Clinical trial NCT03538041
Conditions: Autoimmune Hemolytic Anemia
Keywords: autoimmune hemolytic anemia phosphatidylinositol 3-kinase (PI3K) inhibitor
Sponsor: Incyte Corporation
Start date: 2018-11-21; Completion date: 2024-04-02
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the safety and efficacy of parsaclisib administered orally to participants with autoimmune hemolytic anemia (AIHA) who have decreased hemoglobin and evidence of ongoing hemolysis that requires treatment intervention.

Detailed description:

Arms: arm 1: Parsaclisib at 1 milligram (mg) once daily (QD) for 12 weeks followed by extension period, with a dose-increase option (to 2.5 mg QD) at Week 6 for participants who fulfill dose increase criteria. arm 2: Parsaclisib at 2.5 mg QD for 12 weeks followed by extension period.
Interventions: intervention 1: Parsaclisib
Intervention descriptions: intervention 1: Parsaclisib administered orally.

Protocol documents:
Prot_000.pdf: 
Official Title: 
A Phase 2, Open-Label Study of INCB050465 in Participants With 
Autoimmune Hemolytic Anemia 
NCT Number: 
NCT03538041 
Document Date: 
Clinical Study Protocol Version 5: 02-November-2020 


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Protocol INCB 50465-206 Am 5 
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02 NOV 2020 
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CONFIDENTIAL 
TITLE PAGE 
Clinical Study Protocol 
 
INCB 50465-206 
A Phase 2, Open-Label Study of INCB050465 in Participants With 
Autoimmune Hemolytic Anemia 
 
 
Product: 
INCB050465 
IND Number: 
121,474 
EudraCT Number: 
2017-003652-22 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
07 NOV 2017 
Amendment (Version) 1: 
11 JAN 2018 
Amendment (Version) 1-FRA: 
23 MAY 2018 
Amendment (Version) 2: 
20 JUN 2018 
Amendment (Version) 3: 
01 FEB 2019 
Amendment (Version) 4: 
31 OCT 2019 
Amendment (Version) 5: 
02 NOV 2020 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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Protocol INCB 50465-206 Am 5 
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INVESTIGATOR'S AGREEMENT 
I have read the INCB 50465-206 Protocol Amendment 5 (Version 5 dated 02 NOV 2020) and 
agree to conduct the study as outlined.  I agree to maintain the confidentiality of all information 
received or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR'S AGREEMENT ................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
2. 
INTRODUCTION ......................................................................................................17 
2.1. 
Epidemiology of Autoimmune Hemolytic Anemia ....................................................17 
2.2. 
Mechanisms of Erythrocyte Destruction in Autoimmune Hemolytic Anemia ..........17 
2.3. 
Current Treatment and Unmet Need in Autoimmune Hemolytic Anemia .................18 
2.4. 
Phosphatidylinositol 3-Kinase Delta in Autoimmune Diseases .................................19 
2.5. 
INCB050465 ...............................................................................................................19 
2.6. 
Study Rationale ...........................................................................................................20 
 
21 
 
21 
 
21 
 
22 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................24 
4. 
STUDY DESIGN .......................................................................................................25 
4.1. 
Overall Design ............................................................................................................25 
4.2. 
Overall Study Duration ...............................................................................................25 
4.3. 
Study Termination ......................................................................................................26 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................29 
5.4. 
Screen Failures ............................................................................................................29 
5.5. 
Replacement of Participants .......................................................................................29 
6. 
STUDY TREATMENT ..............................................................................................30 
6.1. 
Study Treatment Administered ...................................................................................30 
6.2. 
Instruction to Participants for Handling Study Drug ..................................................30 
6.3. 
Preparation, Handling, and Accountability ................................................................31 


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6.4. 
Measures to Minimize Bias:  Randomization and Blinding .......................................31 
6.5. 
Study Treatment Compliance .....................................................................................31 
6.6. 
Dose Modifications .....................................................................................................32 
6.6.1. 
Criteria and Procedures for Dose Increases of Study Drug ........................................32 
6.6.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................32 
6.6.3. 
Criteria for Permanent Discontinuation of Study Drug ..............................................33 
6.7. 
Concomitant Medications and Procedures .................................................................33 
6.7.1. 
Permitted Medications and Procedures ......................................................................34 
6.7.1.1. 
Pneumocystis jirovecii Pneumonia Prophylaxis .........................................................34 
6.7.1.2. 
Folic Acid, Vitamin B12, or Iron Deficiencies ...........................................................34 
6.7.2. 
Restricted Medications and Procedures ......................................................................34 
6.7.3. 
Prohibited Medications and Procedures .....................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Permanent Discontinuation of Study Treatment.........................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................35 
7.2. 
Participant Withdrawal From the Study .....................................................................36 
7.3. 
Lost to Follow-Up.......................................................................................................36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................37 
8.1. 
Administrative and General Procedures .....................................................................37 
8.1.1. 
Administration of Informed Consent Form ................................................................37 
8.1.2. 
Screening Procedures ..................................................................................................37 
8.1.3. 
Interactive Response Technology Procedure ..............................................................38 
8.1.4. 
Demography and Medical History ..............................................................................38 
8.1.4.1. 
Demographics and General Medical History .............................................................38 
8.1.4.2. 
Disease Characteristics and Treatment History ..........................................................38 
8.1.5. 
Prior and Concomitant Medications and Procedures ..................................................38 
8.2. 
Efficacy Assessments .................................................................................................38 
8.2.1. 
Hemoglobin Level, Hemolysis Markers, Direct Antiglobulin Test, and 
Complement Assessment ............................................................................................38 
8.2.2. 
Direct Antiglobulin Test and Cold Agglutinin Test ...................................................39 


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39 
8.3. 
Safety Assessments .....................................................................................................39 
8.3.1. 
Adverse Events ...........................................................................................................39 
8.3.2. 
Physical Examinations ................................................................................................39 
8.3.2.1. 
Comprehensive Physical Examination .......................................................................39 
8.3.2.2. 
Targeted Physical Examination ..................................................................................40 
8.3.3. 
Vital Signs ..................................................................................................................40 
8.3.4. 
Electrocardiograms .....................................................................................................40 
8.3.5. 
Laboratory Assessments .............................................................................................40 
8.3.5.1. 
Chemistry and Hematology ........................................................................................41 
8.3.5.2. 
Vitamin B12 and Folic Acid .......................................................................................41 
8.3.5.3. 
Iron Clinical Assessment ............................................................................................41 
8.3.5.4. 
Urinalysis ....................................................................................................................41 
8.3.5.5. 
Coagulation .................................................................................................................41 
8.3.5.6. 
Pregnancy Testing ......................................................................................................42 
8.3.5.7. 
Serology ......................................................................................................................42 
8.4. 
Pharmacokinetic Assessments ....................................................................................44 
8.4.1. 
Blood Sample Collection ............................................................................................44 
 
44 
8.6. 
Unscheduled Visits .....................................................................................................45 
8.7. 
End of Treatment ........................................................................................................45 
8.8. 
Extension Period .........................................................................................................45 
8.9. 
Follow-Up ...................................................................................................................45 
8.9.1. 
Safety Follow-Up ........................................................................................................45 
8.9.2. 
Additional Follow-Up Period .....................................................................................45 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................46 
9.1. 
Adverse Events ...........................................................................................................46 
9.1.1. 
Definitions ..................................................................................................................46 
9.1.2. 
Reporting ....................................................................................................................46 
9.2. 
Laboratory Test Abnormalities ...................................................................................48 
9.3. 
Serious Adverse Events ..............................................................................................48 
9.3.1. 
Definitions ..................................................................................................................48 


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9.3.2. 
Reporting ....................................................................................................................49 
9.4. 
Pregnancy ...................................................................................................................50 
9.5. 
Warnings and Precautions ..........................................................................................50 
9.6. 
Data Monitoring Committee .......................................................................................50 
9.7. 
Product Complaints ....................................................................................................51 
10. 
STATISTICS ..............................................................................................................51 
10.1. 
Sample Size Determination ........................................................................................51 
10.2. 
Populations for Analysis .............................................................................................51 
10.3. 
Level of Significance ..................................................................................................51 
10.4. 
Statistical Analyses .....................................................................................................52 
10.4.1. 
Efficacy Analyses .......................................................................................................52 
10.4.1.1. 
Primary Efficacy Analyses .........................................................................................52 
10.4.1.2. 
Secondary Efficacy Analyses .....................................................................................52 
10.4.1.3. 
Other Efficacy Analyses .............................................................................................52 
10.4.2. 
Safety Analyses ..........................................................................................................52 
10.4.2.1. 
Adverse Events ...........................................................................................................52 
10.4.2.2. 
Clinical Laboratory Tests ...........................................................................................52 
10.4.2.3. 
Vital Signs ..................................................................................................................53 
10.4.2.4. 
Electrocardiograms .....................................................................................................53 
10.4.3. 
Pharmacokinetic Analysis ..........................................................................................53 
 
53 
10.5. 
Interim Analysis ..........................................................................................................53 
10.6. 
Analyses for the Data Monitoring Committee ............................................................53 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................54 
11.1. 
Investigator Responsibilities .......................................................................................54 
11.2. 
Data Management .......................................................................................................55 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................56 
11.4. 
Financial Disclosure ...................................................................................................56 
11.5. 
Publication Policy .......................................................................................................57 
12. 
REFERENCES ...........................................................................................................58 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................60 


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APPENDIX B. FACIT FATIGUE SUB-SCALE (VERSION 4) ...............................................61 
APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS SCORES.......................................................................62 
APPENDIX D. PROTOCOL AMENDMENT SUMMARY OF CHANGES ...........................63 
 
LIST OF TABLES 
Table 1: 
Schedule of Assessments ............................................................................................14 
Table 2: 
Schedule of Assessments for the Extension Period ....................................................16 
Table 3: 
Study Drug Information ..............................................................................................30 
Table 4: 
Guidelines for Interruption and Restarting of Study Drug .........................................33 
Table 5: 
Required Laboratory Analytes ....................................................................................43 
Table 6: 
Sample Collection Time Windows for Pharmacokinetic Assessments for 
INCB050465 ...............................................................................................................44 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................13 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Abbreviation 
Definition 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
AIHA 
autoimmune hemolytic anemia 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC0-t 
area under the concentration-time curve from time = 0 to the last measureable 
concentration at time = t 
BMI 
body mass index 
CAD 
cold agglutinin disease 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CL/F 
apparent oral dose clearance 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration over the dose interval 
CNS 
central nervous system 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DAT 
direct antiglobulin test 
DNA 
deoxyribonucleic acid 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
EOT 
end of treatment 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
full analysis set 
Fc 
fragment crystallizable 


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Abbreviation 
Definition 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
IC50 
concentration that results in 50% inhibition 
IC90 
concentration that results in 90% inhibition 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IL 
interleukin 
IN 
Investigator Notification 
IRB 
institutional review board 
IRT 
interactive response technology 
LDH 
lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
NK 
natural killer 
 
 
PD 
pharmacodynamic 
PD-1 
programmed cell death protein 1 
PI3Kδ 
phosphatidylinositol 3-kinase enzymes delta isoform 
PIP2 
phosphatidylinositol-4,5-bisphosphate 
PIP3 
phosphatidylinositol-3,4,5 trisphosphate 
PJP 
Pneumocystis jiroveci pneumonia 
PK 
pharmacokinetic 
PML 
progressive multifocal leukoencephalopathy 


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Abbreviation 
Definition 
PR 
partial response 
RBC 
red blood cell 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
TEAE 
treatment-emergent adverse event 
tmax 
time to maximum concentration 
Treg 
regulatory T cell 
ULN 
upper limit of normal 
wAIHA 
warm-type autoimmune hemolytic anemia 
WBC 
white blood cell 


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1. 
PROTOCOL SUMMARY 
Protocol Title:  A Phase 2, Open-Label Study of INCB050465 in Participants With 
Autoimmune Hemolytic Anemia 
Protocol Number:  INCB 50465-206 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of INCB050465 in the 
treatment of participants with AIHA. 
• Proportion of participants attaining a CR (defined as 
hemoglobin > 12 g/dL not attributed to transfusion 
effect* and the normalization of hemolytic markers) 
at any visit from Week 6 to Week 12. 
• Proportion of participants attaining a PR (defined as 
hemoglobin 10-12 g/dL or ≥ 2 g/dL increase from 
baseline not attributed to transfusion effect and the 
normalization of hemolytic markers) at any visit 
from Week 6 to Week 12. 
*No transfusion effect definition:  >1 week since last 
transfusion. 
To evaluate the safety of INCB050465 administered as 
repeat doses in participants with AIHA. 
Safety and tolerability will be assessed by monitoring 
AEs, measuring vital signs and ECGs, and conducting 
clinical laboratory blood and urine sample assessments. 
Overall Design: 
Study Phase 
Phase 2 
Clinical Indication 
AIHA 
Population 
Men and women, aged 18 years or older with primary AIHA without 
evidence of a lymphoproliferative malignancy. 
Number of Participants 
Approximately 25 
Study Design 
Open-label, multicenter study 
Estimated Duration of 
Study 
Treatment duration will vary among participants.  The initial study period 
will be 28 weeks in duration.  For participants who are eligible for an 
extension of treatment based on their clinical response, the treatment 
duration may be extended with sponsor approval. 
Safety Review 
Committee 
Yes (internal)  


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Treatment Groups and Duration: 
Participation is 28 weeks for participants who are not eligible for an extension based on clinical 
response and includes the following: 
• Screening:  up to 28 days 
• Treatment:  up to 12 weeks 
• Extension period:  For participants receiving benefit from study drug, further 
participation may continue with sponsor approval until the drug is available through 
another clinical study, or is commercially available, or the sponsor stops the study 
or the study drug development.  
• Follow-up:  up to 12 weeks (3 months) 
Cohort 1:  INCB050465 1 mg QD for up to 12 weeks.  At Week 6, participants who fulfill dose 
increase criteria (see definition below) will be offered INCB050465 2.5 mg QD for up to 
6 weeks.  If there are any tolerability issues in individual participants who received 2.5 mg, the 
dose may be decreased to 1 mg. 
Cohort 2:  INCB050465 2.5 mg QD for up to 12 weeks.  If there are any tolerability issues in 
individual participants, the dose may be decreased to 1 mg. 
Criteria for dose increase:  (1) Continue to require transfusions by Week 6 visit, or (2) do not 
attain a meaningful clinical response (at least a stabilization ≥ 2 g/dL increase in hemoglobin 
from baseline to Week 6).  Dose increases require sponsor preapproval (see Section 6.6). 
Participants who complete the 12-week treatment period and continue to receive clinical benefit 
from study drug may enter into an extension period with sponsor approval to continue receiving 
INCB050465 until the drug is available through another clinical study, or is commercially 
available, or the sponsor stops the study or the study drug development. 
The study design is shown in Figure 1 below. 


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Figure 1: 
Study Design Schema 
 
a Cohort 1:  N = 10; no more than 3 CAD or mixed-type AIHA participants. 
b Cohort 2:  N = approximately 15, with approximately 5 CAD AIHA and up to 8 wAIHA participants; the 
remainder can be wAIHA, CAD, or mixed-type AIHA participants. 
Participants in Cohort 2 may begin enrollment after enrollment of a minimum of 6 wAIHA participants in 
Cohort 1 and review of safety and efficacy through Week 6. 
c (1) At Week 6, participants who receive 1 mg QD study drug and who fulfill dose increase criteria* may have their 
dose increased to 2.5 mg QD of INCB050465 until Week 12. 
(2) If there are any tolerability issues in individual participants who received 2.5 mg, the dose may be decreased to 
1 mg. 
d If there are any tolerability issues in individual participants who received 2.5 mg, the dose may be decreased to 
1 mg. 
e If relapse of AIHA occurs within this period, PD and clinical laboratory markers of hemolysis will be assessed, 
and the participants will be treated based on investigators' decision. 
* Criteria for dose increase in individual participants in Cohort 1 (see Section 6.6): 
(1) Continue to require transfusions by Week 6 visit, or  
(2) Do not attain a meaningful clinical response (at least a stabilization ≥ 2 g/dL increase in hemoglobin from 
baseline to Week 6). 
•
Men and women aged
≥ 18 years 
•
Primary AIHA based on the 
presence of hemolytic anemia 
and serological evidence of 
anti-erythrocyte antibodies
•
No evidence of a 
lymphoproliferative malignancy
•
Hgb: 7-10 g/dL
•
N 25
2.5 mg QD (N=10)
Week 0   1    2        4       6       8      10       12
Assess Efficacy 
(Cohort 1) 
1 mg QD
N = 10
1 mg QD 
Screening (up to 28 days)
2.5 mg QDc
1 mg QD 
Cohort 1a
Treatment (12 weeks)
2.5 mg QDd
N 15
Cohort 2b
Extension
(1 or 2.5 
mg)
Follow-Upe
(3 months)
For 
participants 
who 
continue to 
receive 
clinical 
benefit 
For participants who 
do not enter into the 
extension period


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Table 1: 
Schedule of Assessments 
Procedure 
Protocol 
Section 
Screening 
Treatment 
Follow-Upa 
Days 
-28 to -1 
Day 1 
Wk 1 
± 3 
days 
Wk 2 
± 3 
days 
Wk 4 
± 3 
days 
Wk 6b 
± 3 
days 
Wk 8 
± 3 
days 
Wk 10 
± 3 
days 
Wk 12 
± 3 
days 
(EOT) 
Month 1 
+ 5 days 
Month 2 
± 5 days 
Month 3 
± 5 days 
(EOS) 
Administrative procedures 
Informed consent 
8.1.1 
X 
 
 
 
 
 
 
 
 
 
 
 
Contact IRT 
8.1.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review inclusion and 
exclusion criteria 
5.1, 5.2 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demography and medical 
history 
8.1.4 
X 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
8.1.5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug accountability and 
assess compliance 
6.5 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Study drug dispensing 
6.1 
 
X 
 
 
X 
 
X 
 
 
 
 
 
Prophylactic treatment for PJP 
6.7.1.1 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety procedures/assessments 
Physical examinationc 
8.3.2 
Xc 
Xc,d 
X 
X 
X 
 
