Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
Keywords: Warm Autoimmune Hemolytic Anemia (wAIHA)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 13
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of parsaclisib compared with placebo in participants with Primary Warm Autoimmune Hemolytic Anemia (wAIHA),

Detailed description:
Prospective participants must have primary wAIHA as well as other protocol-defined criteria. After participants have been determined to be eligible for the study, they will be randomized to 2:1, with stratification factor of corticosteroid dose and hemoglobin (Hgb \<9 g/dL or ≥ 9 g/dL). Once a participant has completed the week 24 assessments in the double-blind period, the participant will have the opportunity to receive parsaclisib in the open-label treatment which will last up to another 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period.

Arms:
arm 1: Participants will receive parsaclisib for 24 weeks (double-blind period). Participant who completed the double-blind period and tolerating the study treatment upon investigator's opinion will continue into open-label period for an additional 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period. arm 2: Participants will receive placebo for 24 weeks (double-blind period). Participants who completed the double-blind period will receive parsaclisib in the 24 week open-label period. Participants may then continue to receive parsaclisib in a long-term extension period.

Interventions: intervention 1: parsaclisinib intervention 2: placebo
Intervention descriptions: intervention 1: parsaclisib will be administered QD orally intervention 2: placebo will be administered QD orally follwed by Parsaclisinib in the open label period

Protocol document:
Prot_000.pdf: 
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and 
Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia 
(PATHWAY)
NCT Number: NCT05073458
Document Date: Clinical Study Protocol Amendment Version 2: 10 MAY 2023


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Clinical Study Protocol 
TITLE PAGE 
INCB 50465-309
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the 
Efficacy and Safety of Parsaclisib in Participants With Primary Warm 
Autoimmune Hemolytic Anemia (PATHWAY) 
Product: 
INCB050465 (Parsaclisib) 
IND Number: 
147,208 
EudraCT Number: 
2021-002844-66 
Phase of Study: 
3 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, Delaware, USA 19803 
Original Protocol: 
27 MAY 2021 
Amendment 1: 
18 AUG 2022 
Amendment 2: 
10 MAY 2023 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki (Brazil 2013) and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and 
applicable laws and country-specific regulations, including WMO (Medical Research Involving Human Participants 
Act) and Clinical Trials Regulation (EU) No. 536/2014, in which the study is being conducted. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCB 50465-309 Protocol Amendment 2 (dated 10 MAY 2023) 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 ......................................................................................................24 
2.1. 
Background .................................................................................................................24 
2.1.1. 
Warm Autoimmune Hemolytic Anemia .....................................................................24 
2.2. 
Study Rationale ...........................................................................................................25 
2.2.1. 
Scientific Rationale for Study Design ........................................................................26 
2.2.2. 
Justification for Dose ..................................................................................................27 
2.3. 
Benefit/Risk Assessment ............................................................................................28 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................29 
4. 
STUDY DESIGN .......................................................................................................32 
4.1. 
Overall Design ............................................................................................................32 
4.2. 
Overall Study Duration ...............................................................................................33 
4.3. 
Study Termination ......................................................................................................34 
5. 
STUDY POPULATION .............................................................................................35 
5.1. 
Inclusion Criteria ........................................................................................................35 
5.2. 
Exclusion Criteria .......................................................................................................36 
5.3. 
Lifestyle Considerations .............................................................................................38 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................38 
5.4. 
Screen Failures ............................................................................................................38 
5.5. 
Replacement of Participants .......................................................................................38 
5.6. 
Data Safety Monitoring Board ....................................................................................39 
6. 
STUDY TREATMENT ..............................................................................................40 
6.1. 
Study Treatments Administered .................................................................................40 
6.2. 
Preparation, Handling, and Accountability ................................................................40 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................41 
6.4. 
Study Treatment Compliance .....................................................................................42 
6.5. 
Dose Modifications .....................................................................................................42 


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6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................42 
6.5.2. 
Supportive Care for Diarrhea/Colitis ..........................................................................46 
6.5.3. 
Follow-Up for Immune-Related Adverse Events .......................................................47 
6.5.4. 
COVID-19 ..................................................................................................................47 
6.5.5. 
Criteria for Permanent Discontinuation of Study Drug ..............................................47 
6.6. 
Treatment With Parsaclisib During Long-Term Extension ........................................48 
6.7. 
Concomitant Medications and Procedures .................................................................48 
6.7.1. 
Permitted Medications and Procedures ......................................................................49 
6.7.1.1. 
Pneumocystis jirovecii Pneumonia Prophylaxis .........................................................49 
6.7.1.2. 
Folic Acid, Vitamin B12, or Iron Deficiencies ...........................................................49 
6.7.1.3. 
Vaccinations ...............................................................................................................49 
6.7.1.4. 
Corticosteroids ............................................................................................................49 
6.7.2. 
Restricted Medications and Procedures ......................................................................50 
6.7.3. 
Prohibited Medications and Procedures .....................................................................50 
6.7.4. 
Rescue Treatment .......................................................................................................51 
6.8. 
Treatment After the End of the Study .........................................................................51 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
WITHDRAWAL ........................................................................................................52 
7.1. 
Discontinuation of Study Treatment ...........................................................................52 
7.1.1. 
Reasons for Discontinuation .......................................................................................52 
7.1.2. 
Discontinuation Procedures ........................................................................................52 
7.2. 
Participant Withdrawal From the Study .....................................................................53 
7.3. 
Lost to Follow-Up.......................................................................................................53 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................55 
8.1. 
Administrative and General Procedures .....................................................................55 
8.1.1. 
Informed Consent Process ..........................................................................................55 
8.1.2. 
Screening Procedures ..................................................................................................56 
8.1.3. 
Interactive Response Technology Procedure ..............................................................56 
8.1.4. 
Distribution of Reminder Cards and Diaries ..............................................................56 
8.1.5. 
Demography and Medical History ..............................................................................56 
8.1.5.1. 
Demographics and General Medical History .............................................................56 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................57 
8.2. 
Efficacy Assessments .................................................................................................57 


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8.2.1. 
Hemoglobin Level, 
 and Direct Antiglobulin Test .....................57 
8.3. 
Patient-Reported Outcomes ........................................................................................57 
8.3.1. 
Functional Assessment of Chronic Illness Therapy – Fatigue ...................................57 
8.3.2. 
Six-Minute Walk Test .................................................................................................57 
 
.58 
 
.58 
 
58 
 
.58 
 
58 
 
......................59 
 
59 
8.4. 
Safety Assessments .....................................................................................................60 
8.4.1. 
Adverse Events ...........................................................................................................60 
8.4.2. 
Physical Examinations ................................................................................................61 
8.4.3. 
Vital Signs ..................................................................................................................61 
8.4.4. 
Electrocardiograms .....................................................................................................61 
8.4.5. 
Laboratory Assessments .............................................................................................62 
8.4.5.1. 
Pregnancy Testing ......................................................................................................64 
8.4.5.2. 
Serology ......................................................................................................................64 
 
64 
 
65 
8.7. 
Unscheduled Visits .....................................................................................................65 
8.8. 
Long-Term Extension .................................................................................................65 
8.9. 
End of Treatment ........................................................................................................65 
8.10. 
Post-Treatment Follow-Up .........................................................................................66 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................67 
9.1. 
Definition of Adverse Event .......................................................................................67 
9.2. 
Definition of Serious Adverse Event ..........................................................................68 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........69 
9.4. 
Reporting of Serious Adverse Events .........................................................................71 
9.5. 
Potential Drug-Induced Liver Injury ..........................................................................72 
9.6. 
Events of Clinical Interest ..........................................................................................73 
9.6.1. 
Adverse Events of Special Interest .............................................................................73 


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9.7. 
Emergency Unblinding of Treatment Assignment .....................................................73 
9.8. 
Pregnancy ...................................................................................................................74 
9.9. 
Warnings and Precautions ..........................................................................................74 
9.10. 
Product Complaints ....................................................................................................74 
9.11. 
Treatment of Overdose ...............................................................................................75 
10. 
STATISTICS ..............................................................................................................76 
10.1. 
Sample Size Determination ........................................................................................76 
10.2. 
Populations for Analysis .............................................................................................76 
10.3. 
Statistical Analyses .....................................................................................................76 
10.3.1. 
Primary Analysis ........................................................................................................76 
10.3.2. 
Secondary Analysis ....................................................................................................78 
10.3.3. 
Safety Analyses ..........................................................................................................78 
10.4. 
Interim Analysis ..........................................................................................................79 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................80 
11.1. 
Investigator Responsibilities .......................................................................................80 
11.1.1. 
Identification of the Coordinating Principal Investigator ...........................................81 
11.2. 
Data Management .......................................................................................................81 
11.3. 
Data Quality Assurance ..............................................................................................83 
11.4. 
Data Privacy and Confidentiality of Study Records ...................................................83 
11.5. 
Financial Disclosure ...................................................................................................84 
11.6. 
Publication Policy .......................................................................................................84 
11.7. 
Study and Site Closure................................................................................................85 
12. 
REFERENCES ...........................................................................................................86 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS AND DEFINITIONS ............................................88 
APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS .......................................................................................................90 
APPENDIX C. INSTRUCTIONS TO PARTICIPANTS FOR HANDLING STUDY 
DRUG .........................................................................................................................93 
APPENDIX D. MANAGEMENT OF POTENTIAL HY'S LAW CASES ................................94 
APPENDIX E. CYP3A INHIBITORS AND INDUCERS .........................................................98 
APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................105 
 


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LIST OF TABLES 
Table 1: 
Primary and Secondary Objectives and Endpoints .....................................................11 
Table 2: 
Key Study Design Elements .......................................................................................12 
Table 3: 
Schedule of Activities (Double-Blind) .......................................................................15 
Table 4: 
Schedule of Activities (Open-Label) ..........................................................................19 
Table 5: 
Schedule of Activities (Long-Term Extension) ..........................................................22 
Table 6: 
Objectives and Endpoints ...........................................................................................29 
Table 7: 
Exclusionary Laboratory Values ................................................................................38 
Table 8: 
Study Treatment Information .....................................................................................40 
Table 9: 
Guidelines for Interruption and Restarting of Study Drug .........................................43 
Table 10: Tapering Guidelines for Corticosteroids ....................................................................50 
Table 11: Required Laboratory Analytes ....................................................................................63 
 
65 
Table 13: Populations for Analysis .............................................................................................76 
Table 14: Criteria for Clinically Notable Electrocardiogram Abnormalities .............................79 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema .................................................................................................13 
 


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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
6MWT 
6-minute walk test 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
AIHA 
autoimmune hemolytic anemia 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
ANC 
absolute neutrophil count 
ANSM 
National Agency for the Safety of Medicines and Health Products (France) 
anti-HCV 
hepatitis C virus antibody 
AST 
aspartate transaminase 
BfArM 
The Federal Institute for Drugs and Medical Devices (Germany) 
CAD 
cold agglutinin disease 
CFR 
Code of Federal Regulations 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration Equation 
 
 
CMH 
Cochran-Mantel-Haenszel 
CMV 
cytomegalovirus 
COVID-19 
coronavirus disease 2019 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DAT 
direct antiglobulin test 
DNA 
deoxyribonucleic acid 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
ECI 
Events of Clinical Interest 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eDSMB 
external Data Safety Monitoring Board 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
EOT 
end of treatment 
EQ-VAS 
EuroQol Visual Analogue Scale 
FACIT 
Functional Assessment of Chronic Illness Therapy 


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Abbreviations and 
Special Terms 
Definition 
FACIT-F 
Functional Assessment of Chronic Illness Therapy – Fatigue 
Fc 
fragment crystallizable 
FDA 
Food and Drug Administration (US) 
FSH 
follicle-stimulating hormone 
FUP 
follow-up period 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
Hemoglobin response A hemoglobin level ≥ 10 g/dL with a 2 g/dL increase from baseline (Day 1) 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRT 
hormonal replacement therapy 
IB 
Investigator's Brochure 
IC50 
concentration that results in 50% inhibition 
IC90 
concentration that results in 90% inhibition 
ICF 
informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
IFN-γ 
interferon γ 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IL 
interleukin 
IQRMP 
Integrated Quality Risk Management Plan 
IRB 
institutional review board 
IRT 
interactive response technology 
ITT 
intent to treat 
IVIG 
intravenous immunoglobulin 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines & Healthcare products Regulatory Agency 
NCCN 
National Comprehensive Cancer Network 
PBMC 
peripheral blood mononuclear cell 
 
 
 
 
PHL 
potential Hy's law 


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Abbreviations and 
Special Terms 
Definition 
PI3K 
phosphoinositide 3-kinase 
PJP 
Pneumocystis jirovecii pneumonia 
 
 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PP 
per protocol 
PRO 
patient-reported outcome 
QD 
once daily 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RSI 
Reference Safety Information 
SAE 
serious adverse event 
SoA 
schedule of activities 
SOP 
standard operating procedure 
Study drug 
Parsaclisib or matching placebo 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
 
 
wAIHA 
warm autoimmune hemolytic anemia 
WBC 
white blood cell 
WOCBP 
woman of childbearing potential 
 
 


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1. 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of 
Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia (PATHWAY) 
Protocol Number:  INCB 50465-309 
Objectives and Endpoints: 
Table 1 presents the primary and major/key secondary objectives and endpoints. 
Table 1: 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of parsaclisib in the 
treatment of participants with wAIHA. 
• Proportion of participants attaining a durable 
hemoglobin response, defined as hemoglobin 
≥ 10 g/dL with an increase from baseline of 
≥ 2 g/dL not attributed to rescue therapy at 
≥ 3 of the 4 available visits at Week 12 and/or 
later during the 24-week double-blind treatment 
period. 
Key Secondary 
To further evaluate the efficacy of parsaclisib in 
the treatment of participants with wAIHA. 
• Proportion of participants with a ≥ 3-point 
increase from baseline in FACIT-F score at 
Week 24. 
Overall Design: 
Table 2 presents the key study design elements.  Further study details are presented after the 
table. 


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Table 2: 
Key Study Design Elements 
Study Phase 
Phase 3 
Clinical Indication 
Primary wAIHA 
Population 
Men and women, aged 18 years or older with primary wAIHA, a hemoglobin 
level ≥ 6.5 to < 10 g/dL with symptomatic anemia at screening, a FACIT-F 
score ≤ 43 at screening without an underlying lymphoproliferative malignancy 
or AIHA secondary to an autoimmune-related condition who have failed at 
least 1 prior standard therapy that is known to confer clinical benefit or who 
are intolerant to treatment or for whom treatment is contraindicated. 
Number of 
Participants 
Approximately 100 participants will be randomized 2:1 (approximately 67:33) 
to receive either parsaclisib or matched placebo.  Participants will be stratified 
by hemoglobin at screening as determined by local laboratory (hemoglobin 
< 9 g/dL or ≥ 9 g/dL), and corticosteroid (prednisone or equivalent) dose at 
screening (≤ 20 mg/day vs > 20 mg/day). 
Note:  Japan must meet a minimum enrollment regulatory requirement; 
therefore, enrollment in Japan may continue after enrollment in other countries 
ends. 
Note:  Upon implementation of Protocol Amendment 2, the study will be 
closed to further enrollment due to the change in the regulatory landscape for 
PI3K inhibitors and the challenges and subsequent low numbers in enrollment. 
Study Design 
Randomized, double-blind, placebo-controlled, multicenter study 
 
 
 
 
 
Estimated Duration 
of Study 
Participation 
Screening period:  Up to 32 days. 
Double-blind treatment period:  24 weeks. 
Open-label treatment period:  24 weeks. 
Long-term extension: approximately 2 years 
Post-treatment follow-up visits:  12 weeks. 
It is estimated that an individual will participate for approximately 3 years. 
Note:  Upon implementation of Protocol Amendment 2, protocol-required 
procedures and visits will be reduced or eliminated for ongoing participants. 
DSMB 
Yes (external) 
Coordinating 
Principal 
Investigators 
Prof. 
, Austria 
Dr. 
 
, Italy 
Treatment Groups and Duration: 
The study design is shown in Figure 1.  The SoA for the double-blind treatment period, 
open-label treatment period, and long-term extension are detailed in Table 3, Table 4, and 
Table 5, respectively.  The specific laboratory analytes are described in Table 11. 


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Figure 1: 
Study Design Schema 
 
a Hemoglobin at screening as determined by local laboratory (< 9 g/dL or ≥ 9 g/dL) and corticosteroid (prednisone 
or equivalent) dose at screening (≤ 20 mg/day vs > 20 mg/day) 
b The primary analysis will be conducted when the last randomized participant has completed the 24-week, 
double-blind treatment period. 
Participants will receive parsaclisib 2.5 mg QD or matching placebo QD for 24 weeks during the 
double-blind treatment period.  All participants who complete the double-blind treatment period, 
are tolerating study treatment, and in the investigator's opinion may benefit from treatment may 
continue into an open-label treatment period for an additional 24 weeks of parsaclisib QD.  All 
participants who complete the open-label treatment period, are tolerating study treatment, and in 
the investigator's opinion may benefit from continued treatment may enter into the long-term 
extension.  During the long-term extension, participants may take a drug holiday 1 time with the 
option for re-treatment if they experience worsening of wAIHA after the drug holiday. 
Note:  Upon implementation of Protocol Amendment 2: 
• Participants randomized to placebo during the 24-week double-blind treatment period 
may receive parsaclisib before reaching Week 24.  
• Once treatment with parsaclisib is started, participants will enter the open-label 
treatment period (see Table 4) regardless of visits completed during the double-blind 
treatment period. 
Participants who permanently discontinue study treatment will enter the 12-week post-treatment 
follow-up period, which includes 3 visits (1 every 4 weeks) to assess safety and persistence of 
effect. 
Note:  Upon implementation of Protocol Amendment 2: 
• Participants receiving parsaclisib who permanently discontinue study drug will enter 
the post-treatment follow-up period for 1 visit (FUP1/EOS) approximately 4 weeks 
after the last dose of study drug.   
• Participants receiving placebo who permanently discontinue study drug will no longer 
be required to enter the post-treatment follow-up period and will perform EOT/EOS 
upon discontinuation of treatment.    


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Throughout the study, dose reductions from 2.5 mg to 1 mg are allowed due to intolerable AEs 
or hemoglobin levels in the high end of normal range that in the investigator's opinion requires a 
dose reduction.  During the study, the investigator may treat a participant with low hemoglobin 
or symptomatic anemia requiring treatment according to the rescue treatment plan 
(Section 6.7.4). 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
Note:  Upon implementation of Protocol Amendment 2, protocol-required procedures and visits 
will be reduced or eliminated for ongoing participants (see Table 3, Table 4, and respective 
sections for details). 


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Table 3: 
Schedule of Activities (Double-Blind) 
Visit Day (Range) 
Screening 
Double-Blind Treatment Period 
Notes and Protocol Section 
Day −32 
to −1 
Day 1 
W2 
± 3 d 
W4 
± 3 d 
W6 
± 3 d 
W8 
± 3 d 
W10 
± 3 d 
W12 
± 3 d 
W16 
± 3 d 
W20 
± 3 d 
EOT1a/EOSb 
W24 ± 3 d 
In-office visit 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
Remote visit 
 
 
 
 
X 
 
X 
 
 
 
 
May be performed in office at the discretion of 
the investigator.  Note:  Where local laws and/or 
regulations do not permit remote visits, these 
assessments will be performed in office. 
Administrative procedures 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Section 8.1.1 
Contact IRT 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Section 8.1.3 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Section 5.1 and Section 5.2 
Demography, wAIHA disease 
history and medical history and 
AIHA symptoms 
X 
 
 
 
 
 
 
 
 
 
 
Demography will be collected as permitted per 
local regulations. 
Section 8.1.5 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.7 
Randomize to treatment arm 
 
X 
 
 
 
 
 
 
 
 
 
Section 6.3 and Section 8.1.3 
Distribute reminder cards 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Section 8.1.4 
Dispense study drug 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X* 
*Participants continuing into open-label 
treatment period. 
Section 6.1 and Section 8.1.3 
Study drug return, accountability 
and compliance assessment 
 
 
X 
X 
 
X 
 
X 
X 
X 
X 
Section 6.4  
Prophylactic treatment for PJP 
 
As prescribed by the investigator throughout study 
Section 6.7.1.1 
Healthcare resource utilization* 
 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Section 8.3.8 
*No longer required upon implementation of 
Protocol Amendment 2. 
Safety assessments 
Comprehensive physical 
examination 
X 
 
 
 
 
 
 
 
 
 
X 
Height and weight at screening only. 
Section 8.4.2 
Targeted physical examination 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
Section 8.4.2 


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Table 3: 
Schedule of Activities (Double-Blind) (Continued) 
Visit Day (Range) 
Screening 
Double-Blind Treatment Period 
Notes and Protocol Section 
Day −32 
to −1 
Day 1 
W2 
± 3 d 
W4 
± 3 d 
W6 
± 3 d 
W8 
± 3 d 
W10 
± 3 d 
W12 
± 3 d 
W16 
± 3 d 
W20 
± 3 d 
EOT1a/EOSb 
W24 ± 3 d 
Safety assessments (continued) 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.4.3 
12-lead ECG 
X 
 
 
 
 
 
 
X 
 
 
X 
Section 8.4.4 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 9 
Laboratory assessmentsc 
Serum FSH 
X 
 
 
 
 
 
 
 
 
 
 
Confirmation of lack of childbearing potential. 
Serology 
X 
X* 
Hepatitis tests should be performed early in the 
screening process due to the length of time 
needed to obtain the results. 
*CMV testing only and monitor as clinically 
indicated 
Section 8.4.5.2 
D-dimer 
X 
 
 
X 
 
X 
 
X 
 
X 
X 
Section 8.4.5 
Vitamin B12/folic acid 
X 
 
 
 
 
 
 
 
 
 
 
Section 8.4.5 
Serum pregnancy 
X 
 
 
 
 
 
 
 
 
 
X 
WOCBP only. 
Section 8.4.5.1 
Urine pregnancy 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
WOCBP only. 
Section 8.4.5.1 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
Section 8.4.5 
Serum chemistry 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Section 8.4.5 
Efficacy assessments 
Hematology 
X 
X 
X* 
X 
X* 
X 
X* 
X 
X 
X 
X 
Section 8.2.1 and Section 8.4.5 
*No longer required upon implementation of 
Protocol Amendment 2. 
DAT 
X 
 
 
 
 
 
 
 
 
 
X 
Section 8.2.1 and Section 8.4.5 


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Table 3: 
Schedule of Activities (Double-Blind) (Continued) 
Visit Day (Range) 
Screening 
Double-Blind Treatment Period 
Notes and Protocol Section 
Day −32 
to −1 
Day 1 
W2 
± 3 d 
W4 
± 3 d 
W6 
± 3 d 
W8 
± 3 d 
W10 
± 3 d 
W12 
± 3 d 
W16 
± 3 d 
W20 
± 3 d 
EOT1a/EOSb 
W24 ± 3 d 
PRO and clinical outcome assessments (Note:  Upon implementation of Protocol Amendment 2, the PROs noted herein will no longer be required) 
FACIT-F scale 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
Should be completed before any other 
assessments. 
Must be completed before all other PRO 
assessments. 
Section 8.3.1 
6MWT 
 
X 
 
 
 
 
 
 
 
 
X 
Vital signs should be conducted pre- and 
post-test. 
6MWT must be performed after all other PRO 
assessments are completed. 
Section 8.3.2 


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Table 3: 
Schedule of Activities (Double-Blind) (Continued) 
Visit Day (Range) 
Screening 
Double-Blind Treatment Period 
Notes and Protocol Section 
Day −32 
to −1 
Day 1 
W2 
± 3 d 
W4 
± 3 d 
W6 
± 3 d 
W8 
± 3 d 
W10 
± 3 d 
W12 
± 3 d 
W16 
± 3 d 
W20 
± 3 d 
EOT1a/EOSb 
W24 ± 3 d 
 
a Participants receiving parsaclisib who permanently discontinue study drug will enter the post-treatment follow-up period (see Table 4 and Section 8.10). 
b Participants receiving placebo who permanently discontinue study drug will no longer be required to enter the post-treatment follow-up period and will perform EOT1/EOS upon 
discontinuation of treatment. 
c Fasting is not required for central laboratory assessments. 


