Clinical trial NCT03978637
Conditions: Bronchiolitis Obliterans Syndrome
Keywords: Bronchiolitis obliterans syndrome lung transplant JAK1 inhibitor
Sponsor: Incyte Corporation
Start date: 2020-02-04; Completion date: 2023-10-13
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of itacitinib in participants with post-lung transplant bronchiolitis obliterans syndrome (BOS).

Detailed description:

Arms: arm 1: Phase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration. arm 2: Phase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration. arm 3: Phase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration arm 4: Phase 2: Itacitinib administered orally at the recommended dose from Phase 1.
Interventions: intervention 1: Itacitinib
Intervention descriptions: intervention 1: Itacitinib administered orally at the specified dose.

Protocol documents:
Prot_000.pdf: 
Official Title: 
NCT Number: 
NCT03978637 
Document Date: 
Clinical Study Protocol Version 5: 30-November-2021 
An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of 
Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung 
Transplantation   


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Protocol INCB 39110-214 Am 5 
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TITLE PAGE 
Clinical Study Protocol 
 
INCB 39110-214 
An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety 
and Efficacy of Itacitinib in Participants With Bronchiolitis 
Obliterans Syndrome Following Lung Transplantation 
 
 
Product: 
Itacitinib (INCB039110) 
IND Number: 
109,296 
Phase of Study: 
1/2 
EudraCT Number: 
2019-004171-39 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
29 APR 2019 
Amendment (Version) 1: 
09 DEC 2019 
Amendment (Version) 2: 
04 MAR 2020 
Amendment (Version) 3:  
11 AUG 2020 
Amendment (Version) 4:  
07 APR 2021 
Amendment (Version) 5: 
30 NOV 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, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 39110-214 Protocol Amendment 5 (Version 5 dated 30 NOV 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 ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
2. 
INTRODUCTION ......................................................................................................14 
2.1. 
Background .................................................................................................................14 
2.1.1. 
Post-Lung Transplant Bronchiolitis Obliterans Syndrome .........................................14 
2.1.2. 
Itacitinib ......................................................................................................................16 
2.2. 
Study Rationale ...........................................................................................................16 
2.2.1. 
Justification of Itacitinib Dose ....................................................................................20 
2.2.2. 
Dose Modifications for Concomitant Medications .....................................................20 
2.3. 
Benefit/Risk Assessment ............................................................................................21 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................22 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.2. 
Overall Study Duration ...............................................................................................24 
4.3. 
Study Termination ......................................................................................................24 
5. 
STUDY POPULATION .............................................................................................25 
5.1. 
Inclusion Criteria ........................................................................................................25 
5.2. 
Exclusion Criteria .......................................................................................................26 
5.3. 
Lifestyle Considerations .............................................................................................28 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................28 
5.4. 
Screen Failures ............................................................................................................28 
5.5. 
Replacement of Participants .......................................................................................28 
6. 
STUDY TREATMENT ..............................................................................................29 
6.1. 
Study Treatment Administered ...................................................................................29 
6.1.1. 
Determination of Recommended Phase 2 Dose .........................................................30 
6.2. 
Dose Modifications .....................................................................................................31 
6.2.1. 
Criteria and Procedures for Dose Interruptions of Study Drug ..................................31 
6.2.2. 
Management of Infectious Complications ..................................................................32 
6.3. 
Concomitant Medications and Procedures .................................................................32 


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6.3.1. 
Permitted Medications ................................................................................................32 
6.3.1.1. 
Prophylactic Medications and Immunosuppression ...................................................32 
6.3.1.2. 
Guidelines for Concomitant Use of Antifungal Agents .............................................33 
6.3.2. 
Restricted Medications ...............................................................................................33 
6.3.3. 
Prohibited Medications ...............................................................................................33 
6.3.4. 
Prohibited Procedures .................................................................................................34 
6.4. 
Preparation, Handling, and Accountability ................................................................34 
6.5. 
Measures to Minimize Bias:  Randomization and Blinding .......................................35 
6.6. 
Study Treatment Compliance .....................................................................................35 
6.7. 
Treatment After the End of the Study .........................................................................35 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Reasons for Discontinuation .......................................................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................36 
7.2. 
Participant Withdrawal from the Study ......................................................................37 
7.3. 
Lost to Follow-Up.......................................................................................................37 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................38 
8.1. 
Administrative and General Procedures .....................................................................38 
8.1.1. 
Informed Consent Process ..........................................................................................38 
8.1.2. 
Screening Procedures ..................................................................................................39 
8.1.3. 
Interactive Response Technology Procedure ..............................................................39 
8.1.4. 
Distribution of Reminder Cards ..................................................................................39 
8.1.5. 
Demography and Medical History ..............................................................................39 
8.1.6. 
Disease Characteristics and Treatment History ..........................................................40 
8.2. 
Efficacy Assessments .................................................................................................40 
8.2.1. 
Spirometry ..................................................................................................................40 
8.3. 
Safety Assessments .....................................................................................................40 
8.3.1. 
Adverse Events ...........................................................................................................40 
8.3.2. 
Physical Examinations ................................................................................................41 
8.3.3. 
Vital Signs, Height, and Weight .................................................................................41 
8.3.4. 
Electrocardiograms .....................................................................................................41 
8.3.5. 
Laboratory Assessments .............................................................................................42 


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8.4. 
Unscheduled Visits .....................................................................................................43 
8.5. 
End of Treatment and/or Early Termination ..............................................................43 
8.6. 
Follow-Up ...................................................................................................................44 
8.6.1. 
Safety Follow-Up ........................................................................................................44 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................45 
9.1. 
Definition of Adverse Event .......................................................................................45 
9.2. 
Definition of Serious Adverse Event ..........................................................................46 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........47 
9.4. 
Reporting of Serious Adverse Events .........................................................................49 
9.5. 
Emergency Unblinding of Treatment Assignment .....................................................50 
9.6. 
Pregnancy ...................................................................................................................51 
9.7. 
Warnings and Precautions ..........................................................................................51 
9.8. 
Product Complaints ....................................................................................................51 
9.9. 
Treatment of Overdose ...............................................................................................52 
10. 
STATISTICS ..............................................................................................................53 
10.1. 
Sample Size Determination ........................................................................................53 
10.1.1. 
Phase 1 ........................................................................................................................53 
10.1.2. 
Phase 2 ........................................................................................................................53 
10.2. 
Populations for Analyses ............................................................................................53 
10.3. 
Level of Significance ..................................................................................................53 
10.4. 
Statistical Analyses .....................................................................................................53 
10.4.1. 
Primary Analysis ........................................................................................................53 
10.4.2. 
Efficacy Analysis ........................................................................................................54 
10.4.3. 
Safety Analyses ..........................................................................................................54 
10.4.3.1. 
Adverse Events ...........................................................................................................54 
10.4.3.2. 
Clinical Laboratory Tests ...........................................................................................54 
10.4.3.3. 
Vital Signs ..................................................................................................................55 
10.4.3.4. 
Electrocardiograms .....................................................................................................55 
 
56 
10.5. 
Interim Analysis ..........................................................................................................56 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................56 


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11.1. 
Investigator Responsibilities .......................................................................................56 
11.2. 
Data Management .......................................................................................................57 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................59 
11.4. 
Financial Disclosure ...................................................................................................59 
11.5. 
Publication Policy .......................................................................................................59 
11.6. 
Study and Site Closure................................................................................................60 
12. 
REFERENCES ...........................................................................................................61 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................63 
APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING STUDY 
DRUG (ITACITINIB) ................................................................................................64 
APPENDIX C. STRONG CYP3A INHIBITORS AND INDUCERS .......................................65 
APPENDIX D. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................66 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................68 
 
LIST OF TABLES 
Table 1: 
Primary and Key Secondary Objectives and Endpoints .............................................10 
Table 2: 
Schedule of Activities .................................................................................................12 
Table 3: 
Schedule of Laboratory Assessments .........................................................................13 
Table 4: 
BOS Classification Scheme ........................................................................................15 
Table 5: 
Simulated Itacitinib Daily Exposure By Dose and Concomitant Strong 
CYP3A Inhibitor Administration ...............................................................................21 
Table 6: 
Objectives and Endpoints ...........................................................................................22 
Table 7: 
Exclusionary Laboratory Values ................................................................................27 
Table 8: 
Study Treatment Information .....................................................................................29 
Table 9: 
Itacitinib Dose Levels .................................................................................................29 
Table 10: Guidelines and Procedures for Interruption of Study Drug ........................................31 
Table 11: Required Laboratory Analytes ....................................................................................43 
Table 12: Populations for Analysis .............................................................................................53 
Table 13: Criteria for Vital Sign Abnormalities .........................................................................55 
Table 14: Criteria for Electrocardiogram Abnormalities ............................................................55 
 


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LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................11 
Figure 2: 
Improvement in GVHD Score After Itacitinib Administration ..................................17 
Figure 3: 
Summary of Clinical Studies Using Ruxolitinib in Acute and Chronic 
GVHD .........................................................................................................................18 
Figure 4: 
Itacitinib Efficacy in Patients With Treatment-Naïve or Steroid-Refractory 
Acute GVHD ..............................................................................................................19 
Figure 5: 
Itacitinib Safety in Patients With Treatment-Naïve or Steroid-Refractory 
Acute GVHD ..............................................................................................................19 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
aGVHD 
acute graft-versus-host disease 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
APC 
antigen presenting cells 
AST 
aspartate aminotransferase 
ATG 
antithymocyte globulin 
ATS 
American Thoracic Society 
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 
BOS 
bronchiolitis obliterans syndrome 
cGVHD 
chronic graft-versus-host disease 
CI 
confidence interval 
CLAD 
chronic lung allograft dysfunction 
Cl/F 
apparent oral dose clearance 
Cmax 
maximum observed concentration 
Cmin 
minimum observed plasma or serum concentration over the dose interval 
CMV 
cytomegalovirus 
CNI 
calcineurin inhibitor 
COVID-19 
coronavirus disease 2019 
CsA 
cyclosporine a 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOT 
end of treatment   
EQ-5D-3L 
EuroQol EQ-5D 3 level version 
ERS 
European Respiratory Society 
FAS 
full analysis set 
FDA 
Food and Drug Administration 


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Abbreviations and 
Special Terms 
Definition 
FEF25-75 
forced expiratory flow at 25–75% of forced vital capacity 
FEV1 
forced expiratory volume in 1 second  
GVHD 
graft-versus-host disease 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplant 
ICF 
informed consent form 
ICH 
International Council on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IRB 
institutional review board 
IRT 
interactive response technology  
ISHLT 
International Society for Heart and Lung Transplantation 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
mTORi 
mTOR inhibitor 
ORR 
overall response rate  
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
QD 
once daily 
RAS 
restrictive allograft syndrome 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SGRQ 
St Georges Respiratory Questionnaire 
SoA 
schedule of activities 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and 
Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung 
Transplantation 
Protocol Number:  INCB 39110-214 
Objectives and Endpoints: 
Table 1 presents the primary and key secondary objectives and endpoints of the study. 
Table 1: 
Primary and Key Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1 
To identify an appropriate dose of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
Frequency, severity, and duration of AEs; 
assessment of changes in safety and FEV1; and 
assessment of changes in laboratory parameters, 
PK, and PD. 
Phase 2 
To evaluate the efficacy of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
FEV1 response rate from baseline through the 
Week 12 visit, defined as the proportion of 
participants demonstrating a ≥ 10% absolute 
increase in FEV1 compared to baseline. 
Key Secondary 
Phase 1 and Phase 2 
To evaluate duration of FEV1 response in 
participants with Grade 1 through 3 BOS following 
lung transplantation who are treated with itacitinib. 
Duration of FEV1 response, defined as the time 
of the onset of response (≥ 10% absolute 
increase in FEV1 compared to baseline) to BOS 
progression or loss of clinical benefit as 
determined by the investigator. 
To evaluate time to progression in participants with 
Grade 1 through 3 BOS following lung 
transplantation who are treated with itacitinib. 
Time to progression, defined as the interval 
between the start of treatment and BOS 
progression (≥ 10% absolute decrease in FEV1 
compared to baseline), or death. 
To evaluate quality of life outcomes in participants 
with Grade 1 through 3 BOS following lung 
transplantation who are treated with itacitinib. 
• Change from baseline in SGRQ total score. 
• Change from baseline in QOL-SF-12 
questionnaire.  
• Categorical summary or change from baseline 
in EQ-5D-3L questionnaire. 


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Overall Design: 
Study Phase 
Phase 1/2 
Clinical Indication 
Post–lung transplant BOS 
Population 
Males and females who are at least 18 years of age who have undergone 
double lung transplantation at least 1 year before screening and have a 
diagnosis of Grade 1 through 3 BOS. 
Number of Participants 
Phase 1:  Approximately 24 participants, to be treated at 3 different dose 
levels (n = 8 each) 
Phase 2:  Up to approximately 55 participants 
Study Design 
Phase 1:  Randomized, open-label 
Phase 2:  Single-arm, open-label 
Estimated Duration of 
Study 
Up to 30 days for screening, continuous treatment as long as participants 
are receiving benefit and have not met any criteria for treatment 
discontinuation, 30 days for safety follow-up, and participants enrolled in 
Phase 2 will be followed for long-term survival and retransplantation 
status.  Study participation, including survival follow-up, is expected to 
average approximately 24 months per participant. 
Study Steering Committee 
A steering committee comprised of the coordinating PI and select sponsor 
personnel will review the cumulative Phase 1 data and provide a 
recommendation for the Phase 2 dose. 
Figure 1: 
Study Design Schema 
 
Adherence to the study design requirements, including those specified in the SoA (see Table 2), 
is essential and required for study conduct. 


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Table 2: 
Schedule of Activities 
Visit Day (Range) 
Screening 
Treatment 
EOT 
Safety 
Follow-Up 
(30 d + 7 d) 
Notes 
Days -30 
to -1 
Baseline 
(Day 1) 
Week 1 
(± 1 d) 
Week 2 
(± 3 d) 
Weeks 4 
and 8 
(± 7 d) 
Week 12 
(± 7 d) 
Week 16 and 
Q4W thereafter 
(± 14 d) 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
See Section 8.1.1 for details. 
Register visit in IRT 
X 
X 
 
 
X 
X 
X 
X 
 
See Section 8.1.3  for details. 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
See Section 5 for details. 
Demography 
X 
 
 
 
 
 
 
 
 
See Section 8.1.5 for details. 
Relevant medical and 
transplant history 
X 
 
 
 
 
 
 
 
 
See Sections 8.1.5 and 8.1.6 for details. 
Prior/concomitant 
medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 6.3 for details. 
Study drug dispensing 
and accountability 
 
X 
 
 
X 
X 
X 
X 
 
See Section 6.4 for details. 
Dispense reminder card 
 
X 
X 
X 
X 
X 
X 
X 
 
See Section 8.1.4 for details. 
Safety assessments 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.3.1 for details. 
Comprehensive physical 
X 
 
 
 
 
 
 
 
 
See Section 8.3.2 for details. 
Targeted physical exam 
 
X 
X 
X 
X 
X 
X 
X 
X 
See Section 8.3.2 for details. 
Vital signs/weight 
X* 
X 
X 
X 
X* 
X* 
X* 
X* 
X 
See Section 8.3.3 for details. 
* Weight performed. 
12-Lead ECG 
X 
As clinically indicated 
X 
 
See Section 8.3.4 for details. 
Disease assessments 
Spirometry (FEV1 and 
FVC) 
X 
X 
X 
X 
X 
X 
X 
X 
 
See Section 8.2.1 for details. 


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Table 3: 
Schedule of Laboratory Assessments 
Procedure 
Screening 
Treatment 
EOT 
Safety 
Follow-Up 
(30 d ± 7 d) 
Notes 
Day -30 
to -1 
Baseline 
(Day 1) 
Weeks 1 
and 2 
(± 3 d) 
Week 4 
(± 7 d) 
Week 8 
(± 7 d) 
Week 12 
(± 7 d) 
Week 16 
and Q4W 
thereafter 
(± 14 d) 
Laboratory safety assessments 
Hematology 
X 
X* 
X 
X 
X 
X 
X 
X 
X 
* May be omitted at baseline if screening 
hematology within 14 days. 
Blood chemistry 
X 
X* 
X 
X 
X 
X 
X 
X 
X 
* May be omitted at baseline if screening 
chemistry within 14 days. 
Lipid panel 
X 
 
 
 
 
X* 
X* 
X* 
X* 
* Every 12 weeks starting at Week 12 (eg, 
Week 24, 36). 
Coagulation 
X 
X* 
X 
X 
X 
X 
X 
X 
 
* May be omitted at baseline if screening 
coagulation within 14 days. 
Hepatitis screening  
X 
 
 
 
 
 
 
 
 
 
CNI and mTORi (as 
applicable) levels 
X 
X 
X 
X 
X 
 
 
 
 
Tacrolimus/CsA and mTORi levels (as 
applicable) to be monitored from screening 
through Week 8. 
CMV PCR 
 
X 
X 
X 
X 
X 
X 
X 
 
See Section 8.3.5 for details. 
Serum pregnancy test  
X 
 
 
 
 
 
 
X 
 
Women of childbearing potential only. 
Urine pregnancy test 
 
 
 
X 
X 
X 
X 
 
 
Women of childbearing potential only. 