X 
 
X 
 
 
Xc 
Vital signse 
8.3.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Serologyf 
8.3.5.7 
X 
 
 
 
 
 
 
 
 
 
 
 
D-Dimer 
8.3.5.5 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
Vitamin B12/folic acid 
8.3.5.2  
X 
 
 
 
 
 
 
 
 
 
 
 
FSHg 
8.3.5.6 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancyh 
8.3.5.6 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancyh 
8.3.5.6 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Urinalysis 
8.3.5.4 
X 
 
 
 
 
 
 
 
X 
 
 
 
Serum chemistriesi 
8.3.5.1 
8.3.5.3  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECGj 
8.3.4 
X 
 
 
X 
 
 
X 
 
X 
 
 
 
AE assessment 
8.3.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Table 1: 
Schedule of Assessments (Continued) 
Procedure 
Protocol 
Section 
Screening 
Treatment 
Follow-Upa 
Days 
-28 to -1 
Day 1 
Wk 1 
± 3 
days 
Wk 2 
± 3 
days 
Wk 4 
± 3 
days 
Wk 6b 
± 3 
days 
Wk 8 
± 3 
days 
Wk 10 
± 3 
days 
Wk 12 
± 3 
days 
(EOT) 
Month 1 
+ 5 days 
Month 2 
± 5 days 
Month 3 
± 5 days 
(EOS) 
Efficacy assessments 
Hematology 
8.2.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hemolysis markersk 
8.2.1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xk 
Xk 
Xk 
DAT and cold agglutinin levels 
8.2.2  
X 
 
 
 
 
 
 
 
X 
 
 
 
Complement assessment 
(CH50, C3, and C4) 
8.2.1 
 
X 
 
 
 
 
 
 
X 
 
 
 
FACIT-Fatigue sub-scale 
8.2.3  
 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
PK plasma samplingl 
8.4  
 
 
X 
Xm 
 
 
Xm 
 
X 
 
 
 
a For participants who are not eligible to enter into the extension period. 
b Dose modification. 
c Comprehensive physical examination at screening, Day 1, and EOS; targeted physical examination at all other time points. 
d Height and body weight will only be assessed at Day 1. 
e Vital signs will include body temperature, respiratory rate, blood pressure, and pulse. 
f Serology includes HIV, hepatitis, anti-Streptolysin antibody, and anti-phospholipid antibody tests. 
g For women of nonchildbearing potential only (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined by last menstrual period 
> 12 months before screening and confirmed by FSH). 
h For women of childbearing potential only. 
i Ferritin, iron, and total iron-binding capacity will be tested at screening for all participants and at Week 6 if the participant has ongoing transfusions requirements during the 
study. 
j Single ECG.  At screening, in the event that a single QTcF is > 470 milliseconds for males or > 480 milliseconds for females, triplicate ECG measurements may be performed. 
k Hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin and direct/indirect bilirubin are hemolytic markers will be measured.  During follow-up, these hemolytic 
markers should be assessed if a participant becomes symptomatic or starts new treatment; relevant biomarkers should also be included. 
l Plasma for PK analysis will be collected predose and 1, 2, and 4 hours postdose at Weeks 2 and 8.  Predose PK will be collected at Weeks 1 and 12. 
m No food intake 4 hours predose and 1 hour postdose on Weeks 2 and 8. 
 
 


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Table 2: 
Schedule of Assessments for the Extension Period 
Procedure 
Protocol 
Section 
Extension Period 
EOT 
Extension 
Period 
Follow-Up 
At Least Every 8-12 Weeks in Clinic 
Month 1 
+ 5 days 
Month 2 
± 5 days 
Month 3 
± 5 days 
(EOS) 
Prior/concomitant medications 
8.1.5 
X 
X 
X 
X 
X 
Study drug dispensing 
6.1 
X 
 
 
 
 
Study drug accountability and 
assess compliance 
6.5 
X 
X 
 
 
 
AE assessment 
8.3.1 
X 
X 
X 
X 
X 
Prophylactic treatment for PJP 
6.7.1.1 
X 
X 
X 
X 
X 
Hematologya,b 
8.2.1 
X 
X 
X 
X 
X 
Hemolysis markersa 
8.2.1 
X 
X 
X 
X 
X 
Serum chemistries a  
8.3.5.1 
X 
 
 
 
 
a Performed at each site as per the standard of care for participant's condition and monitoring at the investigator's discretion.  Frequency to be determined by the investigator if it is 
necessary to monitor any other ongoing clinical condition. 
b Hematology panel will be performed at local laboratory. 


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2. 
INTRODUCTION 
INCB050465 is an inhibitor of the Class IA PI3K enzymes, with selectivity for the delta isoform 
(PI3Kδ) that is proposed for development for treatment of hematological malignancies and solid 
tumors.  Uncontrolled B-cell and T-cell proliferation and differentiation are strongly implicated 
in the pathogenesis of hematological malignancies and autoimmune diseases.  PI3Kδ serves a 
critical signal for B-cell and T-cell development.  Over-activated PI3Kδ signaling would 
compromise the normal immune functions.  Therefore, PI3Kδ inhibition represents a potential 
therapeutic strategy in the treatment of hematological malignancies and autoimmune diseases, 
including AIHA. 
2.1. 
Epidemiology of Autoimmune Hemolytic Anemia 
Autoimmune hemolytic anemia is a rare acquired disorder in which autoantibodies directed 
against RBC membrane antigens lead to their accelerated destruction.  The estimated incidence 
of AIHA in adults is 0.8 to 3 per 100,000 per year, with a mortality rate of 11% (Zanella and 
Barcellini 2014).  The disease can be distinguished on the basis of the autoantibody Ig class and 
thermal characteristics in wAIHA (IgG-mediated) and CAD (IgM-mediated).  Mixed-type AIHA 
(7%-8% of all AIHA) coexists of warm autoantibodies and high-titer cold agglutinins.  
Autoimmune hemolytic anemia is also classified as primary (idiopathic), in which hemolysis 
dominates the clinical picture in the absence of any other coexisting disorder, and secondary 
forms, which accompany and are complications of an underlying disease (eg, 
lymphoproliferative disease, infections, immunodeficiency, and tumors).  Warm AIHA accounts 
for 70% to 80% of all cases in adults, and at least half of the wAIHA cases are associated with an 
underlying disease.  Acute CAD is mainly secondary to infections, whereas chronic CAD is 
frequently associated with lymphoproliferative or neoplastic diseases (Oken and Garratty 2004). 
2.2. 
Mechanisms of Erythrocyte Destruction in Autoimmune Hemolytic 
Anemia 
There are several immunologic mechanisms are involved in the pathogenesis of wAIHA that 
include ADCC, phagocytosis, and direct complement-mediated lysis (Barcellini 2015).  The 
most frequent autoantibodies against RBCs are IgG, which mainly determine extravascular 
hemolysis through the ADCC.  Cytotoxic CD8+T cells and NK cells that carry membrane 
receptors for the Fc portion of IgG directly lyse RBCs in the reticuloendothelial system (spleen 
and liver).  Phagocytosis by macrophages is another way RBCs are destroyed.  The macrophage 
surface expresses receptors for the Fc region of IgG, which enables trapping and ingestion of 
opsonized RBCs that are coated with IgG, primary in the spleen.  Moreover, for RBCs heavily 
coated with IgG, the amount of antigen-antibody complex can be sufficient for binding 
complement protein complex C1 and thus activate the classical complement pathway.  Upon 
complement activation in wAIHA, phagocytosis of C3b-opsonized erythrocytes by Kupffer cells 
in the liver is responsible for most of the RBC destruction. 


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In contrast to wAIHA, in CAD, most RBC destruction does not occur in the spleen.  
Immunoglobulin M-cold autoantibody binds complement C1 and initiates the classical 
complement pathway, which results in the cleavage of C3 to C3a and C3b.  When RBCs in the 
peripheral circulation at cooler temperatures return to the central circulation with higher 
temperature, the IgM antibody detaches from the cell surface, while C3b remains bound.  A 
proportion of the C3b-coated RBCs is sequestered by macrophages in the liver, whereas the 
other RBCs are lysed through the activation of C5 by C3b.  C5 complement activation results in 
membrane attack complex formation and intravascular hemolysis that results in severe acute 
exacerbations and profoundly hemolytic patients (Berentsen et al 2015). 
2.3. 
Current Treatment and Unmet Need in Autoimmune Hemolytic 
Anemia 
Currently there is no approved and effective targeted therapy for treatment of AIHA.  For 
wAIHA, corticosteroids remain the first-line therapy; however high initial doses are required, 
responses are often achieved slowly, and only a minority of patients (< 20%) achieve a lasting 
response (< 20%; Barcellini et al 2014).  Since most RBC destruction occurs in the spleen in 
wAIHA, it is not surprising that splenectomy is a reasonably efficient second-line treatment with 
a sustained response rate of 60% to 70%.  In the third-line situation, immunosuppressive drugs 
such as danazol, azathioprine, cyclophosphamide, or cyclosporine are used, although response 
rates are poorly documented, and most publications are single case reports or small retrospective 
studies.  In contrast to wAIHA, only 14% of CAD patients have responses to corticosteroids, and 
other unspecific immunosuppressive drugs have little efficacy.  As CAD is usually not a primary 
disease, recommended first-line therapy is to treat the underlying disease. 
Rituximab is a chimeric monoclonal antibody that targets CD20 antigen on B lymphocytes.  By 
binding to CD20, it induces apoptosis of CD20-positive B cells.  Rituximab has recently been 
licensed in rheumatoid arthritis and is also widely used off-label in various autoantibody-
mediated autoimmune diseases, such as immune thrombocytopenic purpura and systemic lupus 
erythematosus.  Recently, rituximab has been considered as second-line therapy for wAIHA and 
first-line therapy for CAD.  Second-line treatment with rituximab leads to response rates similar 
to splenectomy (~70%), but rituximab-induced responses seem less sustained, and relapses are 
frequent.  Major concerns regarding the adverse effects from rituximab are related to long-lasting 
B-cell suppression and include increased risk of infection including hepatitis B reactivation 
(Artz et al 2010) and possibly PML (Carson et al 2009). 
In recent years, several complement inhibitors have become available in the clinic, some with 
proven efficacy in AIHA.  Eculizumab is a humanized monoclonal antibody that binds to the C5 
component and inhibits terminal complement activation.  There have been 2 case reports 
describing patients with CAD who were successfully treated with eculizumab (Röth et al 2009, 
Gupta and Wang 2014).  However, in these 2 reports, it was only effective in AIHA patients with 
intravascular hemolysis, and also increases the risk of meningococcal infection.  A monoclonal 
antibody (TNT009) targeting C1 to inhibit the classical complement pathway is also under study.  
Other complement inhibition drugs that target either C3 or the classical pathway have only been 
reported in experimental and preclinical studies or in few clinical observations. 


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2.4. 
Phosphatidylinositol 3-Kinase Delta in Autoimmune Diseases 
Phosphatidylinositol 3-kinases belong to a family of lipid signaling kinases that phosphorylate 
phosphoinositides of the inositol ring (Cantley 2002).  Phosphatidylinositol 3-kinase enzymes are 
divided into 3 classes (Class I, II, and III) according to their structure, regulation, and substrate 
specificity.  Class I PI3Ks, which include PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, are dual-specificity 
lipid and protein kinases that catalyze the phosphorylation of PIP2, giving rise to PIP3.  PIP3 
functions as a second messenger that controls a number of cellular processes, including growth, 
survival, adhesion, and migration. 
The delta isoform of PI3K is expressed primarily in hematopoietic cells and plays an essential 
role in B-cell development and function.  Aberrant PI3Kδ signaling activates and proliferates 
self-reactive B cells that produce autoantibodies, act as antigen-presenting cells presenting self-
antigen to autoreactive T cells, and produce pro-inflammatory cytokines, and therefore has been 
strongly linked to autoimmunity (Puri and Gold 2012).  Indeed, PI3Kδ inhibitors such as 
IC87114, have now been shown to reduce the incidence and severity of autoimmune arthritis, 
asthma, experimental autoimmune encephalomyelitis, and systemic lupus erythematosus in 
mouse models.  Clinical studies are now evaluating the potential of PI3Kδ inhibitors for the 
treatment of a variety of inflammatory diseases including allergic rhinitis and chronic obstructive 
pulmonary disease.  The ability of PI3Kδ inhibitors to reduce the severity of these inflammatory 
diseases may be due not only to their actions on B cells, but also to inhibitory effects on other 
immune cells that contribute to autoimmune disease such as T cells, mast cells and neutrophils 
(Fung-Leung 2011).  Given the fact that in addition to B cells, several T cell subsets, including 
Treg, Th17, and Th1 cells, are also involved in AIHA pathogenesis, inhibition of PI3Kδ 
signaling could have benefit in the treatment of patients with current unmet need in AIHA and 
other autoimmune diseases. 
A preclinical study indicated that IL-2 knockout mice developing AIHA improved RBC counts, 
hematocrit, and hemoglobin and reduced anti-RBC reactivity (eg., decreased auto-IgM 
antibodies) after being treated with a PI3Kδ inhibitor (INCB040093, 100 mg/kg BID PO; Incyte 
unpublished data).  This result strengthens the hypothesis that inhibition of PI3Kδ signaling may 
attenuate autoreactive antibody production that destroy RBCs and lead to AIHA. 
2.5. 
INCB050465 
INCB050465 is a potent inhibitor of PI3Kδ 
 with approximately 
 for the other PI3K family members (IB).  B-cell proliferation triggered by 
anti–IgM-mediated cross-linking of the B-cell receptor is known to be PI3Kδ dependent.  
INCB050465 potently inhibits antibody-induced proliferation of human CD19+ B cells with an 
IC50 value of 
 nM. 
 
 
.  These effects were not due to INCB050465 mediated general 
cytotoxicity. 
INCB050465 inhibited the production of IL-17, IFN-γ, and IL-13 by naive T cells cultured under 
Th17, Th1 and Th2 differentiation conditions, respectively.  These data suggest that in addition 
to the effects of PI3Kδ inhibition on B cells, it may also potentially impact some aspects of T cell 
function. 


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Clinical experiences of INCB050465 are solely based on oncology studies in patients with 
cancer who received higher doses for longer periods of time.  In a Phase 1/2, dose-escalation and 
expansion study, INCB050465 is being evaluated as a monotherapy for patients with B-cell 
malignancies.  Sixty-nine participants (as of 30 MAR 2017) received INCB050465 administered 
orally at QD doses of 5, 10, 15, 20, and 45 mg.  INCB050465 has been generally well-tolerated 
in participants with doses up to 45 mg.  The median duration of treatment was 96 days.  The 
most frequently reported treatment-related TEAE was diarrhea (
).  Other treatment-related 
TEAEs occurring ≥ 10% included nausea (
), neutropenia (14.5%), and fatigue (
).  
Serious AEs occurred in 
 (
).  The most frequent SAE reported was diarrhea 
(
).  Serious AEs were observed in all dose cohorts.  Ten participants (
) had SAEs that 
were considered related to INCB050465 by the investigators.  Related SAEs that occurred in 
more than 1 participant were colitis, diarrhea, and dermatitis exfoliative (
 each participant).  
No dose-limiting toxicities were identified, and the maximum tolerated dose was not reached.  
 
  The PD analyses demonstrated robust and sustained pathway inhibition at all dose levels 
tested (Phillips et al 2016).  Refer to the IB for further details. 
2.6. 
Study Rationale 
Currently, there is no approved and effective targeted therapy for treatment of AIHA.  Despite 
current treatment algorithms, there is a significant morbidity and mortality rate, and disease 
relapse remains an ongoing challenge for a significant number of patients with AIHA.  
Therefore, there remains an unmet need for new treatments for AIHA.  In addition to showing 
efficacy in a number of B-cell–related cancers, treatment with INCB050465 has shown 
significant improvement in animal models of AIHA and lupus nephritis, as well as other 
antibody-mediated diseases.  INCB050465 may represent an alternative treatment for 
participants who have failed at least 1 prior treatment.  INCB050465 may be a more flexible 
intervention, as current therapy with rituximab results in profound and sustained depletion of 
circulating B cells. 
The length of treatment in this study is 12 weeks with an observational follow-up of 12 weeks 
(3 months), as AIHA tends to follow a course of remission/relapse following conventional 
therapies.  The length of treatment is expected to allow for recovery of hemoglobin and 
evaluation of hemolytic markers, as well as permit initial safety assessment.  Participants with 
warm, cold (CAD), and mixed-type AIHA who have failed at least 1 prior treatment for AIHA 
will be eligible for enrollment.  To mirror the relative incidence of warm, mixed, and cold 
(CAD) disease, which is about 80% warm AIHA patients and about 20% of mixed and CAD 
patients, a minimum of 7 patients with warm AIHA will be enrolled in Cohort 1, and the 
remaining patients may be CAD or mixed, or the cohort may be completed with warm AIHA 
patients as available.  Cohort 2 (n ≈ 15) distribution and increased number of participants are 
intended to better evaluate CAD AIHA patients and possible signal observed in Cohort 1, as well 
as account for higher baseline variability seen in the wAIHA subpopulation.  Cohort 2 will have 
approximately 5 CAD AIHA participants and up to 8 wAIHA participants; the remainder can be 
wAIHA, CAD, or mixed-type AIHA.  As corticosteroid treatment plays an important role in 
management of the disease, participants will be permitted to continue on a low dose (equivalent 
to ≤ 20 mg/day of prednisone) of corticosteroids or taper corticosteroids as appropriate.  The 


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study is open-label, because the safety and efficacy of INCB050465 in AIHA is unknown, and 
an open-label design will allow careful monitoring in a serious disease that is rare and has a 
heterogeneous population. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 