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Table 4: 
Schedule of Activities (Open-Label) 
Visit Day (Range) 
Open-Label Treatment 
Post-Treatment 
Follow-Up 
Notes and Protocol Section 
W26 
± 3 d 
W28 
± 5 d 
W30 
± 5 d 
W32 
± 5 d 
W36 
± 5 d 
W40 
± 5 d 
W44 
± 5 d 
EOT2 
W48 
± 5 d 
FUP1a/
EOS 
FUP2b 
FUP3b 
In-office visit 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Remote visit 
X 
 
X 
 
 
 
 
 
 
X 
 
May be performed in-office at the 
discretion of the investigator.  Note:  
Where local laws and/or regulations do 
not permit remote visits, these 
assessments will be performed in 
office. 
Administrative procedures 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.7 
Contact IRT 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
Section 8.1.3 
Distribute reminder cards 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Section 8.1.4 
Dispense study drug 
 
X 
 
X 
X 
X 
X 
X* 
 
 
 
*Participants continuing into long-term 
extension. 
Section 6.1 and Section 8.1.3 
Study drug return, accountability 
and compliance assessment 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Section 6.4 
Prophylactic treatment for PJP 
As prescribed by the investigator throughout study 
Section 6.7.1.1 
Healthcare resource utilization* 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
Section 8.3.8 
*No longer required upon 
implementation of Protocol 
Amendment 2. 
Safety assessments 
AE assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.4.1 
Comprehensive physical 
examination 
 
 
 
 
 
 
 
X 
X 
 
X 
Section 8.4.2 
Targeted physical examination 
 
X 
 
X 
X 
X 
X 
 
 
 
 
Section 8.4.2 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.4.3 
12-lead ECG 
 
 
 
 
 
 
 
X 
 
 
 
Section 8.4.4 


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Table 4: 
Schedule of Activities (Open-Label) (Continued) 
Visit Day (Range) 
Open-Label Treatment 
Post-Treatment 
Follow-Up 
Notes and Protocol Section 
W26 
± 3 d 
W28 
± 5 d 
W30 
± 5 d 
W32 
± 5 d 
W36 
± 5 d 
W40 
± 5 d 
W44 
± 5 d 
EOT2 
W48 
± 5 d 
FUP1a/
EOS 
FUP2b 
FUP3b 
Efficacy assessments 
Hematology 
X* 
X 
X* 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.2.1 and Section 8.4.5 
*No longer required upon 
implementation of Protocol 
Amendment 2. 
DAT 
 
 
 
 
 
 
 
X 
 
 
 
Section 8.2.1 and Section 8.4.5 
PRO and clinical outcome assessments (Note:   Upon implementation of Protocol Amendment 2, the PROs noted herein will no longer be required) 
FACIT-F scale 
 
X 
 
X 
 
X 
 
X 
 
 
X 
Should be completed before any other 
assessments. 
Must be completed before all other 
PRO assessments. 
Section 8.3.1 


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Table 4: 
Schedule of Activities (Open-Label) (Continued) 
Visit Day (Range) 
Open-Label Treatment 
Post-Treatment 
Follow-Up 
Notes and Protocol Section 
W26 
± 3 d 
W28 
± 5 d 
W30 
± 5 d 
W32 
± 5 d 
W36 
± 5 d 
W40 
± 5 d 
W44 
± 5 d 
EOT2 
W48 
± 5 d 
FUP1a/
EOS 
FUP2b 
FUP3b 
PRO and clinical outcome assessments (continued) (Note:  Upon implementation of Protocol Amendment 2, the PROs noted herein will no longer be required) 
6MWT 
 
 
 
 
 
 
 
X 
 
 
X 
Vital signs should be conducted 
pre- and post-test. 
6MWT must be performed after all 
other PRO assessments are completed. 
Section 8.3.2 
Laboratory assessmentsc 
D-dimer 
 
X 
 
X 
X 
 
X 
X 
 
 
 
Section 8.4.5 
Serum pregnancy 
 
 
 
 
 
 
 
X 
 
 
X 
WOCBP only. 
Section 8.4.5.1 
 
Urine pregnancy 
 
X 
 
X 
 
X 
 
 
X 
X 
 
WOCBP only. 
Section 8.4.5.1 
Serum chemistry 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Section 8.4.5 
CMV 
X* 
 
 
 
*Monitor as clinically indicated 
a Only required for participants receiving parsaclisib; post-treatment follow-up visit to be conducted 4 weeks (± 5 days) after EOT visit (or after the last dose of study drug if the 
EOT visit was not performed). 
b No longer required upon implementation of Protocol Amendment 2. 
c Fasting is not required for central laboratory assessments. 


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Table 5: 
Schedule of Activities (Long-Term Extension) 
Visit Day (Range) 
Long-Term Extension 
Notes and Protocol Section 
W56 
(± 7 d) 
Every 8 Weeks 
(± 7 d) 
Every 16 Weeks 
(± 7 d) 
EOT3a 
In-office visit 
X 
X 
 
X 
 
Administrative procedures 
Contact IRT 
X 
X 
 
X 
Section 8.1.3 
Prior/concomitant medications 
X 
X 
 
X 
Section 6.7 
Distribute reminder cards 
X 
X 
 
X 
Section 8.1.4 
Dispense study drug 
X 
X 
 
 
Section 6.1 and Section 8.1.3 
Study drug return, accountability and 
compliance assessment 
X 
X 
 
X 
Section 6.4 
Prophylactic treatment for PJP 
As prescribed by the investigator throughout study 
Section 6.7.1.1 
Healthcare resource utilization 
X 
 
X 
X 
Section 8.3.8 
Safety assessments 
Comprehensive physical examination 
 
 
 
X 
Section 8.4.2 
Targeted physical examination 
X 
X 
 
 
Section 8.4.2 
Vital signs 
X 
X 
 
X 
Section 8.4.3 
AE assessment 
X 
X 
 
X 
Section 8.4.1 
Laboratory assessmentsb 
CMV 
X* 
*Monitor as clinically indicated 
D-dimer 
X* 
*Perform as clinically indicated 
Section 8.4.5 
Serum pregnancy 
 
 
 
X 
WOCBP only. 
Section 8.4.5.1 
Urine pregnancy 
X 
X 
 
 
WOCBP only. 
Section 8.4.5.1 
Serum chemistry 
X 
X 
 
X 
Section 8.4.5 
Efficacy assessments 
Hematology 
X 
X 
 
X 
Section 8.2.1 and Section 8.4.5 
DAT 
 
 
 
X 
Section 8.2.1 and Section 8.4.5 


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Table 5: 
Schedule of Activities (Long-Term Extension) (Continued) 
Visit Day (Range) 
Long-Term Extension 
Notes and Protocol Section 
W56 
(± 7 d) 
Every 8 Weeks 
(± 7 d) 
Every 16 Weeks 
(± 7 d) 
EOT3a 
PRO and clinical outcome assessments Note:  Upon implementation of Protocol Amendment 2, the PROs noted herein will no longer be required 
FACIT-F scale 
X 
 
X 
X 
Should be completed before any other 
assessments. 
Must be completed before all other PRO 
assessments. 
Section 8.3.1 
a Participants receiving parsaclisib who permanently discontinue study drug will enter the post-treatment follow-up period (see Table 4 and Section 8.10). 
b Fasting is not required for central laboratory assessments. 


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2. 
INTRODUCTION 
Parsaclisib is a potent inhibitor of PI3Kδ (IC50 value = 1.1 ± 0.5 nM), with approximately 
20,000-fold selectivity for the other PI3K family members (refer to the IB).  B-cell proliferation 
triggered by anti–IgM-mediated cross-linking of the B-cell receptor is known to be PI3Kδ 
dependent.  Parsaclisib potently inhibits antibody-induced proliferation of human CD19+ B cells 
with an IC50 value of 0.21 nM.  In addition, parsaclisib also inhibited B-cell proliferation in 
response to multiple inflammatory stimuli (IL-4, lipopolysaccharides, CD40L, anti-CD40, IL-6, 
and B-cell activation factor).  These effects were not due to parsaclisib-mediated general 
cytotoxicity. 
Parsaclisib 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. 
Clinical experiences of parsaclisib are based on a Phase 2 study (INCB 50465-206) in 
participants with wAIHA, CAD, or mixed-type AIHA, and oncology studies in patients with 
cancer who received higher doses for longer periods of time (refer to the IB). 
2.1. 
Background 
2.1.1. 
Warm Autoimmune Hemolytic Anemia 
Autoimmune hemolytic anemia is a rare acquired disorder in which autoantibodies directed 
against RBC membrane antigens lead to accelerated destruction of RBCs.  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) is the coexistence 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.  Primary CAD accounts for approximately 15% of AIHA and is defined as 
an AIHA mediated by cold agglutinins without any underlying disease such as aggressive 
lymphoma, other overt malignancies, or specific infections (Berentsen 2016). 
There are several immunologic mechanisms 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 natural killer 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 


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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. 
Currently there is no approved therapy for wAIHA.  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 (Barcellini et al 2014).  
Because 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%.  However, there is increasing concern not only with susceptibility to infection 
following splenectomy, but also increasing recognition of thrombosis risk from splenectomy, 
resulting in some reluctance to use this in the treatment algorithm. 
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 is 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.  Rituximab has been considered as second-line therapy for wAIHA.  Second-line 
treatment of wAIHA 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 progressive multifocal leukoencephalopathy (Carson et al 2009). 
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 case reports or small retrospective studies. 
2.2. 
Study Rationale 
Note:  The regulatory landscape for the development and approval of PI3K inhibitors in 
hematologic diseases has recently changed.  Furthermore, enrollment into this study has been 
challenging and only 12 participants have been randomized since the start of the study in 
MAR 2022.  Therefore, upon implementation of Protocol Amendment 2, the study will be closed 
to further enrollment considering these aspects. 
Currently, there is no approved therapy for primary wAIHA and there are limited 
placebo-controlled studies that document the course of the disease.  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 wAIHA.  Therefore, there remains an 
unmet need for new treatments for wAIHA.  In addition to showing efficacy in a number of 
B-cell–related cancers, treatment with parsaclisib has shown significant improvement in animal 
models of AIHA and lupus nephritis, as well as other antibody-mediated diseases.  Parsaclisib 
may represent an alternative treatment for participants who have failed at least 1 prior treatment.  
While many patients with wAIHA respond to prednisone, many patients either do not tolerate 
higher doses of prednisone or are unable to withdraw from prednisone without flare of wAIHA; 
parsaclisib may provide an option to patients who are intolerant to or unable to withdraw from 


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steroids or when corticosteroid treatment is contraindicated.  In addition, parsaclisib may be a 
more flexible intervention, as current therapy with rituximab results in profound and sustained 
depletion of circulating B cells. 
In the ongoing Phase 2 study, efficacy was shown by an increase in hemoglobin at Week 12 and 
an improvement in FACIT-F scores.  In addition, parsaclisib was generally well-tolerated in 
participants treated up to 585 days (mean:  240.57; range:  7-585 days).  The dose and design of 
this Phase 3 study is supported by the preliminary results from Study INCB 50465-206.  The 
rationale for the study design appears in Section 2.2.1. 
2.2.1. 
Scientific Rationale for Study Design 
This Phase 3, double-blind, randomized, multicenter, placebo-controlled study is designed to 
evaluate the efficacy and safety of parsaclisib in participants with primary wAIHA.  The clinical 
manifestations of wAIHA are driven through production of autoantibodies via aberrant B-cell 
activity. 
Eligible participants in this study must have failed at least 1 prior therapy, have been intolerant to 
prior therapy, or other therapy must be contraindicated for them.  Approximately 
100 participants will be eligible for enrollment.  A significant percentage of wAIHA patients fail 
or relapse following first-line therapies, including withdrawal from corticosteroids, and are a 
population who may benefit from novel treatments. 
A placebo comparator was selected in order to evaluate the hemoglobin response and safety of 
parsaclisib.  Placebo control is appropriate when 1) there is no proven effective treatment for the 
condition under study, 2) withholding treatment poses negligible risks to participants, 3) there 
are compelling methodological reasons for using placebo, and 4) the research is intended to 
develop interventions that can be implemented in the population from which study participants 
are drawn and the study does not require participants to forgo treatment they would otherwise 
receive (Millum and Grady 2013). 
As corticosteroid treatment plays an important role in the management of AIHA, participants 
who are eligible for the study and are receiving ≤ 40 mg/day of prednisone at randomization will 
continue on corticosteroids (equivalent to ≤ 40 mg/day of prednisone) during the double-blind 
treatment period.  Taper or withdrawal of steroids will be permitted during the study at the 
investigator's discretion when a stable hemoglobin response has been achieved (see Table 10). 
Due to onset of action of parsaclisib in modulating B-cell function and reducing circulating 
autoantibodies, the effect of parsaclisib on hemoglobin may not be observed until Week 6.  
Given the natural history of wAIHA, participants may require supportive care for hemoglobin 
over the initial 6 weeks.  Participants who experience worsening of wAIHA may receive rescue 
treatment during the study (see Section 6.7.4).  Participants who receive rescue therapy after 
Week 6 will be considered nonresponders in the primary efficacy analysis but may continue in 
the study at the discretion of the investigator. 
At Week 24, all participants who complete the double-blind treatment period, are tolerating 
study treatment, and in the investigator's opinion may benefit from treatment with parsaclisib 
may continue into an open-label treatment period.  These participants will receive 24 weeks of 
parsaclisib QD, which will provide placebo participants access to active treatment and will 
evaluate the long-term efficacy and safety of parsaclisib in participants that originally received 


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parsaclisib.  Access to parsaclisib with further evaluation of long-term efficacy and safety will 
then continue in the long-term extension period of this study.  
The primary endpoint will be the proportion of participants attaining a durable hemoglobin 
response (defined as hemoglobin ≥ 10 g/dL with an increase from baseline of ≥ 2 g/dL not 
attributed to rescue therapy) at ≥ 3 of the 4 available visits at Week 12 and/or later during the 
24-week double-blind treatment period.  Hemoglobin is the most direct indicator of clinical 
severity in hemolytic diseases (Barcellini and Fattizzo 2015).  Because wAIHA is a chronic 
condition, a durable hemoglobin response during the double-blind period may represent a more 
stable and beneficial effect over time for wAIHA patients than a single visit value.  This is 
supported by the data from the Phase 2 study in which most patients who achieved a hemoglobin 
response did so by Week 12. 
The FACIT-F scale was developed to assess anemia related fatigue (Yellen et al 1997).  A 
clinically meaningful change in the FACIT-F score will be defined as ≥ 3-point increase from 
baseline.  In patients with fatigue symptoms associated with anemia, a difference of 3 in the 
FACIT-F score was reported as the minimum clinically important difference (Cella et al 2002). 
2.2.2. 
Justification for Dose 
Parsaclisib 2.5 mg QD or matching placebo will be self-administered for 24 weeks, followed by 
continued treatment with parsaclisib QD in the open-label period for up to 24 weeks and in the 
long-term extension. 
In study INCB 50465-206, exploration of parsaclisib dose in AIHA participants resulted in a 
determination of 2.5 mg QD as the recommended dose. 
In Cohort 1 (N = 10), all participants were initially treated with parsaclisib 1.0 mg QD.  Based on 
insufficient hemoglobin response by Week 6, 8 of the 10 enrolled participants had their dose 
increased to 2.5 mg QD at Week 6 (1 participant remained on 1.0 mg and 1 participant 
discontinued before Week 6). 
In Cohort 2 (N = 15), all participants were treated with parsaclisib 2.5 mg QD for 12 weeks. 
During the course of the study, 7 out of 21 (33.3%) participants (N = 2 Cohort 1, N = 5 for 
Cohort 2) achieved a complete response (hemoglobin ≥ 12 g/dL) at any visit from Week 6 to 
Week 12.  Fourteen of 21 (66.7%) participants (N = 6 Cohort 1, N = 8 Cohort 2) achieved a 
partial response (defined as a hemoglobin of ≥ 10 g/dL or a ≥ 2 g/dL increase from baseline).  
Mean increases in hemoglobin were seen at Week 2 and continued to increase through Week 12 
with Cohort 2 achieving a higher mean increase of 2.4 g/dL compared with 1.3 g/dL in Cohort 1 
at Week 12.  Overall, the dose of parsaclisib 2.5 mg QD is generally well–tolerated (refer to 
parsaclisib IB).  The dose of 2.5 mg is proposed to provide sufficient exposure (estimated to be 
approximately 1 × IC90 at trough) to maintain PI3K pathway inhibition while minimizing the 
frequency of late-onset AEs that may lead to study treatment withdrawal.  Higher doses of 
parsaclisib have been explored in the oncology program (up to 45 mg QD).  In oncology patients, 
higher rates of AEs were observed at doses above 5 mg per day. 
If there are any intolerable AEs or hemoglobin in the high end of normal range in individual 
participants who receive 2.5 mg QD of study treatment, the dose should be decreased to 1 mg 
QD (see Section 6.5). 


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2.3. 
Benefit/Risk Assessment 
Parsaclisib monotherapy provided a durable improvement in hemoglobin in participants with 
AIHA (see Section 2.2.2).  The safety profile for parsaclisib is described in the parsaclisib IB.  
Briefly, AEs were observed in participants administered parsaclisib monotherapy in 
inflammatory and autoimmune indications (N = 35), with the most common (in ≥ 10% of 
participants) being diarrhea and pyrexia (22.9% each); headache and rash (14.3% each); and 
AIHA, nausea, and peripheral edema (11.4% each).  Parsaclisib has effects on the immune 
system and serious infection events have occurred in patients treated with parsaclisib, including 
PJP, CMV, and COVID-19.  Due to the severity, these events may impact the benefit-risk 
balance of parsaclisib if not managed appropriately.  Furthermore, a pharmacological effect of 
concurrent corticosteroid use or recent rituximab therapy can contribute to further 
immunosuppression and such effects pose an additional risk of infections.  In an effort to manage 
this risk, guidelines for managing serious infections have been implemented in this study, and 
include careful monitoring and supportive care measures.  If supportive care interventions are 
unsuccessful and causes other than parsaclisib-related infections have been ruled out, then either 
parsaclisib dose modification or permanent discontinuation is recommended.  Participants are 
required to receive a standard PJP prophylaxis regimen while receiving parsaclisib as described 
in Section 6.7.1.1.  Information regarding the additional risks of diarrhea or colitis, neutropenia, 
and severe cutaneous reactions is outlined in the Warnings and Precautions of the parsaclisib IB.  
Dose modification guidance and supportive care guidelines for these AEs have been 
implemented in this study, and participants will be closely monitored for evidence of toxicities, 
including long-term toxicities. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of parsaclisib may be found in the parsaclisib IB. 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 6 presents the objectives and endpoints. 
Table 6: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of parsaclisib in the 
treatment of participants with wAIHA. 
Proportion of participants attaining a durable 
hemoglobin response, defined as hemoglobin 
≥ 10 g/dL with an increase from baseline of 
≥ 2 g/dL not attributed to rescue therapy at ≥ 3 of 
the 4 available visits at Week 12 and/or later 
during the 24-week double-blind treatment 
period. 
Key Secondary 
To further evaluate the efficacy of parsaclisib in 
the treatment of participants with wAIHA. 
• Proportion of participants with a ≥ 3-point 
increase from baseline in FACIT-F score at 
Week 24. 
Other Secondary 
To further evaluate the efficacy of parsaclisib in 
the treatment of participants with wAIHA. 
• Proportion of participants with a 50 m increase 
from baseline to Week 24 in a 6MWT. 
• Change and percent change from baseline in 
FACIT-F score at each postbaseline visit. 
• Change and percentage change from baseline 
in hemoglobin at each postbaseline visit. 
• Proportion of participants who received 
transfusions from Week 6 to Week 24 and 
from Week 24 to Week 48. 
• Change and percentage change from baseline 
in daily corticosteroid dose at Week 24. 
• Proportion of participants who required rescue 
therapy at any visit from Week 6 through 
Week 24, and from Week 24 to Week 48.  
To evaluate the safety and tolerability of 
parsaclisib in participants with wAIHA. 
• Frequency and severity of AEs, including the 
evaluation of clinical laboratory results, vital 
signs, ECGs, and the results of physical 
examinations. 


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Table 6: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 


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Table 6: 
Objectives and Endpoints (Continued) 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of parsaclisib 2.5 mg QD compared with placebo over a 24-week 
double-blind treatment period followed by a 24-week open-label treatment period of parsaclisib.  
Participants may then continue to receive parsaclisib in a long-term extension period. 
The study will enroll approximately 100 men and women ≥ 18 years with primary wAIHA.  
Participants will be stratified by hemoglobin at screening as determined by local laboratory 
(< 9 g/dL or ≥ 9 g/dL) and corticosteroid (prednisone or equivalent) doses at screening 
(≤ 20 mg/day vs > 20 mg/day). 
Note:  Japan must meet a minimum enrollment regulatory requirement; therefore, enrollment in 
Japan may continue after enrollment in other countries ends. 
Figure 1 presents the study design schema, and Table 3, Table 4, and Table 5 present the SoA for 
the double-blind, placebo-controlled and open-label treatment periods and the long-term 
extension, respectively. 
Note:  Upon implementation of Protocol Amendment 2, the study will be closed to further 
enrollment due to the change in the regulatory landscape for PI3K inhibitors and the challenges 
and subsequent low numbers in enrollment.  
Participants will be screened for up to 32 days before the first dose of study drug (parsaclisib or 
placebo).  Key entry criteria for participants are those with a diagnosis of wAIHA, who were 
inadequately controlled with, were intolerant to, or have a contraindication to other therapies, 
and have a baseline FACIT-F of ≤ 43.  Participants who meet all the study entry inclusion 
criteria and none of the exclusion criteria will return to the study site on Day 1 of dosing and be 
randomized in a 2:1 ratio to parsaclisib 2.5 mg QD or matching placebo QD.  Concomitant 
treatment with corticosteroids (equivalent to ≤ 40 mg/day of prednisone) is allowed throughout 
the study. 
Participants who experience worsening of wAIHA may receive rescue therapy during the study 
as outlined in Section 6.7.4.  Participants who continue to use rescue therapy after Week 6 will 
be considered nonresponders in the primary efficacy analysis but will be allowed to continue in 
the study at the discretion of the investigator.   
All participants who complete the 24-week double-blind treatment period, are tolerating study 
treatment, and in the investigator's opinion may benefit from treatment may enter the 24-week 
open-label treatment period and will receive parsaclisib administered at the same dose and 
schedule as in the double-blind treatment period. 
Note: Upon implementation of Protocol Amendment 2: 
• Participants randomized to placebo during the 24-week double-blind treatment period 
may receive parsaclisib before reaching Week 24.  
• Once treatment with parsaclisib is started, participants will enter the open-label 
treatment period (see Table 4) regardless of visits completed during the double-blind 
treatment period. 