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2. 
INTRODUCTION 
Post–lung transplant BOS is a serious, life-threatening condition which represents a significant 
unmet medical need.  There are few therapeutic trials for BOS, and currently no agents are 
approved by the FDA for the treatment of BOS.  Treatments used in clinical practice are 
associated with significant toxicities and high failure rates. 
Novel treatments with agents targeting JAK-STAT pathways appear to decrease alloreactive 
T-cell damage in both preclinical models of GVHD as well as in completed and ongoing clinical 
trials.  The biology of GVHD shares many similar mechanisms with post–lung transplant BOS 
and it is hypothesized that the selective JAK1 inhibitor, itacitinib, may be an effective therapy 
for post–lung transplant BOS. 
Study INCB 39110-214 is a Phase 1/2 study that will evaluate itacitinib in post–lung transplant 
Grade 1 through 3 BOS.  The study design will comprise of a randomized, open-label, parallel 
dose selection run-in followed by a single arm expansion to evaluate the efficacy in this 
population. 
2.1. 
Background 
2.1.1. 
Post-Lung Transplant Bronchiolitis Obliterans Syndrome 
Allogeneic lung transplantation is an effective therapy for the treatment of a variety of end-stage 
lung disorders, including chronic obstructive pulmonary disease, interstitial lung disease, cystic 
fibrosis, and others.  More than 4500 lung transplants were performed worldwide in 2016 
(Chambers et al 2018), with approximately 2500 of these having been performed in the United 
States (OPTN/SRTR Registry).  Although 1- and 3-year survival rates post-transplant have 
improved, long-term survival rates from transplant have remained stagnant with a median overall 
survival of 6.5 years (Chambers et al 2018).  The most common cause of death from lung 
transplant after 1 year from surgery is CLAD; the most common subset of CLAD is BOS.  
Post-lung transplant BOS affects approximately 50% of patients who survive past 5 years and 
is the leading cause of death for those who survive past 1 year post-transplant (Chambers 
et al 2018).  Post–lung transplant BOS is characterized by an alloreactive immune infiltrate, 
which ultimately leads to progressive bronchiolar ectasia, fibrosis, and ultimately organ failure 
(Boehler and Estenne 2003).  Despite prophylactic treatments with immunosuppressive agents, 
the rate of post–lung transplant BOS remains unchanged.  There are few therapeutic trials for 
post–lung transplant BOS, and currently no agents are approved by the FDA for either the 
prevention or treatment of post–lung transplant BOS.  Restrictive allograft syndrome, is a 
distinct subset of CLAD that is characterized by restrictive functional changes with fibrotic 
processes in peripheral lung tissue rather than the obstructive patterns associated with BOS 
(Sato et al 2011).  Participants that clearly demonstrate an RAS phenotype are excluded from this 
study. 
The diagnosis of post–lung transplant BOS is made clinically and is defined by a persistent 
decline in lung function as measured by FEV1.  To make the diagnosis of post–lung transplant 
BOS, other causes of post-transplant decline including acute rejection, infection, native lung 
problems for single lung recipients, excessive recipient weight gain, anastomotic dysfunction, 


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respiratory muscle dysfunction, effusion, or technical problems such as erroneous measurements 
due to device dysfunction as well as others must be excluded as the cause of lung graft 
dysfunction (Meyer et al 2014). 
The BOS classification scheme (see Table 4), the accepted grading system for post–lung 
transplant BOS, is based off of spirometric evaluation of a persistent decline in FEV1 to ≤ 80% 
of baseline post-transplant baseline FEV1.  Baseline is defined as the average of the 2 best FEV1 
values ≥ 3 weeks apart following functional recovery and stabilization post–lung transplantation. 
Table 4: 
BOS Classification Scheme 
BOS Grade 
Definition 
0 
FEV1 > 90% and FEF25-75%  > 75% 
0-p 
FEV1 81-90% and FEF25-75% ≤ 75% 
1 
FEV1 66-80% 
2 
FEV1 51-65% 
3 
FEV1 ≤ 50% 
FEF25-75% = forced expiratory flow at 25-75% of forced vital capacity; FEV1 = forced expiratory volume in 1 second. 
Note:  Adapted from Meyer et al 2014. 
There is no standard of care or consensus treatment algorithm for BOS therapy, and there are few 
high quality randomized trials which demonstrate clear benefit in BOS patients (Meyer 
et al 2014); a variety of interventions have been investigated in the treatment of post–lung 
transplant BOS including azithromycin, altering immunosuppressive regimens, everolimus, 
montelukast, aerosolized cyclosporine, aerosolized tacrolimus, alemtuzumab, total lymphoid 
irradiation, extracorporeal photopheresis, and ultimately retransplantation. 
Patients with a diagnosis of new onset post–lung transplant BOS are evaluated to ensure they are 
receiving optimal immunosuppression including compliance with prescribed medications and 
immunosuppressants used.  For those patients on cyclosporine, there is evidence indicating that 
switching from cyclosporine to tacrolimus leads to a decrease in the loss of predicted FEV1 
(Sarahrudi et al 2004).  Once the immunosuppression regimen is optimized, there are few 
therapeutic options with any demonstrated efficacy.  Options include the following: 
• Azithromycin:  Azithromycin has demonstrated improvement in lung function, as 
defined by a ≥ 10% increase in FEV1, in approximately 35% to 40% of patients 
across multiple studies.  This response appears to correlate with the presence of 
neutrophilia in BAL fluid (Vos et al 2010).  Patients with an FEV1 response to 
azithromycin had an overall survival advantage with azithromycin as compared to 
those who did not.  In addition, a randomized study of prophylactic azithromycin 
compared to placebo in post–lung transplant BOS led to fewer cases of BOS; 
however, overall survival was not affected (Vos et al 2011). 
• Extracorporeal Photopheresis:  ECP has demonstrated modest activity in a number of 
single institution studies, the largest of which enrolled 51 patients.  In this study, 61% 
of patients had prolonged stable disease defined by FEV1 of -5 to +5 of pre-ECP 
baseline maintained over 6 months (Benden et al 2008). 


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• Montelukast:  A randomized controlled trial enrolled 30 patients to receive 
montelukast vs placebo.  Montelukast had no effect on lung function decline in the 
overall cohort.  However, in a post-hoc subanalysis of BOS Grade 1 patients, 
montelukast attenuated further decline of FEV1 during the study period in both 
absolute and predicted FEV1 (Ruttens et al 2018). 
• Retransplantation:  The definitive therapy for progressive BOS for those who are 
eligible is lung retransplantation.  Survival following a second transplant is markedly 
lower than primary transplants at 2.6 years (Thomas et al 2015). 
2.1.2. 
Itacitinib 
Itacitinib adipate is a small molecule inhibitor of the JAK family of protein tyrosine kinases 
(JAK1, JAK2, JAK3, and TYK2) with selectivity for JAK1 that is being developed for 
inflammatory diseases, GVHD, solid tumors, and hematological malignancies.  Itacitinib is 
approximately 22-fold selective for JAK1 over JAK2, such that minimal inhibition of JAK2 is 
seen at pharmacologically relevant doses of itacitinib in both preclinical and clinical studies.  
Sparing of JAK2 inhibition may reduce the risk of cytopenias in post–lung transplant BOS 
patients following treatment with itacitinib. 
Additional details on pharmacology, toxicology, and other clinical studies may be found in 
the IB. 
2.2. 
Study Rationale 
Itacitinib is currently under clinical investigation in the treatment of both acute and chronic 
post-HSCT GVHD.  Chronic GVHD can affect any organ in the body with the most common 
being skin, liver, and intestines.  Chronic GVHD can also affect the lungs and has a clinical 
presentation that is nearly identical to post–lung transplant BOS.  The correlation between lung 
cGVHD and post–lung transplant BOS was first described in 1995 where clinical data and tissue 
were collected from 9 patients with lung cGVHD and post–lung transplant BOS.  Both groups 
had similar signs and symptoms including progressive dyspnea and an irreversible obstructive 
pattern as well as similar outcomes and histology including diffuse inflammation leading to 
ectasia of the large bronchi (Philit et al 1995). 
A recent review by the NIH cGVHD task force reviewed relevant literature and delineates the 
pathophysiology of lung cGVHD.  Lung cGVHD is initiated during the transplant process 
through the development of normal tissue damage that leads to a tissue damage response 
characterized by a release of cytokines, toll-like receptor agonists, neutrophils, platelets, and 
vascular inflammation (Cooke et al 2017).  CD4 and CD8 cells as well at Th17 cells are recruited 
to the site, however, due to thymic injury or dysfunction, there is impaired negative selection of 
these cells and autoreactive T-cell clones persist.  In addition, the requisite immunosuppression 
regimens used in cGVHD including CNIs lead to Treg depletion.  Ultimately, the initial T-cell 
response leads to the activation of a variety of innate and adaptive immune cells including T, B, 
and NK cells as well as APCs to the site, leading to upregulation of proinflammatory cytokines 
TGFβ, PDGFα, TNFα, and IL17.  This chronic inflammation and fibroblast recruitment ends 
with target organ collagen deposition and with continued dysfunction and fibrosis 
(Cooke et al 2017). 


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Many of the same biologic principles are inherent in post–lung transplant BOS.  The main 
difference being that in cGVHD the immune response is aberrant and leads to transplanted stem 
cells attacking host tissue whereas in post lung transplant BOS, the immune response is 
physiologically normal, although it still leads to poor outcomes for patients.  In post–lung 
transplant BOS the inciting event for alloreactive acute inflammation phase is clear, namely, an 
allogeneic lung graft implant; however, it should be noted that similar to cGVHD, patients with 
events leading to graft tissue injury including an acute rejection episode following transplant, 
CMV infection as well as other tissue damaging phenomena such as GERD and cold ischemic 
time are more likely to develop post–lung transplant BOS (Meyer et al 2014).  Thymic 
dysfunction seen with cGVHD is not relevant in post–lung transplant BOS as alloreactive T cells 
would not be negatively selected.  Importantly, however, roles for an early CD4, CD8, and 
Th17 cell infiltrate, as well as subsequent recruitment of B cell, NK cell, and APCs are all well 
documented in post–lung transplant BOS, even if these are physiologically appropriate (Boehler 
and Estenne 2003, Gupta et al 2017, Fukami et al 2012, Hodge et al 2012, Leonard et al 2000).  
Similar to cGVHD, maintenance immunosuppression regimens use CNIs leading to 
Treg depletion and inhibition (Meyer et al 2014).  Finally, each of the known cytokines, including 
TGFβ, PDGFα, TNFα, and IL-17 as well as cellular mediators of aberrant tissue repair have a 
documented presence in post–lung transplant BOS. 
Additionally, murine models demonstrate that prophylactic and therapeutic dosing with itacitinib 
led to improvement in the GVHD score at either 60 mg/kg per day or 120 mg/kg per day 
indicating the clinical efficacy in an alloreactive mouse model as seen in Figure 2. 
Figure 2: 
Improvement in GVHD Score After Itacitinib Administration 
 
The JAK inhibitor ruxolitinib has demonstrated clinical efficacy in aGVHD; additionally 
ruxolitinib has produced clinical efficacy in cGVHD.  Ruxolitinib is a JAK1/2 inhibitor, whereas 
itacitinib is a selective JAK1 inhibitor.  A summary of prior early clinical studies using 
ruxolitinib in both aGVHD and cGVHD can be found in Figure 3. 


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Figure 3: 
Summary of Clinical Studies Using Ruxolitinib in Acute and Chronic GVHD 
 
Of note, 4 out of 5 patients in the Khoury study with lung cGVHD had FEV1 responses as 
defined by an increase in FEV1 of ≥ 10%.  In addition, a study that looked at the use of 
ruxolitinib in 5 pediatric patients (4 evaluable) with lung cGVHD demonstrated 2 responses with 
1 patient having an increase in FEV1 of 9%.  Four out of five patients were able to wean steroids 
completely and the final patient was able to decrease the steroid requirement by > 50% 
(Schoettler et al 2019). 
Ruxolitinib completed a registrational Phase 2 study in acute steroid-refractory GVHD in the 
post-HSCT setting with a primary endpoint of 28-day ORR.  The 28-day ORR was 55% and best 
ORR at any point during the study was 73% (Jagasia et al 2018).  Additionally, in REACH2, 
which was a Phase 3 randomized study evaluating ruxolitinib versus investigator’s choice of 
therapy in acute steroid-refractory GVHD, ruxolitinib demonstrated a statistically significant 
improvement in overall response, failure-free survival, and overall survival (Zeiser et al 2020).  
Itacitinib has been evaluated in 2 studies in participants with aGVHD.  Study INCB 39110-108 
evaluated the safety and efficacy of 2 doses of itacitinib, 200 mg QD and 300 mg QD, in 
participants with treatment-naïve or steroid-refractory aGVHD (Schroeder et al 2016).  The 
primary endpoint of this study was 28-day ORR.  Efficacy from this study is shown in Figure 4. 


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Figure 4: 
Itacitinib Efficacy in Patients With Treatment-Naïve or Steroid-Refractory 
Acute GVHD 
 
Itacitinib was well-tolerated in this patient population with the most common treatment-related 
TEAE being thrombocytopenia or platelet count decrease as shown in Figure 5. 
Figure 5: 
Itacitinib Safety in Patients With Treatment-Naïve or Steroid-Refractory 
Acute GVHD 
 
Due to the increase in treatment related thrombocytopenia in this patient population, the 
recommended dose of itacitinib for further evaluation in subsequent aGVHD studies was 
200 mg QD. 
Study INCB 39110-301 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.  The study randomized 439 patients 1:1 to receive either itacitinib or 
placebo; all participants received standard doses of corticosteroids.  The primary endpoint was 


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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% percent, respectively), the 
result was not statistically significant (p = 0.08), and there was no difference in nonrelapse 
mortality (approximately 18% in both groups).  There were trends favoring itacitinib with regard 
to the rate of complete response (53% vs 41%, respectively) and progression to cGVHD; 
however, these were not study endpoints and thus were not subject to rigorous statistical 
analysis.  The safety profile observed in INCB 39110-301 was consistent with that observed in 
previously reported studies of itacitinib in combination with corticosteroids, and no new safety 
signals were identified. 
2.2.1. 
Justification of Itacitinib Dose 
As mentioned above, in participants with aGVHD receiving itacitinib 200 mg QD, with dose 
reduction to 100 mg QD in some participants on a strong CYP3A inhibitor, in combination with 
corticosteroids, the Day 28 ORR was not statistically different than placebo in combination with 
corticosteroids.  However, at this dose the safety profile was consistent with that previously 
observed with no new safety signals.  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, > ~6500 nM·h) predicted to be 
> 90%, well above the response rate with corticosteroids alone.  In study INCB 39110-309, 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 cGVHD, 
preliminary data revealed that in participants with relatively high exposures (> 20 μM·h), 
Grade 3/4 AEs, mainly thrombocytopenia, were manageable with dose reductions and/or 
discontinuations.  Itacitinib doses as high as 400 mg BID and 600 mg QD have been studied in 
other patient populations (eg, rheumatoid arthritis, plaque psoriasis, and myelofibrosis) and were 
well tolerated with manageable AEs that were not prohibitive to dosing.  Approximately 10% of 
participants with aGVHD receiving 200 mg QD had predose concentrations that were below the 
limit of quantification, suggesting inhibition of the target (ie, JAK1) was not maintained 
throughout the dosing interval.  Considering the disease pathology of BOS relative to aGVHD 
and cGVHD, the dose range and corresponding safety profile across these populations and other 
autoimmune and oncology populations, and response rates observed in participants with aGVHD 
and cGVHD, doses of 400 mg QD, 600 mg QD, and 300 mg BID were selected for this Phase 2 
dose-ranging study in BOS patients.  These doses should be adjusted to maintain a consistent 
exposure with concomitant use of a strong CYP3A inhibitor; see Section 2.2.2. 
2.2.2. 
Dose Modifications for Concomitant Medications 
Observed preliminary data from study INCB 39110-301 suggested that exposures are similar 
between participants with aGVHD either not on a CYP3A inhibitor or on a weak or moderate 
CYP3A inhibitor; and exposures are similar between participants with aGVHD on various 
CYP3A inhibitors, mainly posaconazole or voriconazole.  Using a preliminary population PK 
model, the impact of a strong CYP3A inhibitor on exposure was characterized, and simulations 
were performed to identify a dose reduction such that exposures remain generally consistent 
when an individual is receiving a strong CYP3A inhibitor and when he/she is not. 


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From Table 5, it is recommended that the dose be adjusted as follows: 
• If on 400 mg QD, dose adjust to 300 mg QD with concomitant administration of a strong 
CYP3A inhibitor (eg, posaconazole, voriconazole, itraconazole, or ketoconazole). 
• If on 600 mg QD, dose adjust to 400 mg QD with concomitant administration of a strong 
CYP3A inhibitor. 
• If on 300 mg BID, dose adjust to 200 mg BID with concomitant administration of a 
strong CYP3A inhibitor. 
Table 5: 
Simulated Itacitinib Daily Exposure By Dose and Concomitant Strong 
CYP3A Inhibitor Administration  
Itacitinib Dose 
Daily AUC (nM·h) Without 
Concomitant Strong 
CYP3A Inhibitor Use 
Daily AUC (nM·h) With 
Concomitant Strong 
CYP3A Inhibitor Use 
200 mg QD 
4220 
6720 
300 mg QD 
7740 
12,700 
400 mg QD 
11,400 
18,300 
600 mg QD 
19,000 
31,200 
200 mg BID 
8120 
12,800 
300 mg BID 
15,000 
24,300 
2.3. 
Benefit/Risk Assessment 
The potential benefit for itacitinib in post–lung transplant BOS patients is derived from the 
biologic similarity to cGVHD, with each entity sharing common features such as increased 
proinflammatory cytokines, presence of CD4, CD8, and Th17 cell infiltrate, as well as 
subsequent recruitment of B cell, NK cell, and APCs.  Preclinical models and small clinical 
studies have demonstrated significant activity when JAK inhibitors are used in cGVHD, 
including improvement and stabilization in FEV1 in patients with lung cGVHD, suggesting that 
JAK inhibitors may also have potential utility in treating post–lung transplant BOS. 
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.  Additionally, the safety profile of the 3 doses to be evaluated has been 
established in prior studies.  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. 
In September 2021, analysis of the data from the Phase 1 portion of the study revealed evidence 
of clinical benefit in a subset of participants with a manageable safety profile. The sponsor 
decided not to proceed to Phase 2 of the study for reasons unrelated to the benefit/risk of 
itacitinib in the study population. The sponsor will continue to consider the benefit/risk favorable 
for participants who are continuing on itacitinib as of Protocol Amendment 5. 


