard of care for allo-HCT confirming an HIV-negative status may be used 
for determining eligibility, and tests do not need to be repeated.  Participants whose HIV status is 
unknown must have results confirming negative status before enrollment.    
8.4. 
Pharmacokinetic Assessments 
8.4.1. 
Blood Sample Collection 
Pharmacokinetic samples will be obtained on Days 1, 7, and 28 for participants in Part 1 and 
Part 1 expansion (except Treatment Group D) as well as the first 70 participants randomized in 
Part 2.  On each of these days, a predose blood sample will be drawn, study treatment will be 
administered, and serial blood samples will be taken at the intervals shown in Table 4 and 
Table 22. 
After the first 70 participants are enrolled in Part 2, only a predose sample on Day 7 and 28 will 
be collected in subsequent participants (ie, participants 71-246). 
The exact date and time of the PK blood draws will be recorded in the eCRF along with the date 
and time of the last dose of study drug preceding the blood draw (if applicable) and the time of 


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the most recent meal.  Instructions for sample preparation and shipping will be provided in the 
Laboratory Manual.  Participants will receive reminder cards in advance of the study visit 
providing instruction to hold the dose of study drug on the day of the visit, as well as a place to 
record the time of the prior dose of study drug and time of the most recent meal or snack 
consumed.  
If PK samples are missing for a participant, PK sample collection should be performed at the 
next visit.  On PK sample collection days, participants must refrain from taking study medication 
before arriving for the visit and should not have consumed any food within 8 hours before 
arriving at the clinic.  A trough (predose) PK sample (30-minute window) should be drawn at 
each of the PK visits.  Following the trough PK sample, the participant should take the assigned 
dose of study treatment, and subsequent timed samples will be taken if applicable.  Food should 
be withheld until 1 hour after study drug administration. 
Participants 71 through 246 in Part 2 of the study will have only predose samples collected on 
Day 7 and Day 28. 
Table 22: 
Pharmacokinetic Sampling for Part 1, Part 1 Expansion, and Participants 1 
Through 70 in Part 2   
Study Day 
Timing of Sample Relative to Itacitinib Administration 
Day 1 
Predose 
1 h ± 15 min 
2 h ± 30 min 
5 h ± 60 min 
Day 7 
Predose 
1 h ± 15 min 
2 h ± 30 min 
5 h ± 60 min 
Day 28 
Predose 
1 h ± 15 min 
2 h ± 30 min 
5 h ± 60 min 
8.4.2. 
Pharmacokinetic Analysis 
Plasma samples will be analyzed for itacitinib by a validated liquid chromatography–tandem 
mass spectrometry assay.  These samples will be analyzed by Incyte Corporation (Wilmington, 
DE) or its designee.  
Pharmacokinetic parameters will be calculated from the plasma concentrations of itacitinib 
according to a model-independent approach or population PK approach.  Instructions regarding 
sample collection, handling, and shipping will be provided in the Laboratory Manual. 
The data will be used to validate the population PK model being developed across healthy 
volunteers and various patient populations including acute GVHD.  If appropriate, the model will 
be used to generate individual post-hoc PK model parameters and calculate and/or simulate 
individual exposures.  Observed PK parameters such as Cmin (all participants) and Cmax and Tmax 
(data permitting) will also be presented and summarized.  Exposure/response analyses may be 
performed using model-based AUCs or using observed trough values (Cmin).     
Data may also be used to further validate or refine PBPK and population PK models of itacitinib.  
These models may be used to aid in dose selection for Part 2 of the study.     
 
 
 
 


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8.6. 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the investigator's discretion, with 
appropriate clinical and laboratory measurements performed based on AEs or other findings.  
Data from these visits should be captured on the appropriate eCRF. 
8.7. 
End of Treatment 
When the participant permanently discontinues study drug, whether the participant is terminating 
the study treatment early or has completed the study treatment, the EOT visit should be 
conducted.  If the EOT visit coincides with a regular study visit, the EOT evaluations will 
supersede those of that scheduled visit, and the data should be entered in the EOT visit in the 
eCRF.  The participant should be encouraged to return for the safety follow-up visit. 
8.8. 
Follow-Up 
8.8.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled safety 
follow-up visit, which should occur at least 30 days after the EOT visit (or after the last dose of 
study drug/treatment 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/treatment, the date of the 
follow-up visit, or the start of a new GVHD therapy 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.  If the participant cannot return to the site for the safety follow-up visit, sites should 
attempt to contact the participant by telephone for assessment of AEs and SAEs.  These contacts 
with the participant should be documented in medical records. 
If a participant is scheduled to begin a new anti-GVHD therapy before the end of the 30 days 
safety follow-up period, the safety follow-up visit should be performed before treatment is 
started.  Once new GVHD therapy has been initiated, the participant will move into the survival 
follow-up period. 
8.8.2. 
Post-Treatment GVHD Follow-Up 
Participants who complete itacitinib/placebo taper after an initial response (CR or PR) or 
discontinue early for reasons other than cGVHD progression and with no requirement for new 


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cGVHD therapy will be followed until cGVHD progression, initiation of a new cGVHD therapy, 
initiation of treatment for relapse/recurrence of the underlying hematologic disease, death, or end 
of study and for a maximum of 24 months from Day 1, at which point the participant may enter 
survival follow-up.  The participant will be followed at clinic visits every 28 days (± 7 days) 
after the safety follow-up visit up to 1 year from Day 1 and then every 8 weeks (± 7 days) up to 
2 years from Day 1. 
8.8.3. 
Survival Follow-Up 
Once a participant has completed the post-treatment GVHD follow-up (ie, 24 months from 
Day 1) or has confirmed GVHD progression or starts a new GVHD therapy, or experiences 
relapse/recurrence of the underlying hematologic disease, then the participant moves into the 
survival follow-up period and should be contacted by telephone, email, or visit at least every 
8 weeks to assess for survival status until death or withdrawal of consent, whichever occurs first. 
For participants having entered the survival follow-up period of the study, the site will use 
continuing participant records to supply data on subsequent treatment regimens, GVHD 
assessments (if discontinued treatment for a reason other than progression), and OS in the eCRF.  
For participants who do not intend to return to the study investigator for their ongoing care, 
follow-up should be maintained by phone contact, patient records, and public records/databases 
at intervals of no longer than 8 weeks. 
8.9. 
Data Monitoring Committee 
An external DMC will be formed to monitor the study.  The DMC will consist of external 
experts in the field of allogeneic transplantation who will function autonomously from all other 
individuals associated with the conduct of the study, including investigators and sponsor 
personnel.  The DMC will be responsible for reviewing results from the prespecified analysis 
and recommending an appropriate course of action based on these data.  Details on the 
composition and responsibilities of the DMC can be found in the DMC charter. 


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9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug-related. 
• An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
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). 
• Abnormal laboratory test results constitute 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 lab result (eg, low hemoglobin, platelet count decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even though they may 
have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication.  Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent.  Such overdoses should be 
reported regardless of sequelae. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an 
AE or SAE.  Such instances will be captured in the efficacy assessments.  However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as an AE or SAE 
if they fulfill the definition of an AE or SAE. 
Events NOT Meeting the Adverse Event Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety assessments that are 
associated with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant's condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant's condition or 
considered to be treatment-related by the investigator. 
• Efficacy endpoints as outlined in Section 3 will not be reported as AE/SAEs, specifically, any event 
that is related to disease progression of the disease under study.  Unblinded aggregated efficacy 
endpoint events and safety data will be monitored to ensure the safety of the participants in the study.  
Any suspected endpoint that upon review is not progression of the disease under study will be 
forwarded to Incyte Pharmacovigilance as a SAE within 24 hours of determination that the event is 
not progression of the disease under study. 


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• Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that leads to the 
procedure is the AE if it occurred after signing informed consent.  If present before entering the 
study, the condition should be captured as medical history. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per 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 occurred.  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 (usually 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 of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person's ability to conduct normal life 
functions. 
• This definition is not intended to include experiences of relatively minor medical significance, such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(eg, sprained ankle), that may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e.  Is a congenital anomaly/birth defect 
f. Other situations (Important Medical Event) 
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 invasive or malignant cancers (excluding the 
disease[s] under study in oncology protocols), intensive treatment in an emergency department or at 
home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse. 


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9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF.  Conditions that were present at the time informed consent was 
given should be recorded on the Medical History Form in the eCRF. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics 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 AE eCRF page. 
• There may be 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 on the copies 
of the medical records before submission. 
• 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 severity grade (CTCAE 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 treatment 
(including study drug(s) and/or reference therapy):  suspected (yes) or not suspected (no).  See below 
for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug as a result of the AE/SAE(s) and/or reference therapy. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on 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 v4.03 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. 


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• Grade 3:  Severe or medical 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 treatment and each occurrence 
of each AE/SAE.  If reference therapy is used in combination with an Incyte study drug or multiple 
Incyte study drugs are used, the relationship to each study drug and/or reference therapy must be 
assessed (ie, for the Incyte product(s) and for the other product(s) that is used in combination with 
the Incyte product).  If appropriate, the relationship to the combination may be assessed as well. 
• A "reasonable possibility" of a relationship conveys that there are 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 relationship. 
• The investigator will also consult the RSI in the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study treatment 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 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 
send a follow-up SAE report with the updated causality assessment. 
Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 
• New or updated information will be recorded in the originally completed eCRF. 
• Any updated SAE data will be submitted to the sponsor (or designee) within 24 hours of receipt of 
the information. 
• Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any changes 
in severity, the suspected relationship to the study drug, the interventions required to treat the event, 
and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves. 


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9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug[s], reference therapy, or study 
procedure[s]), all SAEs occurring after the participant has signed the ICF and up to 30 days after 
the last dose of study treatment or until the participant starts new GVHD therapy, whichever 
occurs earlier) must be reported to the sponsor (or designee) within 24 hours of learning of its 
occurrence, unless otherwise specified by the Protocol.  The investigator will submit any updated 
SAE data to the sponsor (or designee) within 24 hours of it being available.  Any SAEs occurring 
more than 30 days after the last dose of study drug should be reported to the sponsor, or its 
designee, only if the investigator suspects a causal relationship to the study drug. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation.  However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study treatment or study participation, the investigator must notify the 
sponsor (or designee) within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification 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 treatment 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 SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 


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Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must also complete the Incyte Serious Adverse Event Report Form, in English.  
Refer to the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Facsimile or email transmission of the Serious Adverse Event Report Form is the preferred method 
to transmit this information to the PhV team designee.  The contact information of the sponsor's 
study-specific representatives is listed in the investigator manual provided to each site.  The original 
copy of the Serious Adverse Event Report Form and the confirmation sheet must be kept at the study 
site. 
• Follow-up information is recorded on an amended or new Serious Adverse Event Report Form, with 
an indication that it is follow-up to the previously reported SAE and the date of the original report.  
The follow-up report should include information that was not provided on the previous Serious 
Adverse Event Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or participant disposition (eg, continued or withdrew from study participation).  Each 
recurrence, complication, or progression of the original event should be reported as follow-up to that 
event, regardless of when it occurs. 
• In rare circumstances and in the absence of facsimile or computer equipment, notification by 
telephone is acceptable with a copy of the Incyte Serious Adverse Event Report Form sent by 
overnight mail or courier service.  Initial notification via telephone does not replace the need for the 
investigator to complete and sign the Serious Adverse Event Report Form within the designated 
reporting time frames. 
• Contacts for SAE reporting can be found in the study manual. 
9.5. 
Adverse Events of Special Interest 
Not applicable. 
9.6. 
Emergency Unblinding of Treatment Assignment 
In a medical emergency, if knowledge of the treatment assignment is necessary to determine 
optimal medical management of the participant, the procedure for emergency unblinding is 
provided in the IVRS manual.  The responsibility to break the treatment code in an emergency 
situation resides solely with the investigator.  This option may be used only if the participant's 
well-being requires the investigator to be aware of the participant's treatment assignment.  If a 
participant's treatment assignment is unblinded, the sponsor or its designee must be notified 
immediately by telephone. 
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant must be withdrawn from the study treatment, 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. 


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9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a 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). 
• 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. 
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 designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.8. 
Warnings and Precautions 
Special warnings or precautions for the study treatment, 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. 


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The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be 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 
The highest total daily dose evaluated in clinical studies was 1200 mg (600 mg BID) in 
multiple-dose and renal function healthy participant studies.  No unexpected TEAEs were 
associated with doses of this level.  Treatment of suspected overdose with itacitinib should 
consist of general supportive measures. 
Incyte does not recommend specific treatment for an overdose.  
In the event of an overdose, the investigator should: 
• Contact the medical monitor immediately. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities. 
• Obtain a plasma sample for PK analysis within 2 days from the date of the last dose 
of study treatment if requested by the medical monitor (determined on a case-by-case 
basis). 
• Document the quantity of the excess dose as well as the duration of the overdose in 
the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 


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10. 
STATISTICS 
10.1. 
Sample Size Determination 
10.1.1. 
Part 1 
In Part 1, approximately 20 participants will be enrolled to achieve 10 randomly assigned 
participants in each of the 2 dose groups of itacitinib in order to identify an optimal dose for 
further study.  This sample size was chosen based on typical Phase 1 studies employing a 
3 + 3 design that enroll up to 9 participants in order to identify recommended Phase 2 doses.  A 
sample size of 20 participants (10 per treatment group) allows for concurrent enrollment at 
2 dose levels that have been previously characterized in other disease settings and is expected to 
enable the clinical characterization of study treatment across 2 treatment cohorts.  No formal 
statistical comparison will be performed between treatment groups. 
10.1.2. 
Part 1 Expansion 
Sample size in Part 1 expansion is based on clinical feasibility and consideration.  No hypothesis 
test is planned for efficacy.  Up to 35 participants will be enrolled into each treatment group.  
The toxicity of itacitinib will be monitored continuously for Treatment Group B and C using a 
Bayesian approach.  A total of up to 140 participants will be enrolled into Part 1 expansion of the 
study.  Regarding the key secondary endpoint, Month 6 response rate, a table of Bayesian 
posterior probabilities and related descriptions are provided below.  This posterior probability 
may be used to support decision-making on itacitinib dosing/schedule for Part 2, including 
decisions made by the DMC. 
Table 23 presents Bayesian posterior probability of demonstrating a clinically meaningful 
treatment difference 
in Month 6 response rate between any itacitinib group and the 
corticosteroids-only group under various response rates at the end of the expansion. 
Table 23: 
Bayesian Posterior Probability to Demonstrate That There is a Clinically 
Meaningful Difference
Between Any Itacitinib Group and the 
Corticosteroids-Only Group 
Responders in an Itacitinib Group 
(out of 35) 
Responders in Corticosteroids-Only Group (out of 35) 
18 
19 
20 
21 
22 
25 
64.3% 
54.8% 
45.0% 
35.3% 
26.4% 
26 
73.1% 
64.4% 
54.9% 
44.8% 
35.0% 
27 
80.9% 
73.4% 
64.7% 
54.9% 
44.7% 
28 
87.2% 
81.3% 
73.9% 
65.0% 
55.0% 
29 
92.1% 
87.7% 
81.9% 
74.4% 
65.3% 
30 
95.5% 
92.6% 
88.4% 
82.6% 
75.0% 
Note:  With a binomial likelihood, binomial (n, p) with s number of responders out of n participants, and a beta 
prior, Beta (a, b), the posterior is calculated as Beta(a+s, b+n-s) 


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Interpretation: 
 
 
 
 
 
 
 
 
 
10.1.3. 
Part 2 
 
 
 
 
 
 
10.2. 
Populations for Analysis 
The populations that will be included in study-related analyses are described in Table 24. 
Table 24: 
Populations for Analysis 
Population 
Description 
ITT 
All randomized participants. 
Safety 
The safety population includes all enrolled/randomized participants who 
received at least 1 dose of study drug and/or reference therapy.  Treatment 
groups for this population will be determined according to the actual treatment 
the participant received regardless of assigned study drug treatment. 
Safety run-in 
All participants enrolled in the safety run-in portion of the study taking at least 
1 dose of study drug and/or reference therapy comprise the safety run-in 
population.  Treatment groups for this population will be determined 
according to the treatment assignment on Day 1 regardless of the actual study 
drug the participant might take during his/her continued participation in the 
study. 
PK evaluable 
The PK evaluable population will include all participants who received at least 
1 dose of study drug and/or reference therapy and provided at least 
1 corresponding postdose plasma sample (1 PK measurement). 


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10.3. 
Level of Significance 
No formal statistical tests will be performed in Part 1 and Part 1 expansion.  The 1-sided 
significance level for the analysis of the primary endpoint in Part 2 is 0.025.  The 2-sided 
significance level for the analysis of the secondary endpoints in Part 2 is 0.05.  All CIs will be 
95%. 
10.4. 
Statistical Analyses 
The Statistical Analysis Plan 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 
10.4.1.1. Part 1 and Safety Run-In for Part 1 Expansion 
The toxicity of itacitinib will be monitored continuously for each treatment group using the 
Bayesian approach of Thall et al (1995, 1996) as extended by Thall and Sung (1998).  
Dose-limiting toxicities are defined in Section 6.1.1.3. 
Historical data on similar patients show a toxicity rate of 25%.  The probability of toxicity for the 
historical data is modeled by beta distribution (Beta [25, 75]).  The prior probability of toxicity 
for the experimental regimen is also modeled by beta distributions (Beta [0.5, 1.5]), which have 
the same means as the corresponding beta distributions for the historical data.  Denoting the 
historical probability of toxicity rate by p(TOX,H), the following decision criteria will be 
applied: 
Stop if Prob{p(TOX,H) + δTOX < p(TOX,E)| data} > 0.95, where δTOX = 0 
Participants from each treatment group will be monitored according to the following nonbinding 
stopping boundaries for toxicity in Table 25.  If a boundary is reached, the sponsor and external 
DMC will investigate and decide on the most appropriate action. 
Table 25: 
Toxicity Stopping Boundaries  
# Participants (Inclusive) 
Number of DLTs Required to Stop (Inclusive) 
1-2 
No limit 
3-4 
3 
5-6 
4 
7-9 
5 
10-11 
6 
12-14 
7 
15-17 
8 
18-19 
9 
20 
9 


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10.4.1.2. Part 2 
The primary endpoint is Month 6 response rate, defined as the proportion of participants 
demonstrating a CR or PR at Month 6 as per standard criteria (Lee et al 2015).  The comparison 
of Month 6 response rate between treatment cohorts will be conducted once the last participant 
completes the Month 6 visit or withdraws from the study.  A CMH test with normal 
approximation will be used.  Summary statistics and 95% CI will be provided. 
Participants who have missing data for the Month 6 response rate assessment will be considered 
as nonresponders. 
 