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All participants who complete the open-label treatment period, are tolerating study treatment, 
and in the investigator's opinion may benefit from continued treatment, may enter into the 
long-term extension.  Parsaclisib will be administered at the same dose and schedule as in the 
open-label treatment period.  During the long-term extension, participants may take a drug 
holiday 1 time with the option for re-treatment if they experience worsening of wAIHA after 
interrupting parsaclisib (see Section 6.6 for re-treatment criteria). 
Participants will receive study treatment until any of the criteria for permanent discontinuation of 
study drug are met (see Section 7.1.1).  Participants who permanently discontinue study 
treatment will enter the 12-week post-treatment follow-up period with visits scheduled every 
4 weeks for 12 weeks after the last dose of study drug. 
Note: Upon implementation of Protocol Amendment 2: 
• Participants receiving parsaclisib who permanently discontinue study drug will enter 
the post-treatment follow-up period for 1 visit (FUP1/EOS) approximately 4 weeks 
after the last dose of study drug.   
• Participants receiving placebo who permanently discontinue study drug will no longer 
be required to enter the post-treatment follow-up period and will perform EOT1/EOS 
upon discontinuation of treatment.    
An external DSMB will review safety data periodically throughout the study as defined in the 
DSMB charter and may provide recommendations regarding changes in the study conduct (see 
Section 5.6). 
Participants will be assessed for efficacy by monitoring hemoglobin level 
 
and completing the FACIT-F to assess self-reported fatigue and its impact upon daily activities 
and function.  
 
 
  The primary analysis will be conducted when the last randomized 
participant has completed the double-blind treatment period. 
Participants will be assessed for safety and tolerability by monitoring the frequency and severity 
of AEs and performing physical examinations, ECGs, vital sign measurements, and clinical 
laboratory assessments during the study per the SoA. 
 
  
 
 
Note:  Upon implementation of Protocol Amendment 2, protocol-required procedures have been 
reduced or eliminated for ongoing participants. 
The COVID-19 global pandemic may present challenges to the normal conduct of this study and 
require the outline of potential mitigation strategies described in Appendix B. 
4.2. 
Overall Study Duration 
The study begins when the first participant signs the study ICF.  The end of the study is defined 
as the date of the last visit of the last participant in the study or the last scheduled procedure 
shown in the SoAs (see Table 3, Table 4, and Table 5). 


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An individual's participation is estimated to be approximately 3 years including up to 32 days for 
screening, continuous treatment in the double-blind treatment period (24 weeks); the open-label 
treatment period (24 weeks); and the long-term extension (≈2 years), followed by a 12-week 
post-treatment follow-up. 
A participant is considered to have completed the study if they have completed the double-blind, 
open-label, long-term extension, and post-treatment follow-up periods.  The study is considered 
completed when the last participant visit has occurred. 
In EU/EEA, the results of the study will be based on the date of the last visit of the last 
participant in the study globally. 
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/head of the study site (Japan) is to notify 
the IRB/IEC in writing of the study's completion or early termination, send a copy of the 
notification to the sponsor or sponsor's designee, and retain 1 copy for the site study regulatory 
file. 
The sponsor may terminate the study electively, if, for example, required by regulatory decision 
or upon advice of the DSMB.  If the study is terminated prematurely, the sponsor will notify the 
investigators/head of the study site (Japan), the IRBs and IECs, and regulatory bodies of the 
decision and reason for termination of the study.  The DSMB will recommend termination of the 
study if warranted, as described in Section 5.6.  For Japan, the decision from the sponsor will be 
via the head of the study site(s) who will notify the investigators and the IRBs of the decision 
and reason for termination of the study. 


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5. 
STUDY POPULATION 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or participant safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential.  Prospective approval of 
Protocol deviations to recruitment and enrollment criteria, also known as Protocol waivers or 
exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Ability to comprehend and willingness to sign a written ICF for the study. 
2. Men or women, age ≥ 18 years at the time of signing the ICF. 
3. Diagnosis of primary wAIHA based on the presence of hemolytic anemia and serological 
evidence of anti-erythrocyte antibodies, detectable by a DAT positive for IgG only or IgG 
plus C3d. 
Note:  A DAT performed at screening is preferred; however, prior documentation of 
DAT results within 3 months of randomization is permitted. 
4. Participants who were inadequately controlled with, were intolerant to, or have a 
contraindication to other therapies.  There is no limit to the number of prior treatment 
regimens. 
5. Hemoglobin ≥ 6.5 to < 10 g/dL with symptoms of anemia as assessed by the investigator 
at screening (hemoglobin as determined by local laboratory). 
6. FACIT-F score ≤ 43 at screening. 
7. Willingness to avoid pregnancy or fathering children based on the criteria below. 
a. Male participants with reproductive potential must agree to take appropriate 
precautions to avoid fathering children (with 99% certainty) from screening through 
90 days after the last dose of study drug and must refrain from donating sperm during 
this period.  Permitted methods in that are at least 99% effective preventing 
pregnancy (see Appendix A) should be communicated to the participants and their 
understanding confirmed. 
b. Female participants who are WOCBP must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test before randomization and must agree to 
take appropriate precautions to avoid pregnancy (with 99% certainty) from screening 
through 90 days after the last dose of study drug and must refrain from donating 
oocytes during this period.  Permitted methods that are at least 99% effective 
preventing pregnancy (see Appendix A) should be communicated to the participants 
and their understanding confirmed.  
c. A female participant not considered to be of childbearing potential as defined in 
Appendix A is eligible. 
Note:  This criterion does not apply to women of nonchildbearing potential 
(i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR 


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postmenopausal, defined as amenorrhea at least 12 months before screening, 
confirmed by FSH levels at screening). 
8. Willingness to receive PJP prophylaxis during the study period from Day 1 through at 
least 2 to 6 months after the last dose of study drug. 
9. For participants in France only:  COVID-19 vaccination at least 2 weeks prior to 
randomization. 
10. For participants in France only:  Participant is up-to-date with mandatory vaccinations 
according to the national vaccination program as assessed by the investigator. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Women currently pregnant or breastfeeding or participants expecting to conceive or 
father children within the projected duration of the study, starting with the screening visit 
through 90 days from the date of last dose of study drug. 
2. A diagnosis of other types of AIHA; CAD, cold agglutinin syndrome, mixed-type AIHA 
or paroxysmal cold hemoglobinuria. 
3. Warm AIHA suspected to be secondary to a lymphoproliferative malignancy or 
secondary to an autoimmune disease (eg, systemic lupus erythematosus, Castleman's 
disease, Sjögren's syndrome, or other autoimmune diseases) or diagnosis of Evans 
syndrome. 
4. A splenectomy less than 3 months before randomization. 
5. Concurrent conditions or 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 randomization. 
d. Current New York Heart Association Class II to IV congestive heart failure or 
uncontrolled arrhythmia. 
6. Known diagnosis of anti-phospholipid syndrome or history of persistent 
anti-phospholipid antibodies. 
Note:  Participants at risk for thrombosis who are on adequate prophylaxis or those with 
thrombosis on stable treatment for 3 months prior to randomization are eligible. 
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 


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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 triplicate ECGs is < 470 milliseconds for 
males or < 480 milliseconds for females. 
10. Use of the following medications: 
a. Treatment with rituximab within 6 weeks of randomization. 
b. Use of immunosuppressive therapy within 28 days of the randomization.  
Immunosuppressive therapy includes, but is not limited to, cyclosporine A, 
azathioprine, mycophenolate mofetil, or cyclophosphamide. 
Note:  Participants receiving corticosteroids must be at a stable dose level (no change 
in daily dose) ≤ 40 mg/day (prednisone or equivalent corticosteroid dose) for at 
least 14 days prior to randomization. 
c. Use of IVIG or erythropoietin within 2 weeks of randomization. 
d. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, 
or antiviral treatment or exposure to a live vaccine within 30 days of randomization. 
e. Use or expected use during the study of any prohibited medications (see 
Section 6.7.3), including potent CYP3A4 inhibitors or moderate or potent CYP3A4 
inducers, within 14 days or 5 half-lives (whichever is longer) before randomization 
(see Appendix E). 
11. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before 
randomization with another investigational medication, or current enrollment in another 
investigational drug and/or device protocol. 
12. Known hypersensitivity or severe reaction to parsaclisib or its excipients (IB). 
13. 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. 
14. 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. 
15. Participants who, in the opinion of the investigator, are unable or unlikely to comply 
with the dose regimen and study evaluations. 
16. 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. 


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17. Prior treatment with parsaclisib or another PI3Kδ, or a pan-PI3K inhibitor for any 
indication. 
18. Participants with laboratory values at screening defined in Table 7. 
Table 7: 
Exclusionary Laboratory Values 
Laboratory Parametera 
Exclusion Criterion 
Hematology 
a 
Platelets 
≤ 100 × 109/L 
b 
ANC 
≤ 1.5 × 109/L 
c 
WBCs 
≤ 1.5 × 109/L 
Hepatic 
d 
ALT 
≥ 2 × ULN 
e 
AST 
≥ 2 × ULN unless clearly related to active 
hemolysis 
Renal 
f 
eGFR using 2021 CKD-EPI (Inker et al 2021) 
≤ 45 mL/minute/1.73m2 
a If the central laboratory is unable to perform the test due to hemolysis related to wAIHA or the analytical method, 
then local laboratory test results may be used to determine participant eligibility. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Parsaclisib/placebo will be taken orally with water without regard to food except on mornings of 
 clinic visits.  See Section 8.5 for details on further requirements before and after the start of 
. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study treatment. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. 
Tests with results that fail eligibility requirements may be repeated during screening if the 
investigator believes the result to be in error.  Additionally, a participant who fails screening may 
repeat the screening process if the investigator believes that there has been a change in eligibility 
status.  Participants who rescreen must reconsent and be assigned a new participant number. 
5.5. 
Replacement of Participants 
No participants will be replaced at any time during this study.  However, the COVID-19 global 
pandemic may present challenges to the normal conduct of this study and may require the outline 
of potential mitigation strategies described in Appendix B. 


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5.6. 
Data Safety Monitoring Board 
This study will use an eDSMB to monitor safety as detailed in the DSMB charter. 
The voting members of the committee are external to the sponsor.  The members of the eDSMB 
will not be involved with the study in any other way (eg, they cannot be study investigators) and 
will have no competing interests that could affect their roles with respect to the study. 
The eDSMB will make recommendations to the sponsor regarding steps to ensure both 
participant safety and the continued ethical integrity of the study.  Specific details regarding 
composition, responsibilities, and governance, including the roles and responsibilities of the 
various members and the sponsor, IEC, and protocol team; and requirements for and proper 
documentation of eDSMB reports, minutes, and recommendations will be described in the 
eDSMB charter that is reviewed and approved by all eDSMB members. 


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6. 
STUDY TREATMENT 
6.1. 
Study Treatments Administered 
Information regarding study drug and study drug administration is provided in Table 8.  Further 
information regarding study drug administration is provided in Appendix C.  The COVID-19 
global pandemic may present challenges to the normal conduct of this study, requiring the 
outline of potential mitigation strategies described in Appendix B. 
Table 8: 
Study Treatment Information 
Study treatment name: 
Parsaclisib 
Matching Placebo 
Mechanism of action: 
PI3Kδ inhibitor 
Not applicable 
Dosage formulation: 
Tablet 
Matching Tablet 
Unit dose 
strength(s)/dosage 
level(s): 
2.5 mg 
1 mg  
2.5 mg 
1 mg 
Administration 
instructions: 
1 tablet orally QD. 
Parsaclisib or matching placebo will be taken orally with water without regard to 
food except on mornings of 
 clinic visits. 
Participants should not take their dose at home when they have a 
 visit.  
Parsaclisib should be taken at approximately the same time each day. 
Packaging and labeling: 
Parsaclisib and matching placebo will be 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 parsaclisib and matching placebo should be stored at ambient conditions 
(15°C-30°C or 59°F-86°F). 
Status of treatment in 
participating countries: 
Investigational 
Not applicable 
6.2. 
Preparation, Handling, and Accountability 
The investigator, investigational drug storage manager (for Japan), or designee must confirm 
appropriate temperature conditions have been maintained during transit for all study treatments 
received and any discrepancies are reported and resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatment must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator, investigational drug storage 
manager (for Japan), and authorized site staff. 
The investigator, investigational drug storage manager (for Japan), or designee is responsible for 
study treatment accountability, reconciliation, and record maintenance (ie, receipt, reconciliation, 
and final disposition records).  Inventory and accountability records must be maintained and 
readily available for inspection by the study monitor and are open to inspection at any time by 


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any applicable regulatory authorities.  The investigator, investigational drug storage manager (for 
Japan) or designee must maintain records that document the following: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including tablet counts from each supply dispensed. 
• Return of study drug to the investigator, investigational drug storage manager (for 
Japan) or designee by participants. 
The investigational product must be used only in accordance with the Protocol (see Section 6).  
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, investigational 
drug storage manager (for Japan) 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, 
investigational drug storage manager (for Japan), or designee will oversee shipment of any 
remaining study drug back to the sponsor or its designee for destruction according to institutional 
SOPs.  If local procedures mandate on-site destruction of the investigational supply, the site 
should (where local procedures allow) maintain the investigational supply until the study monitor 
inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the Study Pharmacy Manual. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
All participants will be centrally assigned to study treatment using an IRT (see Section 8.1.3).  
Before the study is initiated, the telephone number and call-in directions for the IRT and/or the 
log in information and directions for the IRT will be provided to each site.  Full details will be 
provided in the IRT Study Reference Manual. 
Study drug will be dispensed at the study visits summarized in the SoA (see Table 3 and 
Table 4).  Returned study drug should not be redispensed to the participants. 
Participants, investigators, and the sponsor will remain blinded to each participant's treatment 
assignment throughout the double-blind portion of the study.  Emergency unblinding will occur 
if an AE requires the investigator to be made aware of the participant's treatment assignment (see 
emergency unblinding procedures in Section 9.7 and refer to the IRT Study Reference Manual). 


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6.4. 
Study Treatment Compliance 
Compliance with all study-related treatments should be emphasized to the participant by the site 
personnel, and appropriate steps should be taken to optimize compliance during the study.  
Compliance with study drug will be calculated by the sponsor based on the drug accountability 
documented by the site staff and monitored by the sponsor/designee.  Participants will be 
instructed to bring all unused study drugs with them to the study visits in order for site personnel 
to conduct to assess study drug accountability. 
Compliance with study drug administration will be calculated by the sponsor based on study 
drug accountability records documented by the site staff and monitored by the sponsor/designee. 
Participant compliance must be within 80% to 120%, assessed at each study visit.  If compliance 
is outside of this range, it will be considered a protocol deviation.  Participants consistently 
noncompliant with the study drug may be withdrawn from the study.  The decision to withdraw a 
participant will be made by the investigator after consultation with the sponsor, and relevant 
correspondence will be archived in the site study file. 
6.5. 
Dose Modifications 
Dose modifications will be allowed during the study as defined in Section 6.5.1.  In some 
circumstances, it may be necessary to temporarily interrupt treatment with study drug as a result 
of AEs or laboratory abnormalities that have an unclear relationship to the study drug.  
6.5.1. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study Drug 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment. 
Dose modifications are allowed in the study.  Dose reductions from 2.5 mg QD to 1 mg QD are 
allowed after consultation with the medical monitor, if the participant is experiencing an AE 
assessed as related or of unknown relationship to study drug or for hemoglobin levels in the high 
end of normal range.  Because participants may enter the study with extensive pretreatment 
and/or hemolysis associated with the primary disease, these dose reduction rules are provided as 
guidelines (see Table 9).  Dose re-escalation is permitted provided the investigator consult with 
the sponsor medical monitor and the sponsor approves before dose re-escalation. 
In some circumstances, it may be necessary to temporarily interrupt treatment with parsaclisib as 
a result of AEs or laboratory abnormalities that have an unclear relationship to the study drug 
(see Table 9).  Except in cases of emergency, it is recommended that any laboratory findings be 
confirmed and that the investigator consult with the sponsor medical monitor (or other 
representative of the sponsor) before temporarily interrupting study drug.  Participants who 
experienced a recurrence of the AEs or laboratory abnormalities upon restarting the study drug 
may have the study drug permanently discontinued (see Section 7.1.2). 
During the study, study treatment may be delayed up to 21 days to allow for resolution of 
toxicity.  Participants may resume treatment if no medical condition or other circumstance exists 
that, in the opinion of the investigator, would make the participant unsuitable for further 
participation in the study.  The treating investigator should contact the sponsor to discuss the 


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case of any participant whose treatment has been delayed for more than 7 days before restarting 
study treatment.  See Appendix D for action required for potential Hy's law cases. 
Table 9: 
Guidelines for Interruption and Restarting of Study Drug 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
Grade 2 AST and/or ALT is 
> 3.0 - 5.0 × ULN 
Step 1:  Interrupt study drug up to 21 days and repeat 
ALT/AST assessments weekly for up to 3 weeks (local blood 
collection may be used) or until ALT and/or AST results are 
< 3.0 × ULN. 
Step 2: Restart study drug at the same dose and monitor as 
clinically indicated. 
• 
If ALT and/or AST result(s) do not decrease to 
< 3.0 × ULN after 3 weeks of drug interruption, 
discontinue study drug administration, and the 
participant will enter the post-treatment follow-up 
period. 
• 
If AST or ALT elevation > 3.0-5.0 × ULN reoccurs 
following restarting study medication administration, 
repeat Step 1 and then restart study drug at 1 mg QD 
dose. 
• 
If AST and ALT > 3.0-5.0 × ULN reoccurs on lower 
dose, discontinue study drug administration, and the 
participant will enter the post-treatment follow-up 
period. 
≥ Grade 3 AST and/or ALT is  
> 5.0 × ULN  
Step 1:  Interrupt study drug up to 21 days and repeat 
ALT/AST assessments weekly for up to 3 weeks (local blood 
collection may be used) or until the toxicity has resolved to 
<3.0 x ULN (≤ Grade 1). 
Step 2:  Restart study drug at a 1 mg dose and monitor as 
clinically indicated.  If reoccurs, discontinue study drug and 
monitor as clinically indicated and the participant will enter 
the post-treatment follow-up period. 
Hematology 
• Grade 3 ANC (≤ 1.0 × 109/L), unless 
due to underlying disease 
• Grade 2 platelet count (50 × 109/L to 
< 75 × 109/L) 
Step 1:  Interrupt study drug up to 21 days until the toxicity 
has resolved to ≤ Grade 1 or baseline.  For Grade 3 ANC, 
monitor at least weekly.  
Step 2:  Restart study drug at same dose and monitor as 
clinically indicated.  If reoccurs, repeat Step 1 and then 
restart at the 1 mg QD dose. 
Step 3:  If reoccurs at 1 mg dose, discontinue study drug 
administration and the participant will enter the 
post-treatment follow-up period. 


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Table 9: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
ADVERSE EVENT 
ACTION TAKEN 
Hematology (continued) 
• 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 
• ≥ Grade 3 platelet count 
(< 50 × 109/L) 
Step 1:  Interrupt study drug up to 21 days until the toxicity 
has resolved to ≤ Grade 1 or baseline.  For ≥ Grade 3 ANC, 
monitor at least weekly. 
Step 2:  Restart study drug at same dose and monitor as 
clinically indicated.  If reoccurs, repeat Step 1 and then 
restart at the 1 mg QD dose. 
If event persists, discontinue study drug administration and 
the participant will enter the post-treatment follow-up period. 
Other toxicities 
Diarrhea/colitis (Grade 1) 
Step 1:  Treat with antimotility agents (eg, loperamide) and 
initiate supportive care (see Section 6.5.2).  If not improved 
after 48 hours, treat per guidance for ≥ Grade 2. 
Diarrhea/colitis (Grade 2) 
Step 1:  Interrupt parsaclisib or matching placebo.  Perform 
workup for infection (including CMV, Clostridium difficile, 
etc) immediately.  Initiate or continue supportive care (see 
Section 6.5.2).  Monitor clinical progress closely. 
Step 2:  If improved within 48 hours and/or infection* is 
confirmed, restart parsaclisib/matching placebo at the same 
schedule and dose after resolved to ≤ Grade 1 and continue 
to monitor. 
*For infectious diarrhea/colitis, follow institutional standard-
of-care guidelines and restart parsaclisib/matching placebo 
according to clinical judgment after resolved to ≤ Grade 1.  
Consult with medical monitor if needed. 
Step 3:  If not improved within 48 hours and infection is 
ruled out, start oral steroids or consider IV steroids if 
participant is being given IV fluids.  If no improvement with 
oral steroids, switch to IV steroids. 
Step 4:  When diarrhea resolves to ≤ Grade 1, continue 
supportive care and taper steroids according to institutional 
standard of care.  When taper is complete (eg, no steroid or 
≤ 10 mg/day prednisone or equivalent) and diarrhea is 
≤ Grade 1, restart parsaclisib/matching placebo at the 1 mg 
QD dose with approval of the medical monitor. 
Step 5:  If Grade 2 diarrhea reoccurs, treat per guidance for 
diarrhea (≥ Grade 3)/noninfectious colitis. 
Step 6:  If ≥ Grade 2 diarrhea reoccurs a third time, 
permanently discontinue parsaclisib/matching placebo and 
the participant will enter the post-treatment follow-up period. 


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Table 9: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
ADVERSE EVENT 
ACTION TAKEN 
Other toxicities (continued) 
• Diarrhea (≥ Grade 3) 
• Noninfectious colitis (any grade; 
confirmed or suspected) 
Step 1:  Interrupt parsaclisib or matching placebo.  Perform 
workup for infection (including CMV, C. difficile, etc) 
immediately.  Initiate or continue supportive care (see 
Section 6.5.2).  Consider colonoscopy with biopsy for 
diarrhea ≥ Grade 3 and/or if symptoms suggestive of colitis.  
Monitor clinical progress closely until resolution. 
Step 2:  If infection* is ruled out, start oral steroids or 
consider IV steroids if participant is being given IV fluids.  If 
no improvement with oral steroids within 48 hours, switch to 
IV steroids. 
*For infectious diarrhea/colitis, follow institutional standard-
of-care guidelines and restart parsaclisib or matching placebo 
according to clinical judgment after resolved to ≤ Grade 1.  
Consult with medical monitor if needed. 
Step 3:  When diarrhea/colitis resolves to ≤ Grade 1, 
continue supportive care and taper steroids according to 
institutional standard of care.  When taper is complete (eg, no 
steroid or ≤ 10 mg/day prednisone or equivalent) and 
diarrhea/colitis is ≤ Grade 1, restart parsaclisib or matching 
placebo at 1 mg QD with approval of the medical monitor.  
Continue to monitor.  If reoccurs, discontinue study drug and 
the participant will enter the post-treatment follow-up period. 
Pneumonitis (Grade 1) 
Step 1:  Interrupt parsaclisib or matching placebo until the 
toxicity has resolved. 
Step 2:  Restart parsaclisib or matching placebo at the 1 mg 
QD dose.  Monitor as clinically indicated. 
Pneumonitis (≥ Grade 2) 
Permanently discontinue parsaclisib or matching placebo and 
the participant will enter the post-treatment follow-up period. 
Skin toxicity (eg, rash, pruritus, etc, 
unless otherwise specified; Grade 2-3) 
Step 1:  Interrupt parsaclisib or matching placebo until the 
toxicity has resolved to ≤ Grade 1. 
Step 2:  Restart parsaclisib or matching placebo at the same 
dose.  If assessed as related to parsaclisib or matching 
placebo, restart at the 1 mg QD dose. 
Exfoliative dermatitis (Grade 1) 
Step 1:  Interrupt parsaclisib or matching placebo until the 
toxicity has resolved. 
Step 2:  Restart parsaclisib or matching placebo at the 1 mg 
QD dose.  Monitor as clinically indicated. 
Exfoliative dermatitis (≥ Grade 2) 
Step 1:  Interrupt parsaclisib or matching placebo until the 
toxicity has resolved. 
Step 2:  Restart parsaclisib or matching placebo. 