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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of INCB050465 in the 
treatment of participants with AIHA. 
• Proportion of participants attaining a CR (defined as 
hemoglobin >12 g/dL not attributed to transfusion effect* 
and the normalization of hemolytic markers) at any visit 
from Week 6 to Week 12. 
• Proportion of participants attaining a PR (defined as 
hemoglobin 10-12 g/dL or at least ≥ 2 g/dL increase from 
baseline not attributed to transfusion effect and the 
normalization of hemolytic markers) at any visit from 
Week 6 to Week 12. 
*No transfusion effect definition:  > 1 week since last 
transfusion. 
To evaluate the safety of INCB050465 
administered as repeat doses in participants with 
AIHA. 
Safety and tolerability will be assessed by monitoring AEs, 
measuring vital signs and ECGs, and conducting clinical 
laboratory blood and urine sample assessments. 
Secondary 
To further evaluate the efficacy of INCB050465 
in the treatment of participants with AIHA. 
• Proportion of participants attaining a CR during 
postbaseline visits. 
• Proportion of participants attaining a PR during 
postbaseline visits. 
• Proportion of participants attaining a ≥ 2 g/dL increase in 
hemoglobin from baseline. 
• Mean, change, and percentage change from baseline of 
hemoglobin. 
• Proportion of participants requiring transfusions. 
• Proportion of participants who achieve normalization of 
hemolytic markers. 
(Hemolysis markers:  hemoglobin, haptoglobin, LDH, 
reticulocyte count, total bilirubin, and direct/indirect 
bilirubin.) 
• Change of daily usage of prednisone. 
• FACIT-F sub-scale assessment. 
To evaluate the PK effects of INCB050465. 
PK endpoints:  Cmax, tmax, Cmin, AUC0-t, and CL/F. 
To evaluate the PD effects of INCB050465. 
Change from baseline in PD markers:  reticulocyte count, 
DAT for IgG and C3b, cold agglutinin levels, haptoglobin, 
total bilirubin, direct/indirect bilirubin, LDH, and 
complement assessment (CH50, C3, and C4). 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a multicenter, open-label study designed to evaluate the safety and efficacy of 
INCB050465 administered orally to participants with AIHA who have decreased hemoglobin 
and evidence of ongoing hemolysis that requires treatment intervention.  Participants with 
primary warm, cold (CAD), and mixed-type AIHA without an underlying lymphoproliferative 
malignancy or autoimmune related hemolytic anemia and have failed at least 1 prior treatment 
for AIHA will be eligible for enrollment.  Participants will be treated for 12 weeks.  There are 
2 cohorts in this study:  Cohort 1, with up to 10 participants, with no more than 3 cold 
(CAD)/mixed-type AIHA participants to appropriately reflect response in the overall population, 
which is predominantly warm AIHA; and Cohort 2, with approximately 15 participants, with 
approximately 5 CAD AIHA, up to 8 warm AIHA, and the remainder from any of the 3 AIHA 
types.  Cohort 2 distribution and increased number of participants are intended to better evaluate 
CAD AIHA patients and possible signal observed in Cohort 1, as well as account for higher 
baseline variability seen in the wAIHA subpopulation.  The first cohort (Cohort 1, n = 10 
participants) enrolled will initially receive INCB050465 1 mg QD.  At Week 6, participants who 
continue to require transfusions or do not attain a meaningful clinical response (at least a 
stabilization ≥ 2 g/dL increase in hemoglobin from baseline to Week 6) may have their dose 
increased, with sponsor preapproval, to 2.5 mg QD of INCB050465 until Week 12 (see 
Section 6.6).  If there are any tolerability issues in individual participants who received 2.5 mg, 
the dose may be decreased to 1 mg.  Following enrollment of a minimum of 6 warm AIHA 
participants in the first cohort and review of safety and efficacy through Week 6, Cohort 2 may 
begin enrollment.  Participants in Cohort 2 (n ≈ 15) will receive INCB050465 2.5 mg QD for 12 
weeks.  If there are any tolerability issues, the dose may be decreased to 1 mg.  The investigator 
and sponsor should review and agree any dose increases or decreases.  Following the last dose of 
INCB050465, participants will be eligible for a 12-week (3 months) follow-up for evaluation of 
the safety and durability of response. 
An internal Safety Review Committee (see Section 9.6) will review clinical response and AE 
data.  If there is no clinical response (CR or PR) by Week 12 in the first cohort of 10 participants, 
including those who receive dose escalation to 2.5 mg, the study will be stopped for futility.  If 
there is a clear emerging signal from either Cohort 1 or Cohort 2, the committee may make 
recommendations as to the expanded study of either cohort to obtain additional safety and 
efficacy data at either dose level. 
Participants who complete the 12-week treatment period and demonstrate clinical benefit from 
study drug may enter into an extension period with sponsor approval to continue receiving 
INCB050465 until the drug is available through another clinical study, or is commercially 
available, or the sponsor stops the study or the study drug development.  Visits during the 
extension period will be conducted every 8 to 12 weeks to continue to monitor the effectiveness 
of the clinical response, as well as clinical safety laboratory assessments and adverse events. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the ICF.  Participation through follow-up is 
expected to be approximately 28 weeks for participants who complete treatment at Week 12 and 


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enter the follow-up period.  For participants that are eligible for the extension period, further 
participation may continue with sponsor approval until the drug is available through another 
clinical study, or is commercially available, or the sponsor stops the study or the study drug 
development.  It is estimated that the study will take approximately 12 to 18 months to accrue 
approximately 25 participants, and that the final analysis will be performed 12 months after the 
last participant completes the follow-up visits.  The end of the study will occur when all 
participants have completed all applicable follow-up assessments. 
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. 
5. 
STUDY POPULATION 
Participants with warm, cold (CAD), and mixed-type AIHA without an underlying 
lymphoproliferative malignancy compose the study population.  Participants will be permitted to 
continue on a low dose (equivalent to ≤ 20 mg/day of prednisone) of corticosteroids or taper 
corticosteroids as appropriate. 
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. 
5.1. 
Inclusion Criteria 
A participant who meets all of the following criteria may be included in the study: 
1. Men or women, aged 18 years or older. 
2. Diagnosis of AIHA based on the presence of hemolytic anemia and serological evidence 
of anti-erythrocyte antibodies, detectable by the DAT as follows: 
a. Warm:  DAT positive for IgG only or IgG plus C3d 
b. Cold (CAD):  DAT positive for C3d only, with cold agglutinins of I specificity 
c. Mixed:  DAT positive for IgG and C3d, with coexistence of warm autoantibodies and 
high titer cold agglutinins 
3. Participants who have disease progression after treatment with standard therapies that are 
known to confer clinical benefit or who are intolerant to treatment.  There is no limit to 
the number of prior treatment regimens. 
4. Hemoglobin 7 to 10 g/dL (as determined by local laboratory). 
5. No evidence of a lymphoproliferative malignancy or other autoimmune-related 
underlying conditions (eg, systemic lupus erythematosus, Castleman's disease, Sjögren's 
syndrome, or other autoimmune diseases). 


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6. ECOG performance status score of 0 to 2 (see Appendix C and Oken et al 1982). 
7. Willingness to avoid pregnancy or fathering children based on the criteria below: 
a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or 
bilateral oophorectomy OR postmenopausal, defined by last menstrual period 
> 12 months before screening and confirmed by FSH). 
b. Woman of childbearing potential who has a negative serum pregnancy test at 
screening and who agrees to take appropriate precautions to avoid pregnancy (with at 
least 99% certainty) from screening through at least 93 days after the last dose of 
study drug.  Permitted methods that are at least 99% effective in preventing 
pregnancy (see Appendix A) should be communicated to the participant and her 
understanding confirmed. 
c. Man who agrees to take appropriate precautions to avoid fathering children (with at 
least 99% certainty) from screening through at least 93 days after the last dose of 
study drug.  Permitted methods that are at least 99% effective in preventing 
pregnancy (see Appendix A) should be communicated to the participant and his 
understanding confirmed. 
8. Able to comprehend and willing to sign an ICF. 
9. Willingness to receive PJP prophylaxis during the study period. 
5.2. 
Exclusion Criteria 
A participant who meets any of the following criteria will be excluded from the study: 
1. Pregnant or breastfeeding women. 
2. Concurrent conditions and history of other diseases: 
a. History or clinical manifestations of significant unstable metabolic, hepatic, renal, 
hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, 
or psychiatric disorders. 
b. Current or previous malignancy within 5 years of study entry, except basal or 
squamous cell skin cancer with removal considered to be curative, superficial bladder 
cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other 
noninvasive or indolent malignancy without sponsor approval. 
c. Clinically significant cardiac disease, including unstable angina, acute myocardial 
infarction, and or cardiac conduction issues within 6 months of the date of study drug 
administration. 
d. Current New York Heart Association Class II to IV congestive heart failure or 
uncontrolled arrhythmia. 
3. Inadequate hematologic function defined as follows (as determined by local laboratory): 
a. ANC < 1.5× 109/L. 
b. Platelet count < 100 × 109/L. 
4. Severely impaired liver function (Child-Pugh Class C) or ALT or AST ≥ 2 × ULN on 
repeated assessment. 
5. Impaired renal function with estimated creatinine clearance less than 45 mL/min. 


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6. Anti-phospholipid antibodies positive or elevated anti-streptolysin antibodies. 
7. Hepatitis B (HBV) or hepatitis C (HCV) infection:  Participants who are positive for the 
hepatitis B surface antibody or hepatitis B core antibody will be eligible if they are 
negative for HBV-DNA; these participants should be considered for prophylactic 
antiviral therapy.  Participants who are positive for the anti-HCV antibody will be eligible 
if they are negative for HCV-RNA. 
8. Known HIV infection or positivity on immunoassay.  Note:  HIV screening test is 
optional for participants enrolled in the United States, but participants with known HIV 
infection enrolled in the United States will be excluded. 
9. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically 
meaningful.  Participants with screening QTc interval > 470 milliseconds for males and 
> 480 milliseconds for females (corrected by Fridericia) are excluded.  In the event that a 
single QTcF is > 470 milliseconds for males or > 480 milliseconds for females, the 
participant may enroll if the average QTcF for 3 ECGs is < 470 milliseconds for males or 
< 480 milliseconds for females. 
10. Use of the following medications:  
a. Treatment with rituximab within 3 months of the baseline visit. 
b. Use of immunosuppressive therapy within 28 days of the baseline visit.  
Immunosuppressive therapy includes, but is not limited to, cyclosporine A, 
tacrolimus, or high-dose corticosteroids.  Participants receiving corticosteroids must 
be at a dose level ≤ 20 mg/day (prednisone or equivalent corticosteroid dose) within 
14 days of the baseline visit. 
c. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, 
or antiviral treatment or exposure to a live vaccine within 28 days of the baseline 
visit. 
d. Use or expected use during the study of any prohibited medications, including potent 
CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) 
before the baseline visit. 
e. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) 
before the baseline visit with another investigational medication, or current 
enrollment in another investigational drug protocol. 
f. Use of any prohibited medications (see Section 6.7.3) within 14 days or 5 half-lives 
(whichever is longer) before the baseline visit. 
11. Known hypersensitivity or severe reaction to INCB050465 or its excipients (IB). 
12. Unable to swallow oral medication, malabsorption syndrome, disease significantly 
affecting gastrointestinal function, total resection of the stomach or small bowel, 
ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel 
obstruction.  
13. Current alcohol or drug use that, in the opinion of the investigator, will interfere with the 
participant's ability to comply with the dose regimen and study evaluations. 


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14. Participants who, in the opinion of the investigator, are unable or unlikely to comply with 
the dose regimen and study evaluations. 
15. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits; 
pose a significant risk to the participant; or interfere with interpretation of study data.  
5.3. 
Lifestyle Considerations 
Not applicable. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled into the study.  A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated Standards 
of Reporting Trials publishing requirements and to respond to queries from regulatory 
authorities.  Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAEs. 
Participants may be rescreened for the study if there is a change in their medical status that 
would affect their eligibility such as discontinuation of a prohibited medication or short 
intercurrent illness that has resolved.  Clinical laboratory abnormalities detected at screening 
may be repeated as part of screening and should not be considered criteria for re-screening. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
The study will use an IRT system for management of study enrollment.  The system will assign 
the participant study number, track participant visits, and manage of study drug inventory.  See 
Table 3 for study drug information. 
Extension Period: 
Participants will be dispensed the appropriate amount of study drug until their next scheduled 
visit.  Participants will continue to self-administer INCB050465 per the investigator's instruction 
with study drug compliance continuing to be assessed. 
Table 3: 
Study Drug Information 
Study Drug Name: 
INCB050465 
Dosage Formulation: 
Tablet 
Unit Dose Strength(s)/Dosage 
Level(s): 
1 mg and 2.5 mg 
Route of Administration: 
Oral 
Administration Instructions: 
1 tablet QD. 
INCB050465 will be taken orally with water without regard to food except on 
mornings of PK clinic visits (see Table 1 and Table 6). 
Participants should not take their dose at home when they have a PK visit. 
INCB050465 should be taken at approximately the same time each day. 
Packaging and Labeling: 
INCB050465 will be provided as 1 mg and 2.5 mg tablets packaged in 
high-density polyethylene bottles.  No preparation is required. 
All Incyte investigational product labels will be in the local language and will 
comply with the legal requirements of each country. 
Storage: 
Bottles of INCB050465 should be stored at ambient conditions (15°C-30°C or 
59°F-86°F). 
6.2. 
Instruction to Participants for Handling Study Drug 
Participants must be instructed in the handling of INCB050465 as follows: 
• Store study drug at room temperature (15°C-30°C or 59°F-86°F). 
• Only remove the number of tablets needed from the study drug bottle at the time of 
administration. 
• Do not remove doses in advance of the next scheduled administration. 
• Make every effort to take doses on schedule. 
• Report any missed doses. 
• Keep study drug in a safe place and out of reach of children. 
• Bring all used and unused study drug bottles to the site at each visit. 


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6.3. 
Preparation, Handling, and Accountability 
The investigator is responsible for drug accountability at the study site; however, some of the 
drug accountability duties may be assigned to an appropriate pharmacist or other designee.  
Inventory and accountability records must be maintained and readily available for inspection by 
the study monitor and are open to inspection at any time by any applicable regulatory authorities.  
The investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including pill or unit 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 standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site's standard 
operating procedure. 
6.4. 
Measures to Minimize Bias:  Randomization and Blinding 
Not applicable. 
6.5. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with study drug will be calculated by the sponsor based on the drug accountability 
documented by the site staff and monitored by the sponsor/designee (tablet counts).  Participants 
will be instructed to bring all study drugs with them to the study visits in order for site personnel 
to conduct tablet counts to assess study drug accountability.  The drug accountability 
documentation will be used by the sponsor to calculate treatment compliance. 


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6.6. 
Dose Modifications  
6.6.1. 
Criteria and Procedures for Dose Increases of Study Drug 
At Week 6, participants may be eligible for a dose increase.  Due to the need to receive clinical 
laboratory results and to consult with the sponsor as needed prior to increasing the dose, 
investigators may implement the dose increase either at an unscheduled drug dispensing visit 
between the Week 6 and Week 8 visits or at the scheduled Week 8 visit.  Any other requests for 
dose increase at alternate times may be considered on an individual basis in consultation with the 
sponsor.  Individual participants in Cohort 1 may increase from INCB050465 1 mg QD to 
2.5 mg QD with sponsor preapproval in the following circumstances, provided that protocol 
eligibility criteria are met at the time of escalation: 
• Dose increase criteria, defined as the following: 
− The participant continues to require transfusions by the Week 6 visit or 
− The participant does not attain a meaningful clinical response (at least a 
stabilization ≥ 2 g/dL increase in hemoglobin from baseline to Week 6). 
• The investigator determines there has not been a clinically meaningful response in 
hemoglobin and other hemolysis parameters. 
• The participant is otherwise tolerating the current dose and has not had any 
drug-related adverse events. 
• In the opinion of the investigator, the participant does not have a concurrent condition 
or circumstance that would complicate the dose escalation or PK sampling, or pose an 
increased risk. 
6.6.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Individual decisions regarding dose interruptions and reductions should be made using clinical 
judgment and in consultation with the sponsor's medical monitor, taking into account relatedness 
of the AE to the study drug and the participant's underlying condition. 
In all cases, investigators may employ any measures or concomitant medications, after 
discussion with the sponsor (whenever possible), necessary to optimally treat the participant. 
Adverse events that have a clear alternative explanation or transient (≤ 72 hours) or abnormal 
laboratory values without associated clinically significant signs or symptoms may be exempt 
from dose reduction guidelines.  If there are any tolerability issues in individual participants who 
received 2.5 mg in Cohort 1, the dose may be decreased to 1 mg.  For Cohort 2, dose reduction 
from 2.5 mg QD to 1 mg QD may occur if there are SAEs or AEs that are attributed to be related 
to INCB050465 (see Table 4 for the guidelines).  Dose reduction may occur at any time during 
the 12 weeks of administration; however, consultation between the investigator and sponsor 
should occur if dose reduction is being considered for any participant. 


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Table 4: 
Guidelines for Interruption and Restarting of Study Drug 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
AST and/or ALT is > 3.0 × ULN. 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until the 
toxicity has resolved to ≤ Grade 1 except by approval of the 
medical monitor. 
Step 2:  Restart study drug at same dose.  If assessed as related 
to study drug, restart study drug at 1 mg if receiving 2.5 mg and 
monitor as clinically indicated. 
Hematology 
• ANC ≤ 1.0 × 109/L, unless due to 
underlying disease. 
• Platelet count is 50 × 109/L to 
< 75 × 109/L, unless due to underlying 
disease. 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until the 
toxicity has resolved to ≤ Grade 1 or pretherapy baseline. 
Step 2:  Restart study drug at same dose and monitor as 
clinically indicated. 
• Grade 4 ANC (< 0.5 × 109/L). 
• ≥ Grade 3 ANC with an oral temperature 
of at least 38.5°C OR with ≥ Grade 3 
infection. 
• Platelet count is < 50 × 109/L. 
Discontinue study drug administration and follow-up per 
Protocol.  (Exceptions require approval of sponsor.) 
Other toxicities 
Any Grade 1 or Grade 2 toxicity. 
Continue study drug 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 study drug up to 2 weeks (14 days), until 
toxicity resolves to ≤ Grade 1. 
Step 2:  Restart study drug at same dose.  If assessed as related 
to study drug, restart study drug at 1 mg if receiving 2.5 mg and 
monitor as clinically indicated. 
Any recurrent Grade 3 toxicity after dose 
reduction. 
Discontinue study drug administration and follow-up per 
Protocol.  (Exceptions require approval of sponsor.) 
Any other Grade 4 toxicity. 
Discontinue study drug administration and follow-up per 
Protocol. 
6.6.3. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will be presumed 
to be related to study drug treatment and will require that the study drug be permanently 
discontinued.  Unacceptable toxicity is defined as follows: 
• Occurrence of an AE that is related to treatment with the study drug that, in the 
judgment of the investigator or the sponsor's medical monitor, compromises the 
participant's ability to continue study-specific procedures or is considered to not be in 
the participant's best interest. 
6.7. 
Concomitant Medications and Procedures 
All concomitant medications and treatments must be recorded in the eCRF.  Any prior 
medication received up to 30 days before the baseline visit will be recorded in the eCRF.  