For the interim analysis, the statistical assumptions are specified in Section 10.5. 
10.4.2. 
Secondary Analysis 
10.4.2.1. Part 1 
The following secondary endpoints will be summarized by treatment group using the ITT 
population: 
• Response rate at 3, 6, and 12 months, defined as the proportion of participants who 
achieved response (CR or PR) at each timepoint. 
• Time to response, defined as the interval between randomization and first response. 
• DoR, defined as the interval between first response and cGVHD progression, death, 
or initiation of new systemic cGVHD therapy. 
• OS, defined as the interval between the date of randomization and the date of death 
due to any cause. 
• NRM, defined as the proportion of participants who died due to causes other than a 
relapse of their primary hematologic disease.  
• Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at 
Day 180. 
• Proportion of participants successfully tapered off all corticosteroids at Day 180. 
• Relapse rate of malignant and nonmalignant hematologic diseases, defined as the 
proportion of participants whose underlying disease relapses. 
• Time to primary hematologic disease relapse, defined as the interval between the date 
of randomization and the date of relapse.  Data from clinical safety assessments 
(eg, AEs, infections) will be listed and tabulated by treatment group. 
10.4.2.2. Part 1 Expansion 
For Part 1 Expansion, the key secondary endpoints are response rate at Month 3 and Month 6, 
which are defined as the proportion of participants who demonstrate a CR or PR at each 
timepoint.  The analysis will be conducted once the last participant completes Month 3 and 
Month 6 visits or withdraws from the study by treatment group for response rates at Month 3 and 


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Month 6, respectively.  Summary statistics and 95% CI will be provided by cohort. The primary 
comparisons in Part 1 expansion will involve only the 2 itacitinib groups (A and B) and the 
corticosteroid alone group (D) as a result of Protocol Amendment 8, which discontinued 
Group C (300 mg BID + corticosteroid).  Group C data will be presented only as summary 
statistics but will not be subjected to any statistical comparison. 
Pairwise CMH tests will be conducted to Month 6 response rate for each of the 2 itacitinib 
groups (Treatment Group A and B) and the corticosteroids-only group (Treatment Group D) as 
an exploratory analysis. 
The following secondary endpoints will be summarized by Treatment Groups A, B, and D using 
the ITT population for efficacy-related endpoints and all groups for safety-related endpoints: 
• Response rate at 12 months, defined as the proportion of participants who achieved 
response (CR or PR) at Month 12. 
• Time to response, defined as the interval between randomization and first response. 
• DoR, defined as the interval between first response and cGVHD progression, death, 
or initiation of new systemic cGVHD therapy. 
• OS, defined as the interval between the date of randomization and the date of death 
due to any cause. 
• NRM, defined as the proportion of participants who died due to causes other than a 
relapse of their primary hematologic disease. 
• Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at 
Day 180. 
• Proportion of participants successfully tapered off all corticosteroids at Day 180. 
• Relapse rate of malignant and nonmalignant hematologic diseases, defined as the 
proportion of participants whose underlying disease relapses. 
• Time to primary hematologic disease relapse, defined as the interval between the date 
of randomization and the date of relapse.  Data from clinical safety assessments 
(eg, AEs, infections) will be listed and tabulated by treatment group. 
10.4.2.3. Part 2 
The following secondary endpoints will be summarized by treatment group using the ITT 
population: 
• Parameters collected using the LSS, QOL-SF-36 v2, EQ-5D-3L, PGIC, and PGIS 
will be summarized.  Treatment comparison will be assessed. 
• Response rate at 3 and 12 months, defined as the proportion of participants who 
achieved response (CR or PR) at each timepoint. 
• DoR, defined as the interval between first response and cGVHD progression, death, 
or initiation of new systemic cGVHD therapy.  The comparison between treatment 
groups will be conducted using the log-rank test.  The Kaplan-Meier method will be 
used.  Summary statistics will be provided. 


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• OS, defined as the interval between the date of randomization and the date of death 
due to any cause.  The comparison between treatment groups will be conducted using 
the log-rank test.  The Kaplan-Meier method will be used.  Summary statistics as well 
as overall survival for risk status will be provided. 
• NRM, defined as the proportion of participants who died due to causes other than a 
relapse of their primary hematologic disease.  The comparison between treatment 
groups will be conducted using a 2-sample proportion test with normal 
approximation.  Cumulative incidence rates will be provided.  Summary statistics and 
applicable 95% CI will be provided. 
• Proportion of participants with ≥ 50% reduction in daily corticosteroid dose at 
Day 180.  The comparison between treatment groups will be conducted using a 
2-sample proportion test with normal approximation. 
• Proportion of participants successfully tapered off all corticosteroids at Day 180.  The 
comparison between treatment groups will be conducted using a 2-sample proportion 
test with normal approximation. 
• Relapse rate of malignant and nonmalignant hematologic diseases, defined as the 
proportion of participants whose underlying disease relapses.  The comparison 
between treatment groups will be conducted using the log-rank test.  The 
Kaplan-Meier method will be used.  Summary statistics will be provided. 
• Time to primary hematologic disease relapse, defined as the interval between the date 
of randomization and the date of relapse. 
Exploratory subgroup analyses and/or sensitivity analyses based on baseline prognostic factors 
(eg, primary hematologic disease, prior acute GVHD, type of allogeneic transplant, prior JAK 
inhibitors use) will be prospectively defined as part of the analyses plan and performed based on 
data availability. 
Data from clinical safety assessments (eg, AEs, infections) will be listed and tabulated by 
treatment group. 
10.4.3. 
Safety Analyses 
Safety analyses will be conducted for the safety population.  Adverse events will be coded by the 
MedDRA dictionary, and TEAEs (ie, AEs reported for the first time or worsening of a 
pre-existing event after first dose of study drug/treatment) will be tabulated by preferred term 
and system organ class for all events, related events, and events of Grade 3 or higher.  
Quantitative safety variables and their changes from baseline (laboratory, vital signs, etc) will be 
summarized with descriptive statistics.  Clinically notable abnormal values will be flagged and 
tabulated based on predefined criteria. 
Clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned.  In addition, distributions of key laboratory parameters may be plotted 
over time; these values will also be classified into CTCAE v4.03 toxicity grades and tabulated.  
Descriptive statistics and mean change from baseline will be determined for vital signs at each 
assessment time.  Vital sign results will be reviewed for clinically notable abnormalities. 


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Measures of exposure (eg, days of exposure, dose intensity, etc) of study drug and reference 
therapy will be summarized by means of summary statistics. 
In order to accommodate the changes proposed in Protocol Amendment 8 that resulted in 
discontinuation of Treatment Group C (300 mg BID) and subsequent dose reduction of on-going 
participants in Treatment Group C to 400 mg QD, safety tables (specifically AEs) will be 
presented for the 300 mg BID group with participants who are subject to dose reduction and 
censored at the date of switching to the lower dose (400 mg QD).  In addition, an overall 
summary including both dose groups (participants included before and after the dose reduction) 
will also be presented. 
10.4.4. 
Pharmacokinetic Analyses 
In participants with full profiles, that is, in Part 1, Part 1 expansion, or Part 2 before the IA, the 
PK parameters of Cmax, Tmax, Cmin, AUC0-t, and Cl/F will be calculated from the blood plasma 
concentrations of itacitinib using standard noncompartmental (model-independent) PK methods.  
Pharmacokinetic calculations will be performed using commercial software such as WinNonlin® 
(Pharsight Corporation, Mountain View, CA).  Predose concentrations at Day 7 and Day 28 will 
be summarized for participants in Part 2 after the IA. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
10.5. 
Interim Analysis 
An interim analysis for futility will be performed once 70 participants (35 per arm) have 
completed the Day 180 visit; the final analysis will be performed once all participants have 
completed the Day 180 visit. 


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A group sequential design method for 2-sample binary outcome data was used to calculate the 
lower futility boundary for the interim analysis with an HSD(–4) spending function.  The study 
will be stopped for futility if the test statistic z is less than –0.87.  In the final analysis, if the test 
statistics z is ≥ 1.96, then the superiority of itacitinib plus corticosteroids over placebo plus 
corticosteroids will be claimed. 
Preplanned analyses of safety (Part 1, Part 1 expansion, and Part 2) and efficacy (Part 1 
expansion and Part 2) will be provided to an independent DMC as specified in the DMC charter.  
The process by which the DMC will review data and make recommendations and decisions will 
be documented in the DMC charter. 
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 IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 


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• 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. 
11.2. 
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 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. 
The sponsor (or designee) will be responsible for: 
• The data management of this study including quality checking of the data. 
• 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. 
The investigator will be responsible for: 
• Ensuring participant data relating to the study is recorded in the eCRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, diary data) 
or as otherwise specified in the Protocol.  The investigator is responsible for verifying 
that data entries are accurate and correct by physically or electronically signing the 
eCRF. 


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• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator's site. 
− Data reported on the CRF or 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.  Also, current medical records 
must be available. 
• 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 privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
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 
local data protection laws. 


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11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies participant 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 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 
Armand P, Gibson CJ, Cutler C, et al. A disease risk index for patients undergoing allogeneic 
stem cell transplantation. Blood 2012;120:905-913. 
Armand P, Kim H, Logan B, et al. Validation and refinement of the Disease Risk Index for 
allogeneic stem cell transplantation. Blood 2014;123:3664-3671. 
Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014. http://www.hma.eu/fileadmin/dateien/ 
Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_ 
Contraception.pdf. Accessed October 2, 2017. 
DMB-18.60.1. Pharmacokinetics and pharmacokinetics/pharmacodynamics from a randomized, 
parallel-cohort phase 1 study of itacitinib in combination with corticosteroids for the treatment of 
acute graft-versus-host disease: INCB 39110-108. Wilmington, DE: Incyte Corporation. 
Approval Date: 24 MAY 2019. 
DMB-20.35.1. Noncompartmental Analysis of Itacitinib Pharmacokinetics From a Randomized, 
Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination with 
Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease 
(GRAVITAS-301, INCB 39110-301). Wilmington, DE: Incyte Corporation. Approval 
Date: 20 MAR 2020. 
Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute 
graft-versus-host disease and for chronic graft-versus-host disease according to National 
Institutes of Health consensus criteria. Blood 2011;117:3214-3219. 
Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood 
2015;125:606-615. 
Food and Drug Administration (FDA). Drug Development and Drug Interactions: Table of 
Substrates, Inhibitors and Inducers. 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
onsLabeling/ucm093664.htm#table3-3. Accessed November 1, 2018. 
Holtan SG, Pasquini M, Weisdorf DJ. Acute graft-versus-host disease: a bench-to-bedside 
update. Blood 2014;124;363-373. 
Itacitinib Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Jagasia M, Arora M, Flowers ME, et al. Risk factors for acute GVHD and survival after 
hematopoietic stem cell transplantation. Blood 2012;119:296-307. 
Jagasia MH, Greinix HT, Williams KM, et al. National Institutes of Health Consensus 
Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 
2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant 
2015;21:389-401. 
Lee SJ, Flowers ME. Recognizing and managing chronic graft-versus-host disease. Hematology 
Am Soc Hematol Educ Program 2008:134-141. 


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Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host 
disease. National Institutes of Health consensus development project on criteria for clinical trials 
in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol 
Blood Marrow Transplant 2015;21:984-999. 
MacDonald KP, Hill GR, Blazar BR. Chronic graft-versus-host disease: biological insights from 
preclinical and clinical studies. Blood 2017;129:13-21. 
Martin PJ, Lee SJ, Prezpiorka D, et al. National Institutes of Health Consensus Development 
Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 
Clinical Trial Design Working Group Report. Biol Blood Marrow Transplant 
2015;21:1343-1359. 
Matsuda K, Yamauchi K, Tozuka M, et al. Monitoring of hematopoietic chimerism by short 
tandem repeats, and the effect of CD selection on its sensitivity. Clin Chem 2004;50:2411-2414. 
Niederwieser D, Baldomero H, Szer J, et al. Hematopoietic stem cell transplantation activity 
worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow 
Transplantation Group including the global survey. Bone Marrow Transplant 2016;51:778 785. 
Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014;124:374-384. 
Thall PF, Simon R, Estey EH. Bayesian sequential monitoring designs for single-arm clinical 
trials with multiple outcomes. Stat Med 1995;14:357-379. 
Thall PF, Simon R, Estey EH. New statistical strategy for monitoring safety and efficacy in 
single-arm clinical trials. J Clin Oncol 1996;14:296-303. 
Thall PF, Sung HG. Some extensions and applications of a Bayesian strategy for monitoring 
multiple outcomes in clinical trials. Stat Med 1998;17:1563-1580. 
Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications 
among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow 
Transplant 2009;15:1143-1238. 
Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host 
disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia 
2015:29:2062-2068.  


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For male participants in the study: 
Male participants should use a condom during treatment and through 90 days after the end of 
systemic exposure.  If the male participant has a partner that is of child-bearing potential, the 
partner should also use contraception through 90 days after the end of relevant systemic 
exposure.  In addition, male participants must refrain from donating sperm during the study 
through 90 days after the end of relevant systemic exposure.  Males who have had a vasectomy 
qualify as having met the requirement for a highly effective birth control method. 
For female participants in the study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods. 
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• progestogen-only oral hormonal contraception, where inhibition of ovulation is not 
the primary mode of action 
• male or female condom with or without spermicide5 
• cap, diaphragm or sponge with spermicide5 
• tubal ligation 
For participants in the study in Canada: 
In order to conform to Health Canada guidance6, participants in this clinical study in Canada are 
to use 2 forms of contraception, including at least 1 form of highly effective and 1 effective 
method of contraception.  Participants who are using combined hormonal contraception or 
progestogen-only hormonal contraception will be required to include a barrier method as well. 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the contraception 
method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 


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3  Vasectomised partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. 
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatments.  The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the 
participant. 
5 A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also 
considered acceptable, but not highly effective, birth control methods. 
6 http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/womct_femec-eng.php (accessed May 28, 2019). 
Source:  Clinical Trial Facilitation Group 2014. 


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APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
STUDY DRUG (ITACITINIB OR PLACEBO) 
The participant must be instructed in the handling of study drug as follows: 
• Store the study drug at room temperature. 
• Only remove the number of tablets needed at the time of administration. 
• Not to remove doses in advance of the next scheduled administration. 
• Make every effort to take doses on schedule. 
• Report any missed doses/lost tablets/capsules. 
• Take study drug with a full glass of water. 
• If the participant vomits after taking study drug, the participant should not take 
another dose. 
• Keep study drug in a safe place and out of reach of children. 
• Bring all used and unused study drug bottles/kits to the site at each visit. 
• If a dose of itacitinib/placebo is missed by more than 8 hours, that dose should be 
skipped, and the next scheduled dose should be administered at the usual time. 


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APPENDIX C. DIAGNOSIS AND STAGING OF CHRONIC GVHD (NIH 
CRITERIA) 
Signs and Symptoms of Chronic GVHD (Jagasia et al 2015) 
Organ or Site 
Diagnostic Feature(s) 
(Sufficient to Establish 
the Diagnosis of 
cGVHD) 
Distinctive Featuresa 
(Seen in cGVHD, but 
Insufficient Alone to 
Establish a Diagnosis) 
Other Features or 
Unclassified Entities  
(cGVHD Manifestations 
if Diagnosis is Confirmed) 
Common 
(Seen With Both Acute 
and Chronic GVHD) 
Skin 
• Poikiloderma 
• Lichen planus-like 
features 
• Sclerotic features 
• Morphea-like features 
• Lichen sclerosus-like 
features 
• Depigmentation 
• Papulosquamous 
lesions 
• Sweat impairment 
• Ichthyosis 
• Keratosis pilar 
• Hypopigmentation 
• Hyperpigmenttaion 
• Erythema 
• Maculopapular rash 
• Pruritus 
Nails 
 
• Dystrophy 
• Longitudinal ridging, 
splitting or brittle 
features 
• Onycholysis 
• Pterigium unguis 
• Nail loss 
 
 
Scalp and 
body hair 
 
• New onset of scarring 
or non-scarring scalp 
alopecia (after 
recovery from 
chemoradiotherapy) 
• Loss of body hair 
• Scaling 
• Thinning scalp hair, 
typically patchy, coarse 
or dull (not explained by 
endocrine or other 
causes) 
• Premature gray hair 
 
Mouth 
• Lichen planus-like 
changes 
• Xerostomia 
• Mucoceles 
• Mucosal atrophy 
• Ulcers 
• Pseudomembranes 
 
• Gingivitis 
• Mucositis 
• Erythema 
• Pain 
Eyes 
 
• New onset dry, gritty, 
or painful eyes 
• Cicatricial 
conjunctivitis 
• Keratoconjunctivitis 
sicca 
• Confluent areas of 
punctate keratopathy 
• Photophobia 
• Periorbital 
hyperpigmentation 
• Blepharitis 
 


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Signs and Symptoms of Chronic GVHD (Continued) 
Organ or Site 
Diagnostic Feature(s) 
(Sufficient to Establish 
the Diagnosis of 
cGVHD) 
Distinctive Featuresa 
(Seen in cGVHD, but 
Insufficient Alone to 
Establish a Diagnosis) 
Other Features or 
Unclassified Entities  
(cGVHD Manifestations 
if Diagnosis is Confirmed) 
Common 
(Seen With Both Acute 
and Chronic GVHD) 
GI tract 
• Esophageal web 
• Strictures or stenosis in 
the upper to mid third 
of the esophagus 
 
• Exocrine pancreatic 
insufficiency 
• Anorexia 
• Nausea 
• Vomiting 
• Diarrhea 
• Weight loss 
• Failure to thrive 
(infants and children) 
Liver 
 
 
 
• Total bilirubin, 
Alkaline 
phosphatase, 
ALT > 2 × ULN 
Lung 
• Bronchiolitis obliterans 
diagnosed with lung 
biopsy 
• Bronchiolitis obliterans 
syndrome (BOS)b  
• Air trapping and 
bronchiectasis on chest 
CT 
• Cryptogenetic 
organizing pneumonia 
(COP) 
• Restrictive lung disease 
 
Muscle, fascia, 
joints 
• Fasciitis 
• Joint stiffness or 
contractures secondary 
to fasciitis or sclerosis 
• Myositis or 
polymyositis 
(Diagnosis of cGVHD 
requires biopsy) 
• Edema 
• Muscle cramps 
• Arthralgia or arthritis 
 
Genitalia 
• Lichen planus-like 
features 
• Lichen sclerosus-like 
features 
• Erosions 
• Fissures 
• Ulcers 
 
 
Genitalia 
Females 
• Vaginal scarring or 
clotorial/labial 
agglutination 
 
 
 
Genitalia 
Males 
• Phimosis or 
urethral/meatus 
scarring or stenosis 
 
 
 
Hematopoietic 
and immune 
 
 
• Thrombocytopenia 
• Eosinophilia 
• Lymphopenia 
• Hypo- or hyper-
gammaglobulinemia 
• Autoantibodies (AIHA, 
ITP) 
• Raynaud’s phenomenon 
 


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Signs and Symptoms of Chronic GVHD (Continued) 
Organ or Site 
Diagnostic Feature(s) 
(Sufficient to Establish 
the Diagnosis of 
cGVHD) 
Distinctive Featuresa 
(Seen in cGVHD, but 
Insufficient Alone to 
Establish a Diagnosis) 
Other Features or 
Unclassified Entities  
(cGVHD Manifestations 
if Diagnosis is Confirmed) 
Common 
(Seen With Both Acute 
and Chronic GVHD) 
Other 
 
 
• Pericardial or pleural 
effusions 
• Ascites 
• Peripheral neuropathy 
• Nephrotic syndrome 
• Myastenia gravis 
• Cardiac conduction 
abnormality or 
cardiomyopathy 
 
AIHA = autoimmune hemolytic anemia; ALT = alanine aminotransferase; ITP = idiopathic thrombocytopenic 
purpura; PFTs = pulmonary function tests. 
a In all cases, infection, drug effect, malignancy, or other causes must be excluded. 
b BOS can be diagnostic for lung cGVHD only, if distinctive sign or symptom present in another organ 


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APPENDIX D. STAGING OF CHRONIC GVHD (NIH CRITERIA) 
The definitions for mild, moderate, and severe chronic GVHD are as follows: 
NIH Global Severity of Chronic GVHD 
Mild Chronic GVHD 
• 1 or 2 organs involved with no more than score 1 plus 
• Lung score 0 
Moderate Chronic GVHD 
• 3 or more organs involved with no more than score 1 
OR 
• At least 1 organ or site with a max score of  2 
OR 
• Lung score 1 
Severe Chronic GVHD 
• At least 1 organ with a score of 3 
OR 
• Lung score of 2 or 3 
Key points: 
• In skin: higher of the 2 scores to be used for calculating global severity. 
• In lung: FEV11 is used instead of clinical score for calculating global severity. 
• If the entire abnormality in an organ is noted to be unequivocally explained by a 
non-GVHD documented cause, that organ is not included for calculation of the global 
severity. 
• If the abnormality in an organ is attributed to multifactorial causes (GVHD plus other 
causes), the scored organ will be used for calculation of the global severity regardless 
of the contributing causes (no downgrading of organ severity score). 
1 The FEV1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of 
total lung capacity. 
Staging of chronic GVHD as described by Jagasia et al (2015) should be performed using 
scoring criteria as described below. 