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Table 9: 
Guidelines for Interruption and Restarting of Study Drug (Continued) 
ADVERSE EVENT 
ACTION TAKEN 
Other toxicities (continued) 
CMV infection 
Participants with CMV viremia without associated clinical 
signs of CMV infection should be carefully monitored.  
Consider interrupting parsaclisib or matching placebo for 
participants with CMV viremia and clinical signs of infection 
until the infection has resolved.  Restart parsaclisib or 
matching placebo reduce to 1 mg QD dose if approved by the 
medical monitor. 
Varicella zoster infection 
Interrupt parsaclisib or matching placebo.  Restart parsaclisib 
or matching placebo only by approval of the medical 
monitor. 
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 QD dose if 
receiving 2.5 mg and monitor as clinically indicated. 
Any recurrent Grade 3 toxicity after 
dose reduction 
Discontinue study drug administration and the participant 
will enter the post-treatment follow-up period.  (Exceptions 
require approval of sponsor.) 
Any other Grade 4 toxicity 
Discontinue study drug administration and the participant 
will enter the post-treatment follow-up period. 
6.5.2. 
Supportive Care for Diarrhea/Colitis 
Participants should be informed to immediately report to the investigator any event of diarrhea. 
Participants should receive appropriate supportive care measures as deemed necessary by the 
investigator.  For any ≥ Grade 1 diarrhea, participants should be advised to drink liberal 
quantities of clear fluids.  If sufficient oral fluid intake is not feasible, fluid and electrolytes 
should be substituted via IV infusion.  Participants should try to eat 5 to 6 small meals per day; 
low-fat, high-protein foods; and cooked instead of raw vegetables.  Participants may supplement 
their diet with bananas, rice, applesauce, and toast to reduce the number of bowel movements 
and may also try crackers, gelatin, noodles, or oatmeal.  Participants should avoid fried, fatty, 
greasy, or spicy foods; milk, milk products, and acidic drinks; high-fiber foods and foods that 
cause gas; and alcohol, caffeine, and herbal supplements (Coutré et al 2015). 
For each occurrence, attempts should be made to rule out other causes, such as bacterial or viral 
infection (including CMV), which might require additional supportive care. 
It may be necessary to perform conditional procedures such as colonoscopy with biopsy as part 
of evaluation of the event.  Note that several courses of steroid tapering may be necessary as 
symptoms may worsen when the steroid dose is decreased. 


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Participants should be carefully monitored for signs and symptoms of enterocolitis (such as 
diarrhea, abdominal pain or cramping, blood or mucus in stool, with or without fever) and of 
bowel perforation (such as peritoneal signs and ileus). 
6.5.3. 
Follow-Up for Immune-Related Adverse Events 
An AE with a potential immunologic etiology, or an immune-related AE, may be defined as an 
AE consistent with an immune phenomenon associated with study drug exposure after all other 
etiologies have been eliminated.  Immune-related AEs may be expected based on previous 
experience with parsaclisib and other drugs (eg, idelalisib) that inhibit PI3Kδ.  Special attention 
should be paid to AEs that may be suggestive of potential immune-related AEs.  Suspected 
immune-related AEs should be discussed with the medical monitor when possible.  Participants 
should receive appropriate supportive care measures as deemed necessary by the treating 
investigator.  Suggested supportive care measures for the management of drug-related AEs with 
potential immunologic etiology are outlined in Table 9.  For each AE, attempts should be made 
to rule out other causes, including but not limited to bacterial or viral infection, which might 
require specific supportive care. 
6.5.4. 
COVID-19  
Infection with SARS-CoV-2, the coronavirus that causes COVID-19, is more frequent and 
severe in patients with hematologic dysfunction (Jee et al 2022).  The presence of hematologic 
malignancy, baseline neutropenia and lymphopenia, B-cell depletion, and other factors have been 
identified as risk factors for loss of humoral immunity to COVID-19, poor vaccine response, 
viral persistence, and severe disease (Lee et al 2022, Lyudovyk et al 2022, Shree et al 2022).  
Targeting B-cell function, proliferation, and survival with various therapies are current strategies 
for improving the outcome of several hematologic malignancies.  Pi3K-delta inhibition with 
parsaclisib alone or in combination with other therapies, which may also suppress humoral 
immunity, has the potential to negatively impact SARS-CoV-2 infection risk, vaccine 
effectiveness, recovery from COVID-19, and disease severity (Cheson 2022).  Investigators and 
participants participating in trials of parsaclisib, alone or in combinations, need to be aware of 
these potential risks and consider the local standards of care and available therapies for disease 
prevention, vaccination (see Section 6.7.1.3), and infection management of COVID-19. 
6.5.5. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study drug be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• The occurrence of an AE that is related to study drug that, in the judgment of the 
investigator or the sponsor's medical monitor, compromises the participant's ability to 
continue study-specific procedures or is considered to not be in the participant's best 
interest 
• Adverse events that reoccur and/or persist after reduction to 1 mg QD. 
• Persistent AE requiring a delay of therapy for more than 21 days unless a greater 
delay has been approved by the sponsor. 
• Specific AEs requiring permanent discontinuation as described in Table 9. 


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See Section 7.1.2 for discontinuation procedures. 
6.6. 
Treatment With Parsaclisib During Long-Term Extension 
Participants may take a drug holiday one time during the long-term extension.  Participants who 
take a drug holiday may be eligible to resume parsaclisib if they have worsening of wAIHA after 
the drug holiday.  Note:  Resuming treatment with parsaclisib is not an option for participants 
who permanently discontinue study treatment for criteria described in Section 7.1.1. 
Participants may take a drug holiday during the long-term extension if they meet the following 
condition: 
• Were clinically stable for at least 8 weeks and tolerating treatment before taking a 
drug holiday. 
− Clinically stable defined as hemoglobin ≥ 10 g/dL with an increase from baseline 
of ≥ 2 g/dL not attributed to rescue therapy and no worsening or new symptoms 
of wAIHA 
Re-treatment with parsaclisib is available if the study remains open and the participant meets all 
of the following conditions: 
• Experienced worsening of wAIHA defined as a continuing decline in absolute 
hemoglobin level, a > 1 g/dL decrease in hemoglobin from the prior assessment, or 
the participant develops new or worsening symptoms of wAIHA after the drug 
holiday.  
AND 
• In the opinion of the investigator, resuming treatment with parsaclisib would not pose 
a significant safety risk to the participant. 
Participants will resume parsaclisib at the same dose level and frequency as when they last 
received parsaclisib.  Re-treatment after a drug holiday is permitted one time.  Participants will 
continue study treatment until any of the criteria for permanent discontinuation of study drug are 
met (see Section 7.1.1).  Participants who permanently discontinue study treatment will enter the 
12-week post-treatment follow-up visits scheduled every 4 weeks for 12 weeks after the last dose 
of study drug. 
Note:  Upon implementation of Protocol Amendment 2, participants receiving parsaclisib who 
permanently discontinue study drug will enter the post-treatment follow-up period for 1 visit 
(FUP1/EOS) approximately 4 weeks after the last dose of study drug.   
6.7. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
prior medication received up to 12 weeks before the first dose of study drug and 12 weeks after 
the last dose of study drug, will be recorded in the eCRF.  Any addition, deletion, or change in 
the dose of these medications will also be recorded.  Concomitant treatments/procedures that are 
required to manage a participant's medical condition during the study will also be recorded in the 


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eCRF.  The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
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, which 
will be locally sourced and reimbursed by the sponsor.  The investigator must actively determine 
if a participant has a known sulfa allergy. 
Examples of standard PJP prophylaxis therapies include sulfamethoxazole and trimethoprim, 
atovaquone, dapsone (diaphenylsulfone) with or without pyrimethamine, and pentamidine 
(NCCN 2020).  (In Japan, diaphenylsulfone and pentamidine are not approved for PJP 
prophylaxis and thus will not be used.)  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 must be given while participants are receiving study drug and must continue for at 
least 2 to 6 months after the last dose of study drug. 
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. 
6.7.1.3. 
Vaccinations 
Participants who elect to receive the COVID-19 vaccine during the study should stop study drug 
5 days before and for 10 days after administration of the vaccine.  For other non-live vaccines, 
investigators should consult with the sponsor medical monitor before administration. 
6.7.1.4. 
Corticosteroids 
Continued use of systemic corticosteroid (prednisone or equivalent) doses ≤ 40 mg/day is 
permitted through the EOT visit as long as the dose has been stable for at least 14 days prior to 
randomization. 
Prednisone (or equivalent) may be tapered if the investigator considers it appropriate based on 
the participant's clinical response.  The recommended taper schedule is detailed in Table 10. 


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Table 10: 
Tapering Guidelines for Corticosteroids 
Current Dose of 
Prednisone 
Taper Schedule 
> 20 mg QD 
Taper by 10 mg every 7 days until a 20 mg daily dose is achieved in participants 
with a hemoglobin > 10 g/dL with at least a 2 g/dL increase from Day 1. 
20 mg QD 
Taper by 5 mg every 14 days from 20 mg to 10 mg QD in participants with a 
hemoglobin > 10 g/dL with at least a 2 g/dL increase from Day 1. 
10 mg QD 
Taper by 2.5 mg every 14 days from 10 mg to 5 mg in participants with a 
hemoglobin > 10 g/dL with at least a 2 g/dL increase from Day 1. 
5 mg QD 
Stop prednisone after 14 days in participants with a hemoglobin > 10 g/dL with at 
least a 2 g/dL increase from Day 1. 
Note:  Tapering may proceed according to the clinical judgement of the 
investigator. 
See Section 6.7.4 for use of corticosteroids as rescue treatment. 
6.7.2. 
Restricted Medications and Procedures 
Restricted medications and procedures include the following: 
• Short courses (approximately 2 weeks) of high-dose systemic corticosteroid (doses 
> 40 mg/day prednisone or equivalent) are permitted (eg, for the treatment of severe 
or life-threatening AEs or non-wAIHA limited related conditions) but are otherwise 
discouraged from the screening visit through the EOT visit. 
• Use of weak inducers of CYP3A4 or weak or moderate inhibitors of CYP3A4 or use 
of P-glycoprotein substrates is discouraged, and investigators should seek other 
options where possible (see Appendix E). 
6.7.3. 
Prohibited Medications and Procedures 
Prohibited medications and procedures include the following: 
• Use of moderate or potent inducers of CYP3A4 and potent inhibitors of CYP3A4 is 
prohibited, with the exception of topical ketoconazole because of its low 
bioavailability. 
• Apart from the study treatments, the use of any medications as described in the 
exclusion criteria (see Section 5.2) through the post-treatment follow-up is prohibited. 
− If rituximab is required, the participant must discontinue from study treatment. 
• Exposure to a live vaccine within 30 days of randomization through 3 months after 
the last dose of study drug is prohibited. 


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6.7.4. 
Rescue Treatment 
Given the natural history of wAIHA, participants may require supportive care for hemoglobin 
during the study.  Rescue medications may be permitted to serve as a bridging strategy to allow 
time for study drug to affect hemoglobin.  Rescue medication will be prescribed by the 
investigator and obtained locally.  Rescue medication should be considered if the absolute 
hemoglobin level continues to decline, there is a > 1 g/dL decrease in hemoglobin from the prior 
assessment, or the participant develops new or worsening symptoms of wAIHA.  The following 
protocol-permitted rescue medications may be used during the study: 
• New or increased dose of corticosteroids (prednisone or equivalent) from Day 1 dose 
• Transfusions 
• IVIG 
• Erythropoietin  
The date of rescue medication administration as well as the name and dose regimen of the rescue 
medication must be recorded in the eCRF. 
Participants who continue to receive rescue treatment after Week 6 will be considered 
nonresponders in the primary efficacy analysis, but may continue in the study at the discretion of 
the investigator.  
6.8. 
Treatment After the End of the Study 
Participants who have completed at least 2 months of active study treatment (starting from first 
dose of parsaclisib) and are receiving benefit will have the option to continue to receive 
parsaclisib provided within a rollover study or through commercially available supply where 
applicable. 


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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant becomes pregnant.  
• Informed consent is withdrawn.  
Note:  Consent withdrawn means that the participant has explicitly indicated that they 
do not want to be followed any longer; in this case no further data, except data in 
public domain, may be solicited from or collected on the participant.  Participants 
may choose to discontinue study treatment and remain in the study to be followed for 
safety. 
• Further participation would be injurious to the participant's health or well-being, in 
the investigator's medical judgment. 
• Unacceptable toxicity as noted in Section 6.5.5. 
• Participant has received a prohibited rescue therapy other than those described in 
Section 6.7.4. 
• Participant meets discontinuation criteria as described in Section 6.5. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If 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. 
• If the participant experiences worsening of wAIHA, persistent decline in hemoglobin, 
or the onset of new wAIHA symptoms requiring treatment. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit (EOT1 during the double-blind period, EOT2 during the open-label period, or EOT3 during 
the long-term extension) should be conducted.  The participant will then enter the 12-week 
post-treatment follow-up period.  These visits are described Table 3, Table 4, and Table 5.  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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Note:  Upon implementation of Protocol Amendment 2: 
• Participants receiving parsaclisib who permanently discontinue study drug will enter 
the post-treatment follow-up period for 1 visit (FUP1/EOS) approximately 4 weeks 
after the last dose of study drug. 
• Participants receiving placebo who permanently discontinue study drug will no longer 
be required to enter the post-treatment follow-up period and will perform EOT1/EOS 
upon discontinuation of treatment. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for discontinuation must be documented in the participant's medical 
record and the primary reason for discontinuation must be included in the eCRF. 
• The EOT visit should be performed and date recorded. 
• The status of the participant should be updated to EOT in the IRT. 
• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to Day 1, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up or disease assessment), then no additional data collection 
should occur; however, participants will have the option of withdrawing consent for study 
treatment but continuing in the follow-up period of the study for safety/efficacy assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at their 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 from the study, they may request destruction of any samples taken and 
not tested, and the investigator must document this in the site study records.  If the participant 
withdraws consent for disclosure of future information, the sponsor may retain and continue to 
use any data collected before such a withdrawal of consent.  See Table 3, Table 4, and Table 5 
for data to be collected at the time of study withdrawal and follow-up and for any further 
evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and is unable to be contacted by the study site. 


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The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
See Appendix B for COVID-19–related guidance. 
Note:  Upon implementation of Protocol Amendment 2, protocol-required procedures have been 
reduced for ongoing participants. 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or their representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  An ICF template 
will be provided by the sponsor or its designee.  The sponsor or its designee must 
review and acknowledge the site-specific changes to the ICF template.  The ICF 
must include a statement that the sponsor or its designee and regulatory 
authorities have direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the countries in 
which the study is being conducted as well as the IRB/IEC or study center. 
• The participant must be informed that their personal study-related data will be used 
by the sponsor in accordance with local data protection laws.  The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that their medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative 


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• A participant who is rescreened is not required to sign another ICF if the rescreening 
occurs within 30 days from the previous ICF signature date. 
8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is randomized in the 
study.  Screening may not exceed 32 days.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process.  
Central laboratory results will be used to determine eligibility unless otherwise stated (see 
Section 5.2 and Section 8.4.5).  Hepatitis tests should be performed early in the screening 
process due to the length of time needed to obtain the results. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
randomization or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during screening if the investigator believes the results to be 
in error.  For screening assessments that are repeated, the most recent available result before 
randomization will be used to determine eligibility. 
See Sections 5.4 for information regarding screen failures. 
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 2-letter alpha country International Standards Organization code then a 
3-digit site number, followed by a 3-digit participant number.  Site staff should contact the IRT 
to obtain the participant ID number during screening.  Upon determining that the participant is 
eligible for randomization, the IRT will be contacted to obtain the treatment assignment.  
Additionally, the IRT will be contacted at the study visits detailed in Table 3, Table 4, and 
Table 5 to update the study drug supply.  Additional details are provided in the IRT Manual. 
8.1.4. 
Distribution of Reminder Cards and Diaries 
Participants will be provided with a reminder card at each visit.  The reminder card will indicate 
the date/time of the next visit and will also remind the participant that they should not take their 
morning dose of study drug before coming to the clinic and they should record the most recent 
meal or snack in the diary (see Section 8.5). 
Participants will be instructed on the use of the diary.  The date and time of the last dose of study 
drug and the time of the most recent snack/ meal 
 (see 
Section 8.5 and Table 12) will be recorded in the diary and captured in the eCRF.  Daily study 
drug administration and any concomitant corticosteroid use will be recorded in the diary and 
verified by the investigators or designee at study visits as shown in Table 3, Table 4, and 
Table 5. 
8.1.5. 
Demography and Medical History 
8.1.5.1. 
Demographics and General Medical History 
Demographic data and general medical history will be collected as permitted by local regulations 
at screening by the investigator or qualified designee and will include year of birth/age, race, 
ethnicity, medical and surgical history, and current illnesses.  Medical history will include 


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relevant medical or surgical treatment within the last 10 years that are considered to be clinically 
significant by the investigator. 
8.1.5.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and treatment history including date of diagnosis of primary wAIHA, 
serological test, prior treatment history (all known failed treatments and all treatments within the 
prior year), number of transfusions within the prior year, number of hospitalizations due to 
AIHA within the prior year, and symptoms of wAIHA will be collected at screening.  
8.2. 
Efficacy Assessments 
Note:  Upon implementation of Protocol Amendment 2, the efficacy assessments noted herein 
will be reduced as detailed in Table 3 and Table 4.  
8.2.1. 
Hemoglobin Level, 
 and Direct Antiglobulin Test 
Participants will undergo hematology 
, and a DAT to evaluate type 
of AIHA diagnosis and disease status as detailed in Table 3, Table 4, and Table 5.  Prior 
documentation of DAT results are acceptable for study entry (see Section 5.1). 
Note:  The participants' screening hemoglobin enrollment eligibility will be based on a local 
laboratory assessment.  If hemoglobin and other laboratory values are required for the immediate 
participant management, it is acceptable to use a local laboratory. 
8.3. 
Patient-Reported Outcomes 
Patient reported outcomes will be captured using an electronic PRO device. 
Note:  Upon implementation of Protocol Amendment 2, the PROs noted herein will no longer be 
required. 
8.3.1. 
Functional Assessment of Chronic Illness Therapy – Fatigue 
The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily 
activities and function over the past 7 days.  The questionnaire should be completed by the 
participant using an electronic platform before any procedures are performed at the visits 
specified Table 3, Table 4, and Table 5.  Additionally, the questionnaire must be completed 
before all other PRO assessments. 
8.3.2. 
Six-Minute Walk Test 
The 6MWT is used to evaluate submaximal exercise capacity (ATS 2002).  It is a self-paced 
measurement of the distance that a participant can quickly walk on a flat, hard surface in a period 
of 6 minutes.  The test should be performed after all other PRO assessments have been 
completed as detailed in the Study Manual and at the visits specified in Table 3 and Table 4.  
Approximately 10 minutes before and within 5 minutes after the 6MWT is performed, vital signs 
(blood pressure, pulse, and respiration) should be assessed. 


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• 
 
 
• 
 
 
• 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.4. 
Safety Assessments 
8.4.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
12 weeks after the last dose of study drug.  Adverse events for enrolled participants that begin or 
worsen after informed consent should be recorded on the Adverse Events Form in the eCRF 
regardless of the assumption of a causal relationship with the study drug.  Conditions that were 
already present at the time of informed consent should be recorded on the Medical History Form 
in the eCRF.  Adverse events (including laboratory abnormalities that constitute AEs) should be 
described using a diagnosis whenever possible rather than by individual underlying signs and 
symptoms. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).  The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following-up on AEs that are serious, 
that are considered related to the study drug/procedures, or that caused the participant to 
discontinue the study drug.  Care will be taken not to introduce bias when detecting AEs and/or 
SAEs.  Open-ended and nonleading verbal questioning of the participant, such as "How are you 
feeling?", is the preferred method to inquire about AE occurrences.  Adverse events may also be 
detected when they are volunteered by the participant during the screening process or between 
visits or through physical examinations, laboratory tests, or other assessments.  The definition, 
reporting, and recording requirements for AEs are described in Section 9. 
All SAEs will be reported to the sponsor or designee within 24 hours (immediately in Germany).  
The investigator will submit any updated SAE data to the sponsor within 24 hours (immediately 
in Germany) of it being available. 


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After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
At remote visits, adverse events will also be assessed via a phone call conducted by the study 
site, except for countries where remote visits are not permitted by local laws and/or regulations 
(see Table 3, Table 4, and Table 5). 
8.4.2. 
Physical Examinations 
Physical examinations must be performed by a medically qualified individual, such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law permits 
at the visits detailed in Table 3, Table 4, and Table 5.  Abnormalities identified after the first 
dose of study treatment constitute an AE if they are considered clinically meaningful, induce 
clinical signs or symptoms, require concomitant therapy, or require changes in study drug.  
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
The comprehensive physical examination will include height and body weight, and assessment(s) 
of the following organ or body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; 
cardiovascular system; abdomen (liver, spleen); extremities; and lymph nodes; as well as a brief 
neurological examination. 
A targeted physical examination should be conducted as indicated by symptoms reported by the 
participant, AEs, or other findings.  Abnormalities that are considered clinically significant in the 
judgment of the investigator (or designee) are to be reported as AEs. 
During the study, participants will be assessed by the investigator or medically qualified 
designee per institutional standard of care.  These assessments should be an evaluation as 
indicated by participant symptoms, AEs, or other findings and documented on the AE eCRF. 
8.4.3. 
Vital Signs 
Vital sign measurements (to be taken before blood collection for laboratory tests), include blood 
pressure, pulse, respiratory rate, and body temperature.  If vital signs cannot be taken before 
blood collection for laboratory tests, there must be a minimum of 30 minutes from the 
completion of the blood collection procedures to the beginning of the vital signs collection.  
Blood pressure and pulse will be taken with the participant in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest. 
Abnormal vital sign results identified after the first dose of study drug constitute an AE if they 
are considered clinically meaningful, induce clinical signs or symptoms, require concomitant 
therapy, or require changes in study drug. 
8.4.4. 
Electrocardiograms 
Single 12-lead ECGs will be obtained as outlined in the SoA (see Table 3 and Table 4) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals.  All 12-lead ECGs will be performed with the participant in a recumbent or 
semirecumbent position after 5 minutes of rest. 


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The 12-lead ECGs will be interpreted by the investigator at the site to be used for immediate 
participant management.  Additional 12-lead ECGs may be performed as clinically indicated to 
manage participant safety.  The decision to include or exclude a participant or discontinue study 
treatment 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.  In the event that a single QTc is > 470 milliseconds at screening, the 
participant may enroll if the average QTc for triplicate ECGs conducted over a brief period is 
≤ 470 milliseconds or with approval from the medical monitor.  For participants with an 
intraventricular conduction delay (QRS interval > 120 milliseconds) at screening, the JTc 
interval may be used in place of the QTc with medical monitor approval.  In addition, the JTc 
interval should be used for all subsequent assessments. 
8.4.5. 
Laboratory Assessments 
See Table 11 for the list of clinical laboratory tests to be performed and Table 3, Table 4, and 
Table 5 for the timing and frequency.  A central laboratory will perform all clinical laboratory 
assessments for safety (ie, blood chemistries, hematology assessments, coagulation tests, 
endocrine function, and urinalysis).  Additional testing may be required by the sponsor based on 
emerging safety data.  All Protocol-required laboratory assessments must be conducted in 
accordance with the Laboratory Manual and Table 3, Table 4, and Table 5. 
Note:  The participants' screening hemoglobin enrollment eligibility will be based on a local 
laboratory assessment.  Additionally, if the central laboratory is unable to perform any other 
required screening tests due to hemolysis related to wAIHA or the analytical method, then local 
laboratory test results may be used to determine participant eligibility. 
At-home blood collection will be conducted during remote visits, except for countries where 
remote visits are not permitted by local laws and/or regulations (see Table 3 and Table 4).  
At-home sampling for additional laboratory assessments may also be conducted, except for 
countries where remote visits are not permitted by local laws and/or regulations; see Appendix B 
for COVID-19–related guidance.  Information regarding collection, processing, and shipping of 
samples for laboratory assessment is provided in the Laboratory Manual. 
Clinically significant abnormal laboratory findings are those that are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.  All laboratory tests with values considered clinically significantly 
abnormal during participation in the study or within 30 days after the last dose of study drug 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
If screening laboratory assessments are performed more than 32 days before Day 1, then the tests 
must be repeated and eligibility confirmed before study drug administration on Day 1. 
Laboratory sample collection on Day 1 must be performed before study drug administration. 
See Section 9.1 for information regarding laboratory abnormalities that should be recorded as an 
AE in the eCRF. 