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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 presents the objectives and endpoints. 
Table 6: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1 
To identify an appropriate dose of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
Frequency, severity, and duration of AEs; 
assessment of changes in safety and FEV1; and 
assessment of changes in laboratory parameters, 
PK, and PD. 
Phase 2 
To evaluate the efficacy of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
FEV1 response rate from baseline through the 
Week 12 visit, defined as the proportion of 
participants demonstrating a ≥ 10% absolute 
increase in FEV1 compared to baseline. 
Secondary 
Phase 1 and Phase 2 
To evaluate duration of FEV1 response in 
participants with Grade 1 through 3 BOS 
following lung transplantation who are treated 
with itacitinib. 
Duration of FEV1 response, defined as the time of 
the onset of response (≥ 10% absolute increase in 
FEV1 compared to baseline) to BOS progression 
or loss of clinical benefit as determined by the 
investigator. 
To evaluate time to progression in participants 
with Grade 1 through 3 BOS following lung 
transplantation who are treated with itacitinib. 
Time to progression, defined as the interval 
between the start of treatment and BOS 
progression (≥ 10% absolute decrease in FEV1 
compared to baseline), or death. 
To evaluate quality of life outcomes in 
participants with Grade 1 through 3 BOS 
following lung transplantation who are treated 
with itacitinib. 
• Change from baseline in SGRQ total score. 
• Change from baseline in QOL-SF-12 
questionnaire. 
• Categorical summary or change from baseline 
in EQ-5D-3L questionnaire. 
To evaluate the PK of itacitinib in the study 
population 
Cmax, Cmin, tmax, AUC0-t, and Cl/F. 


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Table 6: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Phase 2 only 
To evaluate overall survival or time to 
retransplantation in participants with Grade 1 
through 3 BOS following lung transplantation 
who are treated with itacitinib. 
Time to retransplantation or death, defined as the 
interval between the start of treatment and the 
date of retransplantation or death due to any 
cause. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of itacitinib in participants 
with post–lung transplant BOS. 
Phase 1 is a dose selection run-in that will employ a randomized, open-label, parallel-cohort 
design to assess the safety, tolerability, PK, and PD and to determine the RP2D of itacitinib in 
participants with post–lung transplant BOS.  A total of 24 participants with Grade 1, 2, or 3 BOS 
will be assigned to receive 1 of 3 itacitinib dose levels (n = 8 each); see Table 9 for additional 
details regarding itacitinib dose levels.  Each Phase 1 dose level will enroll a maximum of 
2 participants with Grade 3 BOS.  Participants will be randomized to 1 of 3 dose levels using an 
IRT system.  Upon completion of Phase 1 enrollment, the RP2D will be selected on the basis of 
AE, laboratory, PK, and PD observations through the Week 12 visit.  Additionally, an efficacy 
analysis will be performed to determine the FEV1 response rate for all participants treated for 
≥ 12 weeks.  The study will proceed to Phase 2 if ≥ 1 responses (defined as ≥ 10% absolute 
increase in FEV1 compared to baseline, confirmed by 2 consecutive spirometric assessments 
≥ 1 week apart) are observed at the dose level selected as the RP2D. 
Phase 2 will employ a single-arm, open-label design to evaluate the efficacy and further 
characterize the safety of itacitinib at the RP2D. 
Itacitinib treatment in Phase 1 and Phase 2 will continue until progression of BOS (defined as a 
≥ 10% absolute decrease from baseline in FEV1, confirmed by 2 consecutive spirometric 
assessments ≥ 3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of 
consent.  Additional criteria for treatment discontinuation are detailed in Section 7.1. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the ICF.  The end of the study may be 
designated as the timepoint at which all participants have discontinued the study or a minimum 
of 6 months after initial study treatment administration, at which time a database lock of the 
study may occur to allow for analysis of the study data.  Any participant continuing on treatment 
at the time of database lock will continue to be treated and followed per Protocol.  The additional 
treatment and follow-up data will be reported in an addendum to the CSR. 
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 or if required by regulatory decision.  If the study 
is terminated prematurely, the sponsor will notify the investigators, the IRBs and IECs, and 
regulatory bodies of the decision and reason for termination of the study. 


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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female, 18 years of age or older. 
2. Ability to comprehend and willingness to sign a written informed consent and assent 
(when appropriate) according to institutional standards and willingness to comply with all 
study visits and procedures. 
3. Double lung transplantation ≥ 1 year before informed consent. 
4. Documented post-transplant baseline FEV1 (average of the 2 highest values measured 
≥ 3 weeks apart per ISHLT criteria [Meyer et al 2014]) following functional recovery and 
stabilization post–lung transplantation. 
5. Confirmed BOS progression to Grade 1, 2, or 3 (per ISHLT 2002 criteria [Estenne et al 
2002]) diagnosed within 1 year of screening. 
a. Grade 1 BOS is defined as a fractional decrease in FEV1 to 66-80% of post-transplant 
baseline FEV1. 
b. Grade 2 BOS is defined as a fractional decrease in FEV1 to 51-65% of post-transplant 
baseline FEV1. 
c. Grade 3 BOS is defined as a fractional decrease in FEV1 to ≤ 50% of post-transplant 
baseline FEV1. 
OR 
Confirmed BOS Grade 1, 2, or 3 diagnosed within 2 years of screening (based on the 
above definitions) AND: 
a. A ≥ 200 mL decrease in FEV1 in the previous 12 months OR  
b. A ≥ 50 mL decrease in FEV1 in the last 2 measurements. 
Note:  BOS grade must be determined by the average of 2 measurements made ≥ 3 weeks 
apart. 
6. Participants may be taking azithromycin and/or montelukast for BOS, however, treatment 
must have been initiated ≥ 3 months before screening and must be at a stable dose. 
7. If a participant is being treated with systemic corticosteroids for BOS, then the dose must 
be stable for ≥ 4 weeks before screening.   
Note:  Participants who have recently undergone a steroid taper and who are currently 
taking physiologic doses (≤ 10 mg/day prednisone equivalent) are not required to have 
been on a stable dose for ≥ 4 weeks before screening. 


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8. 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 
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. 
9. If a participant is being treated with a strong CYP3A inhibitor (see Appendix C), then the 
dose must be stable for > 4 weeks before the first dose of study drug. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. History of a single lung transplant. 
2. FEV1 decline attributable to cause(s) other than BOS, including but not limited to clear 
evidence of RAS, inflammatory complications of the lung allograft, antibody mediated 
rejection, infection, airway dysfunction, allograft compression, impaired graft inflation, 
vascular obstruction, weight gain, or organizing pneumonia. 
3. For participants with Grade 3 BOS as defined in inclusion criterion #5, FEV1 at screening 
< 35% of post-transplant baseline. 
4. Receipt of any other systemic treatment specifically for BOS (with the exception of 
azithromycin and montelukast), including extracorporeal photopheresis, alemtuzumab, 
and/or ATG within the timeframes outlined in Section 6.3.3 and Section 6.3.4 
(as applicable). 
5. Epstein-Barr virus-negative participants (at the time of transplant) who received donor 
EBV IgG positive lungs. 
6. Participants who have received lungs from HCV-infected donors. 
7. Removed during Protocol Amendment 2. 
8. Participants who have had any significant change (eg, addition of new agents) in an 
immunosuppressive regimen in the 4 weeks before screening. 
Note:  Adjustments to dosage of maintenance immunosuppression (eg, tacrolimus) to 
maintain therapeutic levels are encouraged.  Monitoring of CNI levels and any other 
agents that are used for maintenance immunosuppression (eg, mTORi) for which 
therapeutic drug monitoring is routinely performed as local standard of care is required at 
all study visits though Week 8. 


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9. Participant is hospitalized as an inpatient at the time of consent or at study Day 1. 
Note:  Participants who are not hospitalized at the time of informed consent but are later 
hospitalized during the screening period may be enrolled as long as all other eligibility 
criteria continue to be met. 
10. Untreated and/or symptomatic GERD. 
11. Significant infectious comorbidities including invasive fungal disease, B. Cepacia, 
non-TB mycobacteria, or TB. 
12. History of diffuse alveolar hemorrhage. 
13. Receipt of JAK inhibitor therapy after lung transplant for any indication.  Treatment with 
a JAK inhibitor before lung transplant is permitted. 
14. Participants with laboratory values at screening defined in Table 7. 
Table 7: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
a 
ANC 
< 1.5 × 109/L 
b 
Platelet count 
< 120 × 109/L 
c 
Hemoglobin 
< 9.0 g/L 
d 
AST or ALT 
≥ 2 × ULN 
e 
Bilirubin 
≥ 1.5 × ULN, unless due to Gilbert's syndrome 
g 
Creatinine clearance 
< 30 mL/min 
h 
Albumin 
< 3 g/dL 
i 
INR 
> 1.5 × ULN 
15. 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. 
16. Known HIV infection. 
17. History of active malignancy within 3 years of screening, excluding superficial basal and 
squamous cell carcinoma of the skin, DCIS, low-risk prostate cancer (Gleason score of 
6 and a prostate-specific antigen measurement of 10 ng/mL or less and a stage of T2a or 
less), and adequately treated carcinoma in situ of the cervix.  Additional prior or active 
malignancies may be allowed with approval from the medical monitor.  
18. Women who are pregnant or breastfeeding. 
19. Anticipated need for live (including attenuated) vaccines during the first year of study. 


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20. Treatment with an investigational agent, procedure, or device within 30 days of 
enrollment, or within 5 half-lives of the investigational product, whichever is longer. 
21. Known allergies, hypersensitivity, or intolerance to any of the study medications, 
excipients, or similar compounds. 
22. Inability or unlikeliness of the participant to comply with the dose schedule and study 
evaluations, in the opinion of the investigator. 
23. 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. 
24. 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 the exposure to itacitinib. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study treatment. 
Participants who do not meet the criteria for enrollment into this study (screen failure) may be 
rescreened once if the investigator believes that there has been a change in eligibility status.  
Participants who rescreen must reconsent and be assigned a new participant number. 
Tests with results that fail eligibility requirements may be repeated once during the screening 
period if the investigator believes the result to be in error. 
5.5. 
Replacement of Participants 
Participants may be replaced for any of the following reasons: 
• In Phase 1, any participant who takes ≤ 75% of the planned itacitinib doses up to the 
Week 12 visit for any reason. 
• Participants who do not meet the eligibility requirements of the study. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
Information regarding study drug and administration is provided in Table 8. 
Once eligibility is confirmed, participants enrolling into Phase 1 will be randomized to an 
assigned dose level (see Table 9), will begin the treatment period on Day 1, and will continue on 
study treatment until discontinuation criteria are met. 
Participants enrolling into Phase 2, upon confirmation of eligibility, will begin treatment at the 
RP2D determined in Phase 1. 
Table 8: 
Study Treatment Information 
Study treatment name: 
Itacitinib 
Dosage formulation: 
Sustained release tablet 
Unit dose strength: 
100 mg 
Route of administration: 
Oral 
Administration 
instructions: 
During Phase 1, participants will be randomized to 1 of 3 dose levels, 
as outlined in Table 9.  Itacitinib administration will continue daily at 
the assigned dose until treatment discontinuation.  
Phase 2 participants will be administered itacitinib at the RP2D, which 
will be selected based on the criteria outlined in Section 6.1.1. 
Itacitinib may be taken without regard to food except on PK days. 
Missed doses must be taken within 8 hours after the scheduled time of 
administration; however, if this window is not met, the missed dose 
will be documented as not taken and the next scheduled dose will be 
taken as scheduled. 
Packaging and labeling: 
Itacitinib will be provided in 35-count bottles. 
Investigational product labels will be in the local language and will be 
labeled as required per country requirement. 
Storage: 
Ambient 15°C-30°C (59°F-86°F) 
Table 9: 
Itacitinib Dose Levels 
Itacitinib 
Dose Level 
Starting Dose 
First Dose Level 
Reduction 
Second Dose Level 
Reduction 
A: 
No CYP3A 
B: 
With 
CYP3A 
A: 
No CYP3A 
B: 
With 
CYP3A 
A: 
No CYP3A 
B: 
With 
CYP3A 
Dose Level 1 
300 mg BID 
200 mg BID 
200 mg BID 
100 mg BID 
100 mg BID 
100 mg QD 
Dose Level 2 
400 mg QD 
300 mg QD 
300 mg QD 
200 mg QD 
200 mg QD 
100 mg QD 
Dose Level 3 
600 mg QD 
400 mg QD 
400 mg QD 
300 mg QD 
300 mg QD 
200 mg QD 


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The assigned dose level (Dose Level 1, 2, or 3) will determine the dose and schedule of itacitinib 
to be administered as the starting dose as well as any subsequent reductions in dose that may 
occur due to toxicity.  The dose administered will also be determined based on whether the 
participant is taking a concomitant strong CYP3A inhibitor (eg, voriconazole, itraconazole, 
posaconazole, ketoconazole; see Appendix C).  Participants who are not taking concomitant 
strong CYP3A inhibitor will be administered the dose specified in Column A of Table 9.  
Participants who are taking concomitant strong CYP3A inhibitor will be administered the 
dose specified in Column B of Table 9.  If a participant begins taking or discontinues a strong 
CYP3A inhibitor during treatment, the dose should be adjusted accordingly per Table 9 (eg, if 
the participant begins taking a strong CYP3A inhibitor, he/she should be switched to the dose 
specified in Column B).  At the time of either addition or discontinuation of a strong CYP3A 
inhibitor, close monitoring of CNI levels should be undertaken to ensure safety of the study 
participant. 
Participants enrolled before Protocol Amendment 2 who were randomized to receive the 200 mg 
QD dose and who are ongoing at the time of amendment approval may increase their itacitinib 
dose to Dose Level 2 using the same parameters outlined in Table 9, with approval from the 
sponsor.  Participants must have tolerated the 200 mg QD dose and have not experienced any 
AEs ≥ Grade 3 that are considered related to itacitinib.  Additionally, the participant must agree 
to weekly clinic visits for a targeted physical examination and hematology/complete blood count 
assessment for the first 2 weeks after the dose increase. 
Participants may have dose reductions or modifications during the course of treatment based on 
AEs, clinical evaluation, changes to concomitant medications, and laboratory assessments.  Dose 
modifications of itacitinib for toxicity should follow the algorithm outlined for each dose level in 
Table 9. See Section 6.2.1 for criteria and guidelines related to itacitinib dose modifications due 
to AEs and Section 6.3 for guidelines related to itacitinib dose modifications due to select 
concomitant medications. 
Participants are permitted to remain on itacitinib treatment until withdrawal from study treatment 
is considered necessary as per Section 7.1.1. 
6.1.1. 
Determination of Recommended Phase 2 Dose 
After the final participant enrolled into the Phase 1 portion completes the Week 12 visit, a study 
steering committee comprised of the coordinating PI and Incyte personnel representing clinical 
development, pharmacovigilance, and statistics will review the cumulative Phase 1 data and 
provide a recommendation for the Phase 2 dose level.  Additional details regarding the 
composition of the steering committee and the process by which the committee will review data 
and make recommendations will be documented in the steering committee charter. 
The RP2D will be selected on the basis of AE, laboratory, PK, and PD observations through the 
Week 12 visit.  One of 3 doses (Dose Level 1, Dose Level 2, or Dose Level 3) will be chosen to 
take forward into the Phase 2 portion of the study.  Additionally, before opening enrollment into 
Phase 2, an efficacy analysis of FEV1 response will be performed for each dose level to further 
inform RP2D selection, as described in Section 4.1.  Phase 1 participants who are ongoing at the 
time of RP2D selection will remain on their initial dose level for the duration of the treatment 
period. 


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6.2. 
Dose Modifications 
6.2.1. 
Criteria and Procedures for Dose Interruptions 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 may be delayed up to 14 days to allow for resolution of toxicity.  After 
interruption, participants should be evaluated on a weekly basis until resolution/improvement of 
the AE.  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 investigator should contact the medical monitor to discuss the 
case of any participant whose treatment has been delayed for more than 14 days before restarting 
treatment. 
Because participants may enter the study with extensive comorbidities, dose reduction 
recommendations in Table 10 are provided as guidelines.  Each participant may undergo up to 
2 dose reductions for toxicity.  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 drug 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. 
Table 10: 
Guidelines and Procedures for Interruption of Study Drug 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
• AST and/or ALT is > 3.0 × ULN 
Step 1:  Interrupt itacitinib administration up to 14 days until 
the toxicity has resolved to ≤ Grade 1.  Exceptions require 
sponsor approval. 
Step 2:  Restart itacitinib at previous dose.  If assessed as 
related to itacitinib, restart at reduced dose level and monitor as 
clinically indicated. 
• AST and/or ALT is > 5.0 × ULN 
• ALT or AST is > 3.0 × ULN and 
total bilirubin is > 2.0 × ULN or 
INR is > 1.5 on repeat testing 
• AST and/or ALT is > 3.0 × ULN 
with the appearance of fatigue, 
nausea, vomiting, right upper 
quadrant pain or tenderness, fever, 
rash, and/or eosinophilia 
Permanently discontinue itacitinib administration with close 
observation.  Evaluation for other underlying causes should be 
sought. 