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Staging of Chronic GVHD (Jagasia et al 2015) 
 
 
Organ scoring of chronic GVHD.  ECOG indicates Eastern Cooperative Oncology Group; KPS, Karnofsky 
performance status; LPS, Lansky performance status; BSA, body surface area; ADL, activities of daily living; LFTs, 
liver function tests; AP, alkaline phosphatase; ALT, alanine aminotransferase; ULN, normal upper limit.  *Weight 
loss within 3 months. †Skin scoring should use both percentage of BSA involved by disease signs and the cutaneous 
features scales.  When a discrepancy exists between the percentage of total body surface (BSA) score and the skin 
feature score, OR if superficial sclerotic features are present (Score 2), but there is impaired mobility or ulceration 
(Score 3), the higher level should be used for the final skin scoring. To be completed by specialist or trained medical 
providers.  **Lung scoring should be performed using both the symptoms and FEV1 scores whenever possible.  
FEV1 should be used in the final lung scoring where there is discrepancy between symptoms and FEV1 scores. 


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Staging of Chronic GVHD (Continued) 
 
 
Organ scoring of chronic GVHD.  ECOG indicates Eastern Cooperative Oncology Group; KPS, Karnofsky 
performance status; LPS, Lansky performance status; BSA, body surface area; ADL, activities of daily living; LFTs, 
liver function tests; AP, alkaline phosphatase; ALT, alanine aminotransferase; ULN, normal upper limit. *Weight 
loss within 3 months.  †Skin scoring should use both percentage of BSA involved by disease signs and the 
cutaneous features scales. When a discrepancy exists between the percentage of total body surface (BSA) score and 
the skin feature score, OR if superficial sclerotic features are present (Score 2), but there is impaired mobility or 
ulceration (Score 3), the higher level should be used for the final skin scoring. To be completed by specialist or 
trained medical providers.  **Lung scoring should be performed using both the symptoms and FEV1 scores 
whenever possible.  FEV1 should be used in the final lung scoring where there is discrepancy between symptoms 
and FEV1 scores. 


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Staging of Chronic GVHD (Continued) 
 
Organ scoring of chronic GVHD.  ECOG indicates Eastern Cooperative Oncology Group; KPS, Karnofsky 
performance status; LPS, Lansky performance status; BSA, body surface area; ADL, activities of daily living; LFTs, 
liver function tests; AP, alkaline phosphatase; ALT, alanine aminotransferase; ULN, normal upper limit. *Weight 
loss within 3 months.  †Skin scoring should use both percentage of BSA involved by disease signs and the 
cutaneous features scales.  When a discrepancy exists between the percentage of total body surface (BSA) score and 
the skin feature score, OR if superficial sclerotic features are present (Score 2), but there is impaired mobility or 
ulceration (Score 3), the higher level should be used for the final skin scoring.  To be completed by specialist or 
trained medical providers.  **Lung scoring should be performed using both the symptoms and FEV1 scores 
whenever possible.  FEV1 should be used in the final lung scoring where there is discrepancy between symptoms 
and FEV1 scores. 


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APPENDIX E. RESPONSE ASSESSMENT FOR CHRONIC GVHD 
(NIH CRITERIA) 
Response will be assessed using NIH 2014 criteria (Lee et al 2015) 
a) 
Response determination for cGVHD by organ at postbaseline assessment 
(comparison versus baseline) 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after previous 
involvement 
Decrease in NIH Skin Score by 
1 or more points 
Increase in NIH Skin Score by 
1 or more points, except 0 to 1 
Eyes 
NIH Eye Score 0 after previous 
involvement 
Decrease in NIH Eye Score by 
1 or more points 
Increase in NIH Eye Score by 
1 or more points, except 0 to 1 
Mouth 
NIH Modified OMRS 0 after 
previous involvement 
Decrease in NIH Modified 
OMRS of 2 or more points 
Increase in NIH Modified 
OMRS of 2 or more points 
Esophagus 
NIH Esophagus Score 0 after 
previous involvement 
Decrease in NIH Esophagus 
Score by 1 or more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI Score 
by 1 or more points, except 0 to 
1 
Lower GI 
NIH Lower GI Score 0 after 
previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI Score 
by 1 or more points, except from 
0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and Total bilirubin 
after previous elevation of 1 or 
more 
Decrease by 50% 
Increase by 2 × ULN 
Lungs 
• Normal FEV1% after previous 
involvement 
• If PFTs not available, NIH 
Lung Symptom Score 0 after 
previous involvement 
• Increase by 10% predicted 
absolute value of FEV1% 
• If PFTs not available, decrease 
in NIH Lung Symptom Score 
by 1 or more points 
• Decrease by 10% predicted 
absolute value of FEV1% 
• If PFTs not available, increase 
in NIH Lung Symptom Score 
by 1 or more points, except 
0 to 1 
Joints and fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 25 
after previous involvement by at 
least 1 measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more points 
or increase in P-ROM score by 
1 point for any site 
Increase in NIH Joint and Fascia 
Score by 1 or more points or 
decrease in P-ROM score by 
1 point for any site 
Global 
Clinician overall severity score 0 
Clinician overall severity score 
decreases by 2 or more points on 
a 0-10 scale 
Clinician overall severity score 
increases by 2 or more points on 
a 0-10 scale 
Source:  Adapted from Lee et al 2015. 
 


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b) Response assessment for chronic GVHD by organ at baseline and at each post-baseline visit 
 
 


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All abnormalities should be documented; however, the organ is not evaluable if there is another 
well-documented non-chronic GVHD cause. 


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APPENDIX F. PATIENT GLOBAL IMPRESSION OF CHANGE AND 
PATIENT GLOBAL IMPRESSION OF SEVERITY  
Patient Global Impression of Change (PGIC) 
Please choose the response below that best describes the overall change in your chronic graft 
versus host disease symptoms since you started taking the study medication.  My chronic graft 
versus host disease symptoms are: 
  Very Much Better 
  Moderately Better 
  A Little Better 
  No Change 
  A Little Worse 
  Moderately Worse 
  Very Much Worse 
Patient Global Impression of Severity (PGIS) 
Please choose the response below that best describes the severity of your chronic graft versus 
host disease symptoms over the past week.  
  No Symptoms 
  Mild Symptoms 
  Moderate Symptoms 
  Severe Symptoms 
  Very Severe Symptoms 
 


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APPENDIX G. DISEASE RISK INDEX  
Disease at Diagnosis 
Stage at the Time of 
Transplant 
Disease Risk Index 
Group 
Hodgkin lymphoma CR 
 
Low 
Hodgkin lymphoma PR 
 
Intermediate 
Hodgkin lymphoma 
Advanceda 
High 
CLL CR 
 
Low 
CLL PR 
 
Low 
CLL 
Advanceda 
Intermediate 
Mantle cell lymphoma CR 
 
Low 
Mantle cell lymphoma PR 
 
Intermediate 
Mantle cell lymphoma 
Advanceda 
High 
Indolent B-cell NHLb CR 
 
Low 
Indolent B-cell NHLb PR 
 
Low 
Indolent B-cell NHLb 
Advanceda 
Intermediate 
T-cell NHL CR 
 
Intermediate 
T-cell NHL PR 
 
Intermediate 
T-cell NHL 
Advanceda 
High 
Aggressive B-cell NHLc CR 
 
Intermediate 
Aggressive B-cell NHLc PR 
 
Intermediate 
Aggressive B-cell NHLc 
Advanceda 
Very high 
AML favorable cytogenetics CR 
 
Low 
AML favorable cytogenetics 
Advanceda 
High 
AML intermediate cytogenetics CR 
 
Intermediate 
AML intermediate cytogenetics 
Advanceda 
High 
AML adverse cytogenetics CR 
 
High 
AML adverse cytogenetics 
Advanceda 
Very high 
CML chronic phase 1/2 
 
Low 
CML advanced phase 
 
Intermediate 
CML blast phase 
 
Very high 
Myeloproliferative neoplasm 
Any 
Intermediate 
ALL CR1 
 
Intermediate 
ALL CR2 
 
High 
ALL CR3 
 
High 
ALL 
Advanceda 
Very high 
High-risk MDSd adverse cytogenetics 
Earlye 
High 
High-risk MDSd intermediate cytogenetics 
Earlye 
Intermediate 
High-risk MDSd intermediate cytogenetics 
Advanceda 
High 
High-risk MDSd adverse cytogenetics 
Advanceda 
High 
Low-risk MDSf adverse cytogenetics 
Earlye 
Intermediate 
Low-risk MDSf adverse cytogenetics 
Advanceda 
High 
Low-risk MDSf intermediate cytogenetics 
Earlye 
Intermediate 
Low-risk MDSf intermediate cytogenetics 
Advanceda 
Intermediate 
Burkitt lymphoma CR 
 
High 


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Disease at Diagnosis 
Stage at the Time of 
Transplant 
Disease Risk Index 
Group 
Burkitt lymphoma PR 
Advanceda 
Very high 
Multiple myeloma CR/VGPR/PR 
 
Intermediate 
Multiple myeloma 
Advanceda 
High 
CR = complete remission; PR = partial remission; VGPR = very good partial remission. 
a Advanced stage refers to induction failure or active relapse, including stable or progressive disease for NHL, Hodgkin 
lymphoma, and CLL.  
b Indolent B-cell NHL includes follicular lymphoma, marginal zone lymphoma and lymphoplasmacitic lymphoma.  Small 
lymphocytic lymphoma is included in the CLL group. 
c Aggressive B-cell NHL includes diffuse large B-cell lymphoma and transformed indolent B-cell lymphoma 
d High-risk MDS refers to MDS with > 5% blasts (RAEB-1 and RAEB-2). 
e Early stage MDS includes untreated patients and patients in CR. 
f Low-risk MDS refers to MDS ≤ 5% blasts (refractory anemia with or without ringed sideroblasts and refractory cytopenia with 
multilineage dysplasia). 
Source:  Adapted from Armand et al 2014 and Armand et al 2012. 
Cytogenetic groups (Armand et al 2014): 
For AML: 
• AML favorable cytogenetics:  t(8;21), inv(16), t(15,17) 
• AML adverse cytogenetics:  Complex karyotype (≥ 4 abnormalities) 
• AML intermediate cytogenetics:  All others 
For MDS and AML arising from MDS: 
• MDS adverse cytogenetics:  Abnormal chromosome 7 or complex karyotype 
(≥ 4 abnormalities) 
• MDS intermediate cytogenetics:  All others 


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APPENDIX H. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
16 AUG 2018 
Amendment (Version) 2: 
02 NOV 2018 
Amendment (Version) 3: 
30 NOV 2018 
Amendment (Version) 4: 
07 JUN 2019 
Amendment (Version) 5: 
30 AUG 2019 
Amendment (Version) 6: 
16 DEC 2019 
Amendment (Version) 7: 
03 APR 2020 
Amendment (Version) 8: 
30 SEP 2021 
Amendment 8 (30 SEP 2021) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is for the 
discontinuation of Treatment Group C in the Part 1 expansion of the study and to update 
risk/benefit information, the dose reduction scheme for concomitant medications, and the 
frequency of PFTs in GVHD follow-up. 
1. Section 1, Protocol Summary (Figure 1:  Study Design Schema); Section 2.3.2.3, 
Preliminary Results for Part 1 Expansion; Section 2.4, Benefit/Risk Assessment; 
Section 4.1.2, Part 1 Expansion (Table 7:  Treatment Groups and Dose Levels and 
Schedules); Section 6.1.1, Itacitinib/Placebo (Table 9:  Study Treatment 
Information, Part 1 Expansion) 
Description of change:  All relevant sections were updated to discontinue Treatment 
Group C (itacitinib 300 mg BID plus corticosteroids) and include preliminary data to 
provide the rationale for this decision. 
Rationale for change:  Based on emerging data and following the DMC 
recommendation, the sponsor decided to discontinue the itacitinib 300 mg BID study 
arm. 
2. Section 1, Protocol Summary (Table 4:  Schedule of Activities) 
Description of change:  Decreased frequency of FEV1% in GVHD follow-up. 
Rationale for change:  To remain consistent with the frequency of FEV1% assessments 
both on-treatment and in GVHD follow-up following Day 196 on study. 
3. Section 1, Protocol Summary (Table 4:  Schedule of Activities); Section 8.3.8, 
Laboratory Assessments (Table 20:  Clinical Laboratory Analytes); Section 8.3.8.2, 
Serum Chemistry 
Description of change:  Addition of direct and indirect bilirubin for participants with 
high bilirubin levels. 
Rationale for change: To clarify the need for bilirubin fractions (direct and indirect 
bilirubin) in participants with high total bilirubin to aid in cGVHD evaluation. 


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4. Section 2.3.2.4, Dose Modifications for Concomitant Medications (Table 5:  
Preliminary PK Parameters From Part 1 and Part 1 Expansion by Dose, Strong 
CYP3A Inhibitor Coadministration Status, and Day); Section 6.1.1.5, Criteria and 
Procedures for Dose Interruptions and Adjustments of Study Drug (Table 13:  
Itacitinib Dose Reduction for Part 1 Expansion) 
Description of change:  Updated the relevant sections to include the appropriate 
itacitinib dose reduction with concomitant use of strong CYP3A4 inhibitors and include 
rationale for these reductions where appropriate. 
Rationale for change:  To standardize the dose reduction of itacitinib with concomitant 
strong CYP3A4 inhibitors based upon emerging data. 
5. Section 2.4 Benefit/Risk Assessment 
Description of change:  Updated section to include summary of recent animal studies in 
rats. 
Rationale for change:  To include additional data regarding the risk/benefit profile of 
the compound. 
6. Section 10.4.2.2, Part 1 Expansion; Section 10.4.3, Safety Analyses 
Description of change:  Updated the statistics sections to clarify how the efficacy and 
safety analysis will be completed following the discontinuation of treatment group C. 
Rationale for change: For clarification of the statistical analysis for different treatment 
groups in the Part 1 Expansion. 
7. Appendix C, Diagnosis and Staging of Chronic GVHD (NIH Criteria) 
Description of change:  Addition of signs and symptoms of cGVHD. 
Rationale for change:  To provide NIH criteria for the first diagnosis of cGVHD in 
addition to staging criteria supporting eligibility assessment. 
8. 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 7 (03 APR 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is for the 
addition of a Part 1 expansion of the study and to update inclusion criteria, dose reduction 
scheme for concomitant medications, and itacitinib taper. 
1. Title Page; Section 1, Protocol Summary (Table 1:  Objectives and Endpoints, 
Part 1 and Part 1 Expansion; Table 3:  Key Study Design Elements; Figure 1:  
Study Design Schema; Table 6:  Schedule of Activities); Section 2.3.1, Scientific 
Rationale for Study Design; Section 2.3.2.2, Rationale For Part 1 Expansion; 
Section 4.1, Overall Design; Section 4.1.2, Part 1 Expansion; Section 4.1.3, Part 2; 
Section 4.2, Overall Study Duration; Section 5.5, Replacement of Participants; 
Section 6.1.1, Itacitinib/Placebo; Section 6.1.1.3, Dose-Limiting Toxicity Assessment; 
Section 6.1.1.4, Determination of the Part 2 Dose; Section 6.1.2, Corticosteroids; 
Section 6.3.3, Prohibited Medications and Procedures; Section 8.4.1, Blood Sample 
Collection; Section 10.1.2, Part 1 Expansion; Section 10.3, Level of Significance; 
Section 10.4.1.1, Part 1 and Safety Run-In for Part 1 Expansion; Statistical 
Analysis; Section 10.4.2.2, Part 1 Expansion; Section 10.4.4, Pharmacokinetic 
Analyses; Section 10.5, Interim Analysis 
Description of change:  All relevant sections were updated to include the addition of a 
Part 1 expansion to explore additional doses and dosing schedules for itacitinib and the 
addition of a corticosteroids monotherapy cohort. 
Rationale for change:  Entire rationale is provided in Section 2.3.2.1 and is based on 
emerging data. 
2. Section 2.3.2.3, Dose Modifications for Concomitant Medications; Section 6.1.1.3, 
Dose-Limiting Toxicity Assessment; Section 6.1.1.5, Criteria and Procedures for 
Dose Interruptions and Adjustments of Study Drug; Section 6.3.2, Restricted 
Medications and Procedures 
Description of change:  Updated the relevant sections to include the appropriate 
itacitinib dose reduction with concomitant use of strong CYP3A4 inhibitors and include 
rationale for these reductions where appropriate. 
Rationale for change:  To standardize the dose reduction of itacitinib with concomitant 
strong CYP3A4 inhibitors based upon emerging data. 
3. Section 5.1, Inclusion Criteria 
Description of change:  Updated Inclusion Criterion 5. 
Rationale for change:  To ensure a more homogenous patient population with regard to 
bone marrow function at study entry and support a more accurate assessment of 
hematologic toxicity of different dosing/regimens of itacitinib. 


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4. Section 6.1.1.6, Tapering of Itacitinib or Placebo and Treatment Duration 
Description of change:  Updated the duration of treatment with itacitinib/placebo for 
participants achieving a CR or PR.  
Rationale for change:  To recommend for participants that achieved CR or PR, a 
treatment duration of at least 1 year, in accordance with recommendations for systemic 
therapy for moderate-to-severe chronic GVHD (Flowers and Martin 2015).   
5. Section 7.1.1, Reasons for Discontinuation 
Description of change:  Revised to indicate that if during the course of the study a 
participant is found not to have met eligibility criteria, the participant will be 
discontinued unless discontinuation would result in a risk to the participant, as per the 
investigator's medical judgment.  Removed the sponsor medical monitor from the 
sentence. 
Rationale for change:  Determination of participant discontinuation in this situation will 
be based on the judgment of the investigator only. 
6. Section 8.3.8, Laboratory Assessments (Table 18:  Clinical Laboratory Analytes) 
Description of change:  Updated to include cholesterol. 
Rationale for change:  To identify any changes in cholesterol. 
7. 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 6 (16 DEC 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is specify the 
dose for Part 2 based on the analysis of data from Part 1 of the study, update the dose 
modification and interruption guidelines, and provide clarification in several areas of the 
Protocol. 
1. Section 1, Protocol Summary (including Figure 1: Study Design Schema); 
Section 2.3.1, Scientific Rationale for Study Design; Section 2.3.2.1, Preliminary 
Results From Part 1; Section 4.1.2, Part 2; Section 6.1.1, Itacitinib/Placebo (Table 8: 
Study Treatment Information Part 2) 
Description of change:  All relevant sections were updated to include the determined 
dose for Part 2 and the rationale for the dose decision based on Part 1 analysis summary 
where applicable. 
Rationale for change:  To provide the dose for Part 2 of the study. 
2. Section 1, Protocol Summary (Table 4:  Schedule of Activities); Section 8.2.3, 
Hematologic Disease Relapse Monitoring; Section 8.3.8, Clinical Laboratory 
Analytes (Table 16: Clinical Laboratory Analytes); Section 8.8.2, Post-Treatment 
GVHD Follow-Up 
Description of change:  Updated the schedule of activities to change the frequency of 
cGVHD response assessment after 1 year, disease/malignancy relapse, FEV1, several 
quality-of-life assessments, and correlative sample collections. 
Rationale for change:  To decrease the frequency of certain assessments when not 
necessary. 
3. Section 2.3.2.2, Dose Modifications for Concomitant Medications; Section 6.3.2, 
Restricted Medications and Procedures 
Description of change:  Updated the relevant sections to include a dose reduction for 
concomitant medication posaconazole and include rationale from Part 1 analysis where 
appropriate. 
Rationale for change:  To add posaconazole to the list of medications requiring a dose 
reduction of itacitinib. 
4. Section 5.1, Inclusion Criteria 
Description of change:  Updated inclusion criteria 2b to provide clarity of the expected 
corticosteroids. 
Rationale for change:  For clarification. 
5. Section 5.2, Exclusion Criteria 
Description of change:  Updated exclusion criteria 3, 9, and 21 to provide clarity of the 
criteria.  Criterion 5 was removed as it was added to exclusion criterion 9 to provide 
clarification. 
Rationale for change:  For clarification. 