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Table 11: 
Required Laboratory Analytes 
Chemistrya 
Hematologya,b 
Urinalysis With Microscopic 
Examination 
Serology 
Coagulation 
Albumin 
Alkaline phosphatase 
ALT 
AST 
Bicarbonatec 
Blood urea nitrogen 
Calcium 
Chloride 
Creatinine 
Ferritin (screening visit and repeat at 
Week 6 if participant has ongoing 
transfusion requirements) 
Folic acid (screening visit only) 
Glucose 
 
Iron (screening visit and repeat at Week 6 
if participant has ongoing transfusion 
requirements) 
 
Phosphate 
Potassium 
Sodium 
 
Total protein 
Total iron-binding capacity (screening visit 
and repeat at Week 6 if participant has 
ongoing transfusion requirements) 
Uric acid 
Complete blood count, 
including: 
Hemoglobin 
Hematocrit 
Platelet count 
Red blood cell count 
White blood cell count 
 
Differential count, including: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
Absolute values must be 
provided for: 
WBC differential laboratory 
results 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen 
CMV 
Hepatitis B surface antigen 
Hepatitis B surface antigen 
antibody 
Hepatitis B core antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
HIVe 
D-dimer 
 
 
Pregnancy Testing 
 
 
 
 
 
 
 
Female participants of 
childbearing potential only 
require a serum test at 
screening and EOT and a urine 
pregnancy test before the first 
dose on Day 1 and monthly 
during the study. 
Pregnancy tests (serum or 
urine) should be repeated if 
required by local regulations. 
DAT 
DAT for IgG and C3d 
Other Assessments 
Vitamin B12 (screening visit only) 
 
 
FSH 
Note:  Additional tests may be required, as agreed by investigator and sponsor, based on emerging safety data. 
a Chemistry and hematology parameters may be managed in real-time by local laboratory assessments. 
b Hematology panels 
 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 Bicarbonate not applicable in Japan. 
 
 
e HIV screening test is optional for participants enrolled in the US. 


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8.4.5.1. 
Pregnancy Testing 
A serum pregnancy test will be required for all WOCBP during screening (before the first dose 
of study drug) and at the visits indicated in Table 3, Table 4 , and Table 5.  Urine pregnancy tests 
will be performed locally as outlined in Table 3, Table 4, and Table 5 as medically indicated 
(eg, in case of loss of menstrual cycle, when pregnancy is suspected), or per country-specific 
requirement (note that country required- urine pregnancy testing will be outlined and 
communicated to investigational sites under separate cover).  If a urine pregnancy test is positive, 
the results should be confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, the participant should be instructed to 
immediately discontinue study drug (see Section 9.8 for procedures and reporting requirements). 
8.4.5.2. 
Serology 
Hepatitis screening assessments will be performed at the screening visit to rule out hepatitis 
infection; required analytes are shown in Table 11.  Generally, hepatitis tests should be 
performed early in the screening process due to the length of time needed to obtain the results.  
Additional tests may be performed if clinically indicated. 
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
 
 
  
 
 
 


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8.7. 
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. 
8.8. 
Long-Term Extension 
To allow continued treatment with parsaclisib after completion of Week 48, a long-term 
extension is available for all participants who are tolerating study treatment and in the 
investigator's opinion may benefit from continued treatment with parsaclisib.  Parsaclisib will be 
administered at the same dose level and frequency as in the open-label treatment period.  During 
the long-term extension, participants may take a drug holiday one time with the option for 
re-treatment as described in Section 6.6.  Participants who enter the long-term extension will be 
monitored for safety and persistence of effect.  The SoA is detailed in Table 5. 
8.9. 
End of Treatment 
When the participant permanently discontinues study drug, then the EOT visit (EOT1 for 
double-blind period, EOT2 for open-label period, and EOT3 for long-term extension) should be 


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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 enter the post-treatment follow-up visits. 
8.10. 
Post-Treatment Follow-Up 
The post-treatment follow-up period, comprised of 3 visits (one every 4 weeks; FUP1, FUP2, 
and FUP3), is the interval between the EOT visit and the scheduled follow-up visits, which 
should occur at a minimum of 30 days to 84 days after the EOT visit (or after the last dose of 
study drug if the EOT visit was not performed).  The FUP1 and FUP2 visits will be conducted 
remotely, except for countries where remote visits are not permitted by local laws and/or 
regulations.  Adverse events and SAEs must be reported up until 1) at least 84 days after the last 
dose of study drug or 2) until toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer.  Reasonable efforts should be made to have the participant return for the 
FUP3 visit and report any AEs that may occur during this period.  In exceptional cases when the 
participant cannot return to the site for the FUP3 visit, the participant should be contacted by 
telephone for assessment of AEs and SAEs and the site should properly document the contact. 
Note:  Upon implementation of Protocol Amendment 2: 
• Participants receiving parsaclisib who permanently discontinue study drug will enter 
the post-treatment follow-up period for 1 visit approximately 4 weeks after the last 
dose of study drug. 
• Participants receiving placebo who permanently discontinue study drug will no longer 
be required to enter the post-treatment follow-up period and will perform EOT/EOS 
upon discontinuation of treatment. 


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9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or 
not it is considered drug-related. 
• An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. 
Additional Guidance for Events Meeting the Adverse Event Definition 
• Any safety assessments (eg, ECG, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the investigator 
(ie, not related to worsening of underlying disease) are to be reported as an AE. 
• Abnormal laboratory test results are to be reported as an AE if they are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes in 
study drug.  Whenever possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in 
the eCRF rather than the abnormal laboratory test result (eg, low hemoglobin, platelet count 
decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition/disease, including either an increase 
in the frequency and/or intensity of the condition, is to be reported as an AE. 
• New conditions detected or diagnosed after the start of study drug administration are to be reported 
as an AE. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction are to be reported as 
an AE. 
• Signs and/or symptoms from dosing errors of a study drug (eg, overdose) or a concomitant 
medication are to be reported as an AE. 
• "Lack of efficacy," "disease worsening," or "failure of expected pharmacological action" will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy assessments. 
• A condition that leads to a medical or surgical procedure (eg, endoscopy, appendectomy) will be 
reported as an AE if it occurs after obtaining informed consent.  If the condition is present before 
entering the study, then it should be captured as medical history. 
• Pre-existing diseases or conditions with expected fluctuations in signs or symptoms should be 
reported as an AE only if the investigator judges the fluctuation to have worsened more than 
expected during study participation. 


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9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per the definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term "life-threatening" in the definition of "serious" refers to an adverse drug experience that 
places the participant, in the opinion of the initial reporter, at immediate risk of death from the adverse 
experience as it occurs.  This does not include an adverse drug experience that, had it occurred in a 
more severe form, might have caused death. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether hospitalization occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment or planned surgery (eg, stent replacement, hip surgery) is not 
considered an SAE. 
Hospitalization for medical interventions in which no unfavorable medical occurrence occurred 
(ie, elective procedures or routine medical visits) are not considered SAEs. 
d. Results in persistent or significant disability/incapacity 
• The term "disability" means a substantial disruption of a person's ability to conduct normal life 
functions.  This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle), that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is an important medical event 
• An important medical event is an event that may not result in death, be immediately life-threatening, 
or require hospitalization but may be considered serious when, based on appropriate medical 
judgment, the event may jeopardize the participant and may require medical or surgical intervention 
to prevent one of the outcomes listed in the above definition.  Examples of such events include new 
invasive or malignant cancers, intensive treatment in an emergency department or at home for 
allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse, or suspected transmission of an infectious agent via 
a medicinal product.  Secondary malignancies should always be considered SAEs. 
• For Japan, an event that may lead to disability is also considered an important medical event.  It 
includes a case that is exposed to a risk of dysfunction to an extent that interferes with daily life 
when the adverse drug reaction occurs.  It does not include an adverse drug reaction that, had the 
reaction been more severe, may have caused disability. 


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9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the 
Adverse Event Form in the eCRF.  AEs/SAEs should be reported for enrolled participants, but only 
SAEs need to be reported for screen failure participants.  For enrolled participants, conditions that 
were present at the time informed consent was given should be recorded on the Medical History 
eCRF.  For detailed information refer to the eCRF guidelines. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostic reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records 
in lieu of completing the Adverse Event Form in the eCRF. 
• There may be rare instances when copies of medical records for certain cases are requested.  In this 
case, all participant identifiers, with the exception of the participant number, will be redacted by the 
site staff on the copies of the medical records before submission.  These records can be submitted to 
Incyte Pharmacovigilance by email/fax per the contact information listed in the Study Reference 
Manual or as per SAE completing guidelines. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information.  Whenever possible, the diagnosis (not the individual signs/symptoms) 
will be documented as the AE/SAE.  When a clear diagnosis cannot be identified, each sign or 
symptom should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine the following: 
• The severity grade (CTCAE v5.0 Grade 1 to 5).  See below for further instructions on the assessment 
of intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study drug:  suspected 
(yes) or not suspected (no).  See below for further instructions on the assessment of causality. 
• The start and end dates, unless unresolved at the final safety follow-up visit. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication 
or nondrug therapy, this action should be recorded on the Adverse Event Form and the treatment 
should be specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures and 
Non-Drug Therapy). 


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Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v5.0 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity. 
The investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate 
activities of daily living. 
• Grade 3:  Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study drug and each occurrence of 
each AE/SAE.   
• A "reasonable possibility" of a relationship conveys that there are medical facts, evidence, and/or 
arguments to suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the possibility of a relationship. 
• The investigator will also consult the RSI in the IB or Product Information for study drug, or 
marketed products, respectively, in making their assessment. 
• Alternative causes, such as underlying or concurrent disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study drug administration, will be 
considered and investigated. 
• For each AE/SAE, the investigator must document in the medical notes that they have reviewed the 
AE/SAE and have provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report.  However, the causality assessment is one of the criteria 
used when determining regulatory reporting requirements.  Therefore, it is very important that 
the investigator always make an assessment of causality based on the available information 
for every event before the initial transmission of the SAE. 
− The investigator may change their opinion of causality in light of follow-up information and 
submit the updated causality assessment. 
Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature 
and/or causality of the AE or SAE as fully as possible.  This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health care 
professionals. 


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• Once an AE is detected, it should be followed in the AE eCRFs until it has resolved or until it is 
judged to be permanent; assessment should be made at each visit (or more frequently if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide the sponsor with a copy of any postmortem findings, including 
histopathology.   
• Updated SAE information will be recorded in the originally completed eCRF and reported to Incyte 
Pharmacovigilance until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up. 
• Any updated SAE data (including SAEs being downgraded to nonserious) will be submitted to the 
sponsor (or designee) within 24 hours (immediately in Germany) of receipt of the information. 
9.4. 
Reporting of Serious Adverse Events 
Regardless of suspected causality (eg, relationship to study drug, or study procedures), all SAEs 
occurring after the participant has signed the ICF through the last safety visit or at least 30 to 
35 days after the last dose of study drug must be reported to the sponsor (or designee) 
immediately, without undue delay but not later than within 24 hours (immediately in Germany) 
of obtaining knowledge of its occurrence unless otherwise specified by the Protocol.  The 
investigator will submit any updated SAE data to the sponsor (or designee) immediately, without 
undue delay but not later than within 24 hours (immediately in Germany) of it being available.  
For Japan:  This information must also be reported immediately to the head of the study site. 
Investigators are not obligated to actively seek SAE information after the safety follow-up visit 
or 30 to 35 days after the last dose of study drug.  If the investigator learns of any SAE, including 
death, at any time during this period, and they consider the event to be reasonably related to the 
study drug or study participation, then the investigator must notify the sponsor (or designee) 
within 24 hours (immediately in Germany) of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor regarding an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a study 
drug under clinical investigation are met. 
If the SAE is not documented in the RSI of the parsaclisib IB for the study drug (new 
occurrence) and is thought to be related to the study drug, the sponsor or its designee may 
urgently require further information from the investigator for expedited reporting to health 
authorities.  The sponsor or its designee may need to issue an Investigator Notification to inform 
all investigators involved in any study with the same drug that this SAE has been reported.  
Suspected unexpected serious adverse reactions will be collected and reported to the competent 
authorities and relevant ethics committees in accordance with Directive 2001/20/EC or as per 
national regulatory requirements in participating countries.  For Japan, the sponsor will report 


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suspected expected deaths and life-threatening events to the PMDA as per local regulatory 
requirements. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation.  The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate, according to local requirements. 
Serious Adverse Event Reporting 
• Information about all SAEs is collected and recorded on the Adverse Event Form in the eCRF. 
• The investigator must report within 24 hours (immediately in Germany) of learning of its occurrence 
any SAE via the EDC system (primary method) or by completing the Serious Adverse Event Report 
Form in English (only if the EDC system is not available.  The contact information for Incyte 
Pharmacovigilance by email/fax is listed in the Study Reference Manual. 
• In circumstances where the EDC system is not accessible for reporting SAE information (initial 
and/or follow-up SAE information) to the sponsor within 24 hours (immediately in Germany), refer 
to the Incyte Reference Guide for Completing the Serious Adverse Report Form.  Once the EDC 
system is functional, the SAE report should be retrospectively added to the EDC system and 
follow-up should be completed through the EDC.  The original copy of the Serious Adverse Event 
Report Form and the email or facsimile confirmation sheet must be kept at the study site (refer to the 
Incyte Reference Guide for Completing the Serious Adverse Report Form or Study Reference 
Manual for details and for the email address or fax number). 
• Follow-up information is also recorded in the eCRF and transmitted to Incyte Pharmacovigilance via 
the EDC system.  The follow-up report should include information that was not provided previously, 
such as the outcome of the event, treatment provided, action taken with study drug because of the 
SAE (eg, dose reduced, interrupted, or discontinued), or participant disposition (eg, continued or 
withdrew from study participation).  Each recurrence, complication, or progression of the original 
event should be reported as follow-up to that event, regardless of when it occurs. 
9.5. 
Potential Drug-Induced Liver Injury 
For information on management of potential Hy's Law cases, see Appendix D. 


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9.6. 
Events of Clinical Interest 
An ECI is an AE (serious or nonserious) that Incyte wishes to document in an organized manner 
for monitoring or understanding.  An ECI does not require rapid communication by an 
investigator to Incyte unless it meets criteria for rapid communication as an SAE (see 
Section 9.2).  The ECIs include laboratory abnormalities and clinical AEs as follows: 
• ALT ≥ 5 × ULN 
• AST ≥ 5 × ULN 
• Colitis 
• Diarrhea ≥ Grade 2 
• Intestinal perforation 
• Rash ≥ Grade 2 
• Exfoliative dermatitis 
• Pneumonitis 
• PJP 
• CMV infection 
• Herpes simplex  
• Varicella zoster virus infection 
9.6.1. 
Adverse Events of Special Interest 
Not applicable. 
9.7. 
Emergency Unblinding of Treatment Assignment 
In case of a medical emergency, for a participant's safety management, the procedure for 
emergency unblinding is provided to the investigator in the IRT Manual.  The investigator has 
the primary right to break the blind to treat a participant in emergency circumstances. 
If a participant's treatment assignment is unblinded, the sponsor or its designee should be notified 
immediately by telephone for awareness. 
If an investigator, the site personnel performing assessments, or a participant is unblinded, then 
the participant must discontinue study drug unless there are ethical reasons to have the 
participant remain on the study treatment.  In these cases, the investigator must obtain specific 
approval from the sponsor's (or its designee's) medical monitor for the participant to continue in 
the study. 


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9.8. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately (female participants only).  
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form or Study Reference Manual 
for further details. 
Any SAE occurring during pregnancy of a study participant must be recorded and 
reported as described in Section 9.4. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.9. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.10. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 


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The investigator or their designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be recorded as described in Section 9.3. 
If the investigator is asked to return the product for investigation, they will return a copy of the 
product complaint communication with the product. 
For Japan, complaints associated with unapproved medical devices will be reported to the 
sponsor with a Medical Device Defect Report Form, and the sponsor will report medical device 
defects to the PMDA as per local regulatory requirements. 
9.11. 
Treatment of Overdose 
Overdose is not an SAE unless it meets the criteria of an SAE (see Section 9.2). 
For this study, any daily dose of study drug greater than 2.5 mg during the study within a 
24-hour time period (± 4 hours) will be considered an overdose and recorded in the eCRF. 
Incyte does not recommend specific treatment for an overdose.  Overdose with concomitant 
medication treatment will not be recorded in the eCRFs unless it resulted in an AE. 
In the event of an overdose, the investigator should do the following: 
• Contact the medical monitor immediately. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until 
study drug can no longer be detected systemically (at least 3 days). 
• 
 
 
• Document the quantity of the excess dose as well as the duration of the overdose in 
the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.  
Treatment of overdose should consist of general supportive measures. 


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10. 
STATISTICS 
Note:  Upon implementation of Protocol Amendment 2, enrollment has been closed and 
protocol-required procedures have been reduced for ongoing participants.  With limited 
participants enrolled in each treatment group and the option for early cross-over to parsaclisib, 
most of the statistical analyses defined by the protocol are not applicable.  Therefore, the final 
analyses to accommodate those changes will be specified in the Statistical Analysis Plan.   
10.1. 
Sample Size Determination 
Approximately 100 participants will be randomized 2:1 (approximately 67:33) to parsaclisib 
2.5 mg QD or matching placebo using a fixed block size within each stratum.  For the statistical 
comparison on the binary primary efficacy endpoint, the sample size calculation is based on a 
Chi-square test.  
Based on the results of the Phase 2 study (INCB 50465-206), the response rate for the primary 
endpoint is assumed to be 70% for parsaclisib 2.5 mg.  With limited data, such response rates in 
the placebo group are not reported in historical studies.  The response rate for placebo group can 
only be assumed to around 25% from the literature review (Barcellini et al 2014, Birgens et al 
2013, Lechner and Jäger 2010).  Based on these assumptions, the sample size of 100 will provide 
enough power (over 90%) to detect such a difference with a 2-sided alpha of 0.05. 
10.2. 
Populations for Analysis 
The populations for analysis are provided in Table 13. 
Table 13: 
Populations for Analysis 
Population 
Description 
ITT 
The ITT population includes all randomized participants.  Treatment groups 
for this population will be defined according to the treatment assignment at 
randomization. 
PP 
The PP population includes randomized participants who are considered to be 
sufficiently compliant with the Protocol. 
Safety 
The safety population includes all participants who received at least 1 dose of 
study drug.  Treatment groups for this population will be determined 
according to the actual treatment the participant received on Day 1. 
 
 
 
 
 
 
 
10.3. 
Statistical Analyses 
10.3.1. 
Primary Analysis 
The primary analysis will occur after the primary database lock, when the last randomized 
participant has completed the double-blind treatment period.  The primary endpoint is defined as 


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the proportion of participants attaining durable hemoglobin response, defined as hemoglobin 
≥ 10 g/dL with an increase from baseline of ≥ 2 g/dL not attributable to rescue therapy at ≥ 3 of 
the 4 available visits at Week 12 and/or later during the 24-week double-blind treatment period.  
The primary analysis will be based on the intent-to-treat population.  The primary alternative 
hypothesis (superiority of parsaclisib 2.5 mg compared with placebo) will be tested using CMH 
test stratified by stratification factors.  The p-value for between-treatment group testing will be 
compared with 0.05.  Odds ratio and corresponding 95% confidence interval will be provided for 
comparing active and placebo groups.  All nonresponders in the double-blind treatment period, 
as well as all participants who have missing values on the durable response, will be defined as 
nonresponders for the nonresponder imputation analysis.  Participant missing 2 or more values 
on hemoglobin among the 4 visits will be defined as nonresponders for the primary endpoint.  
Participants who continue to receive rescue treatment after Week 6 will be considered 
nonresponders.  Summary of the response rates will be reported for the 2 treatment groups.  The 
response rates difference (parsaclisib 2.5 mg − placebo) will be reported along with the 95% 
confidence interval, which is derived from normal approximation. 
Similar analysis will also be performed in the PP population for the primary endpoint.  The 
following deviations are considered major: 
• Missing 2 or more hemoglobin values among the 4 visits for the primary endpoint; 
• Compliance less than 60%; 
• Using prohibited medications or procedures as specified in Section 6.7.3. 
Participants with 1 or more such deviations will be excluded from the PP population.  In 
addition, protocol deviations related to inclusion/exclusion criteria, discontinuation criteria, and 
use of excluded concomitant medications will be evaluated and decided whether they should be 
excluded.  Any exclusion from the PP population will be decided before breaking the blind. 
In addition, the following sensitivity analyses may be performed.  
• Exact logistic regression:  The primary alternative hypothesis will also be tested using 
exact logistic regression (Mehta and Patel 1995).  This model will include the 
treatment group (parsaclisib 2.5 mg QD and placebo) and stratification factors. 
• Multiple imputation:  A fully conditional specification method (van Buuren et al 
2007) that assumes the existence of a joint distribution for all variables will be used to 
impute hemoglobin values.  A regression model including treatment group, 
stratification factors, and baseline and postbaseline hemoglobin up to Week 24 will 
be specified for the fully conditional specification method.  After the missing values 
are imputed, the binary variables will be derived based on the definition.  The CMH 
tests will be applied to each imputed dataset, and then the results will be combined for 
the inference.  
• Tipping point analysis:  A tipping point analysis will be conducted to examine the 
potential effects of missing data.  The missing binary response on primary endpoint in 
each treatment group will be replaced by a range of values from the most 
conservative case to the most aggressive case.  The most conservative case is that all 
the missing participants in active treatment groups are nonresponders and all the 
missing participants in the placebo group are responders, while the most aggressive 


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case is the other way around.  For each scenario, between-treatment comparisons will 
be performed using a chi-square test. 
Subgroup analysis by baseline character, for example, age and region, will be performed. 
10.3.2. 
Secondary Analysis 
Key secondary efficacy analyses will be conducted in sequence for the ITT population.  The 
gatekeeping testing strategy for the primary and key secondary analyses will be implemented to 
control the overall Type I error rate, 2-sided α = 0.05.  The key secondary endpoint, proportion 
of participants with a ≥ 3-point increase from baseline in FACIT-F score at Week 24, will be 
tested in a fixed sequence at 2-sided α = 0.05 level only if the null hypothesis of the primary 
endpoint is rejected. 
All other secondary 
 efficacy endpoints will be summarized using descriptive 
statistics.  For categorical measurements, summary statistics will include sample size, frequency, 
and percentages.  Similar models as specified in the primary analysis may be used.  For 
continuous measurements, summary statistics, including sample size, mean, median, SD, 
standard error of the mean, minimum, and maximum, will be provided the actual measurement, 
change from baseline, and percentage change from baseline. 
10.3.3. 
Safety Analyses 
Safety analyses will be conducted for the safety population.  Adverse events will be coded by the 
MedDRA dictionary, and TEAE (ie, AEs reported for the first time or worsening of a 
pre-existing event after first dose of study drug) will be tabulated by preferred term and system 
organ class for all events, related events, and events of Grade 3 or higher.  Quantitative safety 
variables and their changes from baseline (laboratory, vital signs, etc) will be summarized with 
descriptive statistics.  Clinically notable abnormal values will be flagged and tabulated based on 
predefined criteria. 
The clinical laboratory data will be analyzed using summary statistics; no formal treatment group 
comparisons are planned.  In addition, distributions of key laboratory parameters may be plotted 
over time; these values will also be classified into CTCAE toxicity grades, and tabulated.  
Descriptive statistics and mean change from baseline will be determined for vital signs at each 
assessment time.  Vital sign results will be reviewed for clinically notable abnormalities. 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for clinically notable 
abnormalities according to predefined criteria (see Table 14).  Participants exhibiting clinically 
notable ECG abnormalities will be listed. 