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Concomitant treatments and/or procedures that are required to manage a participant's medical 
condition during the study will also be recorded in the eCRF. 
6.7.1. 
Permitted Medications and Procedures 
6.7.1.1. 
Pneumocystis jirovecii Pneumonia Prophylaxis 
All participants will receive a PJP prophylaxis regimen determined by the investigator.  
Examples of standard PJP prophylaxis therapies include trimethoprim-sulfamethoxazole, 
atovaquone, dapsone with or without pyrimethamine, and pentamidine (National Comprehensive 
Cancer Network 2017).  Due to reports of cross-sensitivity between sulfonamides and dapsone, 
all participants who have a known or suspected allergy to sulfonamides must receive either 
inhaled pentamidine or atovaquone for PJP prophylaxis.  If inhaled pentamidine or atovaquone 
are not available, the participants should not be enrolled.  Prophylaxis should be given while 
participants are receiving study drug and should continue for at least 2 to 6 months after the last 
dose of study drug. 
The prophylactic agents will be obtained from commercial supplies and will be reimbursed by 
the sponsor.  Investigators are responsible for ensuring that participants receive commercially 
available supplies of the selected prophylactic agents as required per Protocol.  The sponsor may 
provide prophylactic agents where required by applicable law or regulation or under other 
limited circumstances when a participant may not otherwise have access to these therapies.  The 
contents of the label will be in accordance with all applicable regulatory requirements.  Further 
details are available in the Pharmacy Manual. 
6.7.1.2. 
Folic Acid, Vitamin B12, or Iron Deficiencies 
Participants who are noted to be deficient in folic acid, vitamin B12, or iron should have 
replacement determined by the investigator as per current standard of care. 
6.7.2. 
Restricted Medications and Procedures 
Restricted medications and procedures include the following: 
• Use of systemic corticosteroid doses ≤ 20 mg/day prednisone (or equivalent) is 
permitted from the 14 days before the baseline visit through the EOT visit.  
Prednisone (or equivalent) should remain stable and may be tapered if the investigator 
considers it appropriate based on the participant's clinical response. 
• Short courses of systemic corticosteroid doses > 20 mg/day prednisone (or 
equivalent) are permitted (eg, for the treatment of severe or life-threatening AEs) but 
are otherwise discouraged from the screening visit through the EOT visit. 
• Use of weak or moderate inducers or inhibitors of CYP3A4 or P-glycoprotein is 
discouraged, and investigators should seek other options where possible. 
6.7.3. 
Prohibited Medications and Procedures 
Prohibited medications and procedures include the following: 
• Use of potent inducers and inhibitors of CYP3A4 is prohibited, with the exception of 
topical ketoconazole because of its low bioavailability. 


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• Apart from the study treatments, the use of any medications as described in the 
exclusion criteria (see Section 5.2) through the safety follow-up is prohibited. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
The decision to discontinue study drug will not constitute study completion.  In the event that 
study drug is discontinued, the treatment period will be considered complete, and the follow-up 
period will begin. 
7.1.1. 
Permanent Discontinuation of Study Treatment 
Participants must be withdrawn from study drug for the following reasons: 
• The participant becomes pregnant. 
• Consent is withdrawn. 
Note:  Consent withdrawn means that the participant can no longer be followed.  
Participants may choose to discontinue study drug and remain in the study to be 
followed. 
• 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 drug 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 the study. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's opinion, the sponsor should be consulted for instruction on handling 
the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study drug, the EOT visit 
should be conducted.  Reasonable efforts should be made to have the participant return for 
follow-up visits.  These visits are described in Table 1.  The last date of the last dose of study 
drug and the reason for discontinuation of study drug will be recorded in the eCRF. 


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If a participant is discontinued from study drug: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal must be documented in the participant's medical record 
and in the eCRF. 
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the IRT system. 
• Participants must be followed for safety until the time of the follow-up visits or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study drug and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study drug 
but continuing in the follow-up period of the study for safety/efficacy assessments (see 
Section 8.9). 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his or 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 or she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
See Table 1 for data to be collected at the time of study discontinuation and follow-up and for 
any further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or 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 


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or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, he or she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
Participants transitioning into the extension period of the study will have efficacy and safety 
assessments performed in accordance with the standard of care at each investigational site for the 
participant's condition and monitoring at the investigator's discretion and not less than every 8 to 
12 weeks (see Table 2).  Unless noted below, procedures listed in this section are not required to 
be performed in the extension period of the study. 
8.1.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained from the study participant before conducting any 
study-specific procedures using an ICF approved by the local IRB/IEC that contains all elements 
required by ICH E6, and describes the nature, scope, and possible consequences of the study in a 
form understandable to the study participant.  Local and institutional guidelines for ICF content 
and administration must be followed; the original signed ICF must be retained by the 
investigator, and a copy of the signed ICF must be provided to the study participant.  The 
informed consent process for each participant must be documented in writing within the source 
documentation. 
8.1.2. 
Screening Procedures 
Screening is the interval between the signing of the ICF and the day that the participant is 
administrated the first dose of study drug (Day 1).  Informed consent must be obtained before 
performing any study specific procedures.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
All 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.  Tests with results that fail eligibility 
requirements may be repeated during screening if the investigator believes the results to be in 
error.  For screening assessments that are repeated, the most recent available result before 
treatment will be used to determine eligibility and entered into the eCRF.  Treatment should start 
as soon as possible.  Additionally, a participant who fails screening may repeat the screening 
process if the investigator believes there has been a change in eligibility status (eg, after recovery 
from an infection). 


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8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact IRT to obtain the 
participant ID number during screening.  IRT will be contacted at each regular study visit to 
update the study drug supply.  Additional details are provided in the IRT Manual. 
8.1.4. 
Demography and Medical History 
8.1.4.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected at screening. 
8.1.4.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and medication history, including date of diagnosis of AIHA, 
serological test, rituximab treatment history and other details related to the disease under study, 
will be collected at screening.  
8.1.5. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine participant 
eligibility.  All concomitant medications and measures must be recorded in the eCRF, and any 
medication received or procedure performed within screening period before enrollment and up to 
the end of the follow-up period (see Table 1) will be recorded in the eCRF.  The medication 
record will be maintained after signing the ICF to document concomitant medications, including 
any changes to the dose or regimen.  Concomitant medications include any prescription, over-
the-counter, or natural/herbal preparations taken or administered during the study period.  
Concomitant treatments and/or procedures that are required to manage a participant's medical 
condition during the study will also be recorded in the eCRF. 
Extension Period 
Use of concomitant medications should be monitored as described in Table 2 for participants in 
the extension period of the study to verify that participants are not taking any concomitant 
medication prohibited per Section 6.7.3. 
8.2. 
Efficacy Assessments 
Efficacy assessments are conducted at the visits noted in Table 1. 
8.2.1. 
Hemoglobin Level, Hemolysis Markers, Direct Antiglobulin Test, and 
Complement Assessment 
Participants will undergo hematology, serum chemistries, hemolysis markers, DAT, and 
complement assessment (CH50, C3, and C4) to evaluate type of AIHA diagnosis and disease 
status (see Table 5).   
Note:  For the purpose of participants' enrollment eligibility and safety and efficacy assessments, 
blood samples for hematology panels, including CBC and differential count, will sent to a local 
laboratory for analysis (see Table 5).  All other Protocol-required blood samples aside from 
hematology panels will be sent to the central laboratory for analysis.  Local laboratory 


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hematology panel results and central laboratory results for all other assessments will be entered 
into the eCRF. 
8.2.2. 
Direct Antiglobulin Test and Cold Agglutinin Test 
Direct antiglobulin tests for the detection of IgG and complement bound to RBCs will be 
performed at a central laboratory or local laboratory at screening visit (see Table 1 and 
Section 5.1).  If DAT was performed within 28 days before screening at the study site, the 
participant does not need to retest DAT at the screening visit.  However, if DAT was performed 
greater than 28 days before screening or performed in a location other than the study site, the 
sponsor will review and make a recommendation if retesting DAT is required. 
 
 
 
 
 
8.3. 
Safety Assessments 
Safety assessments are conducted at the visits noted in Table 1 and Table 2. 
Extension Period 
Adverse events leading to treatment discontinuation, all AEs suspected to be TEAEs and all 
SAEs regardless of causality relationship will be reported on the AE eCRF during the extension 
period. 
8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF.  Participants will 
be instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, participants will be asked general, 
nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and eCRFs regardless of the assumption of a causal 
relationship with the study drug.  The definition, reporting, and recording requirements for AEs 
are described in Section 9. 
8.3.2. 
Physical Examinations 
Abnormalities that are considered clinical significant in the judgment of the investigator are to be 
reported as AEs.  
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. 
8.3.2.1. 
Comprehensive Physical Examination 
At screening, Day 1, and EOS, a comprehensive physical examination should be conducted.  The 
comprehensive physical examination will include assessment(s) of the following organ or body 


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systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; abdomen 
(liver, spleen); extremities; and lymph nodes; as well as a brief neurological examination.  
Height and body weight will be assessed only at the Day 1 visit. 
8.3.2.2. 
Targeted Physical Examination 
At all other study visits except at screening, Day 1, and EOS, the targeted physical examination 
will be a symptom-directed evaluation.  The targeted physical examination will include 
assessment(s) of the body systems or organs, as indicated by participant symptoms, AEs, or other 
findings. 
8.3.3. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the participant in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest.  Clinically notable abnormalities that are considered 
clinically significant in the judgment of the investigator are to be reported as AEs. 
8.3.4. 
Electrocardiograms 
All 12-lead ECGs will be performed with the participant in a recumbent or semirecumbent 
position after 5 minutes of rest.  The 12-lead ECGs will be performed locally and be interpreted 
by the investigator at the site and used for immediate participant management.  Interpretation of 
the 12-lead ECG will be used to determine eligibility at screening.  An additional ECG will be 
performed at Week 2, Week 8, and the EOT visit (Week 12) or earlier, if the participant 
discontinues treatment).  Throughout the study, a 12-lead ECG may be conducted if associated 
with an AE or other signs or symptoms.  The decision to include or exclude a participant or 
discontinue his or her participation in the study based on an ECG flagged as "Abnormal, 
Clinically Significant" is the responsibility of the investigator, in consultation with the sponsor's 
medical monitor, as appropriate.  Clinically notable abnormalities that are considered clinically 
significant in the judgment of the investigator are to be reported as AEs. 
8.3.5. 
Laboratory Assessments 
Blood draws for laboratory assessments will occur at study visits indicated in the schedule of 
assessments (see Table 1).  Specific laboratory assessments are provided in Table 5.  Blood may 
be drawn in pediatric tubes to minimize blood loss from phlebotomy. 
All laboratory assessments will be performed at a central laboratory, with the exception of the 
following, in which case the investigative site laboratory or an accredited local laboratory may 
be used: 
• Hematology panels (see Table 5), including CBC and differential count, will be sent 
to a local laboratory for analysis (see Section 8.2.1). 
• For local laboratory assessments deemed necessary by the investigator for participant 
management (ie, dose modification, SAE, or COVID-19 restrictions affecting travel 
to the site for extension visits).  Note:  Such assessment data and reference ranges 
must be recorded in the participant's eCRF. 


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Extension Period: 
Laboratory assessments (see Table 5) including hematology panels and hemolysis markers need 
to be performed in accordance with standard of care at each investigational site for the 
participant's condition and monitoring at the investigator's discretion and not less than every 8 to 
12 weeks.  Any other clinical lab monitoring should be done per the investigator's judgment for 
monitoring any other clinical conditions.  Laboratory results will need to be documented in the 
eCRF. 
8.3.5.1. 
Chemistry and Hematology 
All chemistry assessments (see Table 1 and Table 5) will be performed from blood samples 
collected using institutional best practices (refer to the Laboratory Manual).  Hematology panels 
will be analyzed by local laboratories. 
8.3.5.2. 
Vitamin B12 and Folic Acid 
Vitamin B12 and folic acid will be tested at screening.  Participants who are deficient in either 
folic acid or vitamin B12 will have replacement determined by the investigator as per standard of 
care. 
8.3.5.3. 
Iron Clinical Assessment 
All participants will have iron assessments (iron, total iron-binding capacity, ferritin) at 
screening.  If elevated ferritin levels are present (> 200 ng/mL in women or > 250 ng/mL in 
men), additional testing and follow-up recommendations will be provided to the investigator in 
consultation with the medical monitor.  These recommendations will include evaluation of the 
liver (serum transaminases and MRI) and for other causes of iron overload as indicated by the 
participant's medical history. 
Iron assessments will be repeated during the study at Week 6 if the participant has ongoing 
transfusion requirements during the study. 
8.3.5.4. 
Urinalysis 
Urinalysis will be performed by a central laboratory at screening and EOT or if the participant 
discontinues treatment (see Table 1 and Table 5). 
8.3.5.5. 
Coagulation 
A D-dimer assessment (see Table 5) will be performed from blood samples collected using 
institutional best practices (refer to the Laboratory Manual). 


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8.3.5.6. 
Pregnancy Testing 
A serum pregnancy test will be required for all women of childbearing potential during 
screening.  Urine pregnancy tests will be conducted as outlined in Table 1, as medically 
indicated, or per country-specific requirement.  Urine pregnancy tests will be done locally.  If a 
urine pregnancy test is positive, the results should be confirmed with a serum pregnancy test, 
which may be performed locally. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
8.3.5.7. 
Serology 
Anti-Streptolysin antibody, anti-phospholipid antibody, hepatitis, and HIV tests will be 
performed at a central laboratory (see Table 1).  Hepatitis and HIV tests will be conducted during 
the screening period.  If participants are positive for active disease, they should not be enrolled 
per exclusion criteria.  Note:  HIV screening test is optional for participants enrolled in the 
United States, but participants with known HIV infection enrolled in the United States will be 
excluded. 


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Table 5: 
Required Laboratory Analytes 
Serum Chemistries 
Hematologya,b 
Urinalysis With Microscopic 
Examination 
Screening Serology 
Coagulation 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Bicarbonate 
Blood urea nitrogen  
Calcium 
Chloride  
Creatinine 
Ferritin (screening visit and repeat at 
Week 6 if participant has ongoing 
transfusion requirements) 
Folic acid (screening visit) 
Glucose 
Haptoglobin 
Iron (screening visit and repeat at 
Week 6 if participant has ongoing 
transfusion requirements) 
LDH 
Phosphate 
Potassium 
Sodium 
Total bilirubinc 
Total protein 
Total iron-binding capacity 
(screening visit and repeat at Week 6 
if participant has ongoing transfusion 
requirements) 
Uric acid 
CBC, including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• RBC count 
• WBC count 
 
Differential count, including: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
 
Absolute values must be 
provided for WBC differential 
laboratory results: 
• Lymphocytes 
• Neutrophils 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen 
Hepatitis B surface antigen 
Hepatitis B surface antibody 
Hepatitis B core antibody 
Hepatitis C virus antibody 
Hepatitis C virus-RNA (only 
performed if antibody positive) 
HIV antibody 
Anti-streptolysin antibody 
Anti-phospholipid antibody  
D-Dimer 
Hemolysis Markersb 
Haptoglobin (will be measured in serum chemistry panel)  
LDH (will be measured in serum chemistry panel) 
Reticulocyte count (will be measured in hematology panel) 
Hemoglobin (will be measured in hematology panel) 
Total bilirubinc (will be measured in serum chemistry panel) 
DAT and Cold Agglutinin Test 
DAT for IgG and C3d* 
Cold agglutinin levels* 
* Baseline and EOT 
Other Assessments 
Urinalysis 
FSH 
Urine pregnancy test (at site) 
Serum pregnancy test 
Complement assessment (CH50, C3, and C4)* 
* Baseline and EOT 
Vitamin B12 (screening visit) 
Note:  Additional tests may be required, as agreed upon by the investigator and sponsor, based on emerging safety data. 
a Hematology parameters will be managed in real-time by local laboratory assessments. 
b Hematology panels and hemolysis markers need to be performed in accordance with the standard of care at each investigational site for the participant's condition and monitoring 
at the investigator’s discretion. 
c If total bilirubin is elevated above ULN, direct/indirect bilirubin will be measured. 


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8.4. 
Pharmacokinetic Assessments 
8.4.1. 
Blood Sample Collection 
Pharmacokinetic samples will be obtained at the visits and collection times shown (see Table 6) 
for all participants receiving INCB050465. 
The exact date and time of the PK blood draws, the date and time of the last dose of study drug 
preceding the blood draw (if applicable), and the time of the previous meal will be recorded in 
the eCRF. 
Instructions for sample preparation and shipping will be provided in the Laboratory Manual.  
Participants will receive reminder cards in advance of the study visit providing instruction to 
hold the dose of study drug on the day of the visit and a place to record the time of the prior dose 
of study drug and time of the most recent meal or snack consumed. 
Pharmacokinetic sampling will occur on 4 separate days.  If the PK plasma sample collection is 
missed for a visit, then the sample collection should be performed at the next visit.  On the PK 
visit days, participants must refrain from taking study drug before arriving at the research unit.  
Participants should not have consumed any food within 4 hours before arriving at the research 
unit.  A predose (trough) PK sample should be collected at each of the PK visits.  Following 
collection of the predose PK sample, INCB050465 will be administered, and subsequent timed 
samples will be collected (see Table 6).  The participants may have a light meal following the 
1 hour postdose PK sampling at Weeks 2 and 8. 
Table 6: 
Sample Collection Time Windows for Pharmacokinetic Assessments for 
INCB050465 
Study Visit 
Timing of Sample Relative to Study Drug 
Predose 
1 h ± 10 min 
2 h ± 10 min 
4 h ± 30 min 
Week 1 
X 
 
 
 
Week 2a 
X 
X 
X 
X 
Week 8a 
X 
X 
X 
X 
Week 12 
X 
 
 
 
Note:  In case of dose interruption, the new timing of PK sampling should be discussed with sponsor. 
a No food intake 4 hours predose and 1 hour postdose on Weeks 2 and 8.  The participants may have a light meal following the 
1 hour postdose PK sampling at Weeks 2 and 8. 
 