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6. Section 6.1.1.4, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug (Table 10:  Itacitinib/Placebo Dose Modification Guidelines) 
Description of change:  Revised guidelines for itacitinib/placebo dose modifications 
based on safety data from Part 1. 
Rationale for change:  To provide additional guidance on dose modifications. 
7. Section 6.1.1.5, Tapering of Itacitinib or Placebo and Treatment Duration; 
Section 6.1.2.3, Corticosteroid Tapering 
Description of change:  Added clarification of the tapering guidelines and timelines for 
itacitinib, placebo, and corticosteroids. 
Rationale for change:  For clarification. 
8. Section 6.1.2, Corticosteroids; Section 6.1.2.4, Management of Corticosteroids 
During cGVHD Flare 
Description of change:  Added clarification of the expected corticosteroids. 
Rationale for change: For clarification. 
9. 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 5 (30 AUG 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to ensure 
consistency between sections of the Protocol describing the reasons for discontinuation in 
response to VHP request. 
1. Section 7.1.1, Reasons for Discontinuation 
Description of change:  Clarified that a participant must be withdrawn from study 
treatment if "additional systemic therapy is considered due to lack of clinical benefit from 
study treatment." 
Rationale for change:  To ensure consistency between Section 6.1.1.5 and Section 7.1.1 
regarding discontinuation of treatment in the case of a lack of clinical benefit. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 4 (07 JUN 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to update 
and clarify exclusion criteria, definition for treatment failure, DLT criteria, treatment of 
overdose, and maximum duration of study treatment, as well as respond to health authorities. 
1. Section 1, Protocol Summary (Table 3: Key Study Design Elements; Table 4: 
Schedule of Activities); Section 4.1.1, Part 1; Section 4.1.2, Part 2; Section 8.8.2, 
Post-Treatment GVHD Follow-Up 
Description of change:  Revised to clearly define treatment failure in the context of this 
protocol and provide clarification on the post-treatment follow-up portion of the study. 
Rationale for change:  To provide clarification to the definition of treatment failure and 
ensure consistency with Table 5 (Objectives and Endpoints, Part 1). 
2. Section 1, Protocol Summary (Table 3: Key Study Design Elements); Section 4.1.1, 
Part 1; Section 4.1.2, Part 2; Section 4.2, Overall Study Duration 
Description of change:  Updated the estimated duration of study participation. 
Rationale for change:  For clarification. 
3. Section 1, Protocol Summary (Table 2: Objectives and Endpoints, Part 2; Table 4: 
Schedule of Activities); Section 3, Objectives and Endpoints (Table 6: Objectives 
and Endpoints, Part 2);  Section 8.2.4, Patient-Reported Outcomes; Section 10.4.2.2, 
Part 2; Appendix E, Patient Global Impression of Change and Patient Global 
Impression of Severity  
Description of change:  Added the PGIC and PGIS questionnaires to the patient-
reported outcomes and updated all relevant sections. 
Rationale for change:  To collect and provide additional data for patient-reported 
changes. 
4. Section 5.2, Exclusion Criteria 
Description of change:  Updated exclusion criteria 1, 4, and 10 to clarify the criteria.  
Updated exclusion criterion 11 to provide clarity and differentiate between the conflicting 
time frame in exclusion criterion 3, which is specific to the use of corticosteroids for the 
purpose of cGVHD. 
Rationale for change:  Clarification to address frequently asked questions. 
5. Section 6.1.1.3, Dose-Limiting Toxicity Assessment and Determination of Part 2 
Dose (Table 9: Definitions of Dose-Limiting Toxicity) 
Description of change:  Added criteria that transient abnormal laboratory values without 
associated clinically significant signs and symptoms and not leading to hospitalization 
will not be considered as DLTs. 
Rationale for change:  To provide guidance and clarification for events qualifying as a 
DLT. 


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6. Section 6.1.1.4, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug 
Description of change:  Section updated to include additional details and guidance 
regarding dose reductions and modifications. 
Rationale for change:  For clarification. 
7. Section 6.1.1.5, Tapering of Itacitinib or Placebo and Treatment Duration 
Description of change:  Section updated to include the maximum duration for study 
treatment and examples of the taper. 
Rationale for change:  For clarification. 
8. Section 6.3.3, Prohibited Medications and Procedures 
Description of change:  Section updated to include clarification regarding maintenance 
therapy for primary hematologic disease while on study. 
Rationale for change:  For clarification. 
9. Section 8.1.1, Informed Consent Process 
Description of change:  Section updated to include guidance specific to Germany 
regarding authorized legal representation. 
Rationale for change:  Feedback from VHP. 
10. Section 8.1.5.1, Demographics and General Medical History 
Description of change:  Removed language stating that the collection of medical history 
will include "date of birth, race, ethnicity, medical and surgical history, and current 
illnesses.  Medical history will include relevant medical or surgical treatment details that 
are considered to be clinically significant by the investigator.” 
Rationale for change:  To correct an error, since date of birth will not be collected and 
for consistency with other itacitinib protocols. 
11. Section 8.1.5.2, Disease Characteristics and Treatment History  
Description of change:  Updated to include details about disease-targeted medical and 
treatment history. 
Rationale for change:  To provide more detail on information that should be collected. 
12. Section 8.3.5, Infection Monitoring 
Description of change:  Removed testing for herpes simplex virus, human T-cell 
lymphotropic virus 1/2,  hepatitis A, and IgG/IgM toxoplasmosis from routine infection 
monitoring. 
Rationale for change:  Key opinion leader feedback and standard-of-care testing in this 
patient population. 


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13. Section 9.10, Treatment of Overdose 
Description of change:  Updated the guidance on treatment of an overdose to be 
consistent with the current IB. 
Rationale for change:  To ensure consistency with the IB. 
14. Appendix A, Information Regarding Effectiveness of Contraceptive Methods 
Description of change:  Added contraception requirements for study participants in 
Canada. 
Rationale for change:  Health Canada guidance. 
15. Appendix F, Disease Risk Index 
Description of change:  Addition of a disease risk index table to ensure consistency 
across the study. 
Rationale for change:  To provide additional clarification to ensure consistency of 
determination of the disease risk index across the study. 
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. 


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Amendment 3 (30 NOV 2018) 
Overall Rationale for the Amendment:  Response to VHP. 
1. Section 2.4, Benefit/Risk Assessment 
Description of change:  Clarification was added that PML is a rare complication in 
allo-HCT recipients.  Actions to minimize the risk of PML in cGVHD participants will 
follow standard allo-HCT guidelines, including close monitoring of any clinical signs of 
progressive focal neurological symptoms, with prompt diagnostic work-up and treatment.  
Any case of PML should be reported as per the process described in Section 9.4. 


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Amendment 2 (02 NOV 2018) 
Overall Rationale for the Amendment:  Response to VHP. 
1. Section 2.3.2.1, Dose Modifications for Concomitant Medications 
Description of change:  Correction was made to the language with regard to exposure 
when itacitinib is coadministered with a potent CYP3A inhibitor.  
2. Section 2.3.2.2, Dose Rationale for Organ Impairment 
Description of change:  Added clarification that patients with hepatic impairment due to 
cGVHD may potentially benefit from study treatment, with improvement of their liver 
function.  The benefit from treatment could outweigh the risk in these patients; therefore, 
patients with hepatic impairment due to cGVHD may be enrolled in the study under close 
monitoring for response to treatment and liver function improvement.  
3. Section 5, Study Population 
Description of change:  Added clarification that deviations from eligibility are not 
allowed when enrolling a participant into the study 
4. Section 5.1, Inclusion Criteria 
Description of changes: 
• Rewording of criterion 3 that patients with any degree of HLA matching may be 
included. 
• Added clarification to criterion 5 that transfusion to reach a minimum platelet 
count for inclusion is not allowed within the 7 days before the screening 
laboratory assessment. 
5. Section 6.3.3, Prohibited Medications and Procedures 
Description of change:  Added a link to FDA website for the current list of potent 
CPY3A4 inducers. 
6. Section 8.9, Data Monitoring Committee 
Description of change:  New section was added to describe the DMC. 
7. Section 9.6, Emergency Unblinding of Treatment Assignment 
Description of change:  Added a statement that the responsibility to break the treatment 
code in an emergency situation resides solely with the investigator. 
8. Section 10.4.1.1, Part 1 
Description of changes:   
• Added clarification that itacitinib will be monitored continuously for each 
treatment group. 
• Revised Table 19 to clarify that the maximum allowable toxicities for 
20 participants in Part 1 is 9. 
9. Appendix D, Response Assessment for Chronic GVHD (NIH Criteria) 
Description of change:  Included the correct reference to the assessment from the 
manuscript and removed the previous snapshot since it was missing a section. 


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Amendment 1 (16 AUG 2018) 
Overall Rationale for the Amendment:  Response to Regulatory Authority feedback. 
1. Title Page 
Description of change:  Annie Im, MD, and Steven Z. Pavletic, MD, MS, were listed on 
the title page as the Protocol steering committee chair and co-chair, respectively. 
Rationale for change:  To include the steering committee co-chairs in the Protocol. 
2. Section 1, Protocol Summary (Table 1, Objectives and Endpoints, Part 1; Table 2, 
Objectives and Endpoints, Part 2); Section 3, Objectives and Endpoints (Table 5, 
Objectives and Endpoints, Part 1; Table 6, Objectives and Endpoints, Part 2); 
Section 10.4, Statistical Analyses 
Description of changes:   
• Malignancy relapse (MR) was removed from the DoR endpoint for efficacy 
outcomes. 
• Malignancy relapse was replaced with relapse of primary hematologic disease for 
NRM and time to MR endpoints. 
• Malignancy relapse rate was replaced with relapse rate of malignant and 
nonmalignant hematologic diseases. 
Rationale for changes:  To provide clarification for study endpoints 
3. Section 1, Protocol Summary (Table 4, Schedule of Activities); Section 8.3.8.2, 
Serum Chemistry 
Description of changes: 
• “Disease” follow-up was corrected to indicate “GVHD” follow-up. 
• Safety assessments : Clarification/edits 
− Chimerism was clarified to indicate Graft failure/chimerism; these should be 
monitored throughout the study as clinically indicated. 
− Weight should be collected during the GVHD follow-up period. 
− Height was removed.  
• Efficacy assessments: Clarifications/edits 
− FEV1% was added as an assessment and footnoted to indicate a window for 
Day 1 if bronchiolitis obliterans was not diagnosed at screening.   
− Disease/malignancy relapse data should be collected during screening. 
− Clarification/edit was made for quality-of-life assessments (LSS, QOL-SF-36, 
EQ-5D-3L); data do not need to be collected at screening. 
− New cGVHD therapy data do not to be collected during safety follow-up. 


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• Laboratory assessments: Clarifications/edits 
− Lipid panel was added 
− Hematology, chemistry and lipid panel should be collected at the safety follow-up 
visit.   
− Serum chemistry (total bilirubin, ALT, and alkaline phosphatase) should be 
collected during the GVHD follow-up period. 
•  Footnotes were added for clarification 
− To indicate a window for specific assessments that are required on Day 1.   
− If liver cGVHD is diagnosed at screening, then total bilirubin, ALT, and alkaline 
phosphatase should be repeated on Day 1.  
Rationale for changes:  To allow a window for Day 1 assessments; to ensure cGVHD 
response, new cGVHD therapy, safety, laboratory, and quality-of-life assessments are 
performed and data collected at that correct timepoints; and to correct inconsistencies. 
4. Section 2.3.1, Scientific Rationale for Study Design; Section 5.2, Exclusion Criteria 
Description of change:  Clarified that the patient population will include patients with 
various hematologic diseases. 
Rationale for change:  Response to Regulatory Authority feedback. 
5. Section 2.3.2, Justification for Dose 
Description of changes: 
• Revised to include justification for doses chosen for Part 1. 
• Added Section 2.3.2.1 for Dose Modifications for Concomitant Medications. 
• Added Section 2.3.2.2 for Dose Rationale for Organ Impairment 
Rationale for change:  Response to Regulatory Authority feedback. 
6. Section 4.2, Overall Study Duration 
Description of changes:  Clarification that the study will end once all randomized 
participants have reached Month 36, not when 75% of patients have died. 
Rationale for change:  To correct an error. 


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7. Section 5.2, Exclusion Criteria; Section 8.3.8.4, Hepatitis Screening 
Description of changes: 
• Added exclusion for more than 1 prior allo-HCT. 
• Clarified criteria for hepatitis screening. 
• Removed serum creatinine to limit eligibility for renal function to creatinine 
clearance. 
• Added exclusion criterion for participants who started maintenance therapy for the 
primary hematologic disease within 4 weeks before initiation of study treatment 
(Day 1). 
• Added exclusion for FEV1 < 30%. 
Rationale for changes:  Response to Regulatory Authority feedback. 
8. Section 6.1.1.3, Dose-Limiting Toxicity Assessment and Determination of Part 2 
Dose (Table 9, Definitions of Dose-Limiting Toxicity) 
Description of change:  For hematologic toxicity, platelet count was revised to “Platelet 
count < 10 × 109/L that does not recover to at least 20 × 109/L after 2 weeks with no 
requirement for platelet transfusion in the preceding 3 days.” 
Rationale for change:  To provide clarification on the definition for hematologic 
toxicity.  
9. Section 6.1.1.5, Tapering of Randomized Therapy; Section 6.1.2.4, Management of 
Corticosteroids During cGVHD Flare 
Description of change: 
• Added clarification that subsequent tapering may occur within 28 to 56 days after the 
initial taper, as appropriate. 
• Added clarification that a physiological dose of 6 to 8 mg/day of methylprednisolone 
(ie, 7.5-10 mg/day of prednisone) during itacitinib taper is allowed and will not be 
considered treatment failure. 
• Corrected guidance that if a participant requires new systemic therapy or experiences 
a subsequent flare it will be considered progression.  
• Added clarification that a short pulse of corticosteroids may be used once, without 
being considered progression, as long as the dose does not exceed 1 mg/kg per day 
and can be tapered to physiological doses of 6 to 8 mg/day of methylprednisolone (or 
7.5-10 mg/day of prednisone) within 6 weeks from starting. 
Rationale for change:  To provide guidance and clarification with regard to tapering of 
study drug and corticosteroids.  


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10. Section 6.3.2, Restricted Medications and Procedures; Section 6.3.3, Prohibited 
Medications and Procedures 
Description of change:  
• Added clarification with regard to potent CYP3A4 inhibitors and guidance that the 
some potent CYP3A inhibitors (itraconazole, voriconazole, mibefradil, and 
clarithromycin) may require a dose reduction of itacitinib to 100 mg QD, as more 
potent inhibitors have been shown to increase exposure to itacitinib. 
• Added bullet to indicate coadministration with potent CYP3A4 inducers is prohibited. 
• Added clarification that post-transplant maintenance treatment for the primary 
hematologic disease is not permitted. 
• Added clarification that use of targeted therapies with anti-GVHD activity, including 
but not limited to TNF-alpha inhibitors and IL-6R inhibitors, are not permitted. 
Rationale for change:  Response to Regulatory Authority feedback. 
11. Section 7.1.1, Reasons for Discontinuation 
Description of changes: 
• Removed “Completion of 36 months of study treatment.” 
• Revised bullet point for GVHD progression. 
• Added bullet point for “Relapse of primary hematologic disease.” 
Rationale for changes: 
• To provide guidance and clarification with regard to the appropriate reasons for 
discontinuation of study treatment. 
12. Section 8.3.6, Graft Failure and Chimerism Monitoring 
Description of change:  Added clarification that monitoring of graft failure will be 
primarily based on the monitoring of blood counts and supported by chimerism studies, 
defined secondary graft failure.  Chimerism testing using peripheral blood or bone 
marrow will be performed at the treating investigator's discretion according to local 
institutional practice. 
Rationale for change:  To provide guidance and clarification with regard to graft failure 
and chimerism monitoring. 
13. Section 8.3.7, Electrocardiograms 
Description of change:  Added justification for no additional ECG assessments, other 
than what is already proposed. 
Rationale for change:  Response to Regulatory Authority feedback 


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14. Section 8.4.2, Pharmacokinetic Analysis 
Description of changes: Added language to clarify that additional PBPK modeling and 
simulations may be conducted to support the dose for Part 2. 
Rationale for change:  Response to Regulatory Authority feedback. 
15. Section 1, Protocol Summary (Table 3, Key Study Design Elements; Table 4, 
Schedule of Activities); Section 8.8.2, Post-Treatment GVHD Follow-Up; 
Section 8.8.3, Survival Follow-Up 
Description of change:  Added Section 8.8.2 to describe follow-up period for 
participants who complete study treatment or discontinue early for reasons other than 
GVHD progression.  GVHD follow-up period is a maximum of 24 months, and 
participants would then move into survival follow-up. 
Rationale for change:  To provide guidance with regard to post-treatment follow-up. 
16. Section 9.4, Reporting of Serious Adverse Events 
Description of change:  Added language to clarify that any SAEs occurring more than 
30 days after the last dose of study drug should be reported to the sponsor, only if the 
investigator suspects a causal relationship to the drug. 
Rational for change:  To provide clarification for SAE reporting. 
17. Section 10.4.1, Primary Analysis; Section 10.4.2, Secondary Analysis 
Description of changes: 
• Added language to clarify that an exploratory subgroup analysis of moderate and 
severe cGVHD as well as overall survival for risk status will be performed. 
• Added bullet to indicate that exploratory subgroup analyses and/or sensitivity 
analyses based on baseline prognostic factors will be prospectively defined as part of 
the analyses plan and performed based on data availability. 
Rationale for change:  Response to Regulatory Authority feedback. 
18. Appendix C, Staging of Chronic GVHD (NIH Criteria) 
Description of changes:  
• To correct the definition of Moderate Chronic GVHD. 
• To correct the title to “Staging” as opposed to “Grading” of cGVHD. 
Rationale for changes:  To ensure consistency with the staging criteria published by 
Jagasia et al (2015). 