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Table 10: 
Guidelines and Procedures for Interruption of Study Drug (Continued) 
ADVERSE EVENT 
ACTION TAKEN 
Hematology 
• Platelet count is 25 to < 50 × 109/L  Step 1:  Interrupt itacitinib administration until the platelet 
count has resolved to ≥ 100 × 109/L. 
Step 2:  Restart at 1 dose level reduction. 
Second occurrence:  Repeat Steps 1 and 2; consult medical 
monitor before restarting itacitinib.  
Third occurrence:  Discontinue treatment.  
• ANC is 0.5 to < 1.0 × 109/L 
Step 1:  Interrupt itacitinib administration up to 14 days until 
ANC has resolved to ≥ 1.0 × 109/L. 
Step 2:  Restart itacitinib at same dose, and monitor as 
clinically indicated. 
Second occurrence:  Restart at 1 dose level reduction. 
• Platelet count is < 25 × 109/L or 
ANC < 0.5 × 109/L 
Interrupt itacitinib administration until the platelet count has 
resolved to ≥ 100 × 109/L.  May resume treatment at 1 dose 
level lower after approval from medical monitor. 
Other toxicities 
• Any Grade 1 or Grade 2 toxicity 
Continue itacitinib administration, and treat the toxicity; 
monitor as clinically indicated. 
• Any Grade 3 toxicity, if clinically 
significant and not manageable by 
supportive care. 
Step 1:  Interrupt up to 14 days until toxicity resolves to 
≤ Grade 1. 
Step 2:  Restart at same dose; if assessed as related to itacitinib, 
restart at next lower dose and monitor as clinically indicated. 
• Any Grade 4 toxicity 
Discontinue itacitinib administration, and follow-up per 
Protocol. 
6.2.2. 
Management of Infectious Complications 
Viral, bacterial, or fungal infection complications may be managed per institutional standard of 
care.  Itacitinib may be interrupted for treatment of infectious complications at the investigator's 
discretion after consultation with the sponsor's medical monitor.  Required modifications to the 
itacitinib dose in the setting of concomitant administration of certain strong CYP3A inhibitors 
are discussed in Section 6.1. 
6.3. 
Concomitant Medications and Procedures 
6.3.1. 
Permitted Medications 
Concomitant treatments and/or procedures that are required to manage a participant's medical 
condition (including prophylactic and immunosuppressive medications as described in 
Section 6.3.1.1) during the study will be recorded in the eCRF. 
6.3.1.1. 
Prophylactic Medications and Immunosuppression 
Standard infection prophylaxis and immunosuppressive medications initiated before enrollment 
may be continued and titrated per institutional guidelines.  Prophylaxis for CMV 


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reactivation/reinfection is not required but is strongly encouraged.  Monitoring for CMV viremia 
is required from baseline through the EOT visit (see Table 3 and Section 8.3.5). 
6.3.1.2. 
Guidelines for Concomitant Use of Antifungal Agents 
If antifungal agents are adjusted such that a participant is switched from no azole to a strong 
CYP3A-inhibiting azole (eg, voriconazole, itraconazole, ketoconazole) during itacitinib dose 
administration, the itacitinib dose should be adjusted according to the guidance in Section 6.1. 
Conversely, if a participant switches from taking a CYP3A-inhibiting azole to no azole, the 
itacitinib dose should be adjusted according to Section 6.1 and Table 9.  
Note:  Appendix C includes a list of azoles that are considered clinically relevant CYP3A 
inhibitors.  Voriconazole, itraconazole, posaconazole, and ketoconazole are considered clinically 
relevant.  Isavuconazole and fluconazole are not considered clinically relevant CYP3A inhibitors 
(these are moderate, not strong inhibitors) and do not require dose adjustment of itacitinib.  
Participants who are taking isavuconazole or fluconazole should be administered the dose in 
Column A of Table 9 for a given dose level, in the absence of coadministration of any other 
strong CYP3A inhibitors. 
6.3.2. 
Restricted Medications 
The following medications have restrictions on use during the treatment period of the study: 
• Aspirin in doses exceeding 125 mg per day is not permitted.  Low-dose aspirin 
(≤ 125 mg per day) is permitted unless clinically contraindicated. 
• If concomitant administration of an anticoagulant/antiplatelet medication is indicated, 
then caution and enhanced monitoring is required.  History of thrombocytopenia 
should be a factor in the choice of anticoagulant and dose. 
6.3.3. 
Prohibited Medications 
None of the prohibited medications listed below may be initiated during study treatment.  
Medications initiated before the start of treatment are allowed if the specified criteria are met. 
• Azithromycin must have initiated treatment ≥ 3 months before screening and must be 
on a stable dose. 
• Montelukast must have initiated treatment ≥ 3 months before screening and must be 
on a stable dose. 
• The following may not have been administered within the specified time frame before 
the start of itacitinib treatment: 
− Alemtuzumab within 6 months 
− Rabbit ATG, equine ATG, or other ATG within 3 months 
− B-cell targeting agents (eg, rituximab, proteasome inhibitors) within 3 months 
− Investigational agents within 30 days (or 5 half-lives of the investigational 
product, whichever is longer) 
− Nintedanib or pirfenidone within 30 days 


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• Concomitant use of a JAK inhibitor. 
• Initiating therapy with an investigational medication unless otherwise approved by 
the medical monitor. 
• Coadministration with strong CYP3A inducers.  The FDA website provides the most 
current list of strong CYP3A4 inducers. 
• Strong CYP3A inhibitors must have initiated treatment > 4 weeks before the first 
dose of study drug. 
6.3.4. 
Prohibited Procedures 
• Extracorporeal photopheresis within 6 weeks before the start of treatment. 
6.4. 
Preparation, Handling, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatments received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study 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 to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug including pill counts from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  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 


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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.  For additional information related 
to IP, refer to the Pharmacy Manual. 
6.5. 
Measures to Minimize Bias:  Randomization and Blinding 
This is an open-label study; no comparisons will be made between participants or against 
historical controls.  Measurements of safety and efficacy are objective measurements, and only 
comparisons to pretreatment conditions will be made. 
6.6. 
Study Treatment Compliance 
Compliance with study treatment will be calculated by the sponsor based on the drug 
accountability documented on the eCRF by the site staff and monitored by the sponsor/designee. 
6.7. 
Treatment After the End of the Study 
For participants still benefiting from itacitinib after the end of the study, provisions will be made 
to provide itacitinib after discussion between the sponsor and the investigator. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• BOS progression, defined as a ≥ 10% absolute decrease in FEV1 from pretreatment 
baseline, observed in at least 2 consecutive spirometric assessments at least 3 weeks 
apart. 
Note:  If the investigator believes that the participant has met criteria for BOS 
progression due to another reason (eg, infection), then continuation of treatment may 
be permitted after discussion with the medical monitor. 
• 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. 
• The investigator determines that there has been a loss of clinical benefit in the 
absence of Protocol-defined BOS progression. 
• Development of post-transplant lymphoproliferative disorder. 
• Development of BK viremia. 


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• 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. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug/treatment 
administration in the investigator's opinion, the sponsor should be consulted for 
instruction on handling the participant. 
• If the participant becomes pregnant.  If the female participant is no longer pregnant 
and meets the treatment continuation criteria within 12 weeks of the planned 
reinitiation of treatment, study treatment may be resumed after approval has been 
received from the medical monitor (see Section 9.6). 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit.  These visits are described in Table 2 and Table 3.  The last date of the last dose 
of study drug and the reason for discontinuation of study treatment will be recorded in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal must be documented in the participant's medical record, 
and the primary reason for withdrawal must be included in the eCRF. 
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the eCRF. 
• 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 actively withdraws consent for collection of 
follow-up data (safety follow-up) then no additional data collection should occur; however, 


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participants will have the option of withdrawing consent for study treatment but continuing in the 
follow-up period of the study for safety assessments. 
7.2. 
Participant Withdrawal from the Study 
A participant may withdraw from the study at any time at 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 and inform the 
study monitor and sponsor. 
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.  Should this occur, the investigator must inform the 
sponsor. 


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


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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (Day 1).  Screening may not exceed 30 days. 
Procedures conducted as part of the participant's routine clinical management (eg, blood count, 
imaging) and 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 (ie, within 30 days of Day 1).  For participants who are enrolled in the 
study, information associated with eligibility requirements must be entered into the appropriate 
eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment or the administration of study drug/treatment.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results 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 
study treatment will be used to determine eligibility. 
See Section 5.4 and Section 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact the IRT to obtain the 
participant ID number during screening.  Upon determining that the participant is eligible for 
study entry, site staff will register the participant's Baseline (Day 1) visit in the IRT to obtain the 
treatment assignment.  Additionally, site staff will register subsequent on-study visits as 
indicated in Table 2 to obtain treatment assignment.  Site staff will register EOT and 
end-of-study details in the IRT.  Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards 
Participants will be provided with a reminder card starting on Day 1 and at all subsequent visits 
through EOT.  The reminder card will indicate the date/time of the next visit and will also 
remind Phase 1 participants that they should not take their morning dose of itacitinib before 
in-clinic PK draws and, as applicable, provide a space for the participant to record the time of the 
prior dose of study drug and their previous meal.  Any missed doses may also be recorded on the 
reminder card. 
8.1.5. 
Demography and Medical History 
Demographic data and general medical history will be collected at screening by the investigator 
or qualified designee and will include year of birth/age, race, ethnicity, medical and surgical 
history, and current illnesses.  Medical history will include relevant medical or surgical treatment 
within the last 10 years that are considered to be clinically significant by the investigator. 


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8.1.6. 
Disease Characteristics and Treatment History 
A disease-targeted medical/surgical and medication history including indication for lung 
transplant, transplant details (eg, transplant date, donor lung characteristics, history of acute 
rejection, donor-specific antibodies), current BOS grade, current immunosuppressive regimen, 
prior therapy for BOS, and other details related to the disease under study will be collected at 
screening.  In addition, at least 6 months of pretreatment spirometry data, including FEV1 and 
FVC, will be collected for each participant. 
8.2. 
Efficacy Assessments 
8.2.1. 
Spirometry 
Spirometry will be performed locally at screening and visits indicated in Table 2 according to the 
ATS/ERS Guidelines (Miller et al 2005) and will be conducted without the use of 
bronchodilators. 
Multiple forced expiratory efforts (at least 3 but no more than 8) will be performed for each 
spirometry session and the 2 best efforts that meet ATS/ERS acceptability and reproducibility 
criteria will be recorded.  The best efforts will be based on the highest FEV1.  The maximum 
FEV1 of the 2 best efforts will be used for the analysis.  Both the absolute measurement (for 
FEV1 and FVC) and the percentage of predicted normal value will be recorded using appropriate 
reference values.  The highest FVC will also be reported regardless of the effort in which it 
occurred (even if the effort did not result in the highest FEV1). 
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 drug.  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 drug.  Conditions that were already present at the 
time of informed consent should be recorded on the Medical History Form in the eCRF.  
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible rather than by individual underlying signs and symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
considered related to the study 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. 


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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). 
The severity of AEs will be determined per CTCAE v5.0. 
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 drug (see Section 6.2).  Investigators should pay special 
attention to clinical signs related to previous serious illnesses. 
At the screening visit, a comprehensive physical examination should be conducted.  The 
comprehensive physical examination will include height and body weight, and assessment(s) of 
the following organ or body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen; extremities; and lymph nodes; as well as a brief neurological 
examination. 
During the study, participants will be assessed by the investigator or medically qualified 
designee per institutional standard of care.  These assessments should be an evaluation as 
indicated by participant symptoms, AEs, or other findings and documented on the AE eCRF.  
The other physical examination assessments should be performed per Table 2. 
8.3.3. 
Vital Signs, Height, and Weight 
Vital sign measurements (to be taken before blood collection for laboratory tests), include blood 
pressure, pulse, respiratory rate, and body temperature at the timepoints detailed in Table 2.  
Blood pressure and pulse will be taken with the participant in the recumbent, semi recumbent, or 
sitting position after 5 minutes of rest.  If vital signs cannot be taken before blood collection for 
laboratory tests, there must be a minimum of 30 minutes from the completion of blood collection 
procedures to the beginning of vital signs collection.  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.  Weight will be measured at screening, Week 4 and every 4 weeks thereafter, and 
EOT, as outlined in Table 2.  Height will also be measured at screening. 
8.3.4. 
Electrocardiograms 
A 12-lead ECG will be performed during screening and at the EOT visit 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 participant management.  
The decision to include or exclude a participant or withdraw a participant from the study based 


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on an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of the investigator, 
in consultation with the sponsor's medical monitor, as appropriate. 
Based on findings from a concentration-QTc analysis, a QT effect exceeding the threshold of 
concern (10 ms) 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. 
8.3.5. 
Laboratory Assessments 
Clinical safety laboratory analyses (ie, blood chemistries, hematology assessments, coagulation 
tests, serology, lipid panel [fasting], and urinalysis) will be performed in certified local 
laboratories associated with study sites.  Blood and urine samples will be collected for laboratory 
analyses during study visits according to the schedule in Table 3.  Levels of immunosuppressive 
agents, including CNI and mTORi levels, will be monitored through the Week 8 visit according 
to Table 3.  Additionally, blood samples will be collected for CMV PCR testing from baseline 
through the EOT visit, as specified in Table 3.  CMV testing is required for participants with 
CMV donor/recipient mismatch (ie, donor positive/recipient negative or donor negative/recipient 
positive) or participants in which both donor and recipient were positive.  CMV testing is not 
required for participants for whom both donor and recipient were negative at the time of 
transplant but may be performed at the discretion of the treating physician.  
The laboratory analytes to be evaluated are presented in Table 11.  Additional testing may be 
required by the sponsor based on emerging safety data.  Additional tests may also be performed 
if clinically indicated. 
Further detailed information regarding collection, processing, and shipping of laboratory 
assessments is provided in the Laboratory Manual. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.  All laboratory tests with values considered clinically significant during 
participation in the study or within 30 days after the last dose of study treatment should be 
repeated until the values return to normal or baseline, or are no longer considered clinically 
significant by the investigator or medical monitor. 
Screening laboratory assessments for study eligibility evaluation must be performed within 
30 days of Day 1.  If screening hematology, chemistry, and coagulation analyses are performed 
more than 14 days before initial administration of study treatment (Day 1), they must be repeated 
before itacitinib administration to ensure continued study eligibility; if they were performed 
within 14 days of Day 1, they do not need to be repeated. 


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Table 11: 
Required Laboratory Analytes 
Blood Chemistries 
Hematology 
Pregnancy Testing 
Albumin 
ALP 
ALT 
AST 
Bicarbonate or CO2 
Blood urea nitrogen or urea 
Calcium 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
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 urine 
pregnancy every 28 days. 
Pregnancy tests (serum or urine) 
should be repeated if required by 
local regulations. 
Lipid Panel 
Serology 
Coagulation 
Triglycerides 
LDL 
HDL 
Hepatitis B surface antigen 
Hepatitis B surface antibody 
Hepatitis B core antibody 
HCV antibody 
HBV-DNA (if required) 
HCV-RNA (if required) 
PT 
aPTT 
INR 
CNI and mTORi Levels 
CMV Testing 
 
Tacrolimus level (if applicable) 
CsA level  (if applicable) 
mTORi (eg, sirolimus, as 
applicable) 
CMV PCR 
 
aPTT = activated partial thromboplastin time; HDL = high-density lipoprotein; LDL = low-density lipoprotein; PT = prothrombin 
time. 
8.4. 
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. 
8.5. 
End of Treatment and/or Early Termination 
When the participant permanently discontinues study drug, 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 follow-up visit. 


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8.6. 
Follow-Up 
8.6.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 to 37 days after the EOT visit (or after the last dose of study drug if 
the EOT visit was not performed).  Adverse events and SAEs must be reported at least 30 days 
after the last dose of study drug or 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.  The 
participant should be contacted by telephone for assessment of AEs and SAEs if the participant 
cannot return to the site for the safety follow-up visit. 


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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. 
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 cancer 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 cancer under study will be 
forwarded to Incyte Pharmacovigilance as a SAE within 24 hours of determination that the event is 
not progression of the cancer under study. 
• 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. 


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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: 
•  Results in death 
•  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. 
•  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. 
•  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. 
•  Is a congenital anomaly/birth defect 
• 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 itacitinib):  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). 
• 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 v5.0 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity: 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate 
activities of daily living. 


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• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study 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 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 Reference Safety Information 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: 
o 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. 
o 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 or study procedures), all SAEs 
occurring after the participant has signed the ICF through 30 days after the last dose of study 
treatment 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. 
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 suspected unexpected adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing 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. 
Serious Adverse Event Reporting 
SAE reporting procedures will follow the guidelines below from study initiation until study principal 
investigators are notified otherwise; should the sponsor switch the SAE reporting system to solely via 
the eCRF, the guidelines entitled “SAE Reporting via the EDC system” should be followed. 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 


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• 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/designee.  The contact information of the sponsor's 
study-specific representatives is listed in the Study Reference 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 Procedures Manual. 
SAE Reporting via the EDC system: 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must report within 24 hours of learning of its occurrence any SAEs via the EDC 
system (primary method) or by completing the Incyte Serious Adverse Event Report Form, in 
English (only if EDC system is not available). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte PhV via the EDC 
system.  The follow-up report should include information that was not provided previously, 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 circumstances where the EDC system would not work properly, initial and/or follow-up SAE 
information shall be documented on new or amended Serious Adverse Event Report Form.  Refer to 
the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Email transmission (or facsimile) of the Serious Adverse Event Report Form is the preferred method 
to transmit this information to the PhV/designee.  The contact information of the sponsor's 
study-specific representatives is listed in the Study Reference 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. 
• Contacts for SAE reporting can be found in the Study Procedures Manual. 
9.5. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 


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9.6. 
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: 
1. The study drug must be discontinued immediately (female participants only). 
2. If the female participant is no longer pregnant and meets the treatment continuation 
criteria within 12 weeks of the scheduled start of a cycle, study treatment may be 
resumed after approval has been received from the sponsor medical monitor. 
3. 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. 
9.7. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study, as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.8. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 


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All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 
9.9. 
Treatment of Overdose 
For this study, any dose of study treatment greater than 600 mg within a 24-hour time period will 
be considered an overdose. 
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. 
Phase 1 
In Phase 1, approximately 24 participants will be enrolled to participate across the 3 dose levels 
of itacitinib (see Table 9) to identify the RP2D.  A sample size of 24 participants (8 per dose 
level) allows for concurrent enrollment at 3 dose levels that have been previously characterized 
in other disease settings and is expected to enable the clinical characterization of safety and 
efficacy.  No formal statistical comparison will be performed between treatment groups. 
10.1.2. 
Phase 2 
The FEV1 response rate for itacitinib is assumed to be 20%.  In order for the lower confidence 
limit of the 95% CI to exclude 5%, approximately 55 participants are needed. 
10.2. 
Populations for Analyses 
Table 12 presents the populations for analysis. 
Table 12: 
Populations for Analysis 
Population 
Description 
FAS 
The FAS will include all participants enrolled in the study who received at least 
1 dose of study drug.  The FAS will be used for the summary of demographics, 
baseline characteristics, participant disposition, and analyses of all safety, study 
treatment administration, and efficacy data. 
PK evaluable 
The PK population consists of all enrolled participants who received at least 
1 dose of study drug and provided at least 1 postdose PK sample. 
10.3. 
Level of Significance 
No formal efficacy hypotheses will be tested.  All CIs will be 95%. 
10.4. 
Statistical Analyses 
10.4.1. 
Primary Analysis 
The primary endpoint is FEV1 response rate through the Week 12 visit, defined as the proportion 
of participants demonstrating a ≥ 10% absolute increase in FEV1 compared to baseline.  The 
primary analysis will be conducted once the last participant completes the Week 12 visit or 
withdraws from the study.  If a participant withdraws from the study before Week 12, or there is 
no FEV1 data up to and including Week 12, then the participant will be considered a 
nonresponder. 
Summary statistics and 95% CI will be provided.  
Primary efficacy analysis will be conducted for the full analysis data set. 