 
 
 
 
 
 
 
 
 


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8.6. 
Unscheduled Visits 
Unscheduled visits may be held at any time at the investigator's discretion, and appropriate 
clinical and laboratory measurements performed based on AEs or other findings.   
8.7. 
End of Treatment 
When the participant permanently discontinues study drug, then the EOT visit should be 
conducted.  If the EOT visit coincides with a regular study visit, the EOT evaluations will 
supersede those of that scheduled visit, and the data should be entered in the EOT visit in the 
eCRF.  The participant should be encouraged to return for the safety follow-up visits. 
8.8. 
Extension Period 
In the extension period of the study, participants will be required to visit the clinic per standard 
of care but no less frequently than every 8 to 12 weeks for dispensing of study drug (see 
Table 2).  Safety assessments (including laboratory analytes) that are consistent with the standard 
of care for the participant’s condition should be performed per the investigator’s discretion using 
a local laboratory (see Section 8.3.5).  All SAEs, AEs leading to treatment discontinuation, and 
TEAEs will continue to be collected by the sponsor.  Disease status will continue to be 
monitored by laboratory tests including hematology panels and hemolysis markers as appropriate 
at a frequency consistent with the standard of care for the participant's disease. 
8.9. 
Follow-Up 
8.9.1. 
Safety Follow-Up 
For participants who do not enter extension period, the safety follow-up period is the interval 
between the EOT visit (Week 12) and the scheduled follow-up visits, which should occur 30 to 
35 days after the EOT visit (or after the last dose of study drug if the EOT visit was not 
performed).  Adverse events and SAEs must be reported up until at least 30 days after the last 
dose of study drug, the date of the follow-up visits, 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 visits and report any AEs that may occur during this period.  
If the participant cannot return to the site for the safety follow-up visits, the participant should be 
contacted by telephone for assessment of AEs and SAEs.  Sites should be instructed to document 
this contact in the source. 
8.9.2. 
Additional Follow-Up Period 
Participants will have additional follow-up assessments for 12 weeks (3 months) after EOT.  
Safety follow-up is included in this 12-week (3 months) additional follow-up period.  The 
following information will be collected: 
• The start date of new AIHA therapy. 
• Type of therapy. 
• Marker for hemolysis. 


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If the participant withdraws consent for study drug but continues in the follow-up period of the 
study, the above information will also be collected. 
The site will also use continuing participant records to supply data on subsequent treatment 
regimens and disease activities in the eCRF. 
For participants who receive study drug in the extension period, the safety follow-up is included 
in the 12-week (3-month) additional follow-up period and should occur 30 to 35 days after the 
last dose of study drug. 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Adverse Events 
9.1.1. 
Definitions 
For the purposes of this Protocol, an AE is defined as any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug related, that occurs 
after a participant provides informed consent.  Abnormal laboratory values or test results 
occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, 
are considered clinically meaningful, require therapy, or require changes in the study drug. 
Anemia and transfusions should not be reported as AEs unless it represents a clinically 
meaningful decrease from baseline in hemoglobin.   
9.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 30 days after the last dose of study.  Adverse events 
(including laboratory abnormalities that constitute AEs) should be described using a diagnosis 
whenever possible rather than by individual underlying signs and symptoms.  When a clear 
diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
The term "disease progression" should be recorded as an AE/SAE only if there are no other 
identifiable AEs/SAEs associated with the disease progression at the time of reporting.  For 
events associated with disease progression, the relevant signs and symptoms should be reported 
using a diagnosis whenever possible rather than individual underlying signs and symptoms.  
When a clear diagnosis cannot be identified, each sign or symptom should be reported as a 
separate AE.  If the events resulting from disease progression meet the criteria for an SAE 
(eg, resulted in hospitalization, a life-threatening event, or death), the specific event(s) should be 
reported as an SAE(s) as described in Section 9.3.2.  In both cases (ie, AEs or SAEs related to 
disease progression), it should be indicated that each event (reported as a diagnosis or as signs 
and symptoms) is related to disease progression on the Adverse Events form of the eCRF.  


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The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 4.  The CTCAE v5.0 
severity of Grade 5 will not be used; AEs resulting in death will be graded accordingly using 
Grades 1 through 4 and have the outcome noted as fatal.  If an event is not classified by CTCAE, 
the severity of the AE will be graded according to the scale below to estimate the grade of 
severity: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate activities of daily living. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
The occurrence of AEs should be sought by nondirective questioning of the participant during 
the screening process after signing the ICF and at each visit during the study.  Adverse events 
may also be detected when they are volunteered by the participant during the screening process 
or between visits, or through physical examination, laboratory test, or other assessments.  To the 
extent possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 4). 
• Whether there is at least a reasonable possibility that the AE is related to the study 
drug:  suspected (yes) or not suspected (no). 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, 
recovering/resolving, recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per SAE definition provided in Section 9.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements (see Section 9.3.2). 
All AEs should be treated appropriately.  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event form and the treatment should 
be specified on the Prior/Concomitant Medications or Procedures and Non-Drug Therapy form 
in the eCRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 


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When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves.  For example, 
2 separate AEs will be reported if a participant has Grade 1 diarrhea, meeting the definition of an 
AE, that lasts for 3 days before worsening to a Grade 3 severity.  The Grade 1 event will be 
reported as an AE with a start date equal to the day the event met the Grade 1 AE definition and 
a stop date equal to the day that the event increased in severity from Grade 1 to Grade 3.  The 
Grade 3 event will also be reported as an AE, with the start date equal to the day the event 
changed in intensity from Grade 1 to Grade 3 and a stop date equal to the day that the event 
either changed severity again or resolved. 
9.2. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug) should be recorded on the Adverse Event form in the eCRF.  Whenever possible, a 
diagnosis rather than a symptom should be provided (eg, "anemia" instead of "low hemoglobin").  
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or an adequate explanation of the abnormality is found.  When an abnormal 
laboratory test result corresponds to a sign or symptom of a previously reported AE, it is not 
necessary to separately record the laboratory test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 AE does not automatically indicate an SAE unless it meets the definition of 
serious, as defined in Section 9.3.1.  A dose modification for the laboratory abnormality may be 
required (see Section 6.6) and should not contribute to the designation of a laboratory test 
abnormality as an SAE. 
9.3. 
Serious Adverse Events 
9.3.1. 
Definitions 
An SAE is defined as an event that meets at least 1 of the following criteria: 
• Is fatal or life-threatening. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− A routine treatment or monitoring of the studied indication not associated with 
any deterioration in condition. 
− An elective surgery or preplanned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since signing the 
ICF. 
− A treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE and not resulting in hospital admission. 
− Any social reasons and respite care, in the absence of any deterioration in the 
participant's general condition. 


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• Results in persistent or significant disability, incapacity, or a substantial disruption of 
a person's ability to conduct normal life functions. 
• Constitutes a congenital anomaly or birth defect. 
• Is considered to be an important medical event or a medically significant event that 
may not result in death, be immediately life-threatening, or require hospitalization but 
may be considered serious when, based on appropriate medical judgment, the event 
may jeopardize the participant or may require medical or surgical intervention to 
prevent 1 of the outcomes listed above. 
9.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drug(s) or study 
procedure or disease progression), occurring after the participant has signed the ICF through the 
last study visit (or 30 days after the last dose of study drug, whichever is later) must be reported 
to the sponsor (or designee) within 24 hours of learning of its occurrence, unless otherwise 
specified by the Protocol.  Any SAEs occurring more than 30 days after the last dose of study 
drug should be reported to the sponsor or its designee only if the investigator suspects a causal 
relationship to the study drug.   
Information about all SAEs is collected and recorded on the Adverse Event form of the eCRF.  
The investigator must assess and record the causal relationship of each SAE to the study drug.  
The investigator must also complete the Incyte Serious Adverse Event Report Form, in English, 
and send the completed and signed form to the sponsor or designee within 24 hours of becoming 
aware of the SAE.  The investigator must provide a causality assessment, that is, assess whether 
there is at least a reasonable possibility that the SAE is related to the study drug:  suspected (yes) 
or not suspected (no).  Refer to the Incyte Reference Guide for Completing the Serious Adverse 
Event Report Form. 
The contact information of the sponsor's study-specific representatives is listed in the 
Investigator Manual provided to each site.  The original copy of the SAE Report Form and the 
confirmation sheet must be kept at the study site. 
Investigational site personnel must report any new information regarding the SAE within 
24 hours of becoming aware of the information in the same manner that the initial SAE Report 
Form was sent.  Follow-up information is recorded on an amended or new SAE Report Form, 
with an indication that it is follow-up to the previously reported SAE and the date of the original 
report.  The follow-up report should include information that was not provided on the previous 
SAE Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose reduced, interrupted, or 
discontinued), or 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. 


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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 IN 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. 
9.4. 
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 participant safety: 
• The study drug must be discontinued immediately. 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up should be conducted for each pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy form 
and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up information 
should be recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the 
first well-baby visit or the duration specified in local regulations, whichever is later.  Refer to the 
Incyte Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy must be recorded on the SAE report form and 
submitted to the sponsor or designee. 
9.5. 
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 INs.  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 and participants will resign the ICF. 
9.6. 
Data Monitoring Committee 
There will be no formal Data Monitoring Committee.  However, a Safety Review Committee, 
which will include the sponsor's medical monitor, pharmacovigilance representative, and 
statistician, as well as the investigators, will conduct meetings via teleconference on a regular 
basis to review emerging safety and clinical response data and dose modifications.  
Recommendations from this committee may include the option to expand study of Cohort 1, 
pending review of the efficacy response and adverse event data. 


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If there is no clinical response (CR or PR) by Week 12 in the first cohort of 10 participants, 
including those who receive dose escalation to 2.5 mg, the study will be stopped for futility. 
9.7. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his or her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be reported as described in Section 9.1.2 of this Protocol. 
If the investigator is asked to return the product for investigation, he or she will return a copy of 
the product complaint communication with the product. 
10. 
STATISTICS 
10.1. 
Sample Size Determination 
The sample size was based on the precedent of other studies and was not based on statistical 
power calculations (Go et al 2017, Hill et al 2017, Lechner and Jäger 2010).  The study is not 
powered for statistical comparison of efficacy endpoints; the sample size is based on the 
demonstration of preliminary findings of clinical response.  It is anticipated that a sample size of 
approximately 25 participants will permit sufficient data to warrant further investigation.  Also, 
the sample size depends on the occurrence of safety findings.  Approximately 10 participants 
will be enrolled in Cohort 1, and approximately 15 in Cohort 2, which will provide > 89% 
chance of detecting at least 1 AE of interest (eg, colitis, exfoliative dermatitis, infections) if the 
underlying AE rate is 20% for Cohort 1 and > 96% chance for Cohort 2. 
10.2. 
Populations for Analysis 
Full Analysis Set:  All participants enrolled in the study who receive 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 efficacy and safety data. 
Pharmacokinetic/Pharmacodynamic Evaluable:  All participants who receive at least 1 dose 
of study drug and provide at least 1 postdose blood sample for PK or biomarker assessment.  The 
study pharmacokineticist will review data listings of participant administration and sample 
records to identify participants to be excluded from the analysis. 
10.3. 
Level of Significance 
No formal efficacy hypotheses will be tested. 


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10.4. 
Statistical Analyses 
Both efficacy and safety analyses will be conducted using the FAS.  The baseline value for a 
variable will be defined as the last nonmissing value for this variable before or on Day 1, unless 
otherwise specified. 
10.4.1. 
Efficacy Analyses 
10.4.1.1. Primary Efficacy Analyses 
Efficacy assessments of primary endpoint will be summarized using descriptive statistics at each 
visit.  For categorical measurements, summary statistics will include sample size, frequency, and 
percentages.  For continuous measurements, summary statistics will include sample size, mean, 
median, standard deviation, standard error of the mean, minimum, and maximum.  Summary 
statistics for continuous measures will be provided for baseline, the actual measurements at each 
visit, and the change and percentage change from baseline at each visit, if applicable.  All 
analyses will be implemented using SAS® software (SAS Institute Inc., Cary, NC; v9.1 or 
higher). 
10.4.1.2. Secondary Efficacy Analyses 
The secondary endpoints will be analyzed using the similar method as specified in the primary 
analysis. 
10.4.1.3. Other Efficacy Analyses 
The other efficacy endpoints will be summarized using descriptive statistics. 
10.4.2. 
Safety Analyses 
10.4.2.1. Adverse Events 
A treatment-emergent adverse event is any AE either reported for the first time or worsening of a 
pre-existing event after first dose of study drug.  Analysis of AEs will be limited to TEAEs, but 
data listings will include all AEs regardless of their timing to study drug administration.  Adverse 
events will be tabulated by the MedDRA preferred term and system organ class.  Severity of AEs 
will be based on the NCI CTCAE v5.0 using Grades 1 through 4. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated. 
10.4.2.2. Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 


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10.4.2.3. Vital Signs 
Descriptive statistics and mean change from baseline will be determined for vital signs (blood 
pressure, pulse, respiratory rate, and body temperature) at each assessment time. 
10.4.2.4. Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time. 
10.4.3. 
Pharmacokinetic Analysis 
The PK parameters of Cmax, tmax, Cmin, AUC0-t, and CL/F (INCB050465) will be calculated from 
the blood plasma concentrations of INCB050465 using standard noncompartmental 
(model-independent) PK methods.  Pharmacokinetic calculations will be performed, if 
appropriate, using commercial software such as WinNonlin®.  Nominal times will be used in all 
cases, except when the difference between the actual time and nominal time is greater than 
10 minutes for samples collected up to 4 hours after administration and greater than 30 minutes 
for samples collected more than 4 hours after administration; in these cases, actual time will be 
used for PK analysis.  Refer to Section 8.4 for a detailed list and description of the PK 
parameters. 
If there is a sufficient amount of plasma concentration data from this study, the data will be 
analyzed by standard population PK methods using appropriate software (eg, NONMEM). 
 
10.5. 
Interim Analysis 
Not applicable. 
10.6. 
Analyses for the Data Monitoring Committee 
Not applicable. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as defined in 
Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP consolidated guidelines; and 
local regulatory requirements as applicable to the study locations. 
The investigator will be responsible for: 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
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. 
• Obtaining informed consent and ensuring that the study participants' questions have 
been answered and the participants fully understand study procedures: 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the 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. 


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• Obtaining approval from the IRB/IEC before the start of the study and for any 
changes to the clinical study Protocol, important Protocol deviations, routine updates, 
and safety information in accordance with institutional requirements and local law. 
− The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements 
and with the policies and procedures established by the IRB/IEC. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
11.2. 
Data Management 
Data management will be performed in a validated database via an EDC system.  All data entry, 
verification, and validation will be performed in accordance with the current standard operating 
procedures of the Data Management Department at the sponsor or its designee.  The database 
will be authorized for lock once all defined procedures are completed. 
The investigator will be provided with access to an EDC system so that an eCRF can be 
completed for each participant.  Entries made in the eCRF must be verifiable against source 
documents; if updates to the database are not possible, any discrepancies should be explained 
and documented.  The investigator will be responsible for reviewing all data and eCRF entries, 
and will sign and date the designated forms in each participant's eCRF, verifying that the 
information is true and correct.  The investigator is responsible for the review and approval of all 
query responses. 


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Protocol deviations will be identified and recorded in the Protocol Deviation form of the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 
is appropriately documented, reported, and resolved in a timely manner in accordance with the 
plan's requirements. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
Participant names will not be supplied to the sponsor or its designee, if applicable.  Only the 
participant number and participant's initials (participant's initials will only be recorded if 
allowable by local regulations) will be recorded in the eCRF, where permitted; if the participant's 
name appears on any other document (eg, laboratory report), it must be obliterated on the copy of 
the document to be supplied to the sponsor or its designee.  Study findings stored on a computer 
will be stored in accordance with local data protection laws.  The participants will be informed 
that representatives of the sponsor or its designee, IRB or IEC, or regulatory authorities may 
inspect their medical records to verify the information collected, and that all personal 
information made available for inspection will be handled in strictest confidence and in 
accordance with local data protection laws. 
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. 


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11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his or her institution agree that the results of 
the study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 


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12. 
REFERENCES 
Artz AS, Somerfield MR, Feld JJ, et al. American Society of Clinical Oncology provisional 
clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic 
chemotherapy for treatment of malignant diseases. J Clin Oncol 2010;28:3199-3202. 
Barcellini W, Fattizzo B, Zaninoni A, et al. Clinical heterogeneity and predictors of outcome in 
primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood 
2014;124:2930-2936. 
Barcellini W. New insights in the pathogenesis of autoimmune hemolytic anemia. Transfus Med 
Hemother 2015;42:287-293. 
Berentsen S, Sundic T. Red blood cell destruction in autoimmune hemolytic anemia: role of 
complement and potential new targets for therapy. Biomed Res Int 2015;2015:1-11. 
Carson KR, Evens AM, Richey EA, et al. Progressive multifocal leukoencephalopathy after 
rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse 
Drug Events and Reports project. Blood 2009;113:4834-4840. 
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-1657. 
Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014. http://www.hma.eu/ctfg.html. Accessed September 1, 2107. 
Fung-Leung WP. Phosphoinositide 3-kinase delta (PI3Kδ) in leukocyte signaling and function. 
Cell Signal 2011;23:603-608. 
Go RS, Winters JL, Kay NE. How I treat autoimmune hemolytic anemia. Blood 2017;129:2971-
2979. 
Gupta N, Wang ES. Long-term response of refractory primary cold agglutinin disease to 
eculizumab therapy. Ann Hematol 2014;93:343-344. 
Hill QA, Stamps R, Massey E, et al. The diagnosis and management of primary autoimmune 
haemolytic anaemia. Br J Haematol 2017;176:395-411. 
INCB050465 Investigator's Brochure (IB). Wilmington, DE: Incyte Corporation. 
Lechner K, Jäger U. How I treat autoimmune hemolytic anemias in adults. Blood 
2010;116:1831-1838. 
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: B-cell 
Lymphomas Version 1.2017. 2017. https://www.nccn.org/professionals/physician_gls/pdf/b-
cell.pdf. Accessed February 1, 2017. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655. 
Petz LD, Garratty G. Immune Hemolytic Anemias. 2nd ed. Philadelphia, PA: Churchill 
Livingstone; 2004. 