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19. Appendix D, Response Assessment for Chronic GVHD (NIH Criteria) 
Description of changes:  
• To correct the title  
• To add the scoring criteria for response assessments 
Rationale for changes:  To include guidance on response assessments based on NIH 
criteria (Lee et al 2015). 
20. 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-000629 v10.0
Signature Page for VV-CLIN-000629 v10.0
Approval
Document Preparer
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SAP_001.pdf: 
NCT Number: 
Document Date: 
GRAVITAS-309:  A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial 
Treatment for Chronic Graft-Versus-Host Disease 
NCT03584516
Statistical Analysis Plan Amendment Version 1: 03 March 2022
Official Title: 


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STATISTICAL ANALYSIS PLAN 
GRAVITAS-309:  A Phase 2/3 Study of Itacitinib and 
Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host 
Disease 
TITLE PAGE
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 8 dated 30 SEP 2021 
CRF Approval Date: 
13 OCT 2021 
SAP Version: 
Amendment 1 
SAP Author:  
 
, Biostatistics 
Date of Plan: 
03 MAR 2022 
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 
1.1. 
Preliminary Results From Part 1...................................................................................8 
1.2. 
Rationale for Part 1 Expansion .....................................................................................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 .......................................................................................................10 
3.1. 
Randomization ............................................................................................................11 
3.1.1. 
Part 1 ...........................................................................................................................11 
3.1.2. 
Part 1 Expansion .........................................................................................................11 
3.2. 
Control of Type I Error ...............................................................................................11 
3.3. 
Sample Size Considerations .......................................................................................11 
3.3.1. 
Part 1 ...........................................................................................................................11 
3.3.2. 
Part 1 Expansion .........................................................................................................12 
3.4. 
Schedule of Assessments ............................................................................................13 
4.
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................13 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................13 
4.1.1. 
Day 1 ...........................................................................................................................13 
4.1.2. 
Study Day ...................................................................................................................13 
4.1.3. 
Baseline Value ............................................................................................................13 
4.1.4. 
Last Available Value ..................................................................................................14 
4.1.5. 
Handling of Missing and Incomplete Data .................................................................14 
4.2. 
Variable Definitions ....................................................................................................14 
4.2.1. 
Body Mass Index ........................................................................................................14 
4.2.2. 
Body Surface Area ......................................................................................................14 
4.2.3. 
Prior and Concomitant Medication .............................................................................14 
5.
STATISTICAL METHODOLOGY ...........................................................................15 
5.1. 
General Methodology .................................................................................................15 


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5.2. 
Treatment Groups .......................................................................................................15 
5.2.1. 
Part 1 ...........................................................................................................................15 
5.2.2. 
Part 1 Expansion .........................................................................................................15 
5.3. 
Analysis Populations ..................................................................................................15 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................16 
6.1. 
Baseline Demographics, Physical Characteristics, and Disease History ....................16 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................16 
6.1.2. 
Disease History for Chronic Graft-Versus-Host Disease ...........................................16 
6.1.3. 
Medical History ..........................................................................................................16 
6.1.4. 
Primary Hematologic Disease and Transplant Characteristics ...................................16 
6.2. 
Disposition of Participants ..........................................................................................16 
6.3. 
Protocol Deviations ....................................................................................................17 
6.4. 
Exposure .....................................................................................................................17 
6.5. 
Study Drug Compliance .............................................................................................18 
6.6. 
Prior and Concomitant Medication .............................................................................18 
7. 
EFFICACY .................................................................................................................19 
7.1. 
General Considerations ...............................................................................................19 
7.2. 
Primary Analysis ........................................................................................................19 
7.3. 
Analyses of the Secondary Efficacy Parameters ........................................................19 
7.3.1. 
Response Rate .............................................................................................................19 
7.3.2. 
Time to Response .......................................................................................................20 
7.3.3. 
Duration of Response .................................................................................................20 
7.3.4. 
Best Overall Response ................................................................................................21 
7.3.5. 
Overall Survival ..........................................................................................................21 
7.3.6. 
Nonrelapse Mortality Rate ..........................................................................................21 
7.3.7. 
Relapse Rate of Malignant and Nonmalignant Hematologic Diseases ......................21 
7.3.8. 
Time to Primary Hematologic Disease Relapse .........................................................21 
7.3.9. 
Other Efficacy Analyses .............................................................................................22 
8. 
PHARMACOKINETIC ANALYSES 
 ..........22 
8.1. 
Pharmacokinetic Analyses ..........................................................................................22 
 
22 
9. 
SAFETY AND TOLERABILITY ..............................................................................23 


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9.1. 
General Considerations ...............................................................................................23 
9.2. 
Adverse Events ...........................................................................................................23 
9.2.1. 
Adverse Event Definitions ..........................................................................................23 
9.2.2. 
Dose-Limiting Toxicities ............................................................................................24 
9.2.3. 
Adverse Event Summaries ..........................................................................................25 
9.2.4. 
Clinically Notable Adverse Events Based on Customized MedDRA Queries ...........27 
9.3. 
Analyses for the Data Monitoring Committee ............................................................27 
9.4. 
Clinical Laboratory Tests ...........................................................................................27 
9.5. 
Vital Signs ..................................................................................................................27 
9.6. 
Electrocardiograms .....................................................................................................28 
10. 
INTERIM ANALYSES ..............................................................................................28 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................28 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................28 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................28 
12. 
REFERENCES ...........................................................................................................29 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................30 
APPENDIX B. CLINICALLY NOTABLE HEMATOLOGIC EVENTS .................................34 
APPENDIX C. HEMATOLOGIC INFECTION EVENTS ........................................................35 
APPENDIX D. HYPERLIPIDEMIA EVENTS .........................................................................36 
APPENDIX E. QT PROLONGATION EVENTS ......................................................................38 
APPENDIX F. THROMBOEMBOLIC EVENTS......................................................................39 
APPENDIX G. PLANNED TABLES AND FIGURES FOR PHARMACOKINETIC 
AND PHARMACOKINETIC/PHARMACODYNAMIC ANALYSIS ....................45 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints, Part 1 and Part 1 Expansion ...............................................9 
Table 2: 
Treatment Groups and Dose Levels and Schedules ...................................................11 
Table 3: 
Bayesian Posterior Probability to Demonstrate That There Is a Clinically 
Meaningful Difference 
 Between Any Itacitinib Group and the 
Corticosteroids-Only Group .......................................................................................12 
Table 4: 
Populations for Analysis .............................................................................................15 
Table 5: 
Definitions of Dose-Limiting Toxicity .......................................................................24 
Table 6: 
Toxicity Stopping Boundaries ....................................................................................25 


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Table 7: 
Criteria for Vital Sign Abnormalities .........................................................................27 
Table 8: 
Statistical Analysis Plan Versions ..............................................................................28 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
aGVHD 
acute graft-versus-host disease 
AUC 
area under the plasma or serum concentration-time curve 
AUC0-t 
area under the plasma or serum concentration-time curve from time = 0 to the last 
measurable concentration at time = t 
BID 
twice daily 
BMI 
body mass index 
BOR 
best overall response 
BSA 
body surface area 
cGVHD 
chronic graft-versus-host disease 
CI 
confidence interval 
Cl/F 
apparent oral dose clearance 
Cmax 
maximum observed plasma or serum concentration 
Cmin 
minimum observed plasma or serum concentration 
CMV 
cytomegalovirus 
CR 
complete response 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee 
DoR 
duration of response 
EBV 
Epstein-Barr virus 
eCRF 
electronic case report form 
GVHD 
graft-versus-host disease 
ITT 
intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities  
MQ 
MedDRA query 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NRM 
nonrelapse mortality 
ORR 
objective response rate 
OS 
overall survival 
PK 
pharmacokinetic 
PR 
partial response 
PT 
preferred term 


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Abbreviation 
Term 
QD 
once daily 
SAP 
Statistical Analysis Plan 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
This is a 2-part, Phase 2/3 study of itacitinib or placebo in combination with corticosteroids as 
initial treatment for cGVHD.  Part 1 is a run-in that will employ a randomized, open-label, 
parallel-cohort design with the primary objective to assess the safety and tolerability of itacitinib 
in combination with corticosteroids in order to identify the appropriate dose of itacitinib in 
combination with corticosteroids as initial treatment for moderate or severe cGVHD.  A total of 
20 participants with moderate or severe cGVHD will be randomized 1:1 to itacitinib 200 mg QD 
plus corticosteroids or 300 mg QD plus corticosteroids. 
Part 1 expansion is a Phase 2 with an initial safety run-in that will employ a randomized, 
open-label, parallel-cohort design with the primary objective to assess the safety and preliminary 
efficacy of itacitinib in combination with corticosteroids compared with corticosteroids 
monotherapy and identify the appropriate dosing/schedule of itacitinib in combination with 
corticosteroids as initial treatment for cGVHD for Part 2.  A total of up to 140 participants 
(35 per treatment group) with moderate or severe cGVHD will be randomized 1:1 to 1 of 
4 treatment groups:  itacitinib 300 mg QD plus corticosteroids (Treatment Group A), itacitinib 
400 mg QD plus corticosteroids (Treatment Group B), itacitinib 300 mg BID plus corticosteroids 
(Treatment Group C), or corticosteroids monotherapy (Treatment Group D).  Randomization will 
be stratified by cGVHD risk status (moderate vs severe).  Treatment Groups B and C will have 
an initial safety run-in of 10 participants to determine safety and tolerability of the dose before 
expansion.  Participants enrolled in the safety run-in will be monitored continuously. Treatment 
Group C was discontinued as of Amendment 8, and participants in that treatment group who 
were ongoing were allowed to reduce to 400 mg QD plus corticosteroids. 
The purpose of the original version of the SAP was to provide details of the statistical analyses 
that have been outlined in Part 1 of the Protocol. 
The purpose of Amendment 1 is to provide details of the statistical analyses that have been 
outlined in Part 1 expansion of Protocol Amendment 8. 
1.1. 
Preliminary Results From Part 1 
Preliminary data from Part 1 were reviewed by an independent DMC, and the summary data are 
presented in the Protocol.  The DMC recommended that 300 mg QD be chosen as the Part 2 dose 
of itacitinib as no differences emerged between the doses with respect to toxicity. 
1.2. 
Rationale for Part 1 Expansion 
Additional dosing regimens of itacitinib were selected for evaluation in combination with 
corticosteroids in an expansion to Part 1 of the study, and the underlying rationale is presented in 
the Protocol.   


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This amendment of the SAP is based on INCB 39110-309 Protocol Amendment 8 dated 
30 SEP 2021 and CRFs approved 13 OCT 2021.   
2.2. 
Study Objectives and Endpoints 
Study objectives and endpoints for Part 1 and Part 1 expansion are shown in Table 1. 
Table 1: 
Objectives and Endpoints, Part 1 and Part 1 Expansion 
Objectives 
Endpoints 
Primary  
To identify an appropriate dose of itacitinib in 
combination with corticosteroids as initial 
treatment for moderate or severe cGVHD. 
Part 1:  DLT data through Day 28 and additional 
data from clinical safety and laboratory 
assessments. 
Part 1 expansion:  Incidence and severity of 
adverse events, across treatment cohorts. 
Key Secondary (for Part 1 Expansion) 
To evaluate preliminary activity across treatment 
cohorts with respect to response rate at Month 3 
and Month 6. 
Response rate at Month 3 and Month 6, defined as 
the proportion of participants who demonstrate a 
CR or PR at each timepoint. 
Secondary 
To evaluate the PK of itacitinib when 
administered in combination with corticosteroids 
in the study population. 
Cmax, Cmin, Tmax, AUC0-t, and Cl/F. 
To estimate efficacy outcomes for each treatment 
cohort. 
Part 1:  Response rate at Month 3, 6, and 12. 
Part 1 expansion:  Response rate at Month 12. 
Response rate is defined as the proportion of 
participants who demonstrate either a CR or PR at 
each timepoint. 
Time to response, defined as the interval between 
randomization and first response. 
DoR, defined as the interval between first 
response and cGVHD progression, death, or 
initiation of new systemic cGVHD therapy. 
OS, defined as the interval between the date of 
randomization and the date of death due to any 
cause. 
NRM, defined as the proportion of participants 
who died due to causes other than a relapse of 
their primary hematologic disease. 
Proportion of participants with ≥ 50% reduction 
in daily corticosteroid dose at Day 180. 


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Table 1: 
Objectives and Endpoints, Part 1 and Part 1 Expansion (Continued) 
Objectives 
Endpoints 
To estimate efficacy outcomes for each treatment 
cohort (continued). 
Proportion of participants successfully tapered off 
all corticosteroids at Day 180. 
Relapse rate of malignant and nonmalignant 
hematologic diseases, defined as the proportion of 
participants whose underlying disease relapses. 
Time to primary hematologic disease relapse, 
defined as the interval between the date of 
randomization and the date of relapse. 
3. 
STUDY DESIGN 
Part 1 is a run-in that will employ a randomized, open-label, parallel-cohort design to assess the 
safety and tolerability of itacitinib in combination with corticosteroids in order to identify the 
appropriate dose level for initial treatment of moderate or severe cGVHD.  A total of 
20 participants with moderate or severe cGVHD will be randomized 1:1 to itacitinib 200 mg QD 
plus corticosteroids or 300 mg QD plus corticosteroids.  Itacitinib treatment will continue until 
treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), 
unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.  Participants may 
remain on study for a total of 37 months, including the treatment period, safety follow-up, and 
post-treatment GVHD follow-up, unless death or withdrawal of consent occurs earlier. 
Chronic GVHD staging and grading will be assessed using NIH consensus guidelines (Jagasia 
et al 2015, Lee et al 2015); safety and tolerability will be assessed as per NCI CTCAE v4.03. 
An analysis to determine the dose for further study will be performed once the 20th evaluable 
participant completes 28 days of study treatment.  An external DMC will review data from this 
analysis and provide a recommendation on an appropriate dose for Part 2. 
In Part 1, any participant who withdraws from treatment before the completion of the 28-day 
observation period for any reason other than a DLT (eg, not evaluable for DLT) may be replaced 
to ensure a minimum number of evaluable participants. 
Part 1 expansion is a Phase 2 with an initial safety run-in that will employ a randomized, 
open-label, parallel-cohort design with the primary objective to assess the safety and preliminary 
efficacy of itacitinib in combination with corticosteroids compared with corticosteroids 
monotherapy and identify the appropriate dosing/schedule of itacitinib in combination with 
corticosteroids as initial treatment for cGVHD for Part 2.  A total of up to 140 participants 
(35 per treatment group) with moderate or severe cGVHD will be randomized 1:1 to 1 of 
4 treatment groups (see Table 2):  itacitinib 300 mg QD plus corticosteroids (Treatment Group 
A), itacitinib 400 mg QD plus corticosteroids (Treatment Group B), itacitinib 300 mg BID plus 
corticosteroids (Treatment Group C), or corticosteroids monotherapy (Treatment Group D). 


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Table 2: 
Treatment Groups and Dose Levels and Schedules 
Treatment 
Group 
Dose Level and Schedule 
A 
Itacitinib 300 mg QD plus corticosteroids 
B 
Itacitinib 400 mg QD plus corticosteroids 
C 
Itacitinib 300 mg BID plus corticosteroids; may be decreased to 200 mg BID if a 
boundary is reached during safety run-in.  This treatment group was discontinued 
due to concern of a potential increase in relapse rate.  Participants in this 
treatment group who were ongoing were allowed to reduce to 400 mg QD plus 
corticosteroids. 
D 
Corticosteroids monotherapy 
3.1. 
Randomization 
3.1.1. 
Part 1 
A total of 20 participants with moderate or severe cGVHD will be randomized 1:1 to itacitinib 
200 mg QD plus corticosteroids or 300 mg QD plus corticosteroids. 
3.1.2. 
Part 1 Expansion 
A total of up to 140 participants (35 per treatment group) with moderate or severe cGVHD will 
be randomized 1:1 to 1 of 4 treatment groups:  itacitinib 300 mg QD plus corticosteroids 
(Treatment Group A), itacitinib 400 mg QD plus corticosteroids (Treatment Group B), itacitinib 
300 mg BID plus corticosteroids (Treatment Group C), or corticosteroids monotherapy 
(Treatment Group D). 
Randomization will be stratified by cGVHD risk status (moderate vs severe).  Treatment Groups 
B and C will have an initial safety run-in of 10 participants to determine safety and tolerability of 
the dose before expanding (see definition of DLT in Section 6.1.1.3 of the Protocol).  
Participants enrolled in the safety run-in will be monitored continuously using the Bayesian 
approach. Treatment Group C was discontinued as of Amendment 8, and participants in that 
treatment group who were ongoing were allowed to reduce to 400 mg QD plus corticosteroids. 
3.2. 
Control of Type I Error 
No formal statistical tests will be performed in Part 1 and Part 1 expansion.  All CIs will be 95%. 
3.3. 
Sample Size Considerations 
3.3.1. 
Part 1 
In Part 1, approximately 20 participants will be enrolled to achieve 10 randomly assigned 
participants in each of the 2 dose groups of itacitinib in order to identify an optimal dose for 
further study.  This sample size was chosen based on typical Phase 1 studies employing a 3 + 3 
design that enroll up to 9 participants in order to identify recommended Phase 2 doses.  A sample 
size of 20 participants (10 per treatment group) allows for concurrent enrollment at 2 dose levels 


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that have been previously characterized in other disease settings and is expected to enable the 
clinical characterization of study treatment across 2 treatment cohorts.  No formal statistical 
comparison will be performed between treatment groups. 
3.3.2. 
Part 1 Expansion 
Sample size in Part 1 expansion is based on clinical feasibility and consideration.  No hypothesis 
test is planned for efficacy.  Up to 35 participants will be enrolled into each treatment group.  
The toxicity of itacitinib will be monitored continuously for Treatment Groups B and C using a 
Bayesian approach.  A total of up to 140 participants will be enrolled into Part 1 expansion of the 
study.  Regarding the key secondary endpoint, Month 6 response rate, a table of Bayesian 
posterior probabilities and related descriptions are provided below.  This posterior probability 
may be used to support decision-making on itacitinib dosing/schedule for Part 2, including 
decisions made by the DMC 
Table 3 presents Bayesian posterior probability of demonstrating a clinically meaningful 
treatment difference 
in Month 6 response rate between any itacitinib group and the 
corticosteroids-only group under various response rates at the end of the expansion. 
Table 3: 
Bayesian Posterior Probability to Demonstrate That There Is a Clinically 
Meaningful Difference
Between Any Itacitinib Group and the 
Corticosteroids-Only Group 
Responders in an Itacitinib Group 
(out of 35) 
Responders in Corticosteroids-Only Group (out of 35) 
18 
19 
20 
21 
22 
25 
64.3% 
54.8% 
45.0% 
35.3% 
26.4% 
26 
73.1% 
64.4% 
54.9% 
44.8% 
35.0% 
27 
80.9% 
73.4% 
64.7% 
54.9% 
44.7% 
28 
87.2% 
81.3% 
73.9% 
65.0% 
55.0% 
29 
92.1% 
87.7% 
81.9% 
74.4% 
65.3% 
30 
95.5% 
92.6% 
88.4% 
82.6% 
75.0% 
Note:  With a binomial likelihood, binomial (n, p) with s number of responders out of n participants, and a beta 
prior, Beta (a, b), the posterior is calculated as Beta(a+s, b+n-s). 
Interpretation: 
 
 
 
 
 
 
 
 
 
 


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3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 8 dated 30 SEP 2021 for a full description of all study procedures 
and assessment schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of itacitinib is administered to the participants.  For the 
corticosteroids-only group, Day 1 will be defined as the first nonmissing dose day. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as 
Day # = (visit/reporting date – Day 1 date). 
A study day of -1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of study 
treatment (eg, itacitinib with corticosteroids or corticosteroids only).  When itacitinib and 
corticosteroids are started on different days, then the rules mentioned in Section 4.1.1 will be 
followed. 
When scheduled assessments and unscheduled assessments occur on the same day, and 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. 