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10.4.2. 
Efficacy Analysis 
Secondary efficacy analysis will be conducted for the full analysis data set as follows: 
• Duration of FEV1 response is defined as the time of the onset of response (≥ 10% 
absolute increase in FEV1 compared to baseline) to BOS progression or loss of 
clinical benefit.  It will be estimated by the Kaplan-Meier method. 
• Summary statistics will be provided for change from baseline in SGRQ total score at 
each scheduled visit. 
• Summary statistics will be provided for change from baseline in the QOL-SF-12 
questionnaire at each scheduled visit. 
• Summary statistics will be provided for the EQ-5D-3L questionnaire at each 
scheduled visit. 
• Time to progression, defined as the interval between the start of treatment and BOS 
progression, defined as a ≥ 10% absolute decrease in FEV1 from pretreatment 
baseline, observed in at least 2 consecutive spirometric assessments at least 3 weeks 
apart, or death.  It will be estimated by the Kaplan-Meier method. 
• Overall survival, defined as the time from the date of start of study drug to the date of 
retransplantation or death due to any cause.  The Kaplan-Meier method will be used.  
Summary statistics will be provided. 
10.4.3. 
Safety Analyses 
The clinical safety data will be summarized using descriptive statistics using the FAS. 
10.4.3.1. Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event 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 to study drug 
administration.  Adverse events will be tabulated by the MedDRA preferred term and system 
organ class.  Severity of AEs will be based on the NCI CTCAE v5.0. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated. 
10.4.3.2. Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 


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Laboratory data will be classified into Grades 1 through 5 using CTCAE v5.0.  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of participants with worst postbaseline CTCAE grade 
(regardless of baseline value).  Each participant will be counted only for the worst 
grade observed postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 
10.4.3.3. Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time.  Vital sign 
results will be reviewed for abnormalities (see Table 13), 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. 
Table 13: 
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 
10.4.3.4. Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for abnormalities according 
to predefined criteria (see Table 14).  Participants exhibiting ECG abnormalities will be listed. 
Table 14: 
Criteria for Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF/QTcB 
> 450 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
QTcB = Bazett correction; QTcF = Fridericia correction. 


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10.5. 
Interim Analysis 
No formal interim analysis is planned.  A steering committee meeting will occur at the end of 
Phase 1 for RP2D dose determination, for which an informal analysis of safety and efficacy data 
will be performed. 
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 with eCRF completion guidelines for instructions on data entry in the 
eCRF.  The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements.  Other data outside the EDC system required in the study conduct 
of the Protocol such as documents or results transmitted to the sponsor via a central laboratory or 
specialized technical vendors, and as designated by the sponsor, will have their own data flow 
management plans, or study charters, 
 as applicable. 
The sponsor (or designee) will be responsible for: 
• Managing the integrity of the data and the quality of the conduct of the study, such as  
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated, and/or collected including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 


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The investigator will be responsible for: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF.  
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
 photographs, diary data), 
or as otherwise specified in the Protocol.   
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator's site. 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, 
depending on the study.  Also, current applicable medical records must be 
available. 
• May have responsibility for sending participants' data, either as unique samples, or 
copies, or photographs, to be evaluated centrally or analyzed centrally, or both, by a 
qualified vendor designated by the sponsor.  
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other study 
related documents.  The investigator must immediately notify the sponsor when 
contacted by any regulatory authority for the purposes of conducting an 
inspection. 


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11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF; if the participant's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations or require 
otherwise.  No records may be destroyed during the retention period without the written approval 
of the sponsor.  No records may be transferred to another location or party without written 
notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research participants, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 


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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. 
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 
Benden C, Speich R, Hofbauer GF, et al. Extracorporeal photopheresis after lung transplantation: 
a 10-year single-center experience. Transplantation 2008;86:1625-1627. 
Boehler A, Estenne M. Post-transplant bronchiolitis obliterans. Eur Respir J 2003;22:1007-1018. 
Chambers DC, Cherikh WS, Goldfarb SB, et al. The International Thoracic Organ Transplant 
Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung 
and heart-lung transplant report-2018; Focus theme: multiorgan transplantation. J Heart Lung 
Transplant 2018;37:1169-1183. 
Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014. http://www.hma.eu/ctfg.html. Accessed April 29, 2019. 
Cooke KR, Luznik L, Sarantopoulos S, et al. The biology of chronic graft-versus-host disease: a 
task force report from the National Institutes of Health Consensus Development Project on 
Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 
2017;23:211-234. 
Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of 
the diagnostic criteria. J Heart Lung Transplant 2002;21:297-310. 
Food and Drug Administration. Drug Development and Drug Interactions: Table of Substrates, 
Inhibitors and Inducers. 2017. https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed April 29, 
2019. 
Fukami N, Ramachandran S, Takenaka M, Weber J, Subramanian V, Mohanakumar T. An 
obligatory role for lung infiltrating B cells in the immunopathogenesis of obliterative airway 
disease induced by antibodies to MHC class I molecules. Am J Transplant 2012;12:867-876. 
Gupta PK, Wagner SR, Wu Q, Shilling RA. IL-17A blockade attenuates obliterative 
bronchiolitis and IFN-γ cellular immune response in lung allografts. Am J Respir Cell Mol Biol 
2017;56:708-715. 
Hodge G, Hodge S, Holmes-Liew CL, Reynolds PN, Holmes M. Bronchiolitis obliterans 
syndrome is associated with increased peripheral blood natural killer and natural killer T-like 
granzymes, perforin, and T-helper-type 1 pro-inflammatory cytokines. J Heart Lung Transplant 
2012;31:888-895. 
Itacitinib Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the 
treatment of patients with steroid-refractory GVHD: an introduction to the REACH  trials. 
Immunotherapy 2018;10:391-402. 
Khoury HJ, Langston AA, Kota VK, et al. Ruxolitinib: a steroid sparing agent in chronic 
graft-versus-host disease. Bone Marrow Transplant 2018;53:826-831. 
Leonard CT, Soccal PM, Singer L, et al. Dendritic cells and macrophages in lung allografts: A 
role in chronic rejection? Am J Respir Crit Care Med 2000;161:1349-1354. 


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Meyer KC, Raghu G, Verleden GM, et al. An international ISHLT/ATS/ERS clinical practice 
guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J 
2014;44:1479-1503. 
Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 
2005;26:319-338. 
Organ Procurement and Transplantation Network. https://optn.transplant.hrsa.gov/data/view-
data-reports/national-data/#. Accessed April 26, 2019. 
Philit F, Wiesendanger T, Archimbaud E, Mornex JF, Brune J, Cordier JF. Post-transplant 
obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow 
and lung transplant patients. Eur Respir J 1995;8:551-558. 
Ruttens D, Verleden SE, Demeyer H, et al. Montelukast for bronchiolitis obliterans syndrome 
after lung transplantation: A randomized controlled trial. PLoS One 2018;13:e0193564. doi: 
10.1371/journal.pone.0193564. eCollection 2018. 
Sarahrudi K, Estenne M, Corris P, et al. International experience with conversion from 
cyclosporine to tacrolimus for acute and chronic lung allograft rejection. J Thorac Cardiovasc 
Surg 2004;127:1126-1132. 
Sato M, Waddell TK, Wagnetz U, et al. Restrictive allograft syndrome (RAS): a novel form of 
chronic lung allograft dysfunction. J Heart Lung Transplant 2011;30:735-742. 
Schoettler M, Duncan C, Lehmann L, Furutani E, Subramaniam M, Margossian S. Ruxolitinib is 
an effective steroid sparing agent in children with steroid refractory/dependent bronchiolitis 
obliterans syndrome after allogenic hematopoietic cell transplantation [published online ahead of 
print January 25, 2019]. Bone Marrow Transplant. doi: 10.1038/s41409-019-0450-3. 
Schroeder MA, Khoury HJ, Jagasia M, et al. A phase 1 trial of janus kinase (JAK) inhibition 
with INCB039110 in acute graft-versus-host disease (aGVHD). Presented at: 58th American 
Society of Hematology (ASH) Annual Meeting & Exposition; December 3-6, 2016; San Diego, 
CA. Abstract 390. 
Thomas M, Belli EV, Rawal B, Agnew RC, Landolfo KP. Survival after lung retransplantation 
in the United States in the current era (2004 to 2013): better or worse? Ann Thorac Surg 
2015;100:452-457. 
Vos R, Vanaudenaerde BM, Ottevaere A, et al. Long-term azithromycin therapy for bronchiolitis 
obliterans syndrome: divide and conquer? J Heart Lung Transplant 2010;29:1358-1368. 
Vos R, Vanaudenaerde BM, Verleden SE, et al. A randomised controlled trial of azithromycin to 
prevent chronic rejection after lung transplantation. Eur Respir J 2011;37:164-172. 
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. 
Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute 
graft-versus-host disease. N Engl J Med 2020;382:1800-1810. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For male participants in the study: 
Male participants should use a condom from screening 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 from screening 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: 
− Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationa 
• 
oral 
• 
intravaginal 
• 
transdermal 
− Progestogen-only hormonal contraception associated with inhibition of ovulationa 
• 
oral 
• 
injectable 
• 
implantableb 
− Intrauterine deviceb 
− Intrauterine hormone-releasing systemb 
− Bilateral tubal occlusionb 
− Vasectomized partnerbc 
− Sexual abstinenced 
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 spermicidee 
• 
Cap, diaphragm, or sponge with spermicidee 
• 
Tubal ligation 
a Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may 
reduce the efficacy of the contraception method. 
b Contraception methods that in the context of this guidance are considered to have low user dependency. 
c Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the vasectomized partner has received 
medical assessment of the surgical success. 
d In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the 
preferred and usual lifestyle of the participant. 
e 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. 
Source:  Clinical Trial Facilitation Group 2014. 


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APPENDIX B. INSTRUCTION TO PARTICIPANTS FOR HANDLING 
STUDY DRUG (ITACITINIB) 
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 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. STRONG CYP3A INHIBITORS AND INDUCERS 
Drugs or other substances that inhibit CYP3A or induce CYP3A4 may affect the exposure levels 
of itacitinib.  Concomitant administration of strong CYP3A inhibitors with itacitinib requires 
dose modifications per Table 9.  Participants will be allowed to take weak to moderate CYP3A 
inhibitors or CYP3A inducers.  A list of strong CYP3A inhibitors and inducers is provided in 
Table C1. 
Table C1: 
Strong CYP3A Inhibitors and CYP3A4 Inducers 
Strong Inhibitors 
Strong Inducers 
Indinavir 
Ritonavir 
Cobicistat 
Lopinavir 
Elvitegravir 
Ketoconazole 
Itraconazole 
Voriconazole 
Posaconazole 
Boceprevir 
Danoprevir 
Grapefruit juice 
Paritaprevir 
Telaprevir 
Tipranavir 
Troleandomycin 
Carbamazepine 
Enzalutamide 
Mitotane 
Phenytoin 
Rifampin 
St. John's wort 
Apalutamide 
 
Note:  Adapted from FDA DDI website. 
Source:  https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-
substrates-inhibitors-and-inducers#table3-3. 


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APPENDIX D. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic presents challenges to the ongoing conduct of clinical trials.  In 
line with regulatory guidance regarding clinical trial execution during the pandemic, the sponsor 
has issued the following Protocol considerations to ensure participant safety is maintained and 
adequate benefit/risk analyses are applied relative to the completion of study procedures and 
maintaining the investigational product supply chain.  Recognizing the dynamic nature and 
flexibility required to manage the impact of the pandemic on this clinical trial, additional details 
will be incorporated into respective study manuals and site-specific monitoring plans as 
applicable, with institutional requirements as warranted, and communicated to the investigative 
sites as needed.  Relevant test results will be documented in the eCRF, and applicable changes to 
the ICF will be made and monitored. 
Study Site Visits 
If local travel restrictions, isolation requirements, or the investigator's benefit/risk assessment 
determines it to be unsafe for participants to attend study visits at the investigational site, the site 
staff may elect to pursue the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video) or as per site institutional guidelines.  At a minimum, a 
review of AEs and concomitant medications must be completed.  On-site visits 
should be conducted whenever feasible and are required for administration of study 
treatment.  The participant may also be asked to undergo additional safety laboratory 
assessments. 
• In order to support investigator oversight of participant safety and disease 
management, the participant may be asked to undergo some laboratory tests or study 
procedures at a local laboratory or facility closer to the participant's residence rather 
than at the investigational site.  In this case, the study physician will provide the 
participant with the list of parameters to be checked.  These tests should be performed 
in certified laboratories. 
• Some tests, such as spirometry assessments, may require longer windows due to the 
COVID-19 pandemic and may be performed outside the regularly scheduled visit 
window or may be conducted at the next scheduled visit.  It is the investigator's 
responsibility to check with the facility (if performed at a different facility) that the 
data will be obtained and available for evaluation.  General procedures performed 
outside of protocol parameters will be captured as protocol deviations due to 
COVID-19 in the eCRF. 
Participant SARS-CoV-2 Infection and Study Treatment 
An event of active SARS-CoV-2 infection by a participant in the study should be reported as an 
AE or SAE and appropriate medical intervention provided.  Treatment with itacitinib may 
continue at the discretion of the study physician, after consultation with the medical monitor.  
Safety monitoring following COVID-19 should be implemented as per institutional guidance or 
clinical judgment (eg, coagulation factors). 


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COVID-19 Vaccination 
Participants may receive the COVID-19 vaccine.  COVID-19 vaccination will be captured in the 
eCRF as a concomitant medication.  Administration of study treatment may be delayed to ensure 
vaccination is completed.  The medical monitor may be consulted if needed. 
Clinical Trial Monitoring 
Study monitoring visits could be postponed; however, the site monitor and sponsor will continue 
to employ off-site monitoring practices such as routine communication methods (eg, phone calls, 
emails, video visits) with the sites to get information on trial progress, participant status, and 
information on issue resolution.  The study monitor may remotely review data entered into the 
EDC for accuracy and completeness if allowed by the national regulatory body, investigational 
site, and/or in compliance with local authorities. 
Reimbursement of Additional Expenses 
The sponsor will reimburse for any extraordinary expenses, keeping appropriate documentation 
as evidence (eg, travel expenses for the local laboratory visit[s], the costs of local [proximate] 
laboratory tests).  


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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1: 
09 DEC 2019 
Amendment 2: 
04 MAR 2020 
Amendment 3: 
11 AUG 2020 
Amendment 4: 
07 APR 2021 
Amendment 5: 
30 NOV 2021 
Amendment 5 (30 NOV 2021) 
Overall Rationale for the Amendment:  The study sponsor has decided not to proceed to 
Phase 2 of the study; the primary purpose of this amendment is to update the schedule of 
activities and schedule of assessments to simplify and minimize the required assessments for 
study participants who will continue to receive itacitinib as of the date of this decision. 
1. Section 1, Protocol Summary (Table 2:  Schedule of Activities; Table 3:  Schedule of 
Laboratory Assessments); Section 4.2, Overall Study Duration; Section 8.2.1, 
Spirometry; 
; Section 8.2.3, 
High-Resolution Computerized Tomography; Section 8.2.4, Patient Reported 
Outcomes; Section 8.2.5, Health Resource Utilization; Section 8.4, Pharmacokinetic 
Assessments; Section 8.5, Pharmacodynamic and Translational Assessments; 
Section 8.8.2, Survival Follow-Up 
Description of change:  Study assessments were updated and/or removed to reduce 
participant burden. 
Rationale for change:  The study has been terminated to further enrollment, however, 
ongoing participants will continue on itacitinib until withdrawal criteria are met. As the 
study will not be completed, the assessment schedule was updated to minimize data 
collection while continuing to monitor safety. 
2. Section 2.3, Benefit/Risk Assessment 
Description of change:  Added statement regarding termination of further enrollment. 
Rationale for change:  To detail the reason for termination of the study to further 
enrollment and indicate that there were no changes to the overall benefit/risk. 
3. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated and are noted in the redline version of the amendment. 


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Amendment 4 (07 APR 2021) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to add a 
requirement to perform CMV PCR testing during treatment for all study participants. 
1. Section 1, Protocol Summary (Table 3:  Schedule of Laboratory Assessments); 
Section 6.3.1.1, Prophylactic Medications and Immunosuppression; Section 8.3.5, 
Laboratory Assessments (Table 11:  Required Laboratory Analytes) 
Description of change:  Added a requirement to perform blood CMV testing from 
baseline through the EOT visit. 
Rationale for change:  As of the date of Amendment 4, 5 study participants have had 
observed CMV viremia/reactivation, which required treatment with antiviral agents.  The 
requirement for serial CMV testing during study treatment was added to ensure that all 
cases of CMV reactivation are identified and appropriately treated.   
2. Appendix D, COVID-19 Pandemic Mitigation Strategies and Instructions 
Description of change:  Added appendix to provide guidance for protocol considerations 
during the COVID-19 pandemic.  
Rationale for change:  Guidance due to pandemic.   
3. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated and are noted in the redline version of the amendment. 