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Phillips TJ, Ramchandren R, Wertheim MS, et al. An ongoing open-label Phase 1/2 study of 
INCB050465, a selective PI3Kδ inhibitor, in patients with previously treated B-cell 
malignancies. Blood (American Society of Hematology Annual Meeting Abstracts) 
2016;128:4195. 
Puri KD, Gold MR. Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell 
function with potential for treating autoimmune inflammatory diseases and B-cell malignancies. 
Front Immunol 2012;3:256. 
Röth A, Hüttmann A, Rother RP, Dührsen U, Philipp T. Long-term efficacy of the complement 
inhibitor eculizumab in cold agglutinin disease. Blood 2009;113:3885-3886. 
Zanella A, Barcellini W. Treatment of autoimmune hemolytic anemias. Haematologica 
2014;99:1547-1554. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Participants in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomized partner2,3 
• Sexual abstinence4 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• progestogen-only oral hormonal contraception, where inhibition of ovulation is not 
the primary mode of action 
• male or female condom with or without spermicide5 
• cap, diaphragm or sponge with spermicide5 
• tubal ligation 
1  Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of 
the contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomized partner is a highly effective method provided of avoiding pregnancy that partner is the sole sexual 
partner of the woman of childbearing potential trial participant and that the vasectomized partner has received 
medical assessment of the surgical success.  
4   In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the participant. 
5  A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) 
are also considered acceptable, but not highly effective, birth control methods. 
Source:  Clinical Trial Facilitation Group 2014. 


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APPENDIX B. FACIT FATIGUE SUB-SCALE (VERSION 4) 
 


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APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS SCORES 
Grade 
Performance Status  
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up 
and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 


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APPENDIX D. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
11 JAN 2018 
Amendment (Version) 1-FRA: 
23 MAY 2018 
Amendment (Version) 2: 
20 JUN 2018 
Amendment (Version) 3: 
01 FEB 2019 
Amendment (Version) 4: 
31 OCT 2019 
Amendment (Version) 5: 
02 NOV 2020 
Amendment 5 (02 NOV 2020)  
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to allow participants in the open-label extension 
period to continue receiving treatment until the drug is available through another clinical study, 
or is commercially available, or the sponsor stops the study or the study drug development.  In 
addition, due to the impact of the COVID-19 pandemic on study enrollment, and the rare 
occurrence of patients with CAD, Cohort 2 will change the enrollment of CAD AIHA to 
approximately 5 CAD AIHA participants.  
1. Section 1, Protocol Summary (Treatment Groups and Duration); Section 4.1, 
Overall Design; Section 4.2, Overall Study Duration 
Description of change:  Extended the extension period to allow participants receiving 
benefit from study drug to continue receiving INCB050465 until the drug is available 
through another clinical study, or is commercially available, or the sponsor stops the 
study or the study drug development.  
Rationale for change:  To allow participants with limited treatment options to continue 
receiving treatment until the drug is available through another clinical study, or is 
commercially available, or the sponsor stops the study or the study drug development.  
2. Section 1, Protocol Summary (Figure 1:  Study Design Schema footnote); 
Section 2.6, Study Rationale; Section 4.1, Overall Design 
Description of change:  Changed the number of CAD participants from “at least” 5 CAD 
AIHA to approximately 5 CAD AIHA participants.  
Rationale for change:  Approximately 20% of all patients with AIHA have CAD, and 
this will allow completion of enrollment while maintaining the representative mix of type 
for patients with AIHA.   
3. Section 5.3, Lifestyle Considerations 
Description of change:  Removed instruction to avoid excess sun exposure.  
Rationale for change:  Parsaclisib is not phototoxic.  


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4. Section 8.3.5, Laboratory Assessments; Section 8.8, Extension Period 
Description of change:  Specified that laboratory assessments may be conducted at a 
local laboratory due to COVID-19 restrictions affecting travel to the site for extension 
visits.  
Rationale for change:  To facilitate remote safety assessments during the pandemic.  
5. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment.  


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Amendment 4 (31 OCT 2019) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to increase the number of participants in Cohort 2 
(from 10 to approximately 15) and change the proportion of CAD and warm AIHA patients.  
These changes are based on the recommendations from the internal Safety Review Committee 
meeting (18 SEP 2019). 
1. Section 1, Protocol Summary (Overall Design table; Figure 1: Study Design 
Schema); Section 2.6, Study Rationale; Section 4.1, Overall Design; Section 4.2, 
Overall Study Duration; Section 10.1, Sample Size Determination 
Description of change:  Increased the number of participants in Cohort 2 (from 10 to 
approximately 15) and changed the proportion of CAD and warm AIHA patients (at least 
5 CAD AIHA and up to 8 wAIHA participants; the remainder can be wAIHA, CAD, or 
mixed-type AIHA). 
Rationale for change:  To confirm clinical response signal with a slightly larger patient 
population and allow a better evaluation of the CAD AIHA subpopulation. 
2. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 
 


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Amendment 3 (01 FEB 2019) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to add an extension period for participants who are 
receiving clinical benefit from the study treatment and to provide guidance for hematology panel 
collection.  
1. Section 1, Protocol Summary (Figure 1, Study Design Schema and Table 2, Schedule 
of Assessments for the Extension Period); Section 4.1, Overall Design; Section 6.1, 
Study Treatment Administered; Section 8.1, Administrative and General 
Procedures; Section 8.1.5, Prior and Concomitant Medications and Procedures; 
Section 8.3, Safety Assessments; Section 8.3.5, Laboratory Assessments; Section 8.8, 
Extension Period; Section 8.9, Follow-Up 
Description of change:  Added an extension period for participants who are receiving 
clinical benefit from the study treatment per the investigator’s discretion up to the time all 
enrolled participants complete the study.  
Rationale for change:  To continue to provide study treatment to participants who are 
receiving clinical benefit. 
 
  
 
 
  
 
 
 
 
3. Section 2.8.1, Potential Risks of INCB050465 Based on Preclinical Safety 
Description of change:  Added 3- and 9-month preclinical toxicity results in rats and in 
dogs. 
Rationale for change:  To support adding an extension period for participants who are 
receiving clinical benefit from study treatment. 
4. Section 5.2, Exclusion Criteria; Section 6.7.2, Restricted Medications and 
Procedures; Section 6.7.3, Prohibited Medications and Procedures; Appendix B, 
Cytochrome P450 3A4 and P-Glycoprotein Inhibitors and Cytochrome P450 3A4 
Inducers 
Description of change:  Deleted CYP lists and corresponding references to the CYP 
lists. 
Rationale for change:  No longer providing CYP lists in protocols. 


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5. Section 5.1, Inclusion Criteria; Section 5.2, Exclusion Criteria; Section 8.2.1, 
Hemoglobin Level, Hemolysis Markers, Direct Antiglobulin Test, and Complement 
Assessment; Section 8.3.5, Laboratory Assessments (Table 5, Required Laboratory 
Analytes) 
Description of change:  Clarified that blood samples for hematology panels, including 
CBC and differential count, will be sent to a local laboratory for analysis. 
Rationale for change:  To provide real-time management of participants' enrollment 
eligibility and safety and efficacy assessments.  
6. Section 6.6.1, Criteria and Procedures for Dose Increases of Study Drug 
Description of change:  Added unscheduled drug dispensing visit between the Week 6 
and Week 8 visits or at the regularly scheduled Week 8 visit for participants who may be 
eligible for a dose increase. 
Rationale for change:  To allow for clinical laboratory assessments and consultation 
with the sponsor as needed prior to increasing the dose. 
7. Section 5.2, Exclusion Criteria 
Description of change:  In exclusion criterion #7, clarified that participants with positive 
results for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they 
are negative for HBV-DNA and that these participants should be considered for 
prophylactic antiviral therapy.  Participants who are positive for the anti-HCV antibody 
will be eligible if they are negative for HCV-RNA. 
Rationale for change:  Participants who were previously infected with HBV or who 
have received the HBV vaccine can test positive for the hepatitis B surface antigen or 
hepatitis B core antibody.  The exclusion criterion was revised to allow participants who 
were previously infected with HBV or who have received the HBV vaccine to enroll in 
the study.  The study will only exclude current active infection or chronic infection of 
participants with HBV.   
8. Section 9.1.2, Reporting; Section 10.4.2.1, Adverse Events 
Description of change:  Updated CTCAE version from v4.03 to v5.0. 
Rationale for change:  To align with the most recent version of CTCAE. 
9. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 2 (20 JUN 2018) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to clarify that the AIHA population enrolled in this 
study does not include treatment-naive participants and to provide further information on sample 
size determination. 
1. Section 5.1, Inclusion Criteria 
Description of change:  Removed participants who refuse standard treatment.  
Rationale for change:  To address the request of the France Competent Authority to 
remove treatment-naive participants. 
2. Section 5.1, Inclusion Criteria 
Description of change:  New inclusion criterion #9 was added to indicate that 
participants should be willing to receive PJP prophylaxis. 
Rationale for change:  All participants in this study are required to receive PJP 
prophylaxis.  If a participant is not willing to receive PJP prophylaxis or if PJP 
prophylaxis regimens are not available at a study site, the participant should not be 
enrolled. 
3. Section 8.2.2, Direct Antiglobulin Test and Cold Agglutinin Test 
Description of change:  Language was added to allow participants for whom DAT was 
performed within 28 days before screening at the study site not to retest DAT at the 
screening visit. 
Rationale for change:  Direct antiglobulin test is a diagnostic test for AIHA.  It does not 
tend to have significant fluctuation week to week.  This study allows a previous DAT 
result to be used as a screening value if it was performed within 28 days before screening. 
4. Section 10.1, Sample Size Determination 
Description of change:  Language was added to further address that current sample size 
will permit sufficient data to warrant further investigation. 
Rationale for change:  To address the request of the Italy Coordinating Ethics 
Committee to further clarify sample size determination. 
5. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1-FRA (23 MAY 2018) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to clarify that the AIHA population enrolled in this 
study does not include treatment-naive participants. 
1. Section 5.1, Inclusion Criteria 
Description of change:  Removed participants who refuse standard treatment.  
Rationale for change:  To address the request of the France Competent Authority to 
remove treatment-naive participants. 
2. Section 8.2.2, Direct Antiglobulin Test and Cold Agglutinin Test 
Description of change:  Language was added to allow participants for whom DAT was 
performed within 28 days before screening at the study site not to retest DAT at the 
screening visit. 
Rationale for change:  Direct antiglobulin test is a diagnostic test for AIHA.  It does not 
tend to have significant fluctuation week to week.  This study allows a previous DAT 
result to be used as a screening value if it was performed within 28 days before screening. 
3. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 1 (11 JAN 2018) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to limit the AIHA population to participants who have 
disease progression after treatment with standard therapies and to add a stopping rule for futility. 
1. Section 1, Protocol Summary (Table 1, Schedule of Assessments); Section 6.7.1.2, 
Folic Acid, Vitamin B12, or Iron Deficiencies; Section 8.3.5, Laboratory 
Assessments (Table 4, Required Laboratory Analytes); Section 8.3.5.2, Vitamin B12; 
Section 8.3.5.3, Iron Clinical Assessment 
Description of change:  Added assessment of ferritin and iron at Week 6 for participants 
who receive transfusions during the study and assessment of vitamin B12 levels at 
screening.  A subsection was created (Section 6.7.1.2) for permitted medications for folic 
acid, vitamin B12, or iron deficiencies. 
Rationale for change:  Week 6 assessments were added to monitor for the potential risk 
for iron overload in participants who continue to receive transfusions during the study.  
The vitamin B12 assessment was added to avoid the potential risk of neurologic issues in 
participants receiving folic acid supplementation. 
2. Section 4.1, Overall Design; Section 9.6, Data Monitoring Committee 
Description of change:  Language was added to provide guidance regarding the Protocol 
stopping rules for futility. 
Rationale for change:  To address the FDA's request to include guidance for stopping 
rules for futility. 
3. Section 1, Protocol Summary (Table 1, Schedule of Assessments); Section 5.1, 
Inclusion Criteria; Section 5.2, Exclusion Criteria 
Description of change:  Revised Inclusion criterion 3 to remove language describing 
prior treatments and adding language to describe eligible patients as those who have 
disease progression after treatment with standard therapies.  Exclusion criterion 9 was 
revised to reflect that a subject may enroll if the average QTcF for 3 separate ECGs is 
within the upper limit (ie, < 470 milliseconds for males and < 480 milliseconds for 
females); footnote "i" in Table 1 was updated to indicate triplicate ECG may be 
performed at screening.  In exclusion criterion 10b, the corticosteroid dose level limit was 
revised to include "prednisone or equivalent corticosteroid dose" language. 
Rationale for change:  In response to FDA comments, the language in inclusion 
criterion 3 has been revised to reflect that this study population is limited to participants 
who have no other standard treatment options.  Exclusion criteria 9 was clarified for 
circumstances in which a participant with a history of elevated QTcF would be eligible 
for the study.  Exclusion criterion 10b was revised to clarify the dose limit for 
corticosteroids. 


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4. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-000602 v8.0
Signature Page for VV-CLIN-000602 v8.0
Approval
Approver
02-Nov-2020 12:48:49 GMT+0000
Approval
Approver
02-Nov-2020 14:13:03 GMT+0000
Approval
Approver
02-Nov-2020 15:12:21 GMT+0000
Approval
Approver
02-Nov-2020 17:10:10 GMT+0000
Approval
Approver
02-Nov-2020 19:53:17 GMT+0000

SAP_001.pdf: 
Official Title: 
A Phase 2, Open-Label Study of INCB050465 in Participants With 
Autoimmune Hemolytic Anemia 
NCT Number: 
NCT03538041 
Document Date: 
Statistical Analysis Plan Version 1.0: 03-March-2022 


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STATISTICAL ANALYSIS PLAN 
 
INCB 50465-206 
A Phase 2, Open-Label Study of INCB050465 in Participants With 
Autoimmune Hemolytic Anemia 
TITLE PAGE 
 
 
 
IND Number: 
121,474 
EudraCT Number 
2017-003652-22 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
USA 
Protocol Version: 
Protocol Amendment (Version) 5 dated 02 NOV 2020 
CRF Approval Date: 
04 JUN 2020 
SAP Version: 
Amendment 1 
SAP Author:  
 
, Biostatistics 
Date of Plan: 
03 MAR 2022 
 
 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 
 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................6 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................7 
2.1. 
Protocol and Case Report Form Version ......................................................................7 
2.2. 
Objectives and Endpoints .............................................................................................7 
3. 
STUDY DESIGN .........................................................................................................8 
3.1. 
Randomization ..............................................................................................................8 
3.2. 
Control of Type I Error .................................................................................................9 
3.3. 
Sample Size Considerations .........................................................................................9 
3.4. 
Schedule of Assessments ..............................................................................................9 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ....................................9 
4.1. 
Scheduled Study Evaluations .......................................................................................9 
4.1.1. 
Day 1 .............................................................................................................................9 
4.1.2. 
Study Day .....................................................................................................................9 
4.1.3. 
Baseline Value ............................................................................................................10 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................10 
4.2. 
Variable Definitions ....................................................................................................10 
4.2.1. 
Body Mass Index ........................................................................................................10 
4.2.2. 
Prior and Concomitant Medication .............................................................................10 
5. 
STATISTICAL METHODOLOGY ...........................................................................11 
5.1. 
General Methodology .................................................................................................11 
5.2. 
Treatment Groups .......................................................................................................11 
5.3. 
Analysis Populations ..................................................................................................11 
5.3.1. 
Full Analysis Set .........................................................................................................11 
5.3.2. 
Treatment Extension Evaluable Population ................................................................11 
5.3.3. 
Pharmacokinetic/Pharmacodynamic Evaluable Population .......................................12 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................12 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............12 
6.1.1. 
Demographics .............................................................................................................12 


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6.1.2. 
Baseline Disease Characteristics ................................................................................12 
6.1.3. 
Prior Therapy ..............................................................................................................12 
6.1.4. 
General Medical History .............................................................................................12 
6.2. 
Disposition of Participants ..........................................................................................13 
6.3. 
Protocol Deviations ....................................................................................................13 
6.4. 
Exposure .....................................................................................................................13 
6.5. 
Study Drug Compliance .............................................................................................13 
6.6. 
Prior and Concomitant Medication .............................................................................13 
7. 
EFFICACY .................................................................................................................14 
7.1. 
Efficacy Hypotheses ...................................................................................................14 
7.2. 
Efficacy Parameters ....................................................................................................14 
7.3. 
Analysis of Primary Efficacy Parameters ...................................................................14 
7.4. 
Analysis of Secondary Efficacy Parameters ...............................................................14 
7.5. 
FACIT-F Subscale ......................................................................................................15 
7.6. 
Pharmacokinetic Analyses ..........................................................................................16 
7.7. 
Pharmacodynamic Analyses .......................................................................................16 
8. 
SAFETY AND TOLERABILITY ..............................................................................17 
8.1. 
General Considerations ...............................................................................................17 
8.2. 
Adverse Events ...........................................................................................................17 
8.2.1. 
Adverse Event Definitions ..........................................................................................17 
8.2.2. 
Adverse Events of Special Interest .............................................................................18 
8.2.3. 
Adverse Event Summaries ..........................................................................................18 
8.3. 
Clinical Laboratory Tests ...........................................................................................19 
8.3.1. 
Laboratory Value Definitions .....................................................................................19 
8.3.2. 
Laboratory Value Summaries .....................................................................................20 
8.4. 
Vital Signs ..................................................................................................................20 
8.5. 
Electrocardiograms .....................................................................................................20 
9. 
INTERIM ANALYSES ..............................................................................................21 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................22 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................22 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................22 
10.2.1. 
Amendment 1 ..............................................................................................................22 
11. 
REFERENCES ...........................................................................................................23 