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4.1.4. 
Last Available Value 
The last available value is the last nonmissing measurement obtained after starting the study 
treatment.   
4.1.5. 
Handling of Missing and Incomplete Data  
Missing observations will be handled for specific endpoints as detailed in the sections addressing 
each analysis. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.2. 
Body Surface Area 
Body surface area will be calculated based on the Mosteller (1987) formula as follows: 
BSA (m2) = {[weight (kg)  height (cm)] / 3600}½. 
Sites will also record the BSA calculated per institutional standards. 
4.2.3. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of itacitinib 
or corticosteroids for participants on corticosteroids only in the Part 1 expansion. 
Concomitant medication is defined as any nonstudy medication that is started accordingly:  
• Before the date of first administration of itacitinib or corticosteroids only and is 
ongoing throughout the study or ends on/after the date of first itacitinib or 
corticosteroid administration. 
• On/after the date of first administration of itacitinib or corticosteroids only and is 
ongoing or ends during the course of itacitinib or corticosteroid treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after the first dose of itacitinib or corticosteroids only.  Since corticosteroids are part 
of the study medication, they will not appear in the list of prior and concomitant medications 
unless prescribed for an indication other than GVHD.  In the listing, it will be indicated whether 
a medication is prior only, concomitant only, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; v9.4 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 
5.2.1. 
Part 1 
A total of 20 participants with moderate or severe cGVHD will be randomized 1:1 to itacitinib 
200 mg QD plus corticosteroids or itacitinib 300 mg QD plus corticosteroids. 
5.2.2. 
Part 1 Expansion 
A total of up to 140 participants (35 per treatment group) with moderate or severe cGVHD will 
be randomized 1:1 to 1 of 4 treatment groups:  itacitinib 300 mg QD plus corticosteroids 
(Treatment Group A), itacitinib 400 mg QD plus corticosteroids (Treatment Group B), itacitinib 
300 mg BID plus corticosteroids (Treatment Group C), or corticosteroids monotherapy 
(Treatment Group D). 
5.3. 
Analysis Populations 
The populations that will be included in study-related analyses are described in Table 4. 
Table 4: 
Populations for Analysis 
Population 
Description 
ITT 
All randomized participants 
Safety 
All enrolled/randomized participants who received at least 1 dose of study 
drug and/or reference therapy.  Treatment groups for this population will be 
determined according to the actual treatment the participant received 
regardless of assigned study drug treatment. 
Safety run-in 
All participants enrolled in the safety run-in portion of the study who received 
at least 1 dose of study drug and/or reference therapy.  Treatment groups for 
this population will be determined according to the treatment assignment on 
Day 1 regardless of the actual study drug the participant might take during 
their continued participation in the study. 
PK evaluable 
All participants who received at least 1 dose of study drug and/or reference 
therapy and provided at least 1 postdose plasma sample (1 PK measurement).  
The study pharmacokineticist will review data listings of study drug 
administration and sample records to identify participants to be excluded from 
analyses of PK data. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of planned tables, figures, and listings. 
6.1. 
Baseline Demographics, Physical Characteristics, and Disease 
History 
Demographic and baseline characteristics, disease history, and prior therapy will be summarized 
for the safety run-in and Part 1 expansion populations and listed. 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographic and baseline characteristics will be summarized for the safety run-in 
population and Part 1 expansion:  age, sex, race, ethnicity, weight (by sex), height, BMI, BSA, 
and Karnofsky performance status. 
6.1.2. 
Disease History for Chronic Graft-Versus-Host Disease 
Baseline cGVHD staging and grading, time since diagnosis of cGVHD, organs involved, 
aGVHD (yes/no) and grade, conditioning and prophylaxis therapy, donor type, and other details 
related to the disease under study and transplant will be summarized at baseline.  Day 1 
assessment will be used to determine baseline organ involvement. 
Time since cGVHD diagnosis will be calculated as: 
Time since diagnosis (years) = (Day 1 date – date of diagnosis + 1) / 365.25. 
6.1.3. 
Medical History 
For participants in the safety run-in population and participants in the Part 1 expansion, medical 
history will be summarized by assigned treatment group.  This summation will include the 
number and percentage of participants for each body system/organ class as documented on the 
eCRF. 
6.1.4. 
 Primary Hematologic Disease and Transplant Characteristics 
Summary will include disease-targeted medical and treatment history such as participant's 
primary hematologic disease, including diagnosis, prior therapy, disease stage at the time of 
transplantation, disease risk index, and details regarding allogeneic hematopoietic stem cell 
transplantation; prior and current GVHD prophylaxis; history of aGVHD; and current cGVHD 
staging information. 
Cancer history and underlying hematologic disease will also be summarized. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were randomized, treated, completed treatment, 
discontinued study treatment with a primary reason for discontinuation, and withdrew from the 
study with a primary reason for withdrawal will be summarized for the safety run-in population  
and the Part 1 expansion population. 


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6.3. 
Protocol Deviations 
Protocol deviations recorded on the eCRF will be summarized and presented in the participant 
data listings. 
6.4. 
Exposure 
For participants in the safety run-in population and participants in the Part 1 expansion, exposure 
to itacitinib and corticosteroids will be summarized descriptively as follows. 
• Duration of treatment with itacitinib: 
The exposure start date is when trt = itacitinib and exposure timepoint = first dose; 
when a participant does not have first dose record (but has other timepoints) as the 
exposure timepoint, exposure start date should be when trt = itacitinib and dose is not 
missing. 
Duration of treatment (days) = Date of last dose of itacitinib – Date of first dose of 
itacitinib + 1. 
• Average daily dose of itacitinib: 
Average daily dose (mg/day) = Total actual itacitinib dose taken (mg) / Duration of 
treatment with itacitinib (days). 
• Dose modifications of itacitinib: 
Numbers of participants who had itacitinib dose reduction and/or interruption will be 
summarized.  Separate summaries will be generated for participants with dose change 
due to dose tapering (change of dose due to efficacy of treatment) and participants 
with dose change due to other reasons (potential safety concerns). 
• Duration of treatment with corticosteroids: 
For corticosteroids, the first exposure start date is when the dose is not missing. 
Duration of treatment (days) = Date of last dose of corticosteroid – Date of first dose 
of corticosteroid + 1. 
If a participant is being treated with a corticosteroid prior to Day 1, study Day 1 will 
be used if no other data are available to conform to the definition provided in 
Section 4.1.1.  If a participant is prescribed a corticosteroid for a flare during the 
course of the study, duration of treatment will be adjusted to account for the break in 
treatment between completing taper and starting of a short pulse for a flare. 
• Average daily dose of corticosteroids: 
Average daily dose (mg/day) = Total actual corticosteroid dose taken (mg) / Duration 
of treatment with corticosteroids (days). 
Daily dose will account for how the doses are prescribed (eg, BID is converted to 
twice daily). 


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• Reduction in daily dose of corticosteroids and successful tapering of 
corticosteroids  
Numbers of participants who had dose reduction and/or interruption of corticosteroids 
will be summarized as follows: 
• Summary of number of participants with ≥ 50% reduction in daily 
corticosteroid dose at Day 180 
• Summary of participants successfully tapered off all corticosteroids at 
Day 180 
• Summary of number of participants with ≥ 50% reduction in daily 
corticosteroid dose by (4-week) time interval up to Month 6 
• Summary of participants successfully tapered off all corticosteroids by 
(4-week) time interval up to Month 6 
Participants will be considered as having a competing risk at the time of cGVHD progression or 
start of a new systemic therapy for cGVHD, relapse of the underlying hematologic disease, or 
death. 
Sensitivity analyses may be performed for participants who had their corticosteroid dose 
increased during the corticosteroid taper period for a non-GVHD medical condition. 
6.5. 
Study Drug Compliance 
For participants in the safety run-in population and participants in the Part 1 expansion, overall 
compliance (%) for the study treatment will be calculated for all participants as follows: 
Compliance (%) = 100  [total dose actually taken] / [total prescribed dose]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
6.6. 
Prior and Concomitant Medication 
For participants in the safety run-in population and participants in Part 1 expansion, prior 
medications and concomitant medications will be coded using the WHO Drug Dictionary and 
summarized by WHO drug class and WHO drug term.  Results will be summarized as number 
and percentage of participants with prior and concomitant medications by PT and WHO drug 
class. 


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7. 
EFFICACY 
Appendix A provides a list of planned tables, figures, and listings. 
7.1. 
General Considerations 
In Part 1, all efficacy analyses will be performed using the safety run-in population. In Part 1 
Expansion, all efficacy analyses will be performed using the safety population. 
If there are not sufficient data for meaningful statistical inference, the planned analysis will not 
be performed, and only related summary statistics and/or listings will be provided. 
In all efficacy analyses, initiation of new systemic anti-GVHD therapy includes 4 scenarios: 
1. Initiation of new anti-GVHD therapy including a higher dose of corticosteroid than that 
used at Day 1. 
2. The need for a second dose increase in corticosteroids. 
3. A dose increase in corticosteroids that is not tapered back to the previous dose of 
corticosteroids within 6 weeks (± 2 days) of the increase. 
4. Reintroduction of systemic corticosteroids that occurs after complete taper of 
corticosteroids due to response. 
No formal statistical tests will be performed. 
7.2. 
Primary Analysis 
In Part 1, the primary objective is to identify an appropriate dose of itacitinib (200 mg QD or 
300 mg QD) in combination with corticosteroids as initial treatment for moderate or severe 
cGVHD.  The DLT data through Day 28 and additional data from clinical safety and laboratory 
assessments will be used as primary endpoints for this analysis. 
In Part 1 Expansion, the primary objective is to identify an appropriate dose of itacitinib (300 mg 
QD, 400 mg QD, or 300 mg BID) in combination with corticosteroids as initial treatment for 
moderate or severe cGVHD. The selection of the dose is primarily based on the incidence and 
severity of AEs across treatment cohorts and will be supported by cGVHD response data (refer 
to Section 10.1.2 of the Protocol). 
7.3. 
Analyses of the Secondary Efficacy Parameters 
7.3.1. 
Response Rate 
Response rate at 3, 6, and 12 months (Days 90, 180, and 365) is defined as the proportion of 
participants who achieved a response (CR or PR) at each of these timepoints based on an ITT 
population. 
A participant will not be considered a responder for the analysis of ORR at 3, 6, and 12 months if 
any of the following events occurred at or prior to the response assessment at the predefined 
timepoint: 
• cGVHD progression per NIH response criteria or initiation of a new systemic therapy 
for cGVHD  


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• Evidence of progression of the underlying hematologic disease 
• Withdrawal from the study 
• Death 
• Response assessment missing (not performed) at the predefined timepoint 
The proportion of responders will be estimated with 95% CIs.  Confidence intervals will be 
calculated based on the exact method for binomial distributions.  Summary statistics will be 
provided. 
Additional analyses may be performed based on evaluable subsets.  An evaluable population will 
also be considered with participants who have completed 3, 6, or 12 months of follow-up as of 
the cutoff date or discontinued earlier because of new cGVHD progression.  Presentations of 
ORR at Month 3 and Month 6 will include a footnote explaining what "evaluable" means (ie, 
participants who had at least 3 or 6 months of follow-up as of the cutoff date or discontinued 
earlier). 
Summary statistics and 95% CI will be provided by cohort.  The primary comparisons in Part 1 
expansion will involve only the 2 itacitinib groups (Treatment Groups A and B) and the 
corticosteroids-only group (Treatment Group D) as a result of Protocol Amendment 8, in which 
Treatment Group C (300 mg BID + corticosteroids) was discontinued.  Data from Treatment 
Group C will be presented only as summary statistics and will not be subjected to any statistical 
comparison. 
Pairwise Cochran-Mantel-Haenszel tests will be conducted for Month 6 response rate for each of 
the 2 itacitinib groups (Treatment Groups A and B) and the corticosteroids-only group 
(Treatment Group D) as an exploratory analysis. 
The secondary endpoints discussed below will be summarized by Treatment Groups A, B, and D 
using the ITT population for efficacy-related endpoints and all groups for safety-related 
endpoints. 
7.3.2. 
Time to Response 
Time to response is defined as the interval from randomization to first response (CR or PR) 
before initiation of new therapy.  In the time to response analysis, participants without a response 
after randomization will be censored at either study withdrawal, initiation of new systemic anti-
GVHD therapy, death, relapse, or last response assessment prior to or on the cutoff date, 
whichever is earliest. Time to response will be summarized for participants who achieve a 
response using the Kaplan-Meier method. Median time to response and a 95% CI will be 
estimated. 
7.3.3. 
Duration of Response 
Duration of response is defined as the interval between the date of initial documentation of 
response (CR or PR) and the date of cGVHD progression per NIH response criteria, initiation of 
new systemic cGVHD therapy, or death.  Participants experiencing relapse of underlying 
hematologic relapse will be censored at the date of relapse. 


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Duration of response will be summarized for participants who achieve a response.  Duration of 
response will be assessed using the Kaplan-Meier method for participants who achieve a 
response.  Median duration and a 95% CI will be estimated.  Participants who are still 
responding at the time of database lock or discontinuation will be right-censored at the time of 
last valid response assessment. 
7.3.4. 
Best Overall Response 
Best overall response for each participant is defined as best response during the course of the 
study (best in the categories of CR or PR), including responses at unscheduled visits.  
Participants without a BOR (ie, participants not achieving a response of either CR or PR) in the 
treatment phase will be considered as nonresponders for BOR in the responder analysis.  Number 
and percentage of participants in each best response category will be tabulated by treatment 
group. 
7.3.5. 
Overall Survival 
Overall survival is defined as the interval between the date of randomization and the date of 
death due to any cause.  Date of death will be determined using the Death Report, the Survival 
Follow-Up, and the Subject Status CRFs.  The Kaplan-Meier method will be used to estimate the 
survival time distribution and the median survival, if it is applicable.  Participants with no 
observed death or loss to follow-up will be treated as censored at their last date known to be 
alive.  The 95% CI will be calculated using Brookmeyer and Crowley's method (1982).  
Summary statistics will be provided. 
7.3.6. 
Nonrelapse Mortality Rate 
Nonrelapse mortality is defined as the time from date of randomization to date of death not 
preceded by underlying disease relapse/recurrence.  Underlying disease relapse/recurrence is 
considered a competing event.  If a participant is not known to have died or experienced the 
competing event, then NRM will be censored at the latest date the participant was known to be 
event-free (on or before the cutoff date).  Cumulative incidence of NRM and derived 
probabilities at Months 3, 6, and 12 will be estimated, considering underlying disease 
relapse/recurrence as a competing event. 
7.3.7. 
Relapse Rate of Malignant and Nonmalignant Hematologic Diseases  
Relapse rate of malignant and nonmalignant hematologic diseases is defined as the proportion of 
participants whose underlying disease relapses.  Relapse rate of malignant and nonmalignant 
hematologic diseases will be provided with a 95% CI.  The CI will be calculated based on the 
exact method for binomial distributions.  Cumulative incidence rate and summary statistics will 
be provided. 
7.3.8. 
Time to Primary Hematologic Disease Relapse  
Time to primary hematologic disease relapse is defined as the interval between the date of 
randomization and the date of relapse.  Time to the relapse will be assessed using Kaplan-Meier 
method.  Median time to relapse and a 95% CI will be estimated.  Summary statistics will be 
provided. 


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7.3.9. 
Other Efficacy Analyses 
The proportion of participants with ≥ 50% reduction in daily corticosteroid dose at Day 180 will 
be summarized.  Corticosteroid dose on study Day 1 will be defined as the starting dose as 
appropriate. 
The proportion of participants successfully tapered off all corticosteroids at Day 180 will be 
summarized.   
Both time to failure-free survival and average biweekly weight-standardized steroid up to Month 
6 will be plotted. 
8. 
PHARMACOKINETIC ANALYSES 
 
 
Appendix G provides a list of planned tables and figures for the PK and PK/pharmacodynamic 
analyses. 
8.1. 
Pharmacokinetic Analyses 
In participants with full profiles (ie, in Part 1 and Part 1 expansion), the PK parameters of Cmax, 
Tmax, Cmin, AUC0-t, and Cl/F will be calculated from the blood plasma concentrations of itacitinib 
using standard noncompartmental (model-independent) PK methods.  Pharmacokinetic 
calculations will be performed using commercial software such as WinNonlin® (Pharsight 
Corporation, Mountain View, CA). 
Exposure/response analyses may be performed using model-based AUCs or using observed 
trough values (Cmin). 
 
 
 
 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of planned tables and listings. 
9.1. 
General Considerations 
All safety analyses will be conducted for the safety population and summarized by treatment 
group.  Summary tables may be replaced with listings when appropriate.  For instance, an AE 
frequency table may be replaced with a listing if it only contains a few unique PTs reported on 
relatively few participants. 
In order to accommodate the changes proposed in Protocol Amendment 8 that resulted in 
discontinuation of Treatment Group C (300 mg BID) and subsequent dose reduction of ongoing 
participants in Treatment Group C to 400 mg QD, safety tables (specifically AEs) will be 
presented for the 300 mg BID group with participants who are subject to dose reduction and 
censored at the date of switching to the lower dose (400 mg QD). An overall summary including 
both dose groups (participants included before and after the dose reduction) will also be 
presented. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is either an AE reported for the first time or worsening of a pre-existing condition after 
first dose of study drug until 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. 
Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be described 
and graded using the NCI CTCAE v4.03 (NCI 2010).  The CTCAE reporting guidelines and 
grading details are available on the Cancer Therapy Evaluation Program website. 
A grading (severity) scale is provided for each AE term.  If the toxicity is not included in the 
CTCAE v4.03, then it will be rated on a scale of 1 to 5 as follows:  1 = mild, 2 = moderate, 
3 = severe, 4 = life-threatening, and 5 = death due to AE.  All toxicities will be graded based on 
the worst level reached, not the level they may have reached if they had not been treated.  When 
the intensity of an AE changes over time for a reporting period (eg, between visits), then each 
change in intensity will be reported as an AE until the event resolves. 
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, then the AE will be considered to be treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated.  Serious AEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution.  Unresolved 
missing values will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 


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For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 
9.2.2. 
Dose-Limiting Toxicities 
Evaluation of DLTs was performed in Part 1 and in Part I expansion for the safety run-in 
population (first 10 participants) enrolled in Treatment Groups B and C.  The toxicity of 
itacitinib will be monitored continuously for each treatment group using the Bayesian approach 
of Thall et al (1995, 1996) as extended by Thall and Sung (1998).  Dose-limiting toxicities are 
defined in Table 5.  The DLTs will be summarized on the first 28 days of study treatment. 
Table 5: 
Definitions of Dose-Limiting Toxicity 
Toxicity 
Definition 
Nonhematologic 
• Any ≥ Grade 3 nonhematologic toxicity that can be reasonably attributed to study 
treatment.  ≥ Grade 3 nonhematologic toxicities that may be related to underlying GVHD 
(eg, nausea, vomiting, diarrhea, rash, dry eye) will not be considered as DLTs. 
• Any ≥ Grade 3 clinical chemistry laboratory abnormalities that are considered clinically 
significant and related to study treatment.  Transient abnormal laboratory values without 
associated clinically significant signs and symptoms, manageable with adequate medical 
care, and not leading to hospitalization will not be considered as DLTs. 
Hematologic 
• Grade 4 neutropenia lasting more than 7 days or a ≥ 90% decrease in absolute neutrophil 
count from baseline that can reasonably be attributed to study treatment. 
• Platelet count < 10 × 109/L related to study treatment that does not recover to at least 
20 × 109/L after 2 weeks with no requirement for platelet transfusion in the preceding 
3 days. 
Historical data on similar patients show a toxicity rate of 25%.  The probability of toxicity for the 
historical data is modeled by beta distribution (Beta [25, 75]).  The prior probability of toxicity 
for the experimental regimen is also modeled by beta distributions (Beta [0.5, 1.5]), which have 
the same means as the corresponding beta distributions for the historical data.  Denoting the 
historical probability of toxicity rate by p(TOX,H), the following decision criteria will be 
applied: 
Stop if Prob{p(TOX,H) + δTOX < p(TOX,E)| data} > 0.95, where δTOX = 0 
Participants from each treatment group will be monitored according to the following nonbinding 
stopping boundaries for toxicity in Table 6.  If a boundary is reached, the sponsor and external 
DMC will investigate and decide on the most appropriate action. 