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Amendment 3 (11 AUG 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to update 
the schedule of assessments to require monitoring of maintenance immunosuppressive agents 
(eg, CNIs) and to require that participants are on stable doses of strong CYP3A inhibitors prior 
for 4 weeks before starting study drug. 
1. Section 1, Protocol Summary (Table 3, Schedule of Laboratory Assessments); 
Section 5.2, Exclusion Criteria (Criterion 8); Section 8.3.5, Laboratory Assessments 
Description of change:  A requirement was added to monitor levels of maintenance 
immunosuppressive medications at all visits through Week 8. 
Rationale for change:  In this study, elevated levels of tacrolimus have been observed in 
3 of 3 participants who have received doses of itacitinib > 200 mg/day.  No causal 
relationship has been established.  Immunosuppressive medication level monitoring has 
been added as an additional safety measure. 
2. Section 1, Protocol Summary (Table 3, Schedule of Laboratory Assessments) 
Description of change:  Blood chemistry sampling was added to the Schedule of 
Laboratory Assessments at Weeks 1 and 2. 
Rationale for change:  To monitor blood chemistry parameters at Weeks 1 and 2. 
3. Section 2.2, Study Rationale 
Description of change:  Added additional background data regarding REACH2 study 
evaluating ruxolitinib in steroid acute steroid-refractory GVHD. 
Rationale for change:  To provide additional scientific rationale for this study. 
4. Section 5.1, Inclusion Criteria (Criterion 9); Section 6.1, Study Treatments 
Administered; Section 6.3.3, Prohibited Medications 
Description of change:  An inclusion criterion was added that requires if a participant is 
being treated with a strong CYP3A inhibitor, then the dose must be stable for > 4 weeks 
before the first dose of study drug.  A requirement to monitor CNI levels after addition or 
discontinuation of a strong CYP3A inhibitor was added. 
Rationale for change:  Strong CYP3A inhibitors may increase CNI levels; the 
requirement for a stable dose prior to treatment and CNI level monitoring after 
addition/discontinuation of CYP3A inhibitors is to ensure patient safety and ensure 
appropriate maintenance immunosuppression.  
5. Section 5.2, Exclusion Criteria (Criterion 17) 
Description of change:  Exclusion Criterion 17 was modified to allow for medical 
monitor approval of active malignancies not otherwise specified. 
Rationale for change:  To provide flexibility in allowing study participants with 
malignancies to enroll into the study. 


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6. Section 9.4, Reporting of Serious Adverse Events 
Description of change:  Reporting of SAEs instructions were updated to add the 
procedures for reporting via the EDC system. 
Rationale for change:  To provide guidance for SAE reporting via the eCRF should the 
sponsor decide to switch to that reporting method. 
7. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated and are noted in the redline version of the amendment. 


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Amendment 2 (04 MAR 2020) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to update 
the doses evaluated in Phase 1 of the study and the guidance regarding dose modifications when 
itacitinib is coadministered with strong CYP3A inhibitors. 
1. Section 1, Protocol Summary; Section 2.2, Study Rationale; Section 2.2.1, 
Justification of Itacitinib Dose; Section 4.1, Overall Design; Section 6.1, Study 
Treatments Administered (Table 9); Section 6.1.1, Determination of Recommended 
Phase 2 Dose; Section 10.1.1, Phase 1 
Description of change:  Phase 1 of the study was updated to evaluate 3 doses of 
itacitinib in cohorts of 8 participants each. 
Rationale for change:  Based on emerging data from INCB 39110-301, there is an 
exposure/response relationship associated with itacitinib.  Dose levels to be evaluated in 
this study were updated to provide exposures expected to be efficacious. 
2. Section 2.2.2, Dose Modifications for Concomitant Medications; Section 6.1, Study 
Treatments Administered (Table 9); Section 6.3.1.2, Guidelines for Concomitant 
Use of Antifungal Agents; Section 6.3.2, Restricted Medications; Appendix C, 
Strong CYP3A Inhibitors and Inducers 
Description of change:  Guidance for dose adjustments when itacitinib is administered 
concomitantly with strong CYP3A inhibitors was updated based on PK data obtained 
from Study INCB 39110-301. 
Rationale for change:  To refine the guidance related to dose adjustments in the setting 
of coadministration with strong CYP3A inhibitors and to provide dose adjustments that 
are intended to achieve similar exposures with and without strong CYP3A inhibitors. 
3. Section 5.1, Inclusion Criteria 
Description of change:  Inclusion criterion 7 was modified to clarify that participants 
who have recently undergone a steroid taper and who are currently taking physiologic 
doses (≤ 10 mg/day prednisone equivalent) are not required to have been on a stable dose 
for ≥ 4 weeks before screening. 
Rationale for change: To allow for patients who have recently tapered to non-
therapeutic doses of corticosteroids to be eligible for the study. 
4. Section 5.2, Exclusion Criteria 
Description of change: Exclusion criterion 7 was removed. 
Rationale for change:  Guidelines for coadministration with strong CYP3A inhibitors, 
including voriconazole and itraconazole, were added and thus the criterion was no longer 
relevant. 


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5. Section 6.2.1, Criteria and Procedures for Dose Interruptions of Study Drug 
(Table 10) 
Description of change:  Guidance was modified for dose interruptions and reductions or 
discontinuation for reduced platelet count. 
Rationale for change:  To allow for additional dosing flexibility in the setting of 
decreased platelet count. 
6. Section 8.4.1, Blood Sample Collection 
Description of change:  The fasting requirement before PK sample collection days was 
changed from 8 hours to 2 hours before arriving at the clinic. 
Rationale for change:  As there is no significant food effect associated with itacitinib 
exposure, the requirement was adjusted for participant convenience. 
7. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated and are noted in the redline version of the amendment. 


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Amendment 1 (09 DEC 2019) 
Overall Rationale for the Amendment:  The primary purpose of this amendment is to update 
the eligibility criteria, clarify the schedule of assessments with regards to correlative samples, 
and incorporate changes resulting from review by Health Canada. 
1. Section 1, Protocol Summary (Table 1:  Primary and Key Secondary Objectives and 
Endpoints); Section 3, Objectives and Endpoints (Table 5:  Objectives and 
Endpoints); Section 10.4.2, Efficacy Analysis 
Description of change:  The description of secondary endpoints for time to progression 
and quality of life were updated. 
Rationale for change:  To clarify the definition of the endpoints for time to progression 
and quality of life (related to EQ-5D-3L questionnaire). 
2. Section 1, Protocol Summary (Figure 1: Study Design Schema); Section 5.2, 
Exclusion Criteria (Table 6:  Exclusionary Laboratory Values) 
Description of change:  The exclusionary values for platelet count and creatinine 
clearance were changed to < 120 × 109/L and < 30 mL/min, respectively. 
Rationale for change:  The laboratory criteria were updated to allow for enrollment of 
participants with reduced platelet count and/or renal function, as these comorbidities are 
common in the post‒lung transplant population. 
3. Section 1, Protocol Summary (Table 3:  Schedule of Laboratory Assessments) 
Description of change:  The time frame for collection of correlative whole blood and 
serum samples was updated to up to 1 year and at time of BOS progression. 
Rationale for change:  To further specify the timing for collection of correlative 
samples. 
4. Section 5.1, Inclusion Criteria 
Description of change:  Inclusion criterion 5 was updated to allow participants who are 
confirmed BOS Grade 1, 2, or 3 diagnosed within 2 years of screening and who have 
either a 200 mL decrease in FEV1 in the previous 12 months or a decline of at least 
50 mL in the last 2 FEV1 measurements. 
Rationale for change:  To allow participants with a stable BOS grade for up to 2 years 
with concurrent evidence of declining FEV1. 
5. Section 5.2, Exclusion Criteria 
Description of change:  Exclusion criterion 1 was updated to allow participants who 
have received a heart-lung transplant, lung retransplantation, or any other solid organ 
transplant. 
Rationale for change:  To include participants with BOS who have received a heart-lung 
transplant, lung retransplant, or any other solid organ transplant. 


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6. Section 5.2, Exclusion Criteria 
Description of change:  Exclusion criterion 24 was added. 
Rationale for change:  To exclude participants who are unwilling or unable to sign the 
ICF.  
7. Section 6.1.1, Determination of Recommended Phase 2 Dose 
Description of change:  A statement has been added to clarify that Phase 1 participants 
who are ongoing at the time of RP2D selection will remain on their initial dose for the 
duration of the treatment period. 
Rationale for change:  Requested by Health Canada to clarify that the dose of itacitinib 
for Phase 1 participants will not be adjusted in ongoing participants based on the RP2D 
that is selected. 
8. Section 6.2.1, Criteria and Procedures for Dose Interruption (Table 9:  Guidelines 
and Procedures for Interruption of Study Drug) 
Description of change:  Dose interruption and restart guidance was updated for 
management of decreased platelets. 
Rationale for change:  To allow for investigator discretion to continue study drug 
administration if platelet count is ≥ 50 × 109/L. 
9. Section 6.3.4, Prohibited Procedures 
Description of change:  The washout period for extracorporeal photopheresis was 
updated from 3 months before the start of treatment to 6 weeks before the start of 
treatment. 
Rationale for change:  The immunomodulatory effect of extracorporeal photopheresis 
will sufficiently diminish after 6 weeks as to not confound assessment of the clinical 
activity of itacitinib. 
10. Section 7.1.1, Reasons for Discontinuation 
Description of change:  A note was added to clarify that if the participant has met 
criteria for BOS progression due to another reason, then continuation of treatment may be 
permitted after discussion with the medical monitor. 
Rationale for the change:  To allow participants who meet criteria for BOS progression 
to continue treatment if there are potentially confounding concomitant conditions. 
11. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated and are noted in the redline version of the amendment. 


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SAP_001.pdf: 
Official Title: An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy 
of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following 
Lung Transplantation 
NCT Number:  NCT03978637 
Document Date: Statistical Analysis Plan
:   Amendment Version 1: 26 August 2024 


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Statistical Analysis Plan 
TITLE PAGE 
 
 
INCB 39110-214 
An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the 
Safety and Efficacy of Itacitinib in Participants With 
Bronchiolitis Obliterans Syndrome Following Lung Transplantation 
 
 
 
IND Number: 
109,296 
EudraCT Number: 
2019-004171-39 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment (Version 3) dated 11 AUG 2020 
CRF Approval Date: 
22 SEP 2020 
SAP Version: 
Amendment 1 
SAP Author: 
, PhD 
, Biostatistics 
Date of Plan: 
26 AUG 2024 
 
 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives and Endpoints ...................................................................................8 
3. 
STUDY DESIGN .......................................................................................................10 
3.1. 
Randomization ............................................................................................................10 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Considerations .......................................................................................11 
3.4. 
Schedule of Assessments ............................................................................................11 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Last Available Value ..................................................................................................11 
4.1.5. 
Handling of Missing and Incomplete Data .................................................................12 
4.2. 
Variable Definitions ....................................................................................................12 
4.2.1. 
Body Mass Index ........................................................................................................12 
4.2.2. 
Prior and Concomitant Medication .............................................................................12 
4.2.3. 
Creatinine Clearance ...................................................................................................12 
5. 
STATISTICAL METHODOLOGY ...........................................................................13 
5.1. 
General Methodology .................................................................................................13 
5.2. 
Treatment Groups .......................................................................................................13 
5.3. 
Analysis Populations ..................................................................................................13 
5.3.1. 
Full Analysis Set .........................................................................................................13 
5.3.2. 
Pharmacokinetic-Evaluable Population ......................................................................13 
6. 
BASELINE, EXPOSURE, AND DISPOSITION ......................................................14 
6.1. 
Demographics, Baseline Characteristics, and Medical History ..................................14 


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6.1.1. 
Demographics and Baseline Characteristics ...............................................................14 
6.1.2. 
Medical History ..........................................................................................................14 
6.1.3. 
Lung Transplant History .............................................................................................14 
6.1.4. 
Bronchiolitis Obliterans Syndrome History ...............................................................14 
6.1.5. 
Medications for Immunosuppression .........................................................................14 
6.1.6. 
Medications for Treatment of Bronchiolitis Obliterans Syndrome ............................15 
6.2. 
Disposition of Participants ..........................................................................................15 
6.3. 
Protocol Deviations ....................................................................................................15 
6.4. 
Exposure .....................................................................................................................15 
6.5. 
Study Drug Compliance .............................................................................................15 
6.6. 
Prior and Concomitant Medication .............................................................................15 
7. 
EFFICACY .................................................................................................................16 
7.1. 
General Considerations ...............................................................................................16 
7.2. 
Efficacy Hypotheses ...................................................................................................16 
7.3. 
Analysis of the Primary Efficacy Parameter ..............................................................16 
7.4. 
Analysis of the Secondary Efficacy Parameter ..........................................................16 
7.4.1. 
Duration of FEV1 Response ........................................................................................16 
7.4.2. 
Time to Progression or Death .....................................................................................17 
7.4.3. 
SGRQ Total Score ......................................................................................................17 
7.4.4. 
QOL-SF-12 Questionnaire..........................................................................................17 
7.4.5. 
EQ-5D-3L ...................................................................................................................18 
8. 
PHARMACOKINETICS AND PHARMACODYNAMICS .....................................19 
8.1. 
Pharmacokinetic Analyses ..........................................................................................19 
8.1.1. 
Pharmacokinetic Data .................................................................................................19 
8.1.2. 
Participant Demographic, Clinical Laboratory, Disease-Related, and 
Pharmacogenomic Variables and Concomitant Medications .....................................19 
8.1.3. 
Pharmacokinetic Analyses ..........................................................................................19 
8.1.4. 
Report .........................................................................................................................20 
8.2. 
Pharmacodynamic Analyses .......................................................................................20 
9. 
SAFETY AND TOLERABILITY ..............................................................................21 
9.1. 
General Considerations ...............................................................................................21 
9.2. 
Adverse Events ...........................................................................................................21 
9.2.1. 
Adverse Event Definitions ..........................................................................................21 


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9.2.2. 
Adverse Event Summaries ..........................................................................................21 
9.2.3. 
Clinically Notable Treatment-Emergent Adverse Events Based on 
Customized MedDRA Queries ...................................................................................22 
9.3. 
Clinical Laboratory Tests ...........................................................................................23 
9.4. 
Vital Signs ..................................................................................................................23 
9.5. 
Electrocardiograms .....................................................................................................24 
10. 
INTERIM ANALYSES ..............................................................................................24 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................25 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................25 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................25 
11.2.1. 
Amendment 1 ..............................................................................................................25 
12. 
REFERENCES ...........................................................................................................26 
APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS ........................................27 
APPENDIX B. CLINICALLY NOTABLE EVENTS BASED ON CUSTOMIZED 
MEDDRA QUERIES .................................................................................................29 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Sample Collection Times for Pharmacokinetic Assessments of Itacitinib .................19 
Table 3: 
Criteria for Vital Sign Abnormalities .........................................................................24 
Table 4: 
Criteria for Electrocardiogram Abnormalities ............................................................24 
Table 5: 
Statistical Analysis Plan Versions ..............................................................................25 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................10 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
AUC0-t 
area under the plasma or serum concentration-time curve from time = 0 to the 
last measurable concentration at time = t 
AUC0-τ 
area under the steady-state plasma or serum concentration-time curve over 1 dose 
interval 
BMI 
body mass index 
BOS 
bronchiolitis obliterans syndrome 
CI 
confidence interval 
Cl/F 
apparent oral dose clearance 
Cmax 
maximum observed plasma or serum concentration 
Cmin 
minimum observed plasma or serum concentration over the dose interval 
CMV 
cytomegalovirus 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
EBV 
Epstein-Barr virus 
ECP 
extracorporeal photopheresis 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOT 
end of treatment 
EQ-5D-3L 
EuroQol 5-dimension 3-level  
EQ-VAS 
EuroQol visual analogue scale 
EU 
European Union 
FAS 
full analysis set 
FEV1 
forced expiratory volume in 1 second 
FDA 
Food and Drug Administration 
GVHD 
graft-versus-host disease 
HDL 
high-density lipoprotein 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
PK 
pharmacokinetic(s) 
PT 
preferred term 
QOL-SF-12 
Quality of Life 12-Item Short Form 
QOL-SF-36 
Quality of Life 36-Item Short Form 
QTcB 
QT interval corrected using Bazett's formula 
QTcF 
QT interval corrected using Fridericia's formula 
RP2D 
recommended Phase 2 dose 


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CONFIDENTIAL 
Abbreviation 
Term 
SAP 
Statistical Analysis Plan 
SGRQ 
St George's Respiratory Questionnaire 
SOC 
system organ class 
STAT 
signal transducer and activator of transcription 
t½ 
half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to maximum concentration 
US 
United States 
Vz/F 
apparent oral dose volume of distribution 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
Post–lung transplant BOS is a serious, life-threatening condition which represents a significant 
unmet medical need. There are few therapeutic trials for BOS, and currently no agents are 
approved by the FDA for the treatment of BOS. Treatments used in clinical practice are 
associated with significant toxicities and high failure rates. 
Novel treatments with agents targeting JAK-STAT pathways appear to decrease alloreactive 
T-cell damage in both preclinical models of GVHD as well as in completed and ongoing clinical 
trials. The biology of GVHD shares many similar mechanisms with post–lung transplant BOS 
and it is hypothesized that the selective JAK1 inhibitor, itacitinib, may be an effective therapy 
for post–lung transplant BOS. 
Study INCB 39110-214 is a Phase 1/2 study that will evaluate itacitinib in post–lung transplant 
Grade 1 through 3 BOS. The study design comprises a randomized, open-label, parallel dose 
selection run-in followed by a single arm expansion to evaluate the efficacy in this population. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Protocol. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 39110-214 Protocol Amendment (Version 3) dated 11 AUG 2020 
and CRFs approved 22 SEP 2020. Unless superseded by an amendment, this SAP will be 
effective for all subsequent Protocol amendments and eCRF versions. 
2.2. 
Study Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Phase 1 
To identify an appropriate dose of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
Frequency, severity, and duration of AEs; 
assessment of changes in safety and FEV1; and 
assessment of changes in laboratory parameters, 
PK, and pharmacodynamics.  
Phase 2 
To evaluate the efficacy of itacitinib as a 
treatment for Grade 1 through 3 BOS following 
lung transplantation. 
FEV1 response rate from baseline through the 
Week 12 visit, defined as the proportion of 
participants demonstrating a ≥ 10% absolute 
increase in FEV1 compared to baseline. 
Secondary 
Phase 1 and Phase 2 
To evaluate duration of FEV1 response in 
participants with Grade 1 through 3 BOS 
following lung transplantation who are treated 
with itacitinib. 
Duration of FEV1 response, defined as the time of 
the onset of response (≥ 10% absolute increase in 
FEV1 compared to baseline) to BOS progression 
(≥ 10% absolute decrease in FEV1 compared to 
baseline) or loss of clinical benefit as determined 
by the investigator. 
To evaluate time to progression in participants 
with Grade 1 through 3 BOS following lung 
transplantation who are treated with itacitinib. 
Time to progression, defined as the interval 
between the start of treatment and BOS 
progression (≥ 10% absolute decrease in FEV1 
compared to baseline), or death. 
To evaluate quality of life outcomes in 
participants with Grade 1 through 3 BOS 
following lung transplantation who are treated 
with itacitinib. 
• Change from baseline in SGRQ total score. 
• Change from baseline in QOL-SF-12 
questionnaire. 
• Categorical summary or change from baseline 
in EQ-5D-3L questionnaire. 
To evaluate the PK of itacitinib in the study 
population. 
Cmax, Cmin, tmax, AUC0-t, and Cl/F. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Secondary (continued) 
Phase 2 only 
To evaluate overall survival or time to 
retransplantation in participants with Grade 1 
through 3 BOS following lung transplantation 
who are treated with itacitinib. 
Time to retransplantation or death, defined as the 
interval between the start of treatment and the 
date of retransplantation or death due to any 
cause. 