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Table 14: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 460 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
QTcF = Fridericia correction. 
Measures of exposure of parsaclisib will be summarized by means of summary statistics. 
10.4. 
Interim Analysis 
No formal interim analysis is planned in this study. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol Amendments, ICF, IB, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC and health authorities before the study is 
initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require approval from both health authorities 
and the IRB/IEC before implementation of changes made to the study design, except 
for changes necessary to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study during the 
retention period 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. 


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− 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. 
• For Japan:  The record retainer (delegated by the head of the study site) will retain the 
J-GCP–defined essential documentation at this site until the regulatory approval of 
the study drug or at least 3 years after the discontinuation or completion of the study 
conduct, whichever is later.  If the sponsor requires retention of these documents for a 
longer period of time, the duration and method of retention will be decided upon 
through discussion between the sponsor and the study site.  It is the responsibility of 
the sponsor to inform the head of the study site as to when the documents no longer 
need to be retained.  
11.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study.  As part of his or her responsibilities, the coordinating principal investigator will review 
the final CSR.  Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system.  The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided with eCRF completion guidelines for instructions on data entry in the 
eCRF.  The study monitor will reference the Monitoring Plan in order to ensure that each issue 
identified is appropriately documented, reported, and resolved in a timely manner in accordance 
with the plan's requirements.  Other data outside the EDC system required in the study conduct 
of the Protocol, such as documents or results transmitted to the sponsor via a central laboratory 
or specialized technical vendors and as designated by the sponsor, will have their own data flow 
management plans, study charters, 
, as applicable. 
The sponsor (or designee) will be responsible for the following: 
• Managing the integrity of the data and the quality of the conduct of the study, such as 
ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved Protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Managing and reconciling the data generated and/or collected, including documents 
and results such as laboratory or imaging data analyzed centrally by a designated 
vendor of the sponsor. 


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The investigator will be responsible for the following: 
• Recording, or ensuring the recording of, all relevant data relating to the study in the 
eCRF. 
• Delivering, or ensuring the delivery of, all other results, documents, data, know-how, 
or formulas relating to the study to the sponsor or designee electronically and/or 
centrally (eg, laboratory data, imaging data, 
, photographs, diary data) 
or as otherwise specified in the Protocol. 
• Maintaining adequate and accurate source documents and trial records that include all 
pertinent observations on each of the site's trial participants.  Source data should be 
attributable, legible, contemporaneous, original, accurate, and complete.  Changes to 
source data should be traceable, should not obscure the original entry, and should be 
explained if necessary (eg, via an audit trail).  Source data are, in general, all 
information in original records and certified copies of original records of clinical 
findings, observations, or other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial.  Source data are contained in source 
documents (original records or certified copies).  
• Verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF. 
• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF, or sent to a central vendor designated by the sponsor, or as 
described in other study and data flow manuals. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed and 
available at the investigator's site.  Examples of source documents are original 
documents, data, and records (eg, hospital records; electronic hospital records; 
clinical and office charts; laboratory notes; memoranda; participants' diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiches; photographic negatives; microfilm or 
magnetic media; x-rays; participants' files; and e-records/records kept at the 
pharmacy, at the laboratories and at medico-technical departments involved in the 
clinical trial).   
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, 
depending on the study.  Current applicable medical records must be available. 
• Sending participants' data, either as unique samples, or copies, or photographs, to be 
evaluated centrally or analyzed centrally, or both, by a qualified vendor designated by 
the sponsor.  


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• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Quality Assurance 
The sponsor assumes accountability for actions delegated to other individuals (eg, contract 
research organizations).  The sponsor or designee is responsible for the data management of this 
study, including quality checking of the data.  Further, monitoring details describing strategy, 
including definition of study-critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical 
risk-based monitoring), methods, responsibilities, and requirements, including handling of 
noncompliance issues, Protocol deviations, and monitoring techniques (eg, central, remote, or 
on-site monitoring) are provided in the monitoring plan(s). 
Quality tolerance limits will be predefined in the IQRMP to identify systematic issues that can 
impact participants' safety, efficacy results and analysis, and/or reliability of study results.  These 
predefined parameters will be monitored during the study and can be adjusted during the study 
upon data review.  Important deviations from the quality tolerance limits and remedial actions 
taken, including reporting to IRBs/IECs and health authorities if applicable, will be summarized 
in the CSR. 
11.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that personal information is handled in accordance with local data protection laws (including but 
not limited to HIPAA and GDPR) as applicable, and the sponsor operates comprehensive data 
privacy and data security programs that are applicable to this study.  Appropriate notice, or 
notice and consent (as may be required by each applicable jurisdiction), for collection, use, 


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disclosure, and/or transfer (if applicable) of personal information must be obtained in accordance 
with local data protection laws.  Appropriate data protection terms that comply with applicable 
laws will be included in relevant study agreements. 
To ensure confidentiality of records and protect personal data, participant names will not be 
supplied to the sponsor or its designee.  Only the participant number will be recorded in the 
eCRF; if the participant's name appears on any other document (eg, laboratory report), it must be 
obliterated on the copy of the document to be supplied to the sponsor or its designee.  Study 
findings stored on a computer will be stored in accordance with appropriate technical and 
organizational measures as required by local data protection laws. 
In the event of a data breach involving participant data, the sponsor or its designee will follow 
the sponsor’s incident response procedures.  The precise definition of a data breach varies in 
accordance with applicable law but may generally be understood as a breach of security leading 
to the accidental or unlawful destruction, loss, alteration, unauthorized disclosure of, or access to, 
personal data.  In accordance with its incident response procedures, the sponsor will assess the 
breach to consider its notification and remediation obligations under applicable law. 
11.5. 
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 Clinical Investigator Financial Disclosure Form.  During a covered clinical 
study, any changes to the financial information previously reported by a clinical investigator 
must be reported to the sponsor or its designee.  At the conclusion of the covered clinical study, 
the clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.6. 
Publication Policy 
By signing the study Protocol, the investigator and their 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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The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
11.7. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
For Japan:  When the trial is completed, the investigator should inform the head of the study 
site of the completion in writing and submit a written summary of the trial's outcome, and then 
the head of the study site should promptly inform the IRB and sponsor or designee of the 
completion in writing. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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12. 
REFERENCES 
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. 
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS 
statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-117. 
Barcellini W. New insights in the pathogenesis of autoimmune hemolytic anemia. Transfus Med 
Hemother 2015;42:287-293. 
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, Fattizzo B. Clinical applications of hemolytic markers in the differential diagnosis 
and Management of Hemolytic Anemia. Dis Markers 2015;2015:63567. 
Berentsen S. Cold agglutinin disease. Hematology Am Soc Hematol Educ Program 
2016;2016:226-231. 
Birgens H, Frederiksen H, Hasselbalch HC, et al. A phase III randomized trial comparing 
glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune 
haemolytic anaemia. Br J Haematol. 2013;163:393-399. 
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. 
Cella D, Eton DT, Lai JS, Peterman AH, Merkel DE. Combining anchor and distribution-based 
methods to derive minimal clinically important differences on the Functional Assessment of 
Cancer Therapy (FACT) anemia and fatigue scales. J Pain Symptom Manage 2002;24:547-561. 
Cheson BD. Death and clinical trials in the plague years. Accessed July 21, 2022. 
https://ascopost.com/issues/july-10-2022/death-and-clinical-trials-in-the-plague-years. 
Clinical Trials Facilitation and Coordination Group. Recommendations related to contraception 
and pregnancy testing in clinical trials. 2020. 
Coutré SE, Barrientos JC, Brown JR, et al. Management of adverse events associated with 
idelalisib treatment: expert panel opinion. Leuk Lymphoma 2015;56:2779-2786.  
 
 
Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to 
estimate GFR without race. N Engl J Med 2021;385:1737-1749. 
Jee J, Foote MB, Lumish M, et al. Chemotherapy and COVID-19 outcomes in patients with 
cancer. J Clin Oncol 2022;38:3538-3546. 
Lechner K, Jäger U. How I treat autoimmune hemolytic anemias in adults. Blood 
2010;116:1831-1838. 


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Lee CY, Shah MK, Hoyos D, et al. Prolonged SARS-CoV-2 infection in patients with lymphoid 
malignancies. Cancer Discov 2022;12:62-73. 
Lyudovyk O, Kim JY, Qualls D, et al. Impaired humoral immunity is associated with prolonged 
COVID-19 despite robust CD8 T cell responses. Cancer Cell 2022;40:738-753. 
Mehta CR, Patel NR. Exact logistic regression: theory and examples. Stat Med 
1995;14:2143-2160. 
Millum J, Grady C. The ethics of placebo-controlled trials: methodological justifications. 
Contemp Clin Trials 2013;36:510-514. 
National Comprehensive Cancer Network. National Comprehensive Cancer Network Clinical 
Practice Guidelines in Oncology: B-Cell Lymphomas Version 1.2020. 
Parsaclisib Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
 
 
Shree T, Shankar V, Lohmeyer JJK, et al. CD20-targeted therapy ablates de novo antibody 
response to vaccination but spares preestablished immunity. Blood Cancer Discov 
2022;3:95-102. 
van Buuren S. Multiple imputation of discrete and continuous data by fully conditional 
specification. Stat Methods Med Res 2007;16:219-242. 
Yellen SB, Cella D, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other 
anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) 
measurement system. J Pain Symptom Manage 1997;13:63-74. 
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 AND DEFINITIONS 
Definitions 
WOCBP:  A woman who is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below) 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal with 1 of the following:a 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
• Postmenopausal 
− A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 
o A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or HRT.  However, in the absence of 12 months of 
amenorrhea, confirmation with 2 FSH measurements in the postmenopausal range is required. 
− Females on HRT and whose menopausal status is in doubt will be required to use 1 of the nonhormonal, 
highly effective contraception methods if they wish to continue their HRT during the study.  Otherwise, 
they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. 
For male participants of reproductive potentialb 
The following methods during the Protocol-defined timeframe in Section 5.1 are highly effective: 
• Use of a male condom plus partner use of an additional contraceptive method when having penile-vaginal 
intercourse with a woman of childbearing potential who is not currently pregnant. 
• Vasectomy with medical assessment of the surgical success (verified by site personnel's review of the 
participant's medical records) 
• Sexual abstinencec 
− 
Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a 
long-term and persistent basis) and agree to remain abstinent (sexual abstinence is not approved in Japan). 
The following are not acceptable methods of contraception: 
• Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method. 
• Male condom with cap, diaphragm, or sponge with spermicide. 
• Male and female condom used together. 
Note:  Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal 
intercourse or use a male condom during each episode of penile penetration (sexual abstinence is not approved in 
Japan).   


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For female participants who are WOCBP 
The following methods during the Protocol-defined timeframe in Section 5.1 that can achieve a failure rate of less 
than 1% per year when used consistently and correctly are considered as highly effective birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation.d 
− oral 
− intravaginal (administration route is not approved in Japan)   
− transdermal (administration route is not approved in Japan)   
• Progestogen-only hormonal contraception associated with inhibition of ovulationd (progesterone-only 
hormonal contraception is not approved in Japan, so this bullet and its sub-bullets will not apply for Japan) 
− oral 
− injectable 
− implantablee 
• Intrauterine devicee 
• Intrauterine hormone-releasing systeme 
• Bilateral tubal occlusione 
• Vasectomized partnere,f 
• Sexual abstinencec (sexual abstinence is not approved in Japan). 
a Documentation can come from the site personnel's review of the participant's medical records, medical examination, or medical 
history interview. 
b If the male participant has a partner with child-bearing potential the partner should also use contraceptives. 
c In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatments.  The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the 
participant. 
d It is unknown if hormonal contraception may be susceptible to interaction with the investigational medicinal product, which 
may reduce the efficacy of the contraception method.  Therefore, 2 methods of contraception should be used. 
e Contraception methods that in the context of this guidance are considered to have low user dependency. 
f Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual partner of the 
WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success. 
Source:  Clinical Trials Facilitation and Coordination Group (2020). 


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APPENDIX B. COVID-19 PANDEMIC MITIGATION STRATEGIES AND 
INSTRUCTIONS 
The COVID-19 global pandemic is an evolving situation and presents numerous challenges to 
the ongoing conduct of clinical studies.  The sponsor has issued the following Protocol 
considerations to ensure participant safety is maintained and adequate benefit/risk analyses are 
applied relative to the completion of study procedures and maintaining the investigational 
product supply chain. 
Recognizing the flexibility required to manage the impact of the pandemic on this clinical study, 
additional details will be added as needed to respective study manuals and project plan 
documents and communicated to the investigative sites as needed. 
Number of Study Participants 
The evolving situation of the pandemic may result in a substantial number of participants' early 
dropout from the study, which could affect the data integrity of the study.  Because of this risk 
and in order to mitigate it, the sponsor may decide to recruit additional participants in the study, 
beyond the expected number. 
Study Visits 
Remote Site Visit Guidelines: 
In addition to the remote visits already specified in the Protocol, the evolving situation of the 
pandemic may require further travel restrictions and isolation requirements, or the investigator's 
benefit/risk assessment may determine it to be unsafe for participants to attend study visits at the 
investigational site.  Note:  Remote visits are not applicable in locations where remote visits are 
not permitted by local laws and/or regulations.  In such cases, the site staff may elect to pursue 
the following: 
• In order to minimize participant risk, study visits may be conducted via telemedicine 
modalities (phone or video calls).  At a minimum, a review of AEs, concomitant 
medications, and study drug compliance must be completed.  Periodic on-site visits 
should be conducted whenever feasible, in addition to the mandatory on-site visits 
outlined below. 
• No efficacy assessments can be performed via telemedicine (video call, phone call, or 
via photography). 
• Laboratory sampling:  in order to support investigator oversight of participant safety 
and disease management, off-site laboratory sampling (in accordance with the SoA, 
see Table 3 and Table 4) may be allowed in 1 of 2 ways: 
− Use of home nursing services (unless not applicable by local laws and/or 
regulations). 
− Instruct the participant to undergo some laboratory tests at a local (nearby) 
hospital laboratory or facility closer to the participant's residence rather than at the 
investigational site.  In this case, the study physician will provide the participant 
with the list of parameters to be checked.  These tests should be performed at 
certified laboratories and copies of results provided to the site. 


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Mandatory On-Site Visits: 
The visits outlined below must be performed in person in order to capture the investigator's 
efficacy assessments and the patient-reported outcomes, even if the date that the participant 
eventually comes into the clinic deviates from the visit window.  
No efficacy assessments can be performed via telemedicine (video call, phone call, or 
photography). 
The visit window deviation must be documented, and the sponsor's representative must be 
informed of when it is believed that the participant can come into the clinic.  Further instructions 
will be provided if needed. 
During the placebo-controlled period, the following visits must be performed in person: 
• Screening 
• Day 1 (Baseline) 
• Week 12 visit 
• Week 24 visit 
• During the extension period, the following visits must be performed in person: 
• Week 36 visit 
• Week 48 visit 
Investigational Medicinal Product Dispensation and Distribution 
In order to ensure the continuity of providing their participants' clinical supplies within the 
constraints imparted by the pandemic, the site staff can decide to supply study drug via shipment 
to participants. 
If the participant cannot attend a visit at the study site, adequate supplies of study drug 
determined by the investigator can be shipped to the participant by the investigator or 
appropriately delegated staff (eg, the study pharmacy staff) using a third-party service if duly 
authorized by the participant. 
The study site may use their own preferred courier, provided the courier adheres to certain 
standards (eg, use of personal protection equipment, maintenance of temperature-controlled 
transit environment), or one centrally contracted by the sponsor. 
Clinical Study Monitoring 
Study monitoring visits may be postponed due to documented COVID-19–related reasons; 
however, the site monitor will continue to employ off-site monitoring practices such as routine 
communication methods (eg, phone calls, e-mails, video visits) with the sites to get information 
on study progress, subject status, and information on issue resolution.  The study monitor may 
remotely review data entered into the EDC for accuracy and completeness.  If allowed by local 
regulations, remote source data verification may be implemented with agreement of the principal 
investigator and institution, as applicable. 
If the study site monitor cannot be on-site to perform the final drug accountability for 
reconciliation purposes and the operation cannot be postponed, it may be performed by a 


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pharmacist from the hospital pharmacy or by the study coordinator/data manager with suitable 
training.  The study drug can be returned to the sponsor by the hospital pharmacy directly or 
destroyed in accordance with local practices, if applicable, and with sponsor approval. 
Other Considerations 
In case of need, participants may refer to the local health care provider.  Participants will be 
requested to obtain certified copies of the source data at the local health facility with the outcome 
of the contact and provide those to the investigator for appropriate oversight.  The 
investigator/delegate will be requested to enter any relevant information into the EDC. 
Should COVID-19–related restrictions be localized and have an effect on a limited number of 
sites, the affected sites may use direct contracting of third parties to support continuous study 
conduct (eg, home nursing services, couriers, etc). 
Reimbursement of Extraordinary Expenses 
The sponsor will arrange to reimburse participants for any extraordinary expenses, keeping 
appropriate documentation as evidence (eg, travel expenses for the local laboratory visit[s], the 
costs of local [nearby] laboratory tests). 


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APPENDIX C. INSTRUCTIONS TO PARTICIPANTS FOR HANDLING 
STUDY DRUG 
The participant must be instructed in the handling of study drug as follows: 
• Store study drug at room temperature (15°C-30°C/59°F-86°F). 
• Keep study drug in a safe place and out of reach of children. 
• Only remove the number of tablets needed at the time of administration. 
• Do not remove doses in advance of the next scheduled administration. 
• Make every effort to take doses on schedule. 
• Report any missed doses/lost tablets. 
• Take study drug, preferably in the morning, with a full glass of water, without regard 
to food.  Withhold drug self-administration for visits at Week 2, Week 8, Week 12, 
and Week 24, when the dose will be taken at the study site.  The Day 1 dose will also 
be administered at the study site. 
• If vomiting occurs after taking study drug, do not take another dose.  The next 
scheduled dose should be taken at the usual time.  If vomiting is persistent, contact 
the study site. 
• Bring all used and unused study drug kits to the study site at each visit. 
• If a dose is missed within the morning period, it is acceptable to take the dose within 
the same day (afternoon or evening).  The next scheduled dose should occur at the 
usual time in the morning, unless required otherwise. 


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


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


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


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


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APPENDIX E. CYP3A INHIBITORS AND INDUCERS 
CYP3A inhibitors or inducers may alter parsaclisib concentration.  These include, but are not 
limited, to the drugs listed below. 
CYP3A Inhibitors 
Inhibitor 
Therapeutic Class 
Potent CYP3A Inhibitors 
VIEKIRA PAK 
Antivirals 
indinavir/RIT 
Protease inhibitors 
tipranavir/RIT 
Protease inhibitors 
ritonavir 
Protease inhibitors 
cobicistat (GS-9350) 
None 
ketoconazole 
Antifungals 
indinavir 
Protease inhibitors 
troleandomycin 
Antibiotics 
telaprevir 
Antivirals 
danoprevir/RIT 
Antivirals 
elvitegravir/RIT 
Treatments of AIDS 
saquinavir/RIT 
Protease inhibitors 
lopinavir/RIT 
Protease inhibitors 
itraconazole 
Antifungals 
voriconazole 
Antifungals 
mibefradil 
Calcium channel blockers 
LCL161 
Cancer treatments 
clarithromycin 
Antibiotics 
posaconazole 
Antifungals 
telithromycin 
Antibiotics 
grapefruit juice DS 
Food products 
conivaptan 
Diuretics 
nefazodone 
Antidepressants 
nelfinavir 
Protease inhibitors 
saquinavir 
Protease inhibitors 
ribociclib 
Kinase inhibitors 
idelalisib 
Kinase inhibitors 
boceprevir 
Antivirals 
Moderate CYP3A Inhibitors 
erythromycin 
Antibiotics 


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Inhibitor 
Therapeutic Class 
fluconazole 
Antifungals 
atazanavir/RIT 
Protease inhibitors 
darunavir 
Protease inhibitors 
diltiazem 
Calcium channel blockers 
darunavir/RIT 
Protease inhibitors 
dronedarone 
Antiarrhythmics 
crizotinib 
Kinase inhibitors 
atazanavir 
Protease inhibitors 
letermovir 
Antivirals 
GSK2647544 
Alzheimer's disease & dementia treatments 
aprepitant 
Antiemetics 
casopitant 
Antiemetics  
amprenavir 
Protease inhibitors 
faldaprevir 
Antivirals 
imatinib 
Antineoplastic agents 
verapamil 
Calcium channel blockers 
netupitant 
Antiemetics 
nilotinib 
Kinase inhibitors 
grapefruit juice 
Food products 
tofisopam 
Benzodiazepines 
cyclosporine 
Immunosuppressants 
ACT-178882 
Renin inhibitors 
ciprofloxacin 
Antibiotics 
Magnolia vine (Schisandra sphenanthera) 
Herbal medications 
isavuconazole 
Antifungals 
cimetidine 
H-2 receptor antagonists 
FK1706 
Central nervous system agents 
Weak CYP3A Inhibitors 
tabimorelin 
Hormone replacement 
amlodipine 
Calcium channel blockers 
ranolazine 
Cardiovascular drugs 
breviscapine 
Herbal medications 
lomitapide 
Other antilipemics 
fosaprepitant (IV) 
Antiemetics 
Seville orange (Citrus aurantium) juice 
Food products 
amiodarone 
Antiarrhythmics 


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Inhibitor 
Therapeutic Class 
diosmin 
Herbal medications 
chlorzoxazone 
Muscle relaxants 
M100240 
Antihypertensive agents 
fluvoxamine 
Antidepressants 
ranitidine 
H-2 receptor antagonists 
goldenseal 
Herbal medications  
clotrimazole 
Antifungals 
tacrolimus 
Immunosuppressants 
palbociclib 
Kinase inhibitors 
cilostazol 
Antiplatelets 
ticagrelor 
Antiplatelets 
peppermint oil 
Food products 
ivacaftor 
Cystic fibrosis treatments 
GSK2248761 
Transcriptase inhibitors 
Guan Mai Ning 
Herbal medications 
osilodrostat 
Adrenal steroidogenesis inhibitors 
AZD2327 
Depression treatments 
piperine 
Food products 
resveratrol 
Food products 
roxithromycin 
Antibiotics 
suvorexant 
Hypnotics - sedatives 
propiverine 
Anticholinergics 
isoniazid 
Antibiotics 
berberine 
Herbal medications 
oral contraceptives 
Oral contraceptives 
delavirdine 
NNRTIs 
daclatasvir 
Antivirals 
simeprevir 
Protease inhibitors 
atorvastatin 
HMG-CoA reductase inhibitors (Statins) 
tolvaptan 
Vasopressin Antagonists 
almorexant 
Hypnotics - sedatives 
GSK1292263 
Other antilipemics 
evacetrapib 
CETP inhibitors 
linagliptin 
Dipeptidyl peptidase 4 inhibitors 
grazoprevir (ingredient of Zepatier) 
Antivirals 
lacidipine 
Calcium channel blockers 


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Inhibitor 
Therapeutic Class 
cranberry juice 
Food products 
pazopanib 
Kinase inhibitors 
fostamatinib 
Other 
everolimus 
Immunosuppressants 
blueberry juice 
Food products 
flibanserin 
Central nervous system agents 
lapatinib 
Kinase inhibitors 
brodalumab 
Immunomodulators biologics 
AMD070 
Fusion inhibitors  
alprazolam 
Benzodiazepines 
Tong Xin Luo 
Herbal medications 
glecaprevir and pibrentasvir 
Antivirals 
bicalutamide 
Antiandrogens 
sitaxentan 
Endothelin receptor antagonists 
azithromycin 
Antibiotics 
obeticholic acid 
Miscellaneous agents 
ginkgo 
Herbal medications 
teriflunomide 
Other immunomodulators 