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Table 6: 
Toxicity Stopping Boundaries 
# Participants (Inclusive) 
Maximum Allowable Number of Toxicities (Inclusive) 
1-2 
No limit 
3-4 
3 
5-6 
4 
7-9 
5 
10-11 
6 
12-14 
7 
15-17 
8 
18-19 
9 
20 
9 
9.2.3. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 and higher TEAEs 
• Number (%) of participants reporting any DLTs 
• Number (%) of participants reporting any TEAEs related to itacitinib 
• Number (%) of participants who temporarily interrupted itacitinib because of TEAEs 
• Number (%) of participants with itacitinib dose reductions because of TEAEs 
• Number (%) of participants who permanently discontinued itacitinib because of 
TEAEs 
• Number (%) of participants reporting any TEAEs related to corticosteroid 
• Number (%) of participants who temporarily interrupted corticosteroid because of 
TEAEs 
• Number (%) of participants with corticosteroid dose reductions because of TEAEs 
• Number (%) of participants who permanently discontinued corticosteroid because of 
TEAEs 
• Number (%) of participants who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if 10 or fewer participants appear 
in a table, a listing may be appropriate): 
• Number (%) of participants reporting TEAEs by SOC and PT 
• Number (%) of participants reporting TEAEs by PT in decreasing order of frequency 
• Number (%) of participants reporting TEAEs by SOC, PT, and maximum severity 


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• Number (%) of participants reporting itacitinib treatment-related TEAEs by SOC and 
PT 
• Number (%) of participants reporting itacitinib treatment-related TEAEs by PT in 
decreasing order of frequency 
• Number (%) of participants reporting itacitinib treatment-related, Grade 3 or higher 
TEAEs by SOC and PT 
• Number (%) of participants reporting any Grade 3 or higher TEAEs by SOC and PT 
• Number (%) of participants reporting any Grade 3 or higher TEAEs by SOC and PT 
in decreasing order of frequency 
• Number (%) of participants reporting serious TEAEs by SOC and PT 
• Number (%) of participants reporting serious TEAEs by SOC and PT in decreasing 
order of frequency 
• Number (%) of participants reporting itacitinib treatment-related, serious TEAEs by 
SOC and PT 
• Number (%) of participants reporting TEAEs leading to itacitinib dose interruption by 
SOC and PT 
• Number (%) of participants reporting TEAEs leading to itacitinib dose reduction by 
SOC and PT 
• Number (%) of participants reporting TEAEs leading to discontinuation of itacitinib 
by SOC and PT 
• Number (%) of participants reporting corticosteroid treatment-related TEAEs by SOC 
and PT 
• Number (%) of participants reporting corticosteroid treatment-related TEAEs by PT 
in decreasing order of frequency 
• Number (%) of participants reporting corticosteroid treatment-related, Grade 3 or 
higher TEAEs by SOC and PT 
• Number (%) of participants reporting corticosteroid treatment-related, serious TEAEs 
by SOC and PT 
• Number (%) of participants reporting TEAEs leading to corticosteroid dose 
interruption by SOC and PT 
• Number (%) of participants reporting TEAEs leading to corticosteroid dose reduction 
by SOC and PT 
• Number (%) of participants reporting TEAEs leading to discontinuation of 
corticosteroids by SOC and PT 
• Number (%) of participants reporting fatal TEAEs by SOC and PT 


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9.2.4. 
Clinically Notable Adverse Events Based on Customized MedDRA Queries 
There are 9 categories of clinically notable TEAEs (ie, categories of erythropenia [anemia], 
neutropenia, thrombocytopenia, CMV infections, EBV infections, hyperlipidemia, 
QT prolongation, thromboembolic events, fungal infections) that, in particular, are of scientific 
and medical interest specific to itacitinib and the GVHD population.  The lists of MQs are in 
Appendix B through Appendix F. 
Within each category, the number and percentage of participants with at least 1 event occurring 
during treatment tabulated by MedDRA PT will be summarized.  Summaries of clinically 
notable AEs based on customized MQs will be provided by category, PT, and the maximum 
severity. 
9.3. 
Analyses for the Data Monitoring Committee 
All safety data will be closely monitored.  An external DMC will perform a full review of safety, 
efficacy, tolerability, and PK data.  The primary purpose of the DMC is to provide a 
recommendation on an appropriate dose of itacitinib for Part 2.   
Details of the efficacy evaluation will be included in the internal DMC charter.  All safety 
information, including the AE data from the replaced participants, will be reviewed during this 
review process. 
9.4. 
Clinical Laboratory Tests 
Laboratory values and change from baseline values will be summarized descriptively by visit.  
Baseline will be determined according to Section 4.1.3.  If there are multiple values that meet the 
criteria for baseline, additional rules may be provided after consultation with the medical monitor 
to delineate which value will be defined as baseline. 
Laboratory data will be classified based on CTCAE grade.  The incidence of abnormal 
laboratory values and shift tables relative to baseline will be tabulated. 
9.5. 
Vital Signs 
Descriptive statistics and mean change from baseline will be summarized for vital signs 
(ie, blood pressure, pulse, respiratory rate, and body temperature) at each assessment time.  Vital 
sign results will be reviewed for abnormalities (see Table 7), and participants exhibiting vital 
sign abnormalities will be listed.  A value will be considered an "alert" value if it is outside the 
established range and shows a > 25% change from baseline.  The values for participants 
exhibiting alert vital sign abnormalities will be listed. 
Table 7: 
Criteria for Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35.5°C 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 


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9.6. 
Electrocardiograms 
Electrocardiograms will be performed at screening and end of treatment.  Electrocardiograms 
that are identified as abnormal and clinically meaningful compared with the screening 
assessment should be reported as AEs.  No summary of electrocardiogram data is planned. 
10. 
INTERIM ANALYSES 
Preplanned analyses of safety will be provided to an independent DMC as specified in the DMC 
charter. 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 8. 
Table 8: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
06 NOV 2019 
Amendment 1 
03 MAR 2022 
11.1. 
Changes to Protocol-Defined Analyses 
Note that the ITT population is equivalent to the safety analysis set as defined in the Protocol. 
11.2. 
Changes to the Statistical Analysis Plan 
The changes reflected in this version of the SAP include the title of the study as well as Part 1 
expansion details described in Protocol Amendment 7 (addition of Part 1 expansion) and 
Protocol Amendment 8 (closure of the BID treatment group).  More specifically: 
• Section 1 was updated to align with Protocol Amendment 8, which includes all details 
related to Part 1 expansion. 
• Section 2 was updated to include all endpoints related to Part 1 expansion. 
• Section 3 was updated to include the study design for Part 1 expansion. 
• Section 4 was updated to include information on the corticosteroids-only group. 
• Section 5 was updated to include clarifications on study populations. 
• Section 6 was updated to include primary hematologic disease and transplant 
characteristics and to update information on exposure. 
• Section 7 was updated with detailed descriptions of the efficacy endpoints to align 
with Protocol Amendment 8. 
• Section 9 was updated to include a paragraph on the changes in Treatment Group C 
as outlined in Protocol Amendment 8. 
• Appendix A was updated to include all tables/listings/figures intended for Part 1 
expansion. 


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12. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development 
Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 
Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2015;21:389-401. 
Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host 
disease. National Institutes of Health Consensus Development Project on Criteria for Clinical 
Trials in Chronic Graft-Versus-Host Disease: IV. The 2014 Response Criteria Working Group 
report. Biol Blood Marrow Transplant 2015;21:984-999. 
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317:1098.  
National Cancer Institute. Common Terminology Criteria for Adverse Events Version 4.03. 
2010.  
Thall PF, Simon R, Estey EH. Bayesian sequential monitoring designs for single-arm clinical 
trials with multiple outcomes. Stat Med 1995;14:357-379. 
Thall PF, Simon R, Estey EH. New statistical strategy for monitoring safety and efficacy in 
single-arm clinical trials. J Clin Oncol 1996;14:296-303. 
Thall PF, Sung HG. Some extensions and applications of a Bayesian strategy for monitoring 
multiple outcomes in clinical trials. Stat Med 1998;17:1563-1580. 


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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the Clinical Study 
Report.  Standard tables will follow the conventions in the Standard Safety Tables v1.4.  In-text 
tables are identical in structure and content to appendix tables but follow a Rich Text Format. 
Efficacy will use the safety analysis set as described in Section 5.3. 
Tables 
Table No. 
Title 
Population 
1.1.1.1 
Analysis Populations – Part 1 Expansion 
Safety 
1.1.1.2 
Analysis Populations – Part 1 and Part 1 Expansion 
Safety 
1.1.2.1 
Summary of Participant Disposition – Part 1 Expansion 
Safety 
1.1.2.2 
Summary of Participant Disposition – Part 1 and Part 1 Expansion 
Safety 
1.1.3.1 
Summary of Protocol Deviations – Part 1 Expansion 
Safety 
1.1.3.2 
Summary of Protocol Deviations – Part 1 and Part 1 Expansion 
Safety 
1.2.1.1 
Summary of Demographics – Part 1 Expansion 
Safety 
1.2.1.2 
Summary of Demographics – Part 1 and Part 1 Expansion 
Safety 
1.3.1.1.1 
Summary of Baseline Disease Characteristics for Cancer History – Part 1 
Expansion 
Safety 
1.3.1.1.2 
Summary of Baseline Disease Characteristics for Cancer History – Part 1 and Part 1 
Expansion 
Safety 
1.3.1.2.1 
Summary of Baseline Disease Characteristics for GVHD – Part 1 Expansion 
Safety  
1.3.1.2.2 
Summary of Baseline Disease Characteristics for GVHD – Part 1 and Part 1 
Expansion 
Safety 
1.3.2.1 
Summary of Allogeneic Hematopoietic Stem Cell Transplant History – Part 1 
Expansion 
Safety 
1.3.2.2 
Summary of Allogeneic Hematopoietic Stem Cell Transplant History – Part 1 and 
Part 1 Expansion 
Safety 
1.3.2.3 
Summary of Karnofsky Scale 
Safety 
1.3.3.1 
Summary of Prior Anticancer Therapy – Part 1 Expansion 
Safety 
1.3.3.2 
Summary of Prior Anticancer Therapy – Part 1 and Part 1 Expansion 
Safety 
1.4.1.1 
Summary of Prior Medications – Part 1 Expansion 
Safety 
1.4.1.2 
Summary of Prior Medications – Part 1 and Part 1 Expansion 
Safety 
1.4.2.1 
Summary of Concomitant Medications – Part 1 Expansion 
Safety 
1.4.2.2 
Summary of Concomitant Medications – Part 1 and Part 1 Expansion 
Safety 
1.5.1.1 
Summary of General Medical History – Part 1 and Part 1 Expansion 
Safety 
1.5.1.2 
Summary of Conditioning and Prophylaxis Therapy – Part 1 and Part 1 Expansion 
Safety 
2.2.1 
Summary of Overall Response Rate at Months 3, 6, and 12 
Safety 
2.2.2 
Summary of Nonrelapse Mortality Rate 
Safety 
2.2.3 
Summary of Duration of Response 
Safety 
2.2.4 
Summary of Time to Response 
Safety 
2.2.5 
Summary of Relapse Rate of Malignant and Nonmalignant Hematologic Diseases 
Safety 
2.2.6 
Summary of Time to Primary Hematologic Disease Relapse 
Safety 
2.2.7 
Summary of Overall Survival 
Safety 
2.2.8 
Summary of Best Overall Response 
Safety 
2.2.8.1 
Summary of Best Overall Response by GVHD Organ Involved 
Safety 


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Table No. 
Title 
Population 
2.2.8.2 
Summary of Best Overall Response for Skin Sclerotic Findings Subgroup 
Safety 
2.2.9 
Summary of Failure-Free Survival 
Safety 
2.2.11 
Summary of Number of Participants With ≥ 50% Reduction in Daily Corticosteroid 
Dose at Day 180 
Safety 
2.2.12 
Summary of Participants Successfully Tapered Off All Corticosteroids at Day 180 
Safety 
2.2.13 
Summary of Number of Participants With ≥ 50% Reduction in Daily Corticosteroid 
Dose by (4-Week) Time Interval Up to Month 6 
Safety 
2.2.14 
Summary of Participants Successfully Tapered Off All Corticosteroids by (4-Week) 
Time Interval Up to Month 6 
Safety 
3.1.1 
Summary of Itacitinib Exposure, Duration of Exposure, and Dose Adjustment 
Safety 
3.1.2 
Summary of Itacitinib Compliance  
Safety 
3.1.3 
Summary of Corticosteroid Exposure, Duration of Exposure, and Dose Adjustment  
Safety 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events  
Safety 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term  
Safety 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term, and Maximum Severity 
Safety 
3.2.5 
Summary of Itacitinib Treatment-Related, Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
3.2.6 
Summary of Itacitinib Treatment-Related, Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.7 
Summary of Itacitinib Treatment-Related, Grade 3 or Higher Treatment-Emergent 
Adverse Events by MedDRA System Organ Class, and Preferred Term 
Safety 
3.2.8 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
3.2.9 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.10 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term  
Safety 
3.2.11 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.12 
Summary of Itacitinib Treatment-Related, Serious Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.13 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.14 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.15 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
Itacitinib by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.16 
Summary of Corticosteroid Treatment-Related, Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.17 
Summary of Corticosteroid Treatment-Related, Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
3.2.18 
Summary of Corticosteroid Treatment-Related, Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term 
Safety 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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Table No. 
Title 
Population 
3.2.19 
Summary of Treatment-Emergent Adverse Events Leading to Corticosteroid Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.20 
Summary of Treatment-Emergent Adverse Events Leading to Corticosteroid Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.21 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
Corticosteroid by MedDRA System Organ Class and Preferred Term 
Safety 
3.2.22 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term  
Safety 
3.2.23 
Overall Summary of Treatment-Emergent Clinically Notable Hematologic Events 
by Customized MQs  
Safety 
3.2.24 
Summary of Clinically Notable Treatment-Emergent Hematologic Events by 
Customized MQs, Preferred Term, and Maximum Severity  
Safety 
3.2.25 
Overall Summary of Treatment-Emergent CMV Infection Events by Customized 
MedDRA Queries 
Safety 
3.2.26 
Summary of Treatment-Emergent CMV Infection Events by Customized MedDRA 
Queries, Preferred Term, and Maximum Severity  
Safety 
3.2.27 
Overall Summary of Treatment-Emergent EBV Infection Events by Customized 
MedDRA Queries 
Safety 
3.2.28 
Summary of Treatment-Emergent EBV Infection Events by Customized MedDRA 
Queries, Preferred Term, and Maximum Severity  
Safety 
3.2.29 
Overall Summary of Treatment-Emergent Hyperlipidemia Events by Customized 
MedDRA Queries 
Safety 
3.2.30 
Summary of Treatment-Emergent Hyperlipidemia Events by Customized MedDRA 
Queries, Preferred Term, and Maximum Severity  
Safety 
3.2.31 
Summary of Grade 3 or Higher Treatment-Emergent Infections by MedDRA 
System Organ Class and Preferred Term 
Safety 
3.2.32 
Summary of Treatment-Emergent CMV Infection Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
3.2.33 
Summary of Treatment-Emergent QT Prolongation Events by Customized 
MedDRA Queries, Preferred Term, and Maximum Severity  
Safety 
3.2.34 
Overall Summary of Treatment-Emergent Thromboembolic Events by Customized 
MedDRA Queries 
Safety 
3.2.35 
Summary of Treatment-Emergent Thromboembolic Events by Customized 
MedDRA Queries, Preferred Term, and Maximum Severity  
Safety 
3.2.36 
Overall Summary of Treatment-Emergent Fungal Infection Events (MedDRA High 
Level Group Term) by Customized MedDRA Queries 
Safety 
3.2.37 
Summary of Treatment-Emergent Fungal Infection Events (MedDRA High Level 
Group Term) by Customized MedDRA Queries, Preferred Term, and Maximum 
Severity  
Safety 
3.3.1.1 
Summary of Laboratory Values – Hematology 
Safety 
3.3.1.2 
Shift Summary of Hematology Laboratory Values in CTCAE Grade – to the Worst 
Abnormal Value  
Safety 
3.3.2.1 
Summary of Laboratory Values – Chemistry 
Safety 
3.3.2.2 
Shift Summary of Chemistry Laboratory Values in CTCAE Grade – to the Worst 
Abnormal Value 
Safety  
3.3.3.1 
Summary of Laboratory Values - Coagulation 
Safety 
3.4.1 
Summary of Systolic Blood Pressure 
Safety  
3.4.2 
Summary of Diastolic Blood Pressure  
Safety 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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Table No. 
Title 
Population 
3.4.3 
Summary of Pulse  
Safety 
3.4.4 
Summary of Respiratory Rate 
Safety 
3.4.5 
Summary of Body Temperature 
Safety 
3.4.6 
Summary of Body Weight 
Safety 
Figures 
Figure No. 
Title 
4.2.1 
Kaplan-Meier Plot of Time to Failure-Free Survival 
4.3.1 
Average Biweekly Weight-Standardized Steroid Up to Month 6 
Listings 
Listing No. 
Title 
2.1.1 
Participant Enrollment and Disposition Status 
2.4.7 
Posttherapy Medications 
2.6.8 
Deaths 
2.7.7 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of Itacitinib 
99.2.1 
Protocol Deviations by Deviation Coded Term 


Incyte Corporation 
Page 34 of 45 
INCB 39110-309 Statistical Analysis Plan Am 1 
03 MAR 2022 
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CONFIDENTIAL 
APPENDIX B. CLINICALLY NOTABLE HEMATOLOGIC EVENTS 
This appendix provides a list of 3 categories of clinically notable treatment-emergent 
hematologic events based on customized MQs. 
Adverse Event Category 
Preferred Term 
Code 
Anemia 
Anaemia macrocytic 
10002064 
Aplasia pure red cell 
10002965 
Aplastic anaemia 
10002967 
Erythroblast count decreased 
10058505 
Erythropenia 
10015287 
Hypoplastic anaemia 
10021074 
Microcytic anaemia 
10027538 
Red blood cell count decreased 
10038153 
Anaemia 
10002034 
Haematocrit decreased 
10018838 
Haemoglobin decreased 
10018884 
Leukoerythroblastic anaemia 
10053199 
Normochromic normocytic anaemia 
10029783 
Neutropenia 
Agranulocytosis 
10001507 
Band neutrophil count decreased 
10057950 
Febrile neutropenia 
10016288 
Granulocyte count decreased 
10018681 
Granulocytopenia 
10018687 
Neutropenia 
10029354 
Neutropenic infection 
10059482 
Neutropenic sepsis 
10049151 
Neutrophil count decreased 
10029366 
Thrombocytopenia 
Acquired amegakaryocytic thrombocytopenia 
10076747 
Platelet count decreased 
10035528 
Thrombocytopenia 
10043554 
Plateletcrit decreased 
10064784 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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CONFIDENTIAL 
APPENDIX C. HEMATOLOGIC INFECTION EVENTS 
Adverse Event Group 
Preferred Term 
Code 
EBV infections 
Epstein-Barr virus positive mucocutaneous ulcer 
10079386 
Epstein-Barr viraemia 
10065110 
Epstein-Barr virus associated lymphoma 
10071441 
Epstein-Barr virus associated lymphoproliferative disorder 
10068349 
Epstein-Barr virus infection 
10015108 
Hepatitis infectious mononucleosis 
10019781 
Infectious mononucleosis 
10021914 
Oral hairy leukoplakia 
10030979 
Post transplant lymphoproliferative disorder 
10051358 
X-linked lymphoproliferative syndrome 
10068348 
Epstein-Barr virus test positive 
10064545 
Epstein-Barr virus antibody positive 
10052324 
Cytomegaloviral infections 
Congenital cytomegalovirus infection 
10010430 
Cytomegalovirus chorioretinitis 
10048843 
Cytomegalovirus colitis 
10048983 
Cytomegalovirus duodenitis 
10049014 
Cytomegalovirus enteritis 
10049074 
Cytomegalovirus enterocolitis 
10049015 
Cytomegalovirus gastritis 
10049016 
Cytomegalovirus gastroenteritis 
10051349 
Cytomegalovirus gastrointestinal infection 
10052817 
Cytomegalovirus gastrointestinal ulcer 
10075619 
Cytomegalovirus hepatitis 
10011830 
Cytomegalovirus infection 
10011831 
Cytomegalovirus mononucleosis 
10011834 
Cytomegalovirus mucocutaneous ulcer 
10065036 
Cytomegalovirus myelomeningoradiculitis 
10065621 
Cytomegalovirus myocarditis 
10056261 
Cytomegalovirus nephritis 
10079095 
Cytomegalovirus oesophagitis 
10049018 
Cytomegalovirus pancreatitis 
10049566 
Cytomegalovirus pericarditis 
10056721 
Cytomegalovirus syndrome 
10056262 
Cytomegalovirus urinary tract infection 
10051350 
Cytomegalovirus viraemia 
10058854 
Encephalitis cytomegalovirus 
10014586 
Disseminated cytomegaloviral infection 
10049075 
Pneumonia cytomegaloviral 
10035676 
Cytomegalovirus test positive 
10051620 