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3. 
STUDY DESIGN 
This Phase 1/2 study will evaluate the safety, efficacy, PK, and pharmacodynamics of itacitinib 
in participants with post–lung transplant BOS. 
Phase 1 is a dose selection run-in that will employ a randomized, open-label, parallel-cohort 
design to assess the safety, tolerability, PK, and pharmacodynamics and determine the RP2D of 
itacitinib in participants with post–lung transplant BOS. A total of 24 participants with Grade 1, 
2, or 3 BOS will be assigned to receive 1 of 3 itacitinib dose levels (n = 8 each). Each Phase 1 
dose level will enroll a maximum of 2 participants with Grade 3 BOS. Participants will be 
randomized to 1 of 3 dose levels using an interactive response technology system. Upon 
completion of Phase 1 enrollment, the RP2D will be selected on the basis of AE, laboratory, PK, 
and pharmacodynamic observations through the Week 12 visit. Additionally, an efficacy analysis 
will be performed to determine the FEV1 response rate for all participants treated for ≥ 12 weeks. 
The study will proceed to Phase 2 if ≥ 1 responses (defined as ≥ 10% absolute increase in FEV1 
compared with baseline, confirmed by 2 consecutive spirometric assessments ≥ 1 week apart) are 
observed at the dose level selected as the RP2D. 
Phase 2 will employ a single-arm, open-label design to evaluate the efficacy and further 
characterize the safety of itacitinib at the RP2D. 
Itacitinib treatment in Phase 1 and Phase 2 will continue until progression of BOS (defined as a 
≥ 10% absolute decrease from baseline in FEV1, confirmed by 2 consecutive spirometric 
assessments ≥ 3 weeks apart), unacceptable toxicity, loss of clinical benefit, or withdrawal of 
consent. 
Figure 1 presents the study design schema. 
Figure 1: 
Study Design Schema 
 
a Not inclusive. 
3.1. 
Randomization 
In Phase 1, approximately 24 participants will be randomly assigned to receive 1 of 3 itacitinib 
dose levels in a 1:1:1 allocation ratio. 
3.2. 
Control of Type I Error 
No formal efficacy hypotheses will be tested, and no alpha control will be implemented. 


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3.3. 
Sample Size Considerations 
In Phase 1, approximately 24 participants will be enrolled to participate across the 3 dose levels 
of itacitinib to identify the RP2D. A sample size of 24 participants (8 per dose level) allows for 
concurrent enrollment at 3 dose levels that have been previously characterized in other disease 
settings and is expected to enable the clinical characterization of safety and efficacy. 
In Phase 2, the FEV1 response rate for itacitinib is assumed to be 20%. In order for the lower 
confidence limit of the 95% CI to exclude 5%, approximately 55 participants are needed. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment (Version 3) dated 11 AUG 2020 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 the first dose of itacitinib is administered to the participants. 
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 itacitinib. 
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, use the scheduled 
assessment as baseline. 
4.1.4. 
Last Available Value 
The last available value is the last nonmissing measurement obtained after starting itacitinib. 


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4.1.5. 
Handling of Missing and Incomplete Data 
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections. 
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. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started and stopped before the first dose 
of itacitinib. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of itacitinib and is ongoing throughout the 
study or ends on/after the date of first administration of itacitinib. 
• On/after the date of first administration of itacitinib and is ongoing or ends during the 
course of the study. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of itacitinib. 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. 
4.2.3. 
Creatinine Clearance 
Creatinine clearance by Cockcroft-Gault equation (Cockcroft and Gault 1976) is estimated from 
serum creatinine (mg/dL) determination using the following formula: 
Creatinine clearance (mL/min) = [140 − age (years)] × weight (kg) × {0.85 for female 
participants} / [72 × serum creatinine (mg/dL)] 


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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 
In Phase 1, a total of 24 participants with Grade 1, 2, or 3 BOS will be assigned to receive 1 of 
3 itacitinib dose levels (n = 8 each). 
In Phase 2, participants will be treated with itacitinib at the RP2D. 
5.3. 
Analysis Populations 
5.3.1. 
Full Analysis Set 
The FAS will include all participants enrolled in the study who received at least 1 dose of 
itacitinib. The FAS will be used for the summary of demographics, baseline characteristics, 
participant disposition, and analyses of all safety, study treatment administration, and efficacy 
data. 
5.3.2. 
Pharmacokinetic-Evaluable Population 
The PK-evaluable population consists of all enrolled participants who received at least 1 dose of 
itacitinib and provided at least 1 postdose PK sample. 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
6.1. 
Demographics, Baseline Characteristics, and Medical History 
Demographics, baseline characteristics, medical history, lung transplant history, BOS history, 
prior and concomitant medications for immunosuppression, and prior and concomitant 
medications for treatment of BOS will be summarized for the FAS and listed. Procedures and 
nondrug therapies will be listed for the FAS. 
6.1.1. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics include the following: age, sex, race, ethnicity, 
weight, height, and BMI. 
6.1.2. 
Medical History 
For participants in the FAS, medical history will be summarized. This summation will include the 
number and percentage of participants with significant medical history for each body 
system/organ class as documented on the eCRF. 
6.1.3. 
Lung Transplant History 
Time since double lung transplant, indication for transplant, donor CMV status, recipient CMV 
status, donor EBV status, recipient EBV status, history of acute rejection, history of primary 
graft dysfunction, history of donor-specific antibodies, history of gastroesophageal reflux 
disease, history of CMV pneumonitis, history of colonization with aspergillus, post-transplant 
baseline FEV1 (absolute and % predicted), and best post-transplant forced vital capacity will be 
summarized descriptively. Among these variables, summaries for continuous variables will 
include but not be limited to the number of observations, mean, standard deviation, median, 
minimum, and maximum. Summaries for categorical variables will include the number and 
percentage of participants in each category. 
6.1.4. 
Bronchiolitis Obliterans Syndrome History 
Time since BOS diagnosis, BOS grade at diagnosis, BOS grade at screening, augmented 
immunosuppression since onset of BOS (other than ECP), and ECP will be summarized. 
6.1.5. 
Medications for Immunosuppression 
Medications for immunosuppression will be coded using the WHO Drug Dictionary. For 
participants in the FAS, the number and percentage of participants with medications for 
immunosuppression will be summarized separately for the 3 categories of induction, 
maintenance, and treatment for acute rejection. Within each category, the summary will be by 
WHO drug class and WHO drug term. 


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6.1.6. 
Medications for Treatment of Bronchiolitis Obliterans Syndrome 
Prior medications for treatment of BOS will be coded using the WHO Drug Dictionary. For 
participants in the FAS, the number and percentage of participants with prior medications for 
treatment of BOS will be summarized by WHO drug class and WHO drug term. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were randomized, who were treated, who 
discontinued study treatment with a primary reason for discontinuation, and who withdrew from 
the study with a primary reason for withdrawal will be summarized for the FAS. The number of 
participants enrolled by country and/or site will also be provided by treatment group. 
6.3. 
Protocol Deviations 
Protocol deviations recorded on the eCRF will be summarized and listed. 
6.4. 
Exposure 
For participants in the FAS, exposure to itacitinib will be summarized descriptively as follows: 
• Duration of treatment with itacitinib: 
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 of itacitinib (mg/day) = [total actual dose taken (mg)] / [duration 
of treatment with itacitinib (days) – days of itacitinib interruption] 
• Dose modifications of itacitinib: 
Number of participants who had itacitinib dose reduction and/or interruption 
6.5. 
Study Drug Compliance 
For participants in the FAS, overall compliance (%) for itacitinib will be calculated for all 
participants as follows: 
Overall compliance (%) = 100  [total dose actually taken (mg)] / [total prescribed 
dose (mg)] 
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 
Prior medications and concomitant medications (excluding medications for immunosuppression 
and treatment for BOS) will be coded using the WHO Drug Dictionary. For participants in the 
FAS, the number and percentage of participants each with prior and concomitant medications will 
be summarized by WHO drug class and WHO drug term. In the data listing, each medication will 
be recorded as prior, concomitant, or both prior and concomitant. 


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7. 
EFFICACY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
7.1. 
General Considerations 
All efficacy analyses will be done by treatment group using the FAS. The SGRQ Total Score, 
QOL-SF-12 Questionnaire, and EQ-5D-3L analyses will not be performed due to the early study 
termination.  
For continuous measurements, summary statistics will include sample size, mean, median, 
standard deviation, standard error of the mean, minimum, and maximum. For all continuous 
variables, both the actual value and change and/or percentage from baseline (if available) will be 
analyzed. For categorical measurements, summary statistics will include sample size, frequency, 
and percentages. 
All by-visit analyses will include the EOT and follow-up visits if the data are available. 
7.2. 
Efficacy Hypotheses 
Not applicable. 
7.3. 
Analysis of the Primary Efficacy Parameter 
In Phase 1, the primary endpoint is FEV1. Change and percentage change from baseline in FEV1 
and FEV1 % predicted will be summarized by visit and treatment group. 
In Phase 2, the primary endpoint is FEV1 response rate through the Week 12 visit, defined as the 
proportion of participants demonstrating a ≥ 10% absolute increase in FEV1 compared with 
baseline, confirmed by 2 consecutive spirometric assessments ≥ 1 week apart. The primary 
analysis will be conducted once the last participant completes the Week 12 visit or withdraws 
from the study. If a participant withdraws from the study before Week 12, or there is no FEV1 
data up to and including Week 12, the participant will be considered as a nonresponder. 
Summary statistics and 95% CIs will be provided. Confidence intervals will be calculated based 
on the exact method for binomial distributions. 
In Phase 1, FEV1 response rate will also be calculated due to the fact that duration of FEV1 
response is a secondary efficacy endpoint in Phase 1. 
7.4. 
Analysis of the Secondary Efficacy Parameter 
7.4.1. 
Duration of FEV1 Response 
Duration of FEV1 response is defined as the interval between the onset of response and the 
earliest of BOS progression, loss of clinical benefit as determined by the investigator, or death, in 
which: 
• The time of onset of response is defined as the earliest assessment date when ≥ 10% 
absolute increase in FEV1 compared with pretreatment baseline (confirmed by 
2 consecutive spirometric assessments ≥ 1 week apart) is achieved. 


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• BOS progression is defined as ≥ 10% absolute decrease in FEV1 compared with 
pretreatment baseline observed in at least 2 consecutive spirometric assessments at least 
3 weeks apart. The onset of BOS progression is the earliest date of such qualified 
assessments. 
• Time of loss of clinical benefit is the date when a participant discontinues treatment due 
to "lack of efficacy." 
Participants with no observed BOS progression, loss of clinical benefit, or death at the time of 
database lock or discontinuation will be censored at the time of last valid FEV1 assessment. 
Duration of FEV1 response will be assessed using the Kaplan-Meier method for participants who 
achieve a response. Median duration and 95% CIs will be estimated. 
7.4.2. 
Time to Progression or Death 
Time to progression or death, defined as the interval between the start of itacitinib treatment and 
BOS progression (defined as a ≥ 10% absolute decrease in FEV1 from pretreatment baseline 
observed in at least 2 consecutive spirometric assessments at least 3 weeks apart) or death. The 
time of BOS progression follows the same definition as in Section 7.4.1. Participants with no 
observed BOS progression or death at the time of database lock or discontinuation will be 
censored at the time of last valid FEV1 assessment. 
Time to progression or death will be estimated by the Kaplan-Meier method. Median duration 
and 95% CIs will be estimated. 
7.4.3. 
SGRQ Total Score 
The SGRQ (Jones et al 1991) is a disease-specific instrument designed to measure impact on 
overall health, daily life, and perceived well-being in patients with obstructive airway disease. It 
consists of 50 items covering 3 domains: symptoms (8 items), activity (16 items), and impacts 
(26 items). 
A component score will be calculated for each of the 3 domains. If more than 2 items in the 
symptoms domain are missing, the symptom component score will set to be missing. If more 
than 4 items in the activity domain are missing, the activity component score will set to be 
missing. If more than 6 items in the impacts domain are missing, the impacts component score 
will set to be missing. 
One total score will be calculated if none of the component scores is missing. All scales have a 
score range between 0 and 100 with higher scores indicating a worse quality of life. 
Summary statistics will be provided for change from baseline in SGRQ component scores and 
the total score at each scheduled visit. 
7.4.4. 
QOL-SF-12 Questionnaire 
The QOL-SF-12 v2 (Ware et al 1996) is a 12-item subset of the QOL-SF-36 v2 scale that 
captures changes in health status during the course of treatment. The QOL-SF-12 assesses 
8 health concepts related to limitations in physical activities, social activities, bodily pain, 
general mental and physical health, and vitality. 


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For this questionnaire, 1 component score will be provided for each of 8 health concepts. Two 
summary scores, physical component summary and mental component summary, will also be 
provided. For each item, a higher score indicates a better health state. 
Summary statistics will be provided for change from baseline in 2 scales at each scheduled visit. 
7.4.5. 
EQ-5D-3L 
The EQ-5D-3L (EuroQol Research Foundation 2017) essentially consists of 2 components: the 
EQ-5D descriptive scale and the EQ-VAS. 
The EQ-5D-3L descriptive system comprises the following 5 dimensions, each describing a 
different aspect of health: mobility, self-care, usual activities, anxiety/depression, and 
pain/discomfort. Each dimension has 3 levels: no problems, some problems, and extreme 
problems. The EQ-VAS records the respondent's self-rated health on a vertical visual analog 
scale on which the endpoints are labeled as "the best health you can imagine" and "the worst 
health you can imagine." 
At each specific visit (starting on Day 1), the participant will be asked to indicate their health 
state. Missing values will not be imputed. The categorical outcomes for the 5 dimensions 
(mobility, self-care, usual activities, anxiety/depression, and pain/discomfort) will be 
summarized by visit, and summary statistics will include frequency and percentage. The change 
from baseline in EQ-VAS score will be summarized. 


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8. 
PHARMACOKINETICS AND PHARMACODYNAMICS 
8.1. 
Pharmacokinetic Analyses 
Itacitinib PK in this participant population will be estimated by noncompartmental model 
analysis 
. 
8.1.1. 
Pharmacokinetic Data 
Participants will arrive at the clinic having withheld their morning dose of itacitinib. 
Pharmacokinetic samples will be obtained at the visits indicated in Protocol Table 3. After the 
predose PK sample is drawn, participants will take the dose of itacitinib. Predose is defined as 
within 24 hours before administration of itacitinib. The exact date and time of the PK blood 
draws will be recorded on the eCRF along with the date and time of the last dose of study drug 
and details of the last meal before the blood draw. Instructions for sample preparation and 
shipping will be provided in the Laboratory Manual. Sample collection times and windows for 
itacitinib are shown in Table 2. Adjustments to the timing of blood sampling postdose may be 
made based on emerging PK data; however, no more than 6 postdose timepoints will be used, 
and the maximum scheduled timepoint will be no greater than 12 hours postdose. 
Table 2: 
Sample Collection Times for Pharmacokinetic Assessments of Itacitinib 
Visit  
Timing of Sample Relative to Itacitinib Administration 
Baseline (Day 1)a  
Predose 
1 h ± 15 min 
2 h ± 30 min 
5 h ± 60 min 
Week 4  
Predose (−30 min) 
1 h ± 15 min 
2 h ± 30 min 
5 h ± 60 min 
a Phase 1 participants only. 
8.1.2. 
Participant Demographic, Clinical Laboratory, Disease-Related, and 
Pharmacogenomic Variables and Concomitant Medications 
Participant demographic assessments (eg, age, weight, BMI, sex, race) and clinical laboratory 
measurements (eg, FEV1, creatinine clearance, serum albumin, total bilirubin, alkaline 
phosphatase, alanine aminotransferase, aspartate aminotransferase) may be explored as 
time-independent predictors of PK variability. Concomitant medications may be explored as 
time-dependent covariates in the population PK analysis. 
8.1.3. 
Pharmacokinetic Analyses 
The noncompartmental 
 analysis for itacitinib PK will be performed using 
WinNonlin® v8.0 or later (Certara, Princeton, NJ). The following PK parameters will be 
estimated where possible: Cmax, tmax, Cmin, AUC0-t, AUC0-τ, t½, Cl/F, and Vz/F. 
 