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CYP3A Inducers 
Inducers 
Therapeutic Class 
Potent Inducers 
rifampin 
Antibiotics  
mitotane 
Other antineoplastics  
avasimibe 
Other antilipemics  
rifapentine 
Antibiotics  
apalutamide 
Antiandrogens  
phenytoin 
Anticonvulsants  
carbamazepine 
Anticonvulsants  
enzalutamide 
Antiandrogens  
St John's wort extract 
Herbal medications  
lumacaftor 
Cystic fibrosis treatments 
rifabutin 
Antibiotics  
phenobarbital 
Anticonvulsants  
Moderate Inducers 
ritonavir and St. John's wort 
None  
semagacestat 
Alzheimer's treatments 
efavirenz 
NNRTIs 
tipranavir and ritonavir 
Protease inhibitors  
dabrafenib 
Kinase inhibitors  
lesinurad 
Antigout and uricosuric agents 
bosentan 
Endothelin receptor antagonists  
genistein 
Food products  
thioridazine 
Antipsychotics  
nafcillin 
Antibiotics  
talviraline 
NNRTIs 
lopinavir 
Protease inhibitors 
modafinil 
Psychostimulants 
PF-06282999 
Myeloperoxidase inactivators 
etravirine 
NNRTIs 
lersivirine 
NNRTIs 
telotristat ethyl 
Antidiarrheals 
Weak Inducers 
eslicarbazepine 
Anticonvulsants  
telaprevir 
Antivirals  
daclatasvir and asunaprevir and beclabuvir 
Antivirals  


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Inducers 
Therapeutic Class 
amenamevir 
Antivirals  
garlic 
Food products  
bexarotene 
Other antineoplastics 
sarilumab 
Immunomodulators biologics 
artesunate and mefloquine 
Antimalarials 
amprenavir (fosamprenavir) 
Protease inhibitors  
raltegravir 
HIV-integrase strand transfer inhibitors  
vemurafenib 
Kinase inhibitors  
troglitazone 
Thiazolidinediones  
dicloxacillin 
Antibiotics  
sorafenib 
Kinase inhibitors  
rufinamide 
Anticonvulsants  
sirukumab 
Immunomodulators biologics 
pleconaril 
Antivirals  
ginseng 
Herbal medications  
boceprevir 
Antivirals  
sulfinpyrazone 
Antigout and uricosuric agents 
ginkgo 
Herbal medications  
vinblastine 
Vinca alkaloids  
nevirapine 
NNRTIs 
armodafinil (R-modafinil) 
Psychostimulants  
ticagrelor 
Anticoagulants and antiplatelets  
LCL161 
Cancer treatments 
vicriviroc and ritonavir 
Treatments of AIDS 
ritonavir 
Protease inhibitors  
prednisone 
Corticosteroids  
oxcarbazepine 
Anticonvulsants  
danshen 
Herbal medications  
clobazam 
Benzodiazepines 
echinacea 
Herbal medications 
ticlopidine 
Anticoagulants and antiplatelets 
isavuconazole 
Antifungals 
brivaracetam 
Anticonvulsants 
Stribild 
Treatments of AIDS 
pioglitazone 
Thiazolidinediones 
VIEKIRA PAK 
Antivirals  


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Inducers 
Therapeutic Class 
dexamethasone 
Corticosteroids  
terbinafine 
Antifungals  
quercetin 
Food products 
glycyrrhizin 
Herbal medications 
aprepitant 
Neurokinin-1 receptor antagonists 
pretomanid (PA-824) 
Antibiotics 
safinamide 
MAO-B inhibitors 
oritavancin 
Antibiotics 
AZD 7325 
Anxiolytics 
methylprednisolone 
Corticosteroids 
topiramate 
Anticonvulsants 
AIDS = acquired immunodeficiency syndrome; CETP = cholesteryl ester transfer protein; 
HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; MAO-B = monoamine oxidase B; 
NNRTI = non-nucleoside reverse transcriptase inhibitor; RIT = ritonavir. 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment 1 
18 AUG 2022 
Amendment 2 
10 MAY 2023 
Amendment 2 (10 MAY 2023) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to reduce or eliminate protocol-required procedures 
and visits due to closure of study enrollment. 
1. Section 1, Protocol Summary (Table 2:  Key Study Design Elements); Section 2.2, 
Study Rationale; Section 4.1, Overall Design 
Description of change: Added text regarding decision to close the study to further 
enrollment.  
Rationale for change: Due to the change in the regulatory landscape for PI3K inhibitors 
and the challenges in enrollment, a decision was made to close further enrollment into the 
study. 
2. Section 1, Protocol Summary (Table 2:  Key Study Design Elements); 
Table 3:  Schedule of Activities (Double-Blind); Table 4:  Schedule of Activities 
(Open-Label); Table 5: Schedule of Activities (Long-Term Extension); Section 4.1, 
Overall Design; Section 8, Study Assessments and Procedures; Section 8.2, Efficacy 
Assessments; Section 8.3, Patient-Reported Outcomes;
 
 
 
Description of change: Added text regarding reduction or elimination of procedures 
pertaining to efficacy assessments, PROs, and collection of samples for 
 
.  
Rationale for change: To reduce study participation burden for ongoing participants. 
3. Section 1, Protocol Summary; Section 4.1, Overall Design 
Description of change: Added text to allow participants randomized to placebo to 
receive parsaclisib before completing the 24-week double-blind treatment period.  
Rationale for change: To allow earlier access to active study treatment. 
4. Section 1, Protocol Summary; Table 4: Schedule of Activities (Open-Label); 
Section 4.1, Overall Design; Section 6.6, Treatment With Parsaclisib During 
Long-Term Extension; 7.1.2, Discontinuation Procedures; Section 8.10, 
Post-Treatment Follow-Up 
Description of change: Revised post-treatment follow-up period to remove FUP2 and 
FUP3 visits and to clarify that only participants receiving parsaclisib are required to 
perform FUP1 after permanent discontinuation of study drug.  
Rationale for change: Given low number of participants enrolled, persistence of effect 
after discontinuation of parsaclisib will no longer be evaluated. 


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5. Section 6.8, Treatment After the End of the Study 
Description of change: Clarified that participants must complete at least 2 months of 
treatment with parsaclisib before transition to the rollover protocol.  
Rationale for change: Clarification. 
6. Section 10, Statistics 
Description of change: Added text to clarify that planned statistical analyses will no 
longer be applicable due to closure in enrollment and access to parsaclisib before 
completion of Week 24 in participants randomized to placebo.  
Rationale for change: Clarification. 
7. Incorporation of administrative changes.  Other regulatory guidance and 
administrative changes have been incorporated throughout the Protocol and are noted in 
the redline version of the amendment. 


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Amendment 1 (18 AUG 2022) 
Overall Rationale for the Amendment: 
The primary purpose of the amendment is to incorporate feedback from advisory board 
members, which includes the addition of a long-term extension for continued access to 
parscalisib, and to include prior Protocol Administrative Changes.  This amendment also 
includes the changes from local adaptations for Germany (Version 1-DE) and France 
(Version 1-FR).  Additional changes are summarized below. 
1. Title Page 
Description of change: Added study acronym. 
Rationale for change: For completeness. 
2. Section 1, Protocol Summary, (Table 1:  Primary and Secondary Objective 
Endpoints); Section 3, Objectives and Endpoints (Table 6:  Objectives and 
Endpoints) 
Description of change:  Clarified that the key secondary object is to further evaluate the 
efficacy of parsaclisib. 
Rationale for change:  For clarification. 
3. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements) 
Description of change:  Added the names of the coordinating principal investigators. 
Rationale for change:  To update the coordinating principal investigator field in the 
table. 
4. Section 1, Protocol Summary, (Figure 1:  Study Design Schema); Section 4.1, 
Overall Design 
Description of change:  Updated to explain when primary analysis would be conducted. 
Rationale for change:  To be consistent with Section 10.3.1. 
5. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema; Table 4:  Schedule of Activities [Open-Label]; 
Table 5:  Schedule of Activities [Long-Term Extension]); Section 2.2.1, Scientific 
Rationale for Study Design; Section 2.2.2, Justification for Dose; Section 4.1, Overall 
Design; Section 4.2, Overall Study Duration; Section 6.6, Treatment With 
Parsaclisib During Long-Term Extension; Section 7.1.2, Discontinuation 
Procedures; Section 8.8, Long-Term Extension; Section 8.9, End of Treatment 
Description of change:  Added language describing a long-term extension phase of the 
study. 
Rationale for change:  To provide continued access to parsaclisib following the 24-week 
open-label treatment period. 


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6. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema); Section 4.1, Overall Design; Section 5.1, Inclusion 
Criteria (Criterion 2) 
Description of change:  Removed age requirement, ≥ 20 years, specified for study 
population enrolled in Japan. 
Rationale for change:  Effective 01 APR 2022, the age of an adult participant in Japan 
changed from ≥ 20 years to ≥ 18 years; therefore, all adult participants will be ≥ 18 years 
of age. 
7. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements); Section 5.1, 
Inclusion Criteria (Criterion 5) 
Description of change:  Decreased the required hemoglobin value prior to 
randomization from ≥ 7.0 g/dL to ≥ 6.5 g/dL. 
Rationale for change:  To identify participants who may require more frequent rescue 
therapy and; therefore, be in need of new treatment options. 
8. Section 1, Protocol Summary, (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema); Section 4.1, Overall Design; Section 10.1, Sample 
Size Determination 
Description of change:  Changed randomization to study treatment (parsaclisib or 
matching placebo) from a 1:1 ratio to a 2:1 ratio. 
Rationale for change:  To increase the number of participants who will receive 
treatment with parsaclisib (approximately 67 vs 50 participants). 
9. Section 1, Protocol Summary (Table 2:  Key Study Design Elements; 
Figure 1:  Study Design Schema); Section 4.1, Overall Design 
Description of change:  Deleted region (North America vs non-North America) and 
added daily dose of corticosteroids at screening (≤ 20 mg/day vs >20 mg/day) as a 
stratification factor. 
Rationale for change:  The randomization of participants from North American is 
expected to be low; therefore, stratifying by region was deemed unnecessary.  
Corticosteroid treatment plays an important role in the management of AIHA.  Therefore, 
to prevent imbalance between treatment groups, the daily dose of corticosteroids at 
screening was added as a stratification factor. 
10. Section 1, Protocol Summary (Table 2: Key Study Design Elements); Section 4.1, 
Overall Design 
Description of change:  Added language noting Japan will require a minimum 
enrollment of participants as a regulatory requirement. 
Rationale for change:  To ensure Japan meets the regulatory requirement of minimum 
enrollment even if enrollment in other countries may have ended. 


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12. Section 1, Protocol Summary [Table 3:  Schedule of Activities (Double-Blind)]; 
Section 8.1.5.1, Demographics and General Medical History 
Description of change:  A statement was added to indicate that demographic data will be 
collected as permitted by local regulations. 
Rationale for change:  To clarify that collection of certain demographic data may not be 
permitted in some countries. 
13. Section 1, Protocol Summary (Table 3:  Schedule of Activities [Double-Blind]; 
Table 4:  Schedule of Activities [Open-Label]); Section 8.4.5, Laboratory 
Assessments (Table 11:  Required Laboratory Analytes) 
Description of change:  Added test to monitor CMV. 
Rationale for change:  In participants receiving parsaclisib, regular clinical and 
laboratory monitoring of CMV infections is recommended in participants with history of 
CMV infections or having positive CMV serology without associated signs of clinical 
CMV. 
14. Section 1, Protocol Summary (Table 3:  Schedule of Activities [Double-Blind]); 
 
Description of change:  
 
 
 
 
 
 
 


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15. Section 1, Protocol Summary [Table 3:  Schedule of Activities (Double-Blind); 
Table 4:  Schedule of Activities (Open-Label)]; Section 8.4.1, Adverse Events; 
Section 8.4.5, Laboratory Assessments; Section 8.10, Post-Treatment Follow-Up; 
Appendix B, COVID-19 Pandemic Mitigation Strategies and Instructions 
Description of change:  Revised language to note that an in-office visit(s) would be 
required if the scheduled remote visit(s) is not permitted per local laws and/or 
regulations. 
Rationale for change:  To acknowledge that remote visits may not be permitted in some 
countries. 
16. Section 1, Protocol Summary (Table 3:  Schedule of Activities [Double-Blind];); 
Section 4.1, Overall Design; Section 6.5.1, Criteria and Procedures for Dose 
Interruptions and Adjustments of Study Drug (Table 9:  Guidelines for Interruption 
and Restarting of Study Drug); Section 7.1.2, Discontinuation Procedures 
Description of change:  Added and revised language to clarify that all participants who 
permanently discontinue study drug will enter the post-treatment follow-up period. 
Rationale for change:  For clarification. 
17. Section 1, Protocol Summary (Table 4:  Schedule of Activities [Open-Label]) 
Description of change:  Added D-dimer testing. 
Rationale for change:  To continue monitoring participants for blood clotting conditions 
during the open-label treatment period. 
18. Section 1, Protocol Summary (Table 4:  Schedule of Activities [Open-Label]); 
Section 8.10, Post-Treatment Follow-Up 
Description of change:  Changed designation of post-treatment follow-up visits from 
Week 52, Week 56, and Week 60 to FUP1, FUP2, and FUP3, respectively. 
Rationale for change:  Participants can permanently discontinue study treatment at any 
time during the study; therefore, noting a particular week (ie, Week 52) for the 
post-treatment visits is not applicable. 
19. Section 2.2.1, Scientific Rationale for Study Design; Section 4.1, Overall Study 
Design; Section 5.2, Exclusion Criteria (Criterion 10b); Section 6.7.1.4, 
Corticosteroids; Section 6.7.2, Restricted Medications and Procedures 
Description of change:  Increased the allowed daily dose of corticosteroids prior to 
randomization and during the study from ≤ 20 mg/day to ≤ 40 mg/day. 
Rationale for change:  To identify participants who require higher-dose steroids and; 
therefore, may benefit from a new treatment option, which may allow tapering and/or 
weaning off steroids. 
20. Section 2.2.1, Scientific Rationale for Study Design; Section 4.1, Overall Study 
Design; Section 7.1.1, Reasons for Discontinuation 
Description of change:  Deleted repetition of differing definitions of worsening wAIHA. 
Rationale for change:  For clarification. 


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21. Section 2.2.2, Justification for Dose 
Description of change:  Revised language regarding data, which support the selection of 
parsaclisib dose used in this study. 
Rationale for change:  For clarification. 
22. Section 2.3, Benefit/Risk Assessment 
Description of change:  Modified section to delete preclinical and clinical data that are 
presented and will be annually updated in the parsaclisib IB.  Added language regarding 
the effects of parsaclisib on the immune system and risks of serious infection events 
along with the pharmacological effect of concurrent corticosteroid use or recent 
rituximab therapy, which can contribute to further immunosuppression. 
Rationale for change:  To avoid redundancy with information in parsaclisib IB and to 
provide informational language on the risks of immunosuppression given the changes in 
eligibility criteria, which increased the allowed corticosteroid daily dose and decreased 
the washout interval of previous treatment with rituximab. 
23. Section 3, Objectives and Endpoints (Table 6:  Objectives and Endpoints) 
Description of change:  1) Added language to a secondary objective endpoint to 
evaluate percent change from baseline in FACIT-F score at each postbaseline visit; 
 
 
;
 
 
; 
 
 
 
Rationale for change:  1) To allow for analysis of both change and percent change from 
baseline in FACIT-F score; 2) To allow for analysis of duration of hemoglobin response 
in all participants with a response; 3) 
 
; therefore, 
analysis at Week 48 was deleted; and 4) To evaluate the persistence of effect after 
stopping treatment with parsaclisib. 
24. Section 4.1, Overall Study Design 
Description of change:  Added language to describe key eligibility criteria and efficacy 
assessments to be performed during the study. 
Rationale for change:  For completeness of the study design. 


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25. Section 5.1, Inclusion Criteria (Criterion 3) 
Description of change:  Added language to specify that results from DAT at screening is 
preferred and specified a timeframe for when previous DAT results would be acceptable. 
Rationale for change:  Direct antiglobulin test results are necessary for confirmation of 
wAIHA diagnosis; therefore, a test through central laboratory is preferred for eligibility.  
However, due to hemolysis related to wAIHA or the analytical method, central laboratory 
results may not be available; therefore, a prior DAT result within 3 months of 
randomization was deemed acceptable since results would be reflective of current clinical 
picture. 
26. Section 5.1, Inclusion Criteria (Criterion 7b); Section 5.2, Exclusion Criteria 
(Criteria 5c, 10b, 10c, 10d, 10e, and 11); Section 6.7.1.4, Corticosteroids 
Description of change:  Updated references to Day 1 visits to randomization. 
Rationale for change:  Randomization is expected to occur on Day 1; however, due to 
the location of the drug supply (eg, satellite pharmacy), the participant may not dosed 
until the next day. 
27. Section 5.1, Inclusion Criteria (Criteria 9 and 10) 
Description of change:  Added inclusion criteria specific to participants in France to 
indicate:  COVID-19 vaccination is required at least 2 weeks prior to randomization 
(criterion 9) and requirements for up-to-date mandatory vaccinations according to the 
national vaccination program as assessed by the investigator (criterion 10). 
Rationale for change:  Requested by France's Health Authority, ANSM. 
28. Section 5.2, Exclusion Criteria (Criterion 3) 
Description of change:  Added language to exclude participants with Evans syndrome. 
Rationale for change:  To exclude participants that have accompanying 
thrombocytopenia. 
29. Section 5.2, Exclusion Criteria (Criterion 6); Section 8.4.5, Laboratory Assessments 
(Table 11:  Required Laboratory Analytes) 
Description of change:  1) Removed elevated anti-streptolysin antibodies as 
exclusionary and 2) Revised to exclude participants with known diagnosis of 
antiphospholipid syndrome or history of persistent anti-phospholipid antibodies and 
added language to allow randomization of participants at risk for thrombosis if receiving 
adequate prophylaxis and those with thrombosis if on stable treatment for 3 months prior 
to randomization 
Rationale for change:  1) The risk of elevated anti-streptolysin antibodies as a cause of 
AIHA is very rare; and 2) To allow participants deemed at low risk for either developing 
or worsening thrombosis to be randomized. 


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30. Section 5.2, Exclusion Criteria (Criterion 10a) 
Description of change:  Changed the washout period for prior rituximab treatment from 
within 3 months to within 6 weeks of randomization. 
Rationale for change:  Rituximab as treatment for wAIHA may show benefit within 
6 weeks; therefore, the washout period was changed to allow participants not deriving 
benefit to be randomized. 
31. Section 5.2, Exclusion Criteria (Criterion 10e); Section 6.7.2, Restricted Medications 
and Procedures; Section 6.7.3, Prohibited Medications and Procedures 
Description of change: Revised to ensure that moderate or potent inducers of CYP3A4 
and potent inhibitors are included as prohibited medications. 
Rationale for change: Requested by the UK MHRA. 
32. Section 5.2, Exclusion Criteria (Criterion 18) 
Description of change:  1) Added language to clarify that an AST result of ≥ 2 × ULN is 
exclusionary unless clearly related to active hemolysis; 2) Added language to specify 
eGFR will be estimated using 2021 CKD-EPI calculation; and 3) Corrected result 
parameter for WBCs. 
Rationale for change:  1) To allow participants whose AST elevations are associated 
with hemolysis and not due to hepatic etiology to be randomized; 2) To clarify the 
method used to calculate eGFR; and 3) Typographical error. 
33. Section 5.2, Exclusion Criteria (Criterion 18); Section 8.1.2, Screening Procedures; 
Section 8.4.5, Laboratory Assessments 
Description of change:  Added language to clarify that local laboratory test results may 
be used to confirm participant eligibility if the central laboratory is unable to perform the 
test due to hemolysis related to wAIHA or the analytical method. 
Rationale for change:  To address the impact of hemolysis related to wAIHA on the 
laboratory test analysis. 
34. Section 6.5.1, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug 
Description of change:  Added language to clarify that the criteria for dose 
modifications are provided as guidelines and dose re-escalation is permitted after 
consultation with and approval by the sponsor medical monitor.  Added a reference in the 
text to Appendix D for Hy's law case. 
Rationale for change:  For clarification. 
35. Section 6.5.1, Criteria and Procedures for Dose Interruptions and Adjustments of 
Study Drug (Table 9:  Guidelines for Interruption and Restarting of Study Drug) 
Description of change:  Clarified the grading of chemistry and hematology toxicity, and 
simplified actions to be taken in the event of AST and/or ALT elevations.  In addition, 
removed language pertaining to action required for potential Hy's law cases. 
Rationale for change:  For clarification. 


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36. Section 6.5.2, Supportive Care for Diarrhea/Colitis 
Description of change:  Added language describing suggested clinical work-up in 
participants with diarrhea and/or colitis. 
Rationale for change:  For consistency with parsaclisib IB. 
37. Section 6.5.3, Follow-Up for Immune-Related Adverse Events 
Description of change:  Revised language defining immune-related AEs. 
Rationale for change:  For completeness of information consistent with the clinical 
development program of parsaclisib. 
38. Section 6.5.4, COVID-19 
Description of change:  Added new section describing risks associated with COVID-19 
with regards to participants with hematologic disorders and treatment with parsaclisib. 
Rationale for change:  Provided for informational purposes. 
39. Section 6.5.5, Criteria for Permanent Discontinuation of Study Drug 
Description of change:  Added language to further characterize unacceptable toxicity, 
which would meet criteria to permanently discontinue study drug. 
Rationale for change:  For completeness of defining unacceptable toxicity consistent 
with Incyte's standard language for protocol template. 
40. Section 6.7.1.1, Pneumocystis jirovecii Pneumonia Prophylaxis 
Description of change:  Added text that requires investigators to actively determine if a 
participant has a known sulfa allergy. 
Rationale for change:  Requested by the UK MHRA to ensure proper selection of PJP 
prophylaxis given reports of cross-sensitivity between sulfonamides and dapsone. 
41. Section 6.7.1.3, Vaccinations; Section 6.7.1.4, Corticosteroids; Section 6.7.2, 
Restricted Medications and Procedures 
Description of change:  Removed language regarding COVID-19 vaccinations from 
Section 6.7.2 and added Section 6.7.1.3, which is specific to vaccinations.  In addition, 
language was provided to consult sponsor before administration of non-live vaccinations. 
Rationale for change:  To clarify that COVID-19 vaccinations are permitted and when 
consultation with the sponsor is recommended. 
42. Section 6.7.1.4, Corticosteroids (Table 10:  Tapering Guidelines for 
Corticosteroids); Section 6.7.2, Restricted Medications and Procedures 
Description of change:  Removed language regarding permitted corticosteroids from 
Section 6.7.2 and added Section 6.7.1.4, specific to corticosteroids.  For Table 10, 
language was added to allow further tapering according to clinical judgement. 
Rationale for change:  To clarify that corticosteroids are permitted and can be tapered at 
investigator discretion. 


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43. Section 6.7.2, Restricted Medications and Procedures 
Description of change:  Deleted language regarding transfusions. 
Rationale for change:  To clarify that transfusions are permitted as rescue treatment. 
44. Section 6.7.3, Prohibited Medications and Procedures; Section 6.7.4, Rescue 
Treatment 
Description of change:  Language regarding rituximab was removed from Section 6.7.4, 
revised, and added to Section 6.7.3. 
Rationale for change:  To clarify that rituximab is a prohibited treatment. 
45. Section 6.7.4, Rescue Treatment 
Description of change:  A correction was made to indicate that rescue medication should 
be considered if there is a > 1 g/dL decrease in hemoglobin from the prior assessment.  
The documentation of time will not have to be recorded for administration of rescue 
medication. 
Rationale for change:  To correct a typographical error and to specify a less prescriptive 
decrease in hemoglobin to allow for the clinical judgment of the investigator.  
Documentation of the date of rescue therapy administration is sufficient. 
46. Section 6.8, Treatment After the End of the Study 
Description of change:  Revised language regarding access to continued treatment with 
parsaclisib after the completion of the study. 
Rationale for change:  To clarify that parsaclisib will be provided either in a rollover 
study or through commercially available supplies, where applicable. 
47. Section 8.4.1, Adverse Events; Section 9.3, Recording and Follow-Up of Adverse 
Events and/or Serious Adverse Events; Section 9.4, Reporting of Serious Adverse 
Events 
Description of change:  Revised to note that SAE reporting must happen immediately in 
Germany. 
Rationale for change:  Requested by Germany's Health Authority, BfArM. 
48. 
 