Incyte Corporation 
Page 36 of 45 
INCB 39110-309 Statistical Analysis Plan Am 1 
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APPENDIX D. HYPERLIPIDEMIA EVENTS 
Preferred Term 
Code 
Level 
Scope 
Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Acquired lipoatrophic 
diabetes 
10073667 
PT 
Narrow 
A 
0 
Active 
16.1 
16.1 
Acquired mixed 
hyperlipidaemia 
10071236 
PT 
Narrow 
A 
0 
Active 
18.0 
18.0 
Apolipoprotein 
B/Apolipoprotein A-1 ratio 
increased 
10065516 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Autoimmune 
hyperlipidaemia 
10071577 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Blood cholesterol abnormal 
10005423 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Blood cholesterol esterase 
increased 
10071304 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Blood cholesterol increased 
10005425 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Blood triglycerides abnormal 10005837 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Blood triglycerides increased 10005839 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Diabetic dyslipidaemia 
10070901 
PT 
Narrow 
A 
0 
Active 
14.0 
14.0 
Dyslipidaemia 
10058108 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
High density lipoprotein 
abnormal 
10020051 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
High density lipoprotein 
decreased 
10020060 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Hypercholesterolaemia 
10020603 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Hyperlipidaemia 
10062060 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Hypertriglyceridaemia 
10020869 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Hypo HDL cholesterolaemia 
10068961 
PT 
Narrow 
A 
0 
Active 
12.0 
12.0 
Intermediate density 
lipoprotein increased 
10064236 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
LDL/HDL ratio increased 
10049030 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Lipids abnormal 
10024588 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Lipids increased 
10024592 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Lipoprotein (a) abnormal 
10054023 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Lipoprotein (a) increased 
10054009 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Lipoprotein abnormal 
10081355 
PT 
Narrow 
A 
0 
Active 
21.1 
21.1 
Lipoprotein increased 
10081354 
PT 
Narrow 
A 
0 
Active 
21.1 
21.1 
Low density lipoprotein 
abnormal 
10024901 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Low density lipoprotein 
increased 
10024910 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 


Incyte Corporation 
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Preferred Term 
Code 
Level 
Scope 
Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Non-high-density lipoprotein 
cholesterol increased 
10063967 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Remnant-like lipoprotein 
particles increased 
10073041 
PT 
Narrow 
A 
0 
Active 
16.0 
16.0 
Total cholesterol/HDL ratio 
abnormal 
10058633 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Total cholesterol/HDL ratio 
increased 
10058630 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Very low density lipoprotein 
abnormal 
10047352 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 
Very low density lipoprotein 
increased 
10047361 
PT 
Narrow 
A 
0 
Active 
8.1 
8.1 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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CONFIDENTIAL 
APPENDIX E. QT PROLONGATION EVENTS 
Preferred Term 
Code 
Level 
Scope 
Category 
Weight 
Status 
Addition 
Version 
Last 
Modified 
Version 
Electrocardiogram 
QT interval abnormal 
10063748 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 
Electrocardiogram 
QT prolonged 
10014387 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 
Long QT syndrome 
10024803 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 
Long QT syndrome 
congenital 
10057926 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 
Torsade de pointes 
10044066 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 
Ventricular 
tachycardia 
10047302 
PT 
Narrow 
A 
0 
Active 
7.1 
7.1 


Incyte Corporation 
Page 39 of 45 
INCB 39110-309 Statistical Analysis Plan Am 1 
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CONFIDENTIAL 
APPENDIX F. THROMBOEMBOLIC EVENTS 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Arterial Acute aortic syndrome 
10074337 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Acute myocardial infarction 
10000891 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Amaurosis 
10001902 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Amaurosis fugax 
10001903 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Angioplasty 
10002475 
PT 
Narrow 
A 
0 
Active 
16.0 
16.0 
Aortic bypass 
10057617 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Aortic embolus 
10002897 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Aortic surgery 
10061651 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Aortic thrombosis 
10002910 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Aortogram abnormal 
10057794 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterectomy 
10071026 
PT 
Narrow 
A 
0 
Active 
14.0 
14.0 
Arterectomy with graft replacement 10003140 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial angioplasty 
10081731 
PT 
Narrow 
A 
0 
Active 
21.1 
21.1 
Arterial bypass occlusion 
10077766 
PT 
Narrow 
A 
0 
Active 
19.0 
19.0 
Arterial bypass operation 
10056418 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial bypass thrombosis 
10077765 
PT 
Narrow 
A 
0 
Active 
19.0 
19.0 
Arterial graft 
10061655 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial occlusive disease 
10062599 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial stent insertion 
10061657 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial therapeutic procedure 
10052949 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial thrombosis 
10003178 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arteriogram abnormal 
10061659 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arteriogram carotid abnormal 
10003195 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arteriotomy 
10078636 
PT 
Narrow 
A 
0 
Active 
19.1 
19.1 
Atherectomy 
10063025 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Atherosclerotic plaque rupture 
10076604 
PT 
Narrow 
A 
0 
Active 
18.1 
18.1 
Atrial appendage closure 
10079735 
PT 
Narrow 
A 
0 
Active 
20.1 
20.1 
Atrial appendage resection 
10080843 
PT 
Narrow 
A 
0 
Active 
21.0 
21.0 
Basal ganglia infarction 
10069020 
PT 
Narrow 
A 
0 
Active 
12.0 
12.0 
Basilar artery occlusion 
10048963 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Basilar artery thrombosis 
10063093 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Blindness transient 
10005184 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Brachiocephalic artery occlusion 
10069694 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Capsular warning syndrome 
10067744 
PT 
Narrow 
A 
0 
Active 
10.1 
10.1 
Carotid angioplasty 
10071260 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Carotid arterial embolus 
10007684 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Carotid artery bypass 
10053003 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Carotid artery occlusion 
10048964 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Carotid artery stent insertion 
10066102 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Carotid artery thrombosis 
10007688 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Carotid endarterectomy 
10007692 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebellar artery occlusion 
10053633 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebellar artery thrombosis 
10008023 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Arterial Cerebral artery embolism 
10008088 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebral artery occlusion 
10008089 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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VV-CLIN-000166 
CONFIDENTIAL 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Cerebral artery stent insertion 
10081893 
PT 
Narrow 
A 
0 
Active 
22.0 
22.0 
Cerebral artery thrombosis 
10008092 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebral hypoperfusion 
10065384 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebrovascular insufficiency 
10058842 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebrovascular stenosis 
10061751 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coeliac artery occlusion 
10069696 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Coronary angioplasty 
10050329 
PT 
Narrow 
A 
0 
Active 
16.0 
16.0 
Coronary arterial stent insertion 
10052086 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary artery bypass 
10011077 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary artery embolism 
10011084 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary artery occlusion 
10011086 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary artery reocclusion 
10053261 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary artery surgery 
10011090 
PT 
Narrow 
A 
0 
Active 
10.0 
20.1 
Coronary artery thrombosis 
10011091 
PT 
Narrow 
A 
0 
Active 
16.0 
16.0 
Coronary endarterectomy 
10011101 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary revascularisation 
10049887 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Coronary vascular graft occlusion 
10075162 
PT 
Narrow 
A 
0 
Active 
17.1 
17.1 
Embolia cutis medicamentosa 
10058729 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Embolism arterial 
10014513 
PT 
Narrow 
A 
0 
Active 
10.0 
13.1 
Endarterectomy 
10014648 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Femoral artery embolism 
10068365 
PT 
Narrow 
A 
0 
Active 
11.1 
11.1 
Hepatic artery embolism 
10019635 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Hepatic artery occlusion 
10051991 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Hepatic artery thrombosis 
10019636 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Hypothenar hammer syndrome 
10063518 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Iliac artery embolism 
10021338 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Iliac artery occlusion 
10064601 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Intra-aortic balloon placement 
10052989 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Intraoperative cerebral artery 
occlusion 
10056382 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Ischaemic cerebral infarction 
10060840 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Ischaemic stroke 
10061256 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Lacunar infarction 
10051078 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Leriche syndrome 
10024242 
PT 
Narrow 
A 
0 
Active 
13.1 
13.1 
Mesenteric arterial occlusion 
10027394 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Mesenteric arteriosclerosis 
10065560 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Mesenteric artery embolism 
10027395 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Mesenteric artery stenosis 
10027396 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Mesenteric artery stent insertion 
10071261 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Mesenteric artery thrombosis 
10027397 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Myocardial infarction 
10028596 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Myocardial necrosis 
10028602 
PT 
Narrow 
A 
0 
Active 
10.0 
17.0 
Ophthalmic artery thrombosis 
10081144 
PT 
Narrow 
A 
0 
Active 
21.1 
21.1 
Papillary muscle infarction 
10033697 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Penile artery occlusion 
10068035 
PT 
Narrow 
A 
0 
Active 
11.0 
11.0 
Arterial Percutaneous coronary intervention 
10065608 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Peripheral arterial occlusive disease 10062585 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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CONFIDENTIAL 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Peripheral arterial reocclusion 
10069379 
PT 
Narrow 
A 
0 
Active 
12.1 
12.1 
Peripheral artery angioplasty 
10057518 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Peripheral artery bypass 
10072561 
PT 
Narrow 
A 
0 
Active 
15.1 
15.1 
Peripheral artery occlusion 
10057525 
PT 
Narrow 
A 
0 
Active 
10.0 
19.0 
Peripheral artery stent insertion 
10072562 
PT 
Narrow 
A 
0 
Active 
15.1 
15.1 
Peripheral artery surgery 
10082470 
PT 
Narrow 
A 
0 
Active 
22.0 
22.0 
Peripheral artery thrombosis 
10072564 
PT 
Narrow 
A 
0 
Active 
15.1 
15.1 
Peripheral embolism 
10061340 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Peripheral endarterectomy 
10072560 
PT 
Narrow 
A 
0 
Active 
15.1 
15.1 
Popliteal artery entrapment 
syndrome 
10071642 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Post procedural myocardial 
infarction 
10066592 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Postinfarction angina 
10058144 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Precerebral artery occlusion 
10036511 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Precerebral artery thrombosis 
10074717 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Profundaplasty 
10078867 
PT 
Narrow 
A 
0 
Active 
20.0 
20.0 
Pulmonary artery occlusion 
10078201 
PT 
Narrow 
A 
0 
Active 
19.1 
19.1 
Pulmonary artery therapeutic 
procedure 
10063731 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary artery thrombosis 
10037340 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary endarterectomy 
10072893 
PT 
Narrow 
A 
0 
Active 
16.0 
16.0 
Pulmonary tumour thrombotic 
microangiopathy 
10079988 
PT 
Narrow 
A 
0 
Active 
20.1 
20.1 
Renal artery angioplasty 
10057493 
PT 
Narrow 
A 
0 
Active 
15.1 
15.1 
Renal artery occlusion 
10048988 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Renal artery thrombosis 
10038380 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Renal embolism 
10063544 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Retinal artery embolism 
10038826 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Retinal artery occlusion 
10038827 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Retinal artery thrombosis 
10038831 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Silent myocardial infarction 
10049768 
PT 
Narrow 
A 
0 
Active 
12.1 
12.1 
Spinal artery embolism 
10049440 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Spinal artery thrombosis 
10071316 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Splenic artery thrombosis 
10074600 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Splenic embolism 
10068677 
PT 
Narrow 
A 
0 
Active 
11.1 
11.1 
Stress cardiomyopathy 
10066286 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Subclavian artery embolism 
10042332 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Subclavian artery occlusion 
10069695 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Subclavian artery thrombosis 
10042334 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thromboembolectomy 
10064958 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombotic microangiopathy 
10043645 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombotic thrombocytopenic 
purpura 
10043648 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Transient ischaemic attack 
10044390 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Truncus coeliacus thrombosis 
10062363 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Vascular pseudoaneurysm 
thrombosis 
10078269 
PT 
Narrow 
A 
0 
Active 
19.1 
19.1 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
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VV-CLIN-000166 
CONFIDENTIAL 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Arterial Vertebral artery occlusion 
10048965 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Vertebral artery thrombosis 
10057777 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Visual acuity reduced transiently 
10047532 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous Axillary vein thrombosis 
10003880 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Brachiocephalic vein occlusion 
10076837 
PT 
Narrow 
A 
0 
Active 
18.1 
18.1 
Brachiocephalic vein thrombosis 
10063363 
PT 
Narrow 
A 
0 
Active 
10.0 
19.1 
Budd-Chiari syndrome 
10006537 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Catheterisation venous 
10052698 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cavernous sinus thrombosis 
10007830 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Central venous catheterisation 
10053377 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Cerebral venous sinus thrombosis 
10083037 
PT 
Narrow 
A 
0 
Active 
22.1 
22.1 
Cerebral venous thrombosis 
10008138 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Compression garment application 
10079209 
PT 
Narrow 
A 
0 
Active 
20.0 
20.0 
Deep vein thrombosis 
10051055 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Deep vein thrombosis postoperative 10066881 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Embolism venous 
10014522 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Hepatic vein embolism 
10078810 
PT 
Narrow 
A 
0 
Active 
20.0 
20.0 
Hepatic vein occlusion 
10058991 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Hepatic vein thrombosis 
10019713 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Homans' sign positive 
10051031 
PT 
Narrow 
A 
0 
Active 
14.0 
14.0 
Iliac vein occlusion 
10058992 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Inferior vena cava syndrome 
10070911 
PT 
Narrow 
A 
0 
Active 
14.0 
14.0 
Inferior vena caval occlusion 
10058987 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Jugular vein embolism 
10081850 
PT 
Narrow 
A 
0 
Active 
22.0 
22.0 
Jugular vein occlusion 
10076835 
PT 
Narrow 
A 
0 
Active 
18.1 
18.1 
Jugular vein thrombosis 
10023237 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Mahler sign 
10075428 
PT 
Narrow 
A 
0 
Active 
17.1 
17.1 
May-Thurner syndrome 
10069727 
PT 
Narrow 
A 
0 
Active 
13.0 
13.0 
Mesenteric vein thrombosis 
10027402 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Mesenteric venous occlusion 
10027403 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Obstetrical pulmonary embolism 
10029925 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Obstructive shock 
10073708 
PT 
Narrow 
A 
0 
Active 
16.1 
16.1 
Ophthalmic vein thrombosis 
10074349 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Ovarian vein thrombosis 
10072059 
PT 
Narrow 
A 
0 
Active 
15.0 
15.0 
Paget-Schroetter syndrome 
10050216 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pelvic venous thrombosis 
10034272 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Penile vein thrombosis 
10034324 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Peripheral vein occlusion 
10083103 
PT 
Narrow 
A 
0 
Active 
22.1 
22.1 
Peripheral vein thrombus extension 
10082853 
PT 
Narrow 
A 
0 
Active 
22.1 
22.1 
Phlebectomy 
10048874 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Portal vein cavernous transformation 10073979 
PT 
Narrow 
A 
0 
Active 
16.1 
16.1 
Portal vein embolism 
10082030 
PT 
Narrow 
A 
0 
Active 
22.0 
22.0 
Portal vein occlusion 
10058989 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Portal vein thrombosis 
10036206 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Portosplenomesenteric venous 
thrombosis 
10077623 
PT 
Narrow 
A 
0 
Active 
19.0 
19.0 


Incyte Corporation 
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INCB 39110-309 Statistical Analysis Plan Am 1 
03 MAR 2022 
VV-CLIN-000166 
CONFIDENTIAL 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Post procedural pulmonary 
embolism 
10063909 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous Post thrombotic syndrome 
10048591 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Postoperative thrombosis 
10050902 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Postpartum venous thrombosis 
10036300 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary embolism 
10037377 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary infarction 
10037410 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary microemboli 
10037421 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary thrombosis 
10037437 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary vein occlusion 
10068690 
PT 
Narrow 
A 
0 
Active 
11.1 
11.1 
Pulmonary veno-occlusive disease 
10037458 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Pulmonary venous thrombosis 
10037459 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Renal vein embolism 
10038547 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Renal vein occlusion 
10056293 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Renal vein thrombosis 
10038548 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Retinal vein occlusion 
10038907 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Retinal vein thrombosis 
10038908 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Septic pulmonary embolism 
10083093 
PT 
Narrow 
A 
0 
Active 
22.1 
22.1 
SI QIII TIII pattern 
10068479 
PT 
Narrow 
A 
0 
Active 
11.1 
11.1 
Splenic vein occlusion 
10068122 
PT 
Narrow 
A 
0 
Active 
11.0 
11.0 
Splenic vein thrombosis 
10041659 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Subclavian vein occlusion 
10079164 
PT 
Narrow 
A 
0 
Active 
20.0 
20.0 
Subclavian vein thrombosis 
10049446 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Superior sagittal sinus thrombosis 
10042567 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Superior vena cava occlusion 
10058988 
PT 
Narrow 
A 
0 
Active 
10.0 
17.0 
Superior vena cava syndrome 
10042569 
PT 
Narrow 
A 
0 
Active 
10.0 
14.0 
Thrombophlebitis 
10043570 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombophlebitis migrans 
10043581 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombophlebitis neonatal 
10043586 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombophlebitis superficial 
10043595 
PT 
Narrow 
A 
0 
Active 
14.1 
14.1 
Thrombosed varicose vein 
10043605 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Thrombosis corpora cavernosa 
10067270 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Transverse sinus thrombosis 
10044457 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Vena cava embolism 
10047193 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Vena cava filter insertion 
10048932 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Vena cava filter removal 
10074397 
PT 
Narrow 
A 
0 
Active 
17.0 
17.0 
Vena cava thrombosis 
10047195 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venogram abnormal 
10047209 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venoocclusive disease 
10062173 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venoocclusive liver disease 
10047216 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous angioplasty 
10077826 
PT 
Narrow 
A 
0 
Active 
19.0 
19.0 
Venous occlusion 
10058990 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous operation 
10062175 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous recanalisation 
10068605 
PT 
Narrow 
A 
0 
Active 
11.1 
11.1 
Venous repair 
10052964 
PT 
Narrow 
A 
0 
Active 
17.1 
17.1 
Venous stent insertion 
10063389 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous thrombosis 
10047249 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 


Incyte Corporation 
Page 44 of 45 
INCB 39110-309 Statistical Analysis Plan Am 1 
03 MAR 2022 
VV-CLIN-000166 
CONFIDENTIAL 
Group 
Preferred Term 
Code 
Level 
Scope Category Weight Status 
Addition 
Version 
Last 
Modified 
Version 
Venous thrombosis in pregnancy 
10067030 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous Venous thrombosis limb 
10061408 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Venous thrombosis neonatal 
10064602 
PT 
Narrow 
A 
0 
Active 
10.0 
10.0 
Visceral venous thrombosis 
10077829 
PT 
Narrow 
A 
0 
Active 
19.0 
19.0 


Incyte Corporation 
Page 45 of 45 
INCB 39110-309 Statistical Analysis Plan Am 1 
03 MAR 2022 
VV-CLIN-000166 
CONFIDENTIAL 
APPENDIX G. PLANNED TABLES AND FIGURES FOR 
PHARMACOKINETIC AND 
PHARMACOKINETIC/PHARMACODYNAMIC 
ANALYSIS 
Tables 
Table No. 
Title 
Table 1 
Summarization of the Pharmacokinetic Parameters by Dose at Day 1 
Table 2 
Summarization of the Pharmacokinetic Parameters by Dose at Day 7 
Table 3 
Summarization of the Pharmacokinetic Parameters by Dose at Day 28 
Figures 
Figure No. 
Title 
Figure 1 
Mean (± SE) Concentration-Time Profiles by Dose at Day 1 
Figure 2 
Boxplots of Cmax, Cmin, and AUC on Day 7 by NRM at 6 Months 
Figure 3 
Boxplots of Cmax, Cmin, and AUC on Day 7 by Overall Response at 6 Months 
Figure 4 
Boxplots of Cmax, Cmin, and AUC on Day 7 by Chronic GVHD Grading at 6 Months 
Figure 5 
Boxplots of Cmax, Cmin, and AUC on Day 7 by Chronic GVHD Liver Staging at Day 7 
Figure 6 
Boxplots of Cmax, Cmin, and AUC on Day 28 by Chronic GVHD Liver Staging at Day 28 
Figure 7 
Boxplots of Cmax, Cmin, and AUC on Day 7 by Chronic GVHD GI Staging at Day 7 
Figure 8 
Boxplots of Cmax, Cmin, and AUC on Day 28 by Chronic GVHD GI Staging  at Day 28 
Pharmacokinetic tables and/or figures may be modified or additional PK tables and/or figures 
may be created as needed based on study findings.  For example, plots may be modified to 
indicate participants taking potent CYP3A4 inhibitors and those who are not, or plots may be 
modified to highlight a participant who had a particular safety finding.