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APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................24 
 
LIST OF TABLES 
Table 1: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................20 
Table 2: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................21 
Table 3: 
Statistical Analysis Plan Versions ..............................................................................22 
 
LIST OF FIGURES 
Figure 1: 
FACIT-F Subscale (Version 4) ...................................................................................15 
Figure 2: 
FACIT-F Subscale Calculation...................................................................................16 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
AESI 
adverse events of special interest 
AIHA 
autoimmune hemolytic anemia 
AUC0-t 
area under the concentration-time curve from time = 0 to the last measureable 
concentration at time = t 
BMI 
body mass index 
CAD 
cold agglutinin disease 
CL/F 
apparent oral dose clearance 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration over the dose interval 
CMV 
cytomegalovirus 
CR 
complete response 
CRF 
case report form 
CTC 
Common Terminology Criteria 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAT 
direct antiglobulin test 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FACIT-F 
The Functional Assessment of Chronic Illness Therapy - Fatigue 
FAS 
full analysis set 
IgG 
immunoglobulin G 
LDH 
lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
PD 
pharmacodynamic 
PJP 
Pneumocystis jiroveci pneumonia 
PK 
pharmacokinetic 
PR 
partial response 
PT 
preferred term 
QD 
once daily 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SOC 
system organ class 
TE 
treatment extension 
TEAE 
treatment-emergent adverse event 
tmax 
time to maximum concentration 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This is a multicenter, open-label study designed to evaluate the safety and efficacy of 
INCB050465 administered orally to participants with AIHA who have decreased hemoglobin 
and evidence of ongoing hemolysis that requires treatment intervention.  Participants with 
primary warm, cold (CAD), and mixed-type AIHA, without an underlying lymphoproliferative 
malignancy or other autoimmune disease and have failed at least 1 prior treatment for AIHA will 
be eligible for enrollment.  Participants will be treated for 12 weeks.  There are 2 cohorts in this 
study: Cohort 1, with up to 10 participants, with no more than 3 cold (CAD)/mixed-type AIHA 
participants to appropriately reflect response in the overall population, which is predominantly 
warm AIHA; and Cohort 2, with approximately 15 participants, with approximately 5 CAD 
AIHA, up to 8 warm AIHA, and the remainder from any of the 3 AIHA types.  Cohort 2 
distribution and increased number of participants are intended to better evaluate CAD AIHA 
patients and possible signal observed in Cohort 1, as well as account for higher baseline 
variability seen in the warm AIHA subpopulation.  The first cohort (Cohort 1, 
n = 10 participants) enrolled will initially receive INCB050465 1 mg QD.  At Week 6, 
participants who continue to require transfusions or do not attain a meaningful clinical response 
(at least a stabilization ≥ 2 g/dL increase in hemoglobin from baseline to Week 6) may have their 
dose increased, with sponsor preapproval, to 2.5 mg QD of INCB050465 until Week 12.  If there 
are any tolerability issues in individual participants who received 2.5 mg, the dose may be 
decreased to 1 mg.  Following enrollment of a minimum of 6 warm AIHA participants in the first 
cohort and review of safety and efficacy data through Week 6, Cohort 2 may begin enrollment.  
Participants in Cohort 2 (n ≈ 15) will receive INCB050465 2.5 mg QD for 12 weeks.  If there are 
any tolerability issues, the dose may be decreased to 1 mg.  The investigator and sponsor should 
review and agree any dose increases or decreases.  Following the last dose of INCB050465, 
participants will be eligible for a 12-week (3 months) follow-up for evaluation of the safety and 
durability of response. 
Autoimmune hemolytic anemia is a rare acquired disorder in which autoantibodies directed 
against red blood cell membrane antigens lead to their accelerated destruction.  The estimated 
incidence of AIHA in adults is 0.8 to 3 per 100,000 per year, with a mortality rate of 11% 
(Zanella and Barcellini 2014). 
Currently, there is no approved and effective targeted therapy for treatment of AIHA.  In 
addition to showing efficacy in a number of B-cell–related cancers, treatment with INCB050465 
has shown significant improvement in animal models of AIHA and lupus nephritis, as well as 
other antibody-mediated diseases.  The purpose of Study INCB 50465-206 is to evaluate the 
efficacy and safety of INCB050465 in the treatment of participants with AIHA. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 50465-206 Protocol Amendment (Version) 5.  The scope of this plan includes 
the final analyses that are planned and will be executed by the Department of Biostatistics or 
designee. 


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2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 50465-206 Protocol Amendment (Version) 5 dated 02 NOV 2020 
and CRFs approved 04 JUN 2020.  Unless superseded by an amendment, this SAP will be 
effective for all subsequent Protocol Amendments and CRF versions. 
2.2. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of INCB050465 
in the treatment of participants with 
AIHA. 
• Proportion of participants attaining a CR (defined as 
hemoglobin ≥ 12 g/dL not attributed to transfusion 
effect*) at any visit from Week 6 to Week 12. 
• Proportion of participants attaining a PR (defined as 
hemoglobin 10-12 g/dL or at least ≥ 2 g/dL increase 
from baseline not attributed to transfusion effect) at 
any visit from Week 6 to Week 12. 
*No transfusion effect definition:  > 1 week since last 
transfusion. 
• To evaluate the safety of INCB050465 
administered as repeat doses in 
participants with AIHA. 
• Safety and tolerability will be assessed by monitoring 
AEs, measuring vital signs and ECGs, and conducting 
clinical laboratory blood and urine sample 
assessments. 
Secondary 
• To further evaluate the efficacy of 
INCB050465 in the treatment of 
participants with AIHA. 
• Proportion of participants attaining a CR during 
postbaseline visits. 
• Proportion of participants attaining a PR during 
postbaseline visits. 
• Proportion of participants attaining a ≥ 2 g/dL 
increase in hemoglobin from baseline. 
• Mean, change, and percentage change from baseline 
of hemoglobin. 
• Proportion of participants requiring transfusions. 
• Proportion of participants who achieve normalization 
of hemolytic markers. 
(Hemolysis markers:  hemoglobin, haptoglobin, LDH, 
reticulocyte count, total bilirubin, and direct/indirect 
bilirubin.) 
• Change of daily usage of prednisone. 
• FACIT-F subscale assessment. 
• To evaluate the PK effects of 
INCB050465. 
• PK endpoints:  Cmax, tmax, Cmin, AUC0-t, and CL/F. 


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Objectives 
Endpoints 
• To evaluate the PD effects of 
INCB050465. 
• Change from baseline in PD markers:  reticulocyte 
count, DAT for IgG and C3b, cold agglutinin levels, 
haptoglobin, total bilirubin, direct/indirect bilirubin, 
LDH, and complement assessment (CH50, C3, and 
C4). 
3. 
STUDY DESIGN 
This is a multicenter, open-label study designed to evaluate the safety and efficacy of 
INCB050465 administered orally to participants with AIHA who have decreased hemoglobin 
and evidence of ongoing hemolysis that requires treatment intervention.  Participants with 
primary warm, cold (CAD), and mixed-type AIHA, without an underlying lymphoproliferative 
malignancy or other autoimmune disease and have failed at least 1 prior treatment for AIHA will 
be eligible for enrollment.  Participants will be treated for 12 weeks.  There are 2 cohorts in this 
study: Cohort 1, with up to 10 participants, with no more than 3 cold (CAD)/mixed-type AIHA 
participants to appropriately reflect response in the overall population, which is predominantly 
warm AIHA; and Cohort 2, with approximately 15 participants, with approximately 5 CAD 
AIHA, up to 8 warm AIHA, and the remainder from any of the 3 AIHA types.  Cohort 2 
distribution and increased number of participants are intended to better evaluate CAD AIHA 
patients and possible signal observed in Cohort 1, as well as account for higher baseline 
variability seen in the warm AIHA subpopulation.  The first cohort (Cohort 1, 
n = 10 participants) enrolled will initially receive INCB050465 1 mg QD.  At Week 6, 
participants who continue to require transfusions or do not attain a meaningful clinical response 
(at least a stabilization ≥ 2 g/dL increase in hemoglobin from baseline to Week 6) may have their 
dose increased, with sponsor preapproval, to 2.5 mg QD of INCB050465 until Week 12.  If there 
are any tolerability issues in individual participants who received 2.5 mg, the dose may be 
decreased to 1 mg.  Following enrollment of a minimum of 6 warm AIHA participants in the first 
cohort and review of safety and efficacy data through Week 6, Cohort 2 may begin enrollment.  
Participants in Cohort 2 (n ≈ 15) will receive INCB050465 2.5 mg QD for 12 weeks.  If there are 
any tolerability issues, the dose may be decreased to 1 mg.  The investigator and sponsor should 
review and agree any dose increases or decreases.  Following the last dose of INCB050465, 
participants will be eligible for a 12-week (3 months) follow-up for evaluation of the safety and 
durability of response. 
3.1. 
Randomization 
Not applicable. 


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3.2. 
Control of Type I Error 
All statistical analyses are exploratory in nature.  No alpha control will be implemented.  Unless 
otherwise specified, all confidence intervals provided will be at the 95% confidence level. 
3.3. 
Sample Size Considerations 
The sample size is based on the precedent of other studies and is not based on statistical power 
calculations (Go et al 2017, Hill et al 2017, Lechner and Jäger 2010).  The study is not powered 
for statistical comparison of efficacy endpoints; the sample size is based on the demonstration of 
preliminary findings of clinical response.  It is anticipated that a sample size of approximately 
25 participants will permit sufficient data to warrant further investigation.  Also, the sample size 
depends on the occurrence of safety findings.  Approximately 10 participants will be enrolled in 
Cohort 1, and approximately 15 participants in Cohort 2, which will provide > 89% chance of 
detecting at least 1 AE of interest (eg, colitis, exfoliative dermatitis, infections) if the underlying 
AE rate is 20% for Cohort 1 and > 96% chance for Cohort 2. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment (Version) 5 dated 02 NOV 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 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug INCB050465 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. 


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4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCB050465. 
When scheduled assessments and unscheduled assessments occur on the same day and time of 
the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
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 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 before the first dose of 
INCB050465. 
Concomitant medication is defined as any nonstudy medication that is: 
• Started before the date of first administration of INCB050465 and is ongoing 
throughout the study or ends on/after the date of first administration of INCB050465. 
• Started on/after the date of first administration of INCB050465 and is ongoing or 
ends during the course of study treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first administration of INCB050465.  In the listing, it will be indicated whether 
a medication is prior-only, concomitant-only, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS® software (SAS Institute Inc, Cary, NC; Version 9.1 or later) will 
be used for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries 
for continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum, and both the actual value and change 
and/or percentage from baseline (if available) will be analyzed.  Descriptive summaries for 
categorical variables will include the number and percentage of participants in each category.  
All by-visit analyses will include the follow-up period if the data are available. 
5.2. 
Treatment Groups 
This is a multicenter, open-label, increasing dose strength study of INCB050465 administered as 
1 tablet QD.  There are 2 cohorts and approximately 10 participants will be enrolled in Cohort 1, 
and approximately 15 participants in Cohort 2. 
Cohort 1:  INCB050465 1 mg QD for up to 12 weeks.  At Week 6, participants who fulfill dose 
increase criteria (see definition below) will be offered INCB050465 2.5 mg QD for up to 
6 weeks.  If there are any tolerability issues in individual participants who received 2.5 mg, the 
dose may be decreased to 1 mg. 
Cohort 2:  INCB050465 2.5 mg QD for up to 12 weeks.  If there are any tolerability issues in 
individual participants, the dose may be decreased to 1 mg. 
Criteria for dose increase:  (1) Continue to require transfusions by Week 6 visit, or (2) do not 
attain a meaningful clinical response (at least a stabilization ≥ 2 g/dL increase in hemoglobin 
from baseline to Week 6).  Dose increases require sponsor preapproval (refer to Protocol, 
Section 6.6). 
Participants will be summarized overall and based on the dose regimen initially assigned in the 
study. 
5.3. 
Analysis Populations 
5.3.1. 
Full Analysis Set 
The FAS includes all participants enrolled in the study who receive at least 1 dose of 
INCB050465. 
The FAS will be used for the summary of demographics, baseline characteristics, participant 
disposition, and analyses of all efficacy and safety data. 
5.3.2. 
Treatment Extension Evaluable Population 
Participants who apply at least 1 dose of INCB050465 in the extension period will constitute the 
TE evaluable population. 


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5.3.3. 
Pharmacokinetic/Pharmacodynamic Evaluable Population 
The PK/PD population will include all participants who received at least 1 dose of study drug 
and provided at least 1 postdose blood sample (1 PK/PD measurement).  The study 
pharmacokineticist will review data listings of participant dosing and sample records to identify 
participants to be excluded from the analysis. 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of data displays and sample data displays. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
6.1.1. 
Demographics 
The following demographics will be summarized for the FAS:  age, sex, race, ethnicity, weight, 
height, and BMI. 
6.1.2. 
Baseline Disease Characteristics 
The following baseline disease characteristics will be summarized for the FAS: 
• Years since first onset of AIHA (< 2 years, 2-5 years, > 5 years) 
• Type of AIHA (warm/cold/mixed type/other) 
• Number of hospitalizations due to hemolytic anemia in the past year 
• Failed therapies (no/yes [prednisone/rituximab/other]) 
• Transfusions in the past year (no/yes) 
• Splenectomy received (no/yes) 
6.1.3. 
Prior Therapy 
Prior medication information for AIHA will be used to identify medication received by 
participants before enrollment into the study.  Prior medications for AIHA will be summarized. 
6.1.4. 
General Medical History 
For participants in the FAS, general medical history will be summarized by assigned cohort.  
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. 


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6.2. 
Disposition of Participants 
The number and percentage of participants who were treated, completed the study, discontinued 
study treatment with a primary reason for discontinuation, and discontinued from the study with 
a primary reason for withdrawal will be summarized for the treatment period (FAS) and the 
extension period (TE) separately.  The number of participants enrolled by site will also be 
provided. 
6.3. 
Protocol Deviations 
Protocol deviations recorded on the eCRF will be presented in the participant data listings.  
A summary table of major Protocol deviations will also be provided for the treatment period 
(FAS) and extension period (TE) separately. 
6.4. 
Exposure 
For participants in the FAS and TE, descriptive statistics will be provided for duration of 
treatment, average daily dose, and total dose separately.  Duration of treatment with 
INCB050465 is defined as the number of days from Day 1 to the date of last record of 
INCB050465 administration.  In addition, daily usage of prednisone (or equivalent) will be 
summarized using descriptive statistics. 
6.5. 
Study Drug Compliance 
For participants in the FAS, overall compliance (%) for INCB050465 will be calculated for all 
participants as: 
Compliance (%) = 100  [total dose taken] / [total intended dose]. 
The total intended dose will be based on the earliest study day of permanent discontinuation of 
the study medication.  Intended dose is defined as the sum of the doses prescribed by the 
investigator accounting both for planned dose reductions as well as those reductions or increases 
mandated by the investigator. 
6.6. 
Prior and Concomitant Medication 
For participants in the FAS, prior medications and concomitant medications will be coded using 
the WHO Drug Dictionary and summarized by WHO drug class and WHO drug term.  Results 
will be summarized as number and percentage of participants with prior and concomitant 
medications by WHO drug term and WHO drug class. 


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7. 
EFFICACY 
Sample data displays are provided in Appendix A.  All efficacy analyses are exploratory.  Hence, 
no p-values will be provided and no multiple adjustment will be made. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Efficacy Parameters 
A CR for a given visit is attained if the following 2 conditions are satisfied: 
1. Hemoglobin ≥ 12 g/dL. 
2. Last transfusion occurred > 1 week before the date of visit. 
A PR for a given visit is achieved if the following 2 conditions are satisfied: 
1. Hemoglobin 10-12 g/dL or ≥ 2 g/dL increase from baseline. 
2. Last transfusion occurred > 1 week before the date of visit. 
7.3. 
Analysis of Primary Efficacy Parameters 
The primary endpoints include: 
1. Proportion of participants attaining a CR at any visit from Week 6 to Week 12 and 
2. Proportion of participants attaining a PR at any visit from Week 6 to Week 12 
The primary endpoints will be summarized using descriptive statistics. 
7.4. 
Analysis of Secondary Efficacy Parameters 
The secondary endpoints include: 
1. Proportion of participants attaining a CR during postbaseline visits. 
2. Proportion of participants attaining a PR during postbaseline visits. 
3. Proportion of participants attaining a ≥ 2 g/dL increase in hemoglobin from baseline. 
4. Mean, change, and percentage change from baseline of hemoglobin. 
5. Proportion of participants requiring transfusions, defined as "Yes" if the last transfusion 
is within 7 days of the visit date and "No" otherwise. 
6. Proportion of participants who achieve normalization of hemolytic markers (hemolysis 
markers:  hemoglobin, haptoglobin, LDH, reticulocyte count, total bilirubin, and 
direct/indirect bilirubin). 
7. Daily usage of prednisone. 
8. FACIT-F subscale assessment. 
All secondary endpoints will be summarized using descriptive statistics. 