 
 
 
 
 
 
 


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8.1.4. 
Report 
A PK report will be prepared to include listings of observed itacitinib plasma concentration data 
and estimated PK parameters in accordance with guidance of both US and EU regulatory 
authorities. 
8.2. 
Pharmacodynamic Analyses 
Baseline and pharmacodynamic analyses of serum cytokines, 
 
 will be conducted as follows: 
• Baseline differences in inflammatory mediators between responders and 
nonresponders will be assessed using: 
− Unadjusted logistic regression models, with FEV1 response as a binary variable. 
− Unadjusted general linear models, with change in FEV1 as a continuous variable. 
− Statistically significant unadjusted models will be adjusted for baseline FEV1, 
age, sex, itacitinib dose, and prior immunosuppressive therapy. If fewer than 
10 observations are available per covariate, covariates will be removed in order 
from weakest to strongest statistical association with the inflammatory mediator 
(outcome) of interest, until at least 10 observations per covariate are available. 
Alternatively, if variables are determined to be biologically relevant to the 
analysis, the model will include the principal component analysis scores for the 
covariates. Only scores with eigenvalues > 1 will be included. 
• Pharmacodynamic changes from baseline will be compared between responders and 
nonresponders using paired t-tests. 
• Significance will be reported at p < 0.05 and fold change > |15%|. 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays are included in a separate 
document. 
9.1. 
General Considerations 
All safety analyses will be conducted using the FAS and summarized by treatment group. 
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 event after first 
dose of itacitinib until 30 days after the last dose of itacitinib. Analysis of AEs will be limited to 
TEAEs, but data listings will include all AEs regardless of their timing in relation to the 
administration of itacitinib. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be described 
and graded using the NCI CTCAE v5.0 (2017). 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 v5.0 criteria, then it will be rated on a scale of 1 to 4 as follows: 1 = mild, 2 = moderate, 
3 = severe, and 4 = life-threatening. 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 itacitinib will be considered to 
be treatment-related AEs. If the investigator does not specify the relationship of the AE to 
itacitinib, 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. Unsolved missing 
values will be handled according to the following rules: 
• An unsolved missing causality will be considered treatment-related. 
• An unsolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 
9.2.2. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any TEAEs related to itacitinib 


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• Number (%) of participants who temporarily interrupted itacitinib because of TEAEs 
• Number (%) of participants with itacitinib dose reduction because of TEAEs 
• Number (%) of participants who permanently discontinued itacitinib because of 
TEAEs 
• Number (%) of participants who had a fatal TEAE 
The following summaries will be produced by MedDRA term: 
• Summary of TEAEs by MedDRA SOC and PT 
• Summary of TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of TEAEs by MedDRA SOC, PT, and maximum severity 
• Summary of Grade 3 or higher TEAEs by MedDRA SOC and PT 
• Summary of Grade 3 or higher TEAEs by MedDRA PT in decreasing order of 
frequency 
• Summary of serious TEAEs by MedDRA SOC and PT 
• Summary of serious TEAEs by MedDRA PT in decreasing order of frequency 
• Summary of itacitinib treatment-related TEAEs by MedDRA SOC and PT 
• Summary of itacitinib treatment-related TEAEs by MedDRA PT in decreasing order 
of frequency 
• Summary of itacitinib treatment-related serious TEAEs by MedDRA SOC and PT 
• Summary of TEAEs with a fatal outcome by MedDRA SOC and PT 
• Summary of TEAEs leading to discontinuation of itacitinib by MedDRA SOC and PT 
• Summary of TEAEs leading to itacitinib dose reduction by MedDRA SOC and PT 
• Summary of TEAEs leading to itacitinib dose interruption by MedDRA SOC and PT 
9.2.3. 
Clinically Notable Treatment-Emergent Adverse Events Based on Customized 
MedDRA Queries 
The following categories of clinically notable events will be summarized based on customized 
MedDRA queries (see Appendix B): 
• Anemia 
• Neutropenia 
• Thrombocytopenia 
• QT prolongation 
• Hyperlipidemia 
• EBV infection 
• CMV infection 


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Within each category, the number and percentage of participants with at least 1 TEAE occurring 
during the treatment phase tabulated by MedDRA PT will be summarized. Summaries of 
clinically notable TEAEs based on customized MedDRA queries will be provided by treatment 
group, category, PT, and the highest grade or outcome as follows: 
• Overall summary of clinically notable TEAEs in the treatment phase based on 
customized MedDRA queries. 
• Number (%) of participants with clinically notable TEAEs in the treatment phase 
based on customized MedDRA queries by PT and outcome. 
• Number (%) of participants with clinically notable TEAEs in the treatment phase 
based on customized MedDRA queries by PT and highest grade. 
9.3. 
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. 
Summaries for abnormally high and abnormally low laboratory values will be provided when the 
laboratory parameter has both high and low grading criteria. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low (but never high), normal, high (but never 
low), and both low and high will be calculated for each test. This shift summary will be produced 
for each parameter for the FAS. The denominator for the percentage calculation will use the 
number of participants in the baseline category (ie, low, high, normal, missing) as the 
denominator for the percentage in each of the categories during the study. 
Severity grades will be assigned to laboratory test values based on the numerical component of 
CTCAE v5. Shift tables will be presented showing change in CTCAE grade from baseline to 
worst grade postbaseline. The denominator for the percentage calculation will be the number of 
participants in the baseline category. 
9.4. 
Vital Signs 
Descriptive statistics and mean change from baseline will be summarized for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time by treatment 
group. Vital sign results will be reviewed for abnormal values (see Table 3), and participants 
exhibiting abnormal vital sign values will be summarized and 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 summarized and 
listed. 


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Table 3: 
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 
9.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, RR, QT, QRS, QTcB, and QTcF intervals will be obtained for 
each participant during the study. Abnormal ranges for ECG values are defined in Table 4. 
Electrocardiogram values will also be considered abnormal if the absolute percentage change 
from baseline is more than 25%. Participants exhibiting ECG abnormalities will be listed with 
study visit and assigned treatment group. Abnormal values for participant with alert ECG values, 
defined as both the absolute value and the percentage change from baseline being outside normal 
ranges, will be identified and listed. Clinically significant ECG values, in the judgment of the 
investigator, will also be summarized and listed. 
Table 4: 
Criteria for Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF/QTcB 
> 450 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
10. 
INTERIM ANALYSES 
No formal interim analysis is planned. A steering committee meeting will occur at the end of 
Phase 1 for RP2D dose determination, for which an informal analysis of safety and efficacy data 
will be performed. 


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11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 5 . 
Table 5: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
12 APR 2023 
Amendment 1 
26 AUG 2024  
11.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
11.2. 
Changes to the Statistical Analysis Plan 
11.2.1. 
Amendment 1 
The following updates were made for SAP Amendment 1 to align with early study termination: 
• The planned tables, figures, and listings were updated in Appendix A to remove those 
that were not needed. 
• Analyses for SGRQ Total Score, QOL-SF-12 Questionnaire, and EQ-5D-3L were 
removed. 
• Text was updated to address the analyses not being performed. 
Other minor administrative changes have been incorporated throughout and are noted in the 
redline version of the document. 


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12. 
REFERENCES 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41. 
EuroQol Research Foundation. EQ-5D-3L. Accessed January 31, 2023.https://euroqol.org/eq-5d-
instruments/eq-5d-3l-about/ 
Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med 
1991;85 Suppl B:25-37. 
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 
5.0. 2017. 
Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales 
and preliminary tests of reliability and validity. Med Care 1996;34:220-233. 


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APPENDIX A. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings. Standard tables will 
follow the conventions in the Standard Safety Tables current version if necessary.  
Tables 
Table No. 
Title 
Population 
Baseline and Demographic Characteristics 
1.1.1 
Analysis Populations 
All Screened 
1.1.2 
Summary of Participant Disposition 
FAS 
1.1.3 
Summary of Number of Participants Enrolled by Site 
FAS 
1.1.4 
Summary of Protocol Deviations 
FAS 
1.2.1 
Summary of Demographics and Baseline Characteristics  
FAS 
Efficacy 
2.1 
Summary of FEV1 Response  
FAS 
2.2.1 
Summary of FEV1 by Visit  
FAS 
2.3.1 
Summary of Duration of FEV1 Response  
FAS 
2.3.2 
Summary of Time to Progression or Death  
FAS 
Safety 
3.1.1 
Summary of Exposure and Duration of Exposure to Itacitinib 
FAS 
3.1.2 
Summary of Study Drug Compliance 
FAS 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events  
FAS 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term  
FAS 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term 
in Decreasing Order of Frequency 
FAS 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term, and Maximum Severity 
FAS 
3.2.5 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term  
FAS 
3.2.7 
Summary of Serious Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term  
FAS 
3.2.9 
Summary of Itacitinib Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.10 
Summary of Itacitinib Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA Preferred Term in Decreasing Order of Frequency 
FAS 
3.2.11 
Summary of Itacitinib Treatment-Related Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and Preferred Term  
FAS 
3.2.12 
Summary of Treatment-Emergent Adverse Events With a Fatal Outcome by 
MedDRA System Organ Class and Preferred Term 
FAS 
3.2.13 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation 
of Itacitinib by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.14 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Reduction by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.15 
Summary of Treatment-Emergent Adverse Events Leading to Itacitinib Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
FAS 


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Listings 
Listing No. 
Title 
Baseline Demographic and Characteristic 
2.1.1 
Participant Enrollment and Disposition Status 
2.2.1 
Protocol Deviations 
2.4.1 
Demographic and Baseline Characteristics 
2.4.2 
Lung Transplant History 
2.4.3 
Bronchiolitis Obliterans Syndrome History 
2.4.4 
Medications for Immunosuppression 
2.4.5 
Medications for Treatment of Bronchiolitis Obliterans Syndrome 
2.4.6 
Prior and Concomitant Medications  
2.4.7 
Medical History 
2.5.1 
Itacitinib Exposure and Compliance 
Efficacy 
2.6.1 
FEV1 Assessment 
2.6.2 
FEV1 Response Assessment 
2.6.3 
Time to Progression or Death Events and Assessment 
2.6.4 
Duration of FEV1 Response Events and Assessment 
2.6.6 
Deaths 
Safety 
2.7.1 
Adverse Events  
2.7.2 
Serious Adverse Events 
2.7.3 
Grade 3 and Higher Adverse Events 
2.7.4 
Fatal Adverse Events 
2.7.5 
Treatment-Related Adverse Events 
2.7.6 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of Itacitinib  
2.8.1 
Clinical Laboratory Values – Hematology 
2.8.2 
Clinical Laboratory Values – Chemistry 
2.8.3 
Clinical Laboratory Values – Coagulation 
2.8.4 
Clinical Laboratory Values – Lipid Panel 
2.9.1 
Vital Signs 
2.10.1 
12-Lead ECG 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.4 
Clinically Significant 12-Lead ECG Values 


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APPENDIX B. CLINICALLY NOTABLE EVENTS BASED ON 
CUSTOMIZED MEDDRA QUERIES 
This appendix provides the categories of clinically notable events based on customized MedDRA 
queries. 
Clinically Notable Hematological Events 
Category 
Preferred Term 
Anemia 
Anaemia macrocytic 
Anemia 
Aplasia pure red cell 
Anemia 
Aplastic anaemia 
Anemia 
Erythroblast count decreased 
Anemia 
Erythropenia 
Anemia 
Hypoplastic anaemia 
Anemia 
Microcytic anaemia 
Anemia 
Red blood cell count decreased 
Anemia 
Anaemia 
Anemia 
Haematocrit decreased 
Anemia 
Haemoglobin decreased 
Anemia 
Leukoerythroblastic anaemia 
Neutropenia 
Agranulocytosis 
Neutropenia 
Band neutrophil count decreased 
Neutropenia 
Febrile neutropenia 
Neutropenia 
Granulocyte count decreased 
Neutropenia 
Granulocytopenia 
Neutropenia 
Neutropenia 
Neutropenia 
Neutropenic infection 
Neutropenia 
Neutropenic sepsis 
Neutropenia 
Neutrophil count decreased 
Thrombocytopenia 
Acquired amegakaryocytic thrombocytopenia 
Thrombocytopenia 
Platelet count decreased 
Thrombocytopenia 
Thrombocytopenia 
Thrombocytopenia 
Plateletcrit decreased 


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Hematological Infection 
Category 
Preferred Term 
EBV infection 
Epstein-Barr virus positive mucocutaneous ulcer 
EBV infection 
Epstein-Barr viraemia 
EBV infection 
Epstein-Barr virus associated lymphoma 
EBV infection 
Epstein-Barr virus associated lymphoproliferative disorder 
EBV infection 
Epstein-Barr virus infection 
EBV infection 
Hepatitis infectious mononucleosis 
EBV infection 
Infectious mononucleosis 
EBV infection 
Oral hairy leukoplakia 
EBV infection 
Post transplant lymphoproliferative disorder 
EBV infection 
X-linked lymphoproliferative syndrome 
EBV infection 
Epstein-Barr virus test positive 
EBV infection 
Epstein-Barr virus antibody positive 
Cytomegaloviral infections 
Congenital cytomegalovirus infection 
Cytomegaloviral infections 
Cytomegalovirus chorioretinitis 
Cytomegaloviral infections 
Cytomegalovirus colitis 
Cytomegaloviral infections 
Cytomegalovirus duodenitis 
Cytomegaloviral infections 
Cytomegalovirus enteritis 
Cytomegaloviral infections 
Cytomegalovirus enterocolitis 
Cytomegaloviral infections 
Cytomegalovirus gastritis 
Cytomegaloviral infections 
Cytomegalovirus gastroenteritis 
Cytomegaloviral infections 
Cytomegalovirus gastrointestinal infection 
Cytomegaloviral infections 
Cytomegalovirus gastrointestinal ulcer 
Cytomegaloviral infections 
Cytomegalovirus hepatitis 
Cytomegaloviral infections 
Cytomegalovirus infection 
Cytomegaloviral infections 
Cytomegalovirus mononucleosis 
Cytomegaloviral infections 
Cytomegalovirus mucocutaneous ulcer 
Cytomegaloviral infections 
Cytomegalovirus myelomeningoradiculitis 
Cytomegaloviral infections 
Cytomegalovirus myocarditis 
Cytomegaloviral infections 
Cytomegalovirus nephritis 
Cytomegaloviral infections 
Cytomegalovirus oesophagitis 
Cytomegaloviral infections 
Cytomegalovirus pancreatitis 
Cytomegaloviral infections 
Cytomegalovirus pericarditis 
Cytomegaloviral infections 
Cytomegalovirus syndrome 
Cytomegaloviral infections 
Cytomegalovirus urinary tract infection 
Cytomegaloviral infections 
Cytomegalovirus viraemia 
Cytomegaloviral infections 
Encephalitis cytomegalovirus 
Cytomegaloviral infections 
Disseminated cytomegaloviral infection 
Cytomegaloviral infections 
Pneumonia cytomegaloviral 
Cytomegaloviral infections 
Cytomegalovirus test positive 


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Hyperlipidemia 
Category 
Preferred Term 
Hyperlipidemia 
Acquired lipoatrophic diabetes 
Hyperlipidemia 
Acquired mixed hyperlipidaemia 
Hyperlipidemia 
Apolipoprotein B/Apolipoprotein A-1 ratio increased 
Hyperlipidemia 
Autoimmune hyperlipidaemia 
Hyperlipidemia 
Blood cholesterol abnormal 
Hyperlipidemia 
Blood cholesterol esterase increased 
Hyperlipidemia 
Blood cholesterol increased 
Hyperlipidemia 
Blood triglycerides abnormal 
Hyperlipidemia 
Blood triglycerides increased 
Hyperlipidemia 
Diabetic dyslipidaemia 
Hyperlipidemia 
Dyslipidaemia 
Hyperlipidemia 
High density lipoprotein abnormal 
Hyperlipidemia 
High density lipoprotein decreased 
Hyperlipidemia 
Hypercholesterolaemia 
Hyperlipidemia 
Hyperlipidaemia 
Hyperlipidemia 
Hypertriglyceridaemia 
Hyperlipidemia 
Hypo HDL cholesterolaemia 
Hyperlipidemia 
Intermediate density lipoprotein increased 
Hyperlipidemia 
LDL/HDL ratio increased 
Hyperlipidemia 
Lipids abnormal 
Hyperlipidemia 
Lipids increased 
Hyperlipidemia 
Lipoprotein (a) abnormal 
Hyperlipidemia 
Lipoprotein (a) increased 
Hyperlipidemia 
Lipoprotein abnormal 
Hyperlipidemia 
Lipoprotein increased 
Hyperlipidemia 
Low density lipoprotein abnormal 
Hyperlipidemia 
Low density lipoprotein increased 
Hyperlipidemia 
Non-high-density lipoprotein cholesterol increased 
Hyperlipidemia 
Remnant-like lipoprotein particles increased 
Hyperlipidemia 
Total cholesterol/HDL ratio abnormal 
Hyperlipidemia 
Total cholesterol/HDL ratio increased 
Hyperlipidemia 
Very low density lipoprotein abnormal 
Hyperlipidemia 
Very low density lipoprotein increased 


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QT Prolongation 
Category 
Preferred Term 
QT prolongation 
Electrocardiogram QT interval abnormal 
QT prolongation 
Electrocardiogram QT prolonged 
QT prolongation 
Long QT syndrome 
QT prolongation 
Long QT syndrome congenital 
QT prolongation 
Torsade de pointes 
QT prolongation 
Ventricular tachycardia