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7.5. 
FACIT-F Subscale 
FACIT-F subscale is a 13-item instrument designed to assess fatigue/tiredness and its impact on 
daily activities and functioning in a number of chronic diseases.  The 13 items are shown in 
Figure 1, where the gray bar on the left is the item code.  If 7 or more item scores are 
nonmissing, then the FACIT-F subscale score will be calculated as shown in Figure 2; otherwise, 
the FACIT-F subscale score will be set to missing.  Actual measurements, change, and 
percentage change from baseline will be summarized for the fatigue subscale score. 
Figure 1: 
FACIT-F Subscale (Version 4) 
 


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Figure 2: 
FACIT-F Subscale Calculation 
 
7.6. 
Pharmacokinetic Analyses 
The data will be analyzed by standard population PK methods using appropriate software 
(eg, NONMEM®).  An attempt will be made to evaluate the effect of demographic characteristics 
and baseline characteristics (eg, age, weight, sex, race, renal function) on the population PK 
profile.  Additionally, exposure-response analyses for key efficacy and safety parameters may 
also be considered if there are sufficient data available. 
7.7. 
Pharmacodynamic Analyses 
  
Biomarkers from blood samples will be summarized using descriptive statistics by treatment 
group.  Additionally, subgroup analysis will include participants with other baseline 
characteristics, including duration of autoimmune hemolytic anemia, concomitant autoimmune 
disease, and prior treatments. 


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8. 
SAFETY AND TOLERABILITY 
Sample data displays are provided in Appendix A. 
8.1. 
General Considerations 
The analyses in this section will be provided for the FAS in the treatment period and TE 
evaluable population in the extension period.  Safety tables will be summarized for the treatment 
period and extension period separately. 
Summary tables may be replaced with listings when appropriate.  For instance, an AE frequency 
table may be replaced with a listing if it only contains a few unique PTs reported on relatively 
few participants. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first administration of study drug and within 30 days of the last dose of study drug.  Analysis of 
AEs (as discussed below) will be limited to TEAEs, but data listings will include all AEs 
regardless of their timing in relation to study drug administration. 
Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be graded 
using the NCI CTCAE.  The CTCAE v5 is used for this study.  The CTCAE reporting guidelines 
and grading details are available on the Cancer Therapy Evaluation Program website. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs.  The incidence of AEs and treatment-related AEs will be tabulated.  
Serious AEs will also be tabulated. 
Any missing onset date, causality, or severity must be queried for resolution.  Unresolved 
missing causality and severity will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment-emergent. 


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8.2.2. 
Adverse Events of Special Interest 
Adverse events of special interest will be summarized in the following categories by treatment 
and extension periods separately: 
• Colitis 
• CMV infection 
• Diarrhea 
• Exfoliative dermatitis 
• Febrile neutropenia 
• Herpes simplex 
• Intestinal perforation 
• PJP 
• Pneumonia 
• Pneumonitis 
• Rash 
• Varicella zoster virus infection 
8.2.3. 
Adverse Event Summaries 
An overall summary of AEs will include: 
• Number (%) of participants reporting any TEAEs. 
• Number (%) of participants reporting any SAEs. 
• Number (%) of participants reporting any Grade 3 or 4 TEAEs. 
• Number (%) of participants who had a TEAE leading to death. 
• Number (%) of participants reporting any treatment-related TEAEs. 
• Number (%) of participants who temporarily interrupted study treatment because of 
TEAEs. 
• Number (%) of participants who permanently discontinued study treatment because 
of TEAEs. 
The following summaries will be produced by MedDRA term (if 2 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT. 
• Summary of TEAEs by PT in decreasing order of frequency. 
• Summary of TEAEs by SOC, PT, and maximum severity. 
• Summary of treatment-related AEs by SOC and PT. 


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• Summary of treatment-related AEs by PT in decreasing order of frequency. 
• Summary of treatment-related AEs by SOC, PT, and maximum severity. 
• Summary of Grade 3 or 4 TEAEs by SOC and PT. 
• Summary of Grade 3 or 4 treatment-related TEAEs by SOC and PT. 
• Summary of TEAEs leading to death by SOC and PT. 
• Summary of treatment-emergent SAEs by SOC and PT. 
• Summary of treatment-emergent SAEs by PT in descending order of frequency. 
• Summary of treatment-related SAEs by SOC and PT. 
• Summary of TEAEs leading to dose interruption by SOC and PT. 
• Summary of TEAEs leading to discontinuation of treatment by SOC and PT. 
• Summary of nonserious TEAEs by SOC and PT. 
• Summary of AESI by SOC and PT. 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
All laboratory assessments will be performed using a central laboratory, with the exception of 
the following, in which case the investigative site laboratory or an accredited local laboratory 
may be used: 
• Hematology panels, including complete blood count and differential count, will be 
sent to a local laboratory for analysis (refer to Protocol, Section 8.2.1). 
• For local laboratory assessments deemed necessary by the investigator for participant 
management (ie, dose modification, SAE, or COVID-19 restrictions affecting travel 
to the site for extension visits).  Note:  Such assessment data and reference ranges 
must be recorded in the participant's eCRF. 
In the case of both local laboratory and central laboratory assessments are available, local lab 
will be used for analysis.  Laboratory values, change from baseline values, and percent change 
from baseline values will be summarized descriptively by visit.  Baseline values will be 
determined using the nonmissing values collected before the first administration, prioritizing 
scheduled assessments over unscheduled visits.  For baseline laboratory candidates with the 
same date and time in the same priority category, additional rules may be provided after 
consultation with the medical monitor to delineate which value will be defined as baseline. 
Laboratory test values outside the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading.  The 
incidence of abnormal laboratory values and shift tables relative to baseline will be tabulated. 


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8.3.2. 
Laboratory Value Summaries 
Clinical laboratory tests, including hematology, serum chemistry, urinalysis, coagulation, 
pregnancy testing, and serology (refer to Protocol, Section 8, Table 5), will be performed for 
each participant during the study in accordance with study schedule of assessments.  If specific 
safety issues arise, additional unscheduled laboratory tests/analyses may be performed at the 
discretion of the investigator. 
All test results and associated normal ranges from central laboratories will be reported in SI 
units.  All tests with numeric values will have a unique unit per test. 
Laboratory hematology and serum chemistry parameters identified in Protocol Section 8, Table 5 
will be summarized.  Numeric laboratory values will be summarized descriptively in SI units, 
and non-numeric test values will be tabulated when necessary.  In addition, box-and-whisker 
plots will be provided for laboratory parameters if applicable. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low, normal, high, and missing will be tabulated 
for each test and each visit. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, and body 
temperature will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 1.  The abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed along 
with their assigned cohort.  Alert vital signs are defined as an absolute value outside the defined 
range and percentage change greater than 25%.  The abnormal values for participants exhibiting 
alert vital sign abnormalities will be listed. 
Table 1: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 160 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 
Temperature 
> 38°C 
< 35.5°C 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QRS, QT, QTcB, QTcF, and RR intervals will be obtained for 
each participant during the study.  Change and percentage change from baseline will be 
calculated at each postbaseline assessment time.  Descriptive statistics will be determined for 
each ECG parameter. 


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Incidences of clinically notable ECG abnormalities are defined in Table 2.  Participants 
exhibiting clinically notable ECG abnormalities will be listed with study visit and assigned 
treatment group.  Abnormal values for subjects 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. 
Table 2: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Percent Change 
PR 
> 220 ms 
< 75 ms 
± 25% 
QRS 
> 120 ms 
< 50 ms 
± 30% 
QT 
> 500 ms 
< 300 ms 
± 25% 
QTcB 
> 460 ms 
< 295 ms 
± 25% 
QTcF 
> 460 ms 
< 295 ms 
± 25% 
RR 
> 1330 ms 
< 600 ms 
± 25% 
QTcF = Fridericia correction. 
9. 
INTERIM ANALYSES 
An interim analysis will be performed when all participants have completed the Week 12 
treatment period. 


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10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 3. 
Table 3: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
13 SEP 2018 
Amendment 1 
03 MAR 2022 
10.1. 
Changes to Protocol-Defined Analyses 
A portion of the primary endpoints that relate to hemolysis factors was removed as well as a 
change in the range for hemoglobin.  This is a change from the Protocol in order to react to the 
evolving regulatory interactions and more useful information from other developments in this 
area. 
The addition of the treatment extension evaluable population is for analysis of participants who 
enrolled into the open-label extension period. 
An interim analysis was added for when all participants have complete Week 12 treatment.  This 
change from the Protocol was made to support publications and a possible Phase 3 development 
plan for CAD participants. 
10.2. 
Changes to the Statistical Analysis Plan 
10.2.1. 
Amendment 1 
The primary purpose of this amendment is to update the definition of the primary endpoints.  
Section 2.2, Section 5.3.2, Section 6.2 through Section 6.4, Section 7.2, Section 7.4, and 
Appendix A have been modified to address edits made to the SAP based on Section 10.1. 
• Section 1, Section 3, Section 3.3, Section 5.2, Section 8.3.1 were updated to align 
with Protocol Amendments 3, 4, and 5. 
• Section 8.1 was updated to provide more details for the safety analysis. 
• Section 8.2.2, AESIs were added in align with parsaclisib program. 
• Section 4.2.1, the definition of age was removed due to date of birth cannot be 
collected according to the new requirement from agency and CRF was updated to 
collect age instead. 
• Section 4.1.4, Last Available Value was removed since it is not applicable to this 
study. 
• Other minor changes have been incorporated throughout the SAP. 


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11. 
REFERENCES 
Go RS, Winters JL, Kay NE. How I treat autoimmune hemolytic anemia. Blood 
2017;129:2971-2979. 
Hill QA, Stamps R, Massey E, et al. The diagnosis and management of primary autoimmune 
haemolytic anaemia. Br J Haematol 2017;176:395-411. 
Lechner K, Jäger U. How I treat autoimmune hemolytic anemias in adults. Blood 
2010;116:1831-1838. 
Zanella A, Barcellini W. Treatment of autoimmune hemolytic anemias. Haematologica 
2014;99:1547-1554. 


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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables and listings for the clinical study report.  
Standard tables will follow the conventions in the Standard Safety Tables initial version.  Shells 
are provided for nonstandard tables.  In-text tables are identical in structure and content as 
appendix tables, but follow a Rich Text Format. 
The list of tables, listings, and the shells are to be used as guideline.  Modifications of the list or 
shells that do not otherwise affect the nature of the analysis will not warrant an amendment to the 
SAP. 
Tables 
Table No. 
Title 
Population 
Baseline and Demographic Characteristics 
1.1  Disposition 
1.1.1 
Analysis Populations 
FAS 
1.1.2.1 
Summary of Participant Disposition in the Treatment Period 
FAS 
1.1.2.1 
Summary of Participant Disposition in the Extension Period 
TE 
1.1.3 
Summary of Number of Participants Enrolled by Site 
FAS 
1.2  Demography 
1.2.1 
Summary of Demographics 
FAS 
1.3  Baseline Characteristics 
1.3.1 
Summary of Baseline Disease Characteristics 
FAS 
1.4  Prior Medication and Concomitant Medication 
1.4.1 
Summary of Prior Medications 
FAS 
1.4.2 
Summary of Prior Medications for AIHA 
FAS 
1.4.3 
Summary of Concomitant Medications 
FAS 
1.5  Others 
1.5.1 
Summary of General Medical History 
FAS 
1.5.2.1 
Summary of Protocol Deviations by Category in the Treatment Period 
FAS 
1.5.2.2 
Summary of Protocol Deviations by Category in the Extension Period 
TE 
Efficacy 
2.1  Primary Efficacy 
2.1.1 
Summary of Participants Attaining a Complete Response at any Visit From Week 6 
to Week 12 
FAS 
2.1.2 
Summary of Participants Attaining a Partial Response at any Visit From Week 6 to 
Week 12 
FAS 
2.2  Secondary Efficacy 
2.2.1 
Summary of Participants Attaining a Complete Response by Visit 
FAS 
2.2.2 
Summary of Participants Attaining a Partial Response by Visit 
FAS 
2.2.3 
Summary of Participants Attaining a ≥ 2 g/dL Increase in Hemoglobin From 
Baseline 
FAS 
2.2.4 
Summary of Hemoglobin by Visit 
FAS 


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Table No. 
Title 
Population 
2.2.5 
Summary of Participants Requiring Transfusions 
FAS 
2.2.6 
Summary of Participants Achieving Normalization of Hemolytic Markers by Visit 
FAS 
2.2.7 
Summary of Daily Usage of Prednisone by Visit 
FAS 
2.2.8 
Summary of FACIT-F Subscale by Visit 
FAS 
Safety 
3.1  Study Drug Exposure 
3.1.1.X 
Summary of Drug Compliance 
FAS 
3.1.2.X 
Summary of Study Drug Exposure 
FAS 
3.2  Adverse Events 
3.2.1.X 
Overall Summary of Treatment-Emergent Adverse Events 
FAS 
3.2.2.X 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term 
FAS 
3.2.3.X 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
3.2.4.X 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ 
Class, Preferred Term, and Maximum Severity 
FAS 
3.2.5.X 
Summary of Treatment-Related Adverse Events by MedDRA System Organ Class 
and Preferred Term 
FAS 
3.2.6.X 
Summary of Treatment-Related Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
3.2.7.X 
Summary of Treatment-Related Adverse Events by MedDRA System Organ Class, 
Preferred Term, and Maximum Severity 
FAS 
3.2.8.X 
Summary of Grade 3 or 4 Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
FAS 
3.2.9.X 
Summary of Grade 3 or 4 Treatment-Related Treatment-Emergent Adverse Events 
by MedDRA Preferred Term 
FAS 
3.2.10.X 
Summary of Treatment-Emergent Adverse Events Leading to Death by MedDRA 
System Organ Class and Preferred Term 
FAS 
3.2.11.X 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA System 
Organ Class and Preferred Term 
FAS 
3.2.12.X 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency 
FAS 
3.2.13.X 
Summary of Treatment-Related Serious Adverse Events by MedDRA System 
Organ Class and Preferred Term 
FAS 
3.2.14.X 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption by 
MedDRA System Organ Class and Preferred Term 
FAS 
3.2.15.X 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
Study Drug by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.16.X 
Summary of Nonserious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term 
FAS 
3.2.17.1.X 
Summary of Colitis by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.2.X 
Summary of CMV infection by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.3.X 
Summary of Diarrhea by MedDRA System Organ Class and Preferred Term 
FAS 


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Table No. 
Title 
Population 
3.2.17.4.X 
Summary of Exfoliative Dermatitis by MedDRA System Organ Class and 
Preferred Term 
FAS 
3.2.17.5.X 
Summary of Febrile Neutropenia by MedDRA System Organ Class and Preferred 
Term 
FAS 
3.2.17.6.X 
Summary of Herpes Simplex by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.7.X 
Summary of Intestinal Perforation by MedDRA System Organ Class and Preferred 
Term 
FAS 
3.2.17.8.X 
Summary of PJP by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.9.X 
Summary of Pneumonia by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.10.X 
Summary of Pneumonitis by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.11.X 
Summary of Rash by MedDRA System Organ Class and Preferred Term 
FAS 
3.2.17.12.X 
Summary of Varicella Zoster Virus Infection by MedDRA System Organ Class and 
Preferred Term 
FAS 
3.3  Laboratory 
3.3.1.X 
Summary of Laboratory Values - Hematology 
FAS 
3.3.2.X 
Summary of Laboratory Values - Chemistry  
FAS 
3.3.3.X 
Shift Summary of Hematology Values in CTC Grade - to the Worst Abnormal 
Value 
FAS 
3.3.4.X 
Shift Summary of Chemistry Values in CTC Grade - to the Worst Abnormal Value 
FAS 
3.4  Vital Signs 
3.4.1.X 
Summary of Systolic Blood Pressure 
FAS 
3.4.2.X 
Summary of Diastolic Blood Pressure  
FAS 
3.4.3.X 
Summary of Pulse  
FAS 
3.4.4.X 
Summary of Respiratory Rate 
FAS 
3.4.5.X 
Summary of Body Temperature 
FAS 
3.5 ECG 
3.5.1.X 
Summary of 12-Lead ECG:  PR Interval Values  
FAS 
3.5.2.X 
Summary of 12-Lead ECG:  QRS Interval Values  
FAS 
3.5.3.X 
Summary of 12-Lead ECG:  QT Interval Values  
FAS 
3.5.4.X 
Summary of 12-Lead ECG:  QTcB Interval Values  
FAS 
3.5.5.X 
Summary of 12-Lead ECG:  QTcF Interval Values  
FAS 
3.5.6.X 
Summary of 12-Lead ECG:  RR Interval Values  
FAS 
Note:  For tables ending with "X," separate tables will be provided for the treatment period (FAS) and extension period (TE). 
Listings 
Listing No. 
Title 
Demographic and Baseline Characteristics 
1.1.1 
Participant Enrollment and Disposition Status 
1.1.2 
Participant Inclusion and Exclusion Criteria Violations 
1.1.3 
Protocol Deviations 
1.2.1 
Demographic  


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Listing No. 
Title 
1.2.2 
Baseline Disease Characteristics 
1.3 
General Medical History 
1.4.1 
Prior and Concomitant Medications 
1.4.2 
Prior Medications for AIHA 
1.5 
Study Drug Compliance  
Efficacy 
2.1 
Hemoglobin 
2.2 
Transfusion 
2.3 
Daily Usage of Prednisone  
2.4 
FACIT-F Subscale 
Adverse Events and Exposure 
3.2.1 
Adverse Events 
3.2.2 
Serious Adverse Events 
3.2.3 
Grade 3 or 4 Adverse Events 
3.2.4 
Adverse Events Leading to Death 
3.2.5 
Treatment-Related Adverse Events 
3.2.6 
Adverse Events Leading to Interruption of Study Drug 
3.2.7 
Adverse Events Leading to Discontinuation of Study Drug 
Laboratory Data 
3.3.1 
Clinical Laboratory Values – Hematology 
3.3.2 
Clinical Laboratory Values – Serum Chemistry 
3.3.3 
Abnormal Clinical Laboratory Values – Hematology 
3.3.4 
Abnormal Clinical Laboratory Values – Serum Chemistry 
Vital Signs 
3.4.1 
Vital Signs 
3.4.2 
Abnormal Vital Sign Values 
3.4.3 
Alert Vital Sign Values 
ECG 
3.5.1 
12-Lead ECG Values  
3.5.2 
Abnormal 12-Lead ECG Values  
3.5.3 
Alert 12-Lead ECG Values