 
Description of change:  
 
 
Rationale for change:  For clarification. 
49. Section 9.5, Events of Clinical Interest 
Description of change:  Added language regarding ECI consistent with the clinical 
development program of parsaclisib. 
Rationale for change:  To ensure organized documentation of ECIs for the sponsor’s 
monitoring and understanding. 


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50. Section 9.6, Emergency Unblinding of Treatment Assignment 
Description of change:  Added language regarding emergency unblinding if an AE 
requires the investigator to be made aware of the participant's treatment assignment. 
Rationale for change:  Requested by the UK MHRA. 
51. Section 9.10, Treatment of Overdose 
Description of change:  Added language regarding treatment of overdose. 
Rationale for change:  For consistency with Incyte's standard language for clinical 
protocols. 
52. Section 10.1, Sample Size Determination 
Description of change:  Added language describing type of randomization. 
Rationale for change:  Requested by France's Ethics Committee. 
53. Section 10.2, Populations for Analysis (Table 13:  Population for Analysis) 
Description of change:  Corrected 'applied 'to 'received' with regard to study treatment. 
Rationale for change:  Typographical error 
54. Section 10.3.1, Primary Analysis 
Description of change:  Corrected language describing study treatment and updated the 
major deviations defining the PP population.  In addition, 'disease type' was deleted as a 
factor for subgroups analyses. 
Rationale for change:  To correct a typographical error which listed the incorrect 
concentration and frequency.  For the PP population, to clarify the missing endpoint and 
include the use of prohibited medications or procedures.  Only participants with wAIHA 
will be randomized; therefore, 'disease type' should not be included. 
55. Section 10.3.1, Primary Analysis; Section 10.4, Interim Analysis 
Description of change:  Removed language regarding primary analysis from 
Section 10.4 and added to Section 10.3.1.  In addition, language regarding unblinding 
was removed from Section 10.4. 
Rationale for change:  For clarification. 
56. Section 11.3, Data Quality Assurance; Section 11.4, Data Privacy and 
Confidentiality of Study Records 
Description of change:  Revised and added language regarding data management, data 
quality, and data privacy and protection. 
Rationale for change:  To be consistent with Incyte's standard language for clinical 
protocols. 


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57. Appendix A, Information Regarding Effectiveness Of Contraceptive Methods And 
Definitions 
Description of change:  Revised footnote "d" to clarify that it is unknown if hormonal 
contraception interacts with the investigational medicinal product and as a result may 
reduce the efficacy of the contraception method; therefore, 2 methods of contraception 
should be used. 
Rationale for change:  Requested by the UK MHRA. 
58. Appendix B, COVID-19 Pandemic Mitigation Strategies and Instructions  
Description of change:  The Week 52 visit was replaced with a Week 48 visit as a 
mandatory visit. 
Rationale for change:  Week 48 is the end of the open-label treatment period and 
therefore, is a mandatory visit. 
59. Appendix C, Instructions to Participants for Handling Study Drug 
Description of change:  Corrected the visits at which participants will withhold 
self-administration of study drug 
. 
Rationale for change:  To correct typographical error and maintain consistency with the 
 section(s) of the Protocol. 
60. Appendix E, CYP3A4 Inhibitors and Inducers 
Description of change:  Added medications known to be inhibitors and inducers of 
CYP3A4. 
Rationale for change:  Provided for informational purposes. 
61. 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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SAP_001.pdf: 
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the 
Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic 
Anemia (PATHWAY)
NCT Number: NCT05073458
Document Date: Statistical Analysis Plan Original Version: 17 JAN 2024


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Statistical Analysis Plan 
TITLE PAGE 
INCB 50465-309 
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the 
Efficacy and Safety of Parsaclisib in Participants With Primary Warm 
Autoimmune Hemolytic Anemia (PATHWAY) 
IND Number: 
147,208 
EudraCT Number: 
2021-002844-66 
Phase of Study: 
3 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
United States 
Protocol Version: 
Protocol Amendment 2 dated 10 MAY 2023 
CRF Approval Date: 
27 APR 2023 
SAP Version: 
Original 
SAP Author: 
 Biostatistics 
Date of Plan: 
17 JAN 2024 
This study is being conducted in compliance with Good Clinical Practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................5 
1. 
INTRODUCTION ........................................................................................................6 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................6 
2.1. 
Protocol and Case Report Form Version ......................................................................6 
2.2. 
Objectives and Endpoints .............................................................................................6 
3. 
STUDY DESIGN .........................................................................................................9 
3.1. 
Randomization ..............................................................................................................9 
3.2. 
Control of Type I Error ...............................................................................................10 
3.3. 
Sample Size Consideration .........................................................................................10 
3.4. 
Schedule of Assessments ............................................................................................10 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................11 
4.1. 
Scheduled Study Evaluations .....................................................................................11 
4.1.1. 
Day 1 ...........................................................................................................................11 
4.1.2. 
Study Day ...................................................................................................................11 
4.1.3. 
Baseline Value ............................................................................................................11 
4.1.4. 
Handling of Missing and Incomplete Data .................................................................11 
4.2. 
Variable Definitions ....................................................................................................11 
4.2.1. 
Body Mass Index ........................................................................................................11 
4.2.2. 
Prior and Concomitant Medication .............................................................................11 
5. 
STATISTICAL METHODOLOGY ...........................................................................12 
5.1. 
General Methodology .................................................................................................12 
5.2. 
Treatment Groups .......................................................................................................12 
5.3. 
Analysis Populations ..................................................................................................12 
5.3.1. 
Safety Population ........................................................................................................12 
 
............................12 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................13 
6.1. 
Demographics, Baseline Characteristics, and Disease History ..................................13 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................13 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................13 


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6.1.3. 
Prior Therapy ..............................................................................................................13 
6.1.4. 
Medical History ..........................................................................................................13 
6.2. 
Disposition of Participant ...........................................................................................13 
6.3. 
Protocol Deviations ....................................................................................................13 
6.4. 
Exposure .....................................................................................................................14 
6.5. 
Study Drug Compliance .............................................................................................14 
6.6. 
Prior and Concomitant Medication .............................................................................14 
7. 
EFFICACY .................................................................................................................15 
7.1. 
Efficacy Hypotheses ...................................................................................................15 
7.2. 
Analysis of the Primary Efficacy Parameters .............................................................15 
 
.16 
 
....................................16 
 
16 
9. 
SAFETY AND TOLERABILITY ..............................................................................16 
9.1. 
General Considerations ...............................................................................................16 
9.2. 
Adverse Events ...........................................................................................................16 
9.2.1. 
Adverse Event Definitions ..........................................................................................16 
9.2.2. 
Adverse Event Summaries ..........................................................................................17 
9.3. 
Clinical Laboratory Tests ...........................................................................................18 
9.3.1. 
Laboratory Value Definitions .....................................................................................18 
9.3.2. 
Laboratory Value Summaries .....................................................................................18 
9.4. 
Vital Signs ..................................................................................................................18 
9.5. 
Electrocardiograms .....................................................................................................19 
10. 
INTERIM ANALYSES ..............................................................................................20 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................20 
11.1. 
Changes to Protocol-Defined Analyses ......................................................................20 
11.2. 
Changes to the Statistical Analysis Plan .....................................................................20 
12. 
REFERENCES ...........................................................................................................21 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................22 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................6 
Table 2: 
Criteria for Clinically Notable Vital Sign Abnormalities for ≥ 18 Years Old ............19 
Table 3: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................19 
Table 4: 
Statistical Analysis Plan Versions ..............................................................................20 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schema ...................................................................................................9 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
 
  
6MWT 
6-minute walk test 
AE 
adverse event 
AIHA 
autoimmune hemolytic anemia 
BMI 
body mass index 
 
 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FACIT-F 
Functional Assessment of Chronic Illness Therapy - Fatigue 
MedDRA 
Medical Dictionary for Regulatory Activities 
PD 
pharmacodynamic 
 
 
 
 
Pi3K  
phosphoinositide 3-kinase 
 
 
PT 
preferred term 
QD 
once daily 
QTcF 
Fridericia's correction 
SAP 
statistical analysis plan 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
 
 
wAIHA 
warm autoimmune hemolytic anemia 
 
 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of parsaclisib 2.5 mg QD compared with placebo over a 24-week 
double-blind treatment period followed by a 24-week open-label treatment period of parsaclisib. 
Participants may then continue to receive parsaclisib in a long-term extension period. 
On 17 APR 2023, Incyte decided to terminate this Phase 3 study. The decision was based on the 
change in the regulatory landscape for Pi3k-delta inhibitors combined with enrollment 
challenges. At the time of this decision, 13 participants had been randomized and received study 
drug in this study. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the INCB 50465-309 Protocol. The scope of this plan includes the final analyses, which will be 
executed by the Department of Biostatistics or designee. 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 50465-309 Protocol Amendment 2 dated 10 MAY 2023 and CRF 
approved 27 APR 2023. Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and eCRF versions. 
2.2. 
Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of parsaclisib in the 
treatment of participants with wAIHA. 
Proportion of participants attaining a durable hemoglobin 
response, defined as hemoglobin ≥ 10 g/dL with an increase 
from baseline of ≥ 2 g/dL not attributed to rescue therapy at 
≥ 3 of the 4 available visits at Week 12 and/or later during the 
24-week double-blind treatment period. 
Key Secondary 
To further evaluate the efficacy of parsaclisib in 
the treatment of participants with wAIHA. 
Proportion of participants with a ≥ 3-point increase from 
baseline in FACIT-F score at Week 24. 


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Table 1: 
Objectives and Endpoints (Continued) 
Objectives 
Endpoints 
Other Secondary 
To further evaluate the efficacy of parsaclisib in 
the treatment of participants with wAIHA. 
• Proportion of participants with a 50 m increase from 
baseline to Week 24 in a 6MWT. 
• Change and percent change from baseline in FACIT-F score 
at each postbaseline visit. 
• Change and percentage change from baseline in 
hemoglobin at each postbaseline visit. 
• Proportion of participants who received transfusions from 
Week 6 to Week 24 and from Week 24 to Week 48. 
• Change and percentage change from baseline in daily 
corticosteroid dose at Week 24. 
• Proportion of participants who required rescue therapy at 
any visit from Week 6 through Week 24 and from 
Week 24 to Week 48. 
To evaluate the safety and tolerability of 
parsaclisib in participants with wAIHA. 
Frequency and severity of AEs, including the evaluation of 
clinical laboratory results, vital signs, ECGs, and the results 
of physical examinations. 


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Table 1: 
Objectives and Endpoints (Continued) 


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3. 
STUDY DESIGN 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of parsaclisib 2.5 mg QD compared with placebo over a 24-week 
double-blind treatment period followed by a 24-week open-label treatment period of parsaclisib. 
Participants may then continue to receive parsaclisib in a long-term extension period. 
Participants will receive parsaclisib 2.5 mg QD or matching placebo QD for 24 weeks during the 
double-blind treatment period. All participants who complete the double-blind treatment period, 
tolerate study treatment, and (per investigator's opinion) may benefit from treatment, may remain 
in the study for an additional 24-week, open-label treatment period in which they will receive 
parsaclisib administered at the same dose and schedule as in the double-blind treatment period. 
All participants who complete the open-label treatment period, tolerate study treatment, and (per 
investigator's opinion) may benefit from continued treatment, may enter into the long-term 
extension. Parsaclisib will be administered at the same dose and schedule as in the open-label 
treatment period. During the long-term extension, participants may take a drug holiday one time 
with the option for re-treatment, should they experience worsening of wAIHA during the drug 
holiday. 
The study schema is shown below in Figure 1. All participants will have follow-up assessments 
12 weeks after the last dose of study drug. 
Figure 1: 
Study Design Schema 
 
ICF = informed consent form. 
a Hemoglobin, at screening, as determined by local laboratory (< 9 g/dL or ≥ 9 g/dL) and corticosteroid (prednisone or 
equivalent) dose at screening (≤ 20 mg/day vs > 20 mg/day). 
b The primary analysis will be conducted when the last randomized participant has completed the 24-week, double-blind 
treatment period. 
3.1. 
Randomization 
Approximately 100 participants will be randomized 2:1 to receive initial double-blind study 
treatment (parsaclisib:matched placebo) for 24 weeks. Participants will be stratified by the 
hemoglobin value at screening as determined by local laboratory (hemoglobin < 9 g/dL or 
≥ 9 g/dL) and corticosteroid (prednisone or equivalent) dose at screening (≤ 20 mg/day vs 
> 20 mg/day). 


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3.2. 
Control of Type I Error 
For the primary and key secondary endpoints, the overall 2-sided Type I error is 0.05. 
The gatekeeping testing strategy for the primary and key secondary analyses will be 
implemented to control the overall Type I error rate, 2-sided α = 0.05. The p-value for 
between-treatment group testing for the primary endpoint will be compared at 2-sided 
α = 0.05 level. The key secondary endpoint will be tested at 2-sided α = 0.05 level only if the 
null hypothesis of the primary endpoint is rejected. 
3.3. 
Sample Size Consideration 
Approximately 100 participants will be randomized 2:1 (approximately 67:33) to receive either 
parsaclisib 2.5 mg QD or matching placebo using a fixed block size within each stratum. For the 
statistical comparison on the binary primary efficacy endpoint, the sample size calculation will 
be based on a Chi-square test. 
Based on the results of the Phase 2 study (INCB 50465-206), the response rate for the primary 
endpoint is assumed to be 70% for parsaclisib 2.5 mg QD. With limited data, such response rates 
in the placebo group are not reported in historical studies. The response rate for the placebo 
group can only be assumed to around 25% from the literature reviewed (Barcellini et al 2014, 
Birgens et al 2013, Lechner and Jäger 2010). Based on these assumptions, the sample size of 100 
will provide enough power (over 90%) to detect such a difference with a 2-sided alpha of 0.05. 
3.4. 
Schedule of Assessments 
Refer to Protocol Amendment 2 dated 10 MAY 2023 for a full description of all procedures and 
assessment schedules for this study. 


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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 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 follows: 
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 follows: 
Day # = (visit/reporting date – Day 1 date) 
A study day of −1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of study 
drug. 
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 this section or relevant sections. 
4.2. 
Variable Definitions 
4.2.1. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of study drug. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first dose of study drug and is ongoing throughout the study or 
ends on/after the date of first study drug administration. 
• On/after the date of first dose of study drug and is ongoing or ends during the course 
of study treatment. 


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A prior medication could also be classified as "both prior and concomitant medication," if the end 
date is on or after the first dose of parsaclisib. 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. 
5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS software (SAS Institute Inc, Cary, NC; v9.1 or later) will be used 
for the generation of all tables, graphs, and statistical analyses. Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, maximum, first quartile, third quartile, and 95% 
confidence interval. Descriptive summaries for categorical variables will include the number and 
percentage of participants in each category. 
5.2. 
Treatment Groups 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate 
the efficacy and safety of parsaclisib 2.5 mg QD. Data will be summarized based on the actual 
treatment that the participant received at Day 1. 
Unless other specified, the treatment groups will be parsaclisib 2.5 mg QD and placebo QD. 
For exposure, compliance, and adverse events, the treatment groups will be placebo QD, placebo 
QD to parsaclisib 2.5 mg QD, and parsaclisib 2.5 mg QD. 
5.3. 
Analysis Populations 
Upon implementation of Protocol Amendment 2, enrollment closed and Protocol-required 
procedures have been reduced for ongoing participants. With limited participants enrolled in 
each treatment group, as well as the option for early crossover to parsaclisib, the statistical 
analyses, as defined by the Protocol, will not be applicable; as a result, only the safety population 
 will be used for analysis. 
5.3.1. 
Safety Population 
All randomized participants who received at least 1 dose of study drug will constitute the safety 
population. Treatment groups for this population will be determined according to the actual 
treatment the participant received on Day 1 regardless of assigned study treatment. 
All safety and efficacy analyses will be conducted using the safety population. 
 
 
 
 
 


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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of planned tables and listings. Sample data displays are included in a 
separate document. 
6.1. 
Demographics, Baseline Characteristics, and Disease History 
6.1.1. 
Demographics and Baseline Characteristics 
The following demographics will be summarized for the safety population: age, sex, race, 
ethnicity, weight, height, and BMI. 
6.1.2. 
Baseline Disease Characteristics and Disease History 
The following baseline disease characteristics and disease history will be summarized for the 
safety population and will include, but will not be limited to the following: 
• Years since first onset (primary) wAIHA (< 2 years, 2-5 years, or > 5 years) 
• Serological evidence 
• Symptoms of wAIHA 
• Number of hospitalizations due to hemolytic anemia in the year prior to screening 
• Number of transfusions in the year prior to screening 
• Failed therapies (no/yes) 
• Any therapies contraindicated for the participant (no/yes) 
6.1.3. 
Prior Therapy 
Prior medication information for wAIHA will be used to identify other nonpredefined 
medication received by participants before enrollment into the study. Prior medication for 
wAIHA will be summarized by treatment group. 
6.1.4. 
Medical History 
Medical history will be summarized by treatment group. This summary will include the number 
and percentage of participants with medical history for each body SOC/PT as documented in the 
eCRF. 
6.2. 
Disposition of Participant 
The number and percentage of participants who were enrolled, who were randomized 
(double-blind period only), who were treated, and who completed treatment for each period will 
be summarized for the safety populations. 
6.3. 
Protocol Deviations 
Protocol deviations will be summarized and listed. 


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6.4. 
Exposure 
For participants in the safety population, exposure will be summarized descriptively for duration 
of treatment, average daily dose, and total dose. The treatment groups will be provided based on 
the actual treatment received (see Section 5.2). 
Duration of treatment with study drug is defined as the number of days from Day 1 to the date of 
last record of study drug administration. In addition, daily usage of prednisone (or equivalent) 
will be summarized using descriptive statistics. 
6.5. 
Study Drug Compliance 
For the participants in the safety population, overall compliance (%) for study drug 
administration will be calculated as follows: 
Compliance (%) = 100 × [total dose taken] / [total intended dose] 
The total number of intended doses defined as the number of dose prescribed. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary. 
The number and percentage of participants in the safety population for each prior and 
concomitant medication will be summarized by WHO drug class and WHO drug preferred name. 
Prior and concomitant medications will also be summarized (and listed) by treatment group. 


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7. 
EFFICACY 
With limited participants enrolled in each treatment group, as well as the option for early 
crossover to parsaclisib, the statistical analyses, as related to efficacy and defined by the 
Protocol, will not be applicable; as a result, no p-values will be provided and no multiple 
adjustment will be made. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Analysis of the Primary Efficacy Parameters 
The primary endpoint will be defined as a success if the proportion of participants attain a 
durable hemoglobin response ≥ 10 g/dL with an increase from baseline of ≥ 2 g/dL. The key 
secondary endpoint will be considered a success if the proportion of participants have a ≥ 3-point 
increase from baseline in FACIT-F score at Week 24. 
For primary and key secondary endpoints, postbaseline visits will be summarized by treatment 
received on Day 1 of the study; the visits will use descriptive statistics. 


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9. 
SAFETY AND TOLERABILITY 
Appendix A provides a list of data displays. Sample data displays will be included in a separate 
document. 
9.1. 
General Considerations 
Analyses in this section will be provided for the safety population. Treatment groups will be 
provided based on the actual treatment received (see Section 5.2). For participants who cross 
over treatments, the date of first dose is treatment-specific; the end date will be either 30 days 
after the date of the last dose of this treatment or the date of the first dose in the next treatment, 
whichever comes first. Analysis of AEs will be limited to TEAEs, but data listings will include 
all AEs regardless of their timing in relation to study drug administration. 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. 
9.2. 
Adverse Events 
9.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose 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 dose administration. 
Adverse events will be tabulated by MedDRA PT and SOC. Severity of AEs will be graded 
using the National Cancer Institute CTCAE v5. 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 
treatment-related AEs. If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related. The incidence of AEs and 
treatment-related AEs will be tabulated. Serious AEs will also be tabulated. 


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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. 
9.2.2. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any serious TEAEs 
• Number (%) of participants reporting any Grade 3 or higher TEAEs 
• Number (%) of participants reporting any treatment-related TEAEs 
• Number (%) of participants who temporarily interrupted study drug because of 
TEAEs 
• Number (%) of participants who permanently discontinued study drug because of 
TEAEs 
• Number (%) of participants who had any fatal TEAE 
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 SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of Grade 3 or higher TEAEs by SOC and PT 
• Summary of serious TEAEs by SOC and PT 
• Summary of treatment-related TEAEs by SOC and PT 
• Summary of TEAEs with a fatal outcome by SOC and PT 
• Summary of TEAEs leading to dose interruption of study drug by SOC and PT 
• Summary of TEAEs leading to discontinuation of study drug by SOC and PT 


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9.3. 
Clinical Laboratory Tests 
9.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline will be summarized descriptively by central 
laboratory. Baseline will be determined according to Section 4.1.3, with exceptions listed below, 
in which case the investigative site laboratory or an accredited local laboratory may be used: 
• Hematology panels (ie, complete blood count and differential count), will be sent to a 
local laboratory for analysis. 
• Participant management, which includes dose modification, serious adverse event, or 
COVID-19 restrictions (eg, travel), for local laboratory assessments deemed 
necessary by the investigator for participant management. Note: Such assessment data 
and reference ranges must be recorded in the participant's eCRF. 
In the event both local and central laboratory assessments are available, local laboratory 
assessment 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 values with 
the same date and time in the same priority category, additional rules may be provided following 
consultation with the medical monitor to delineate the value that will be defined as baseline. 
9.3.2. 
Laboratory Value Summaries 
Clinical laboratory tests, including hematology, serum, and chemistry, will be performed for 
each participant per the schedule of assessments. If specific safety issues arise, additional 
unscheduled laboratory tests/analyses will 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. 
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. 
9.4. 
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. 
Criteria for clinically notable vital sign abnormalities are defined in Table 2. The abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed along 
with their assigned treatment group. Alert vital signs are defined as an absolute value outside the 
defined range and percentage change > 25%. The abnormal values for participants exhibiting 
alert vital sign abnormalities will be listed. 


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Table 2: 
Criteria for Clinically Notable Vital Sign Abnormalities for ≥ 18 Years Old 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 20 breaths/min 
< 8 breaths/min 
9.5. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be summarized for each ECG 
parameter at each assessment time. Electrocardiogram results will be reviewed for clinically 
notable abnormalities according to predefined criteria (see Table 3). Participants exhibiting 
clinically notable ECG abnormalities will be listed. 
Table 3: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 460 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 


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10. 
INTERIM ANALYSES 
No formal interim analysis is planned in this study. 
11. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 4. 
Table 4: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
17 JAN 2024 
11.1. 
Changes to Protocol-Defined Analyses 
On 17 APR 2023, Incyte decided to terminate this Phase 3 study. The decision was based on 
change in the regulatory landscape for Pi3k-delta inhibitors combined with enrollment 
challenges. 
With limited enrollment in each treatment group, as well as participant option for early crossover 
(to parsaclisib), most of the Protocol-defined statistical analyses on efficacy endpoints will not be 
applicable; therefore, summary statistics will only be provided for hemoglobin response and 
FACIT-F scores and listings will only be provided for all other efficacy endpoints. Additionally, 
no p-values will be provided and no statistical comparisons will be made. 
11.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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12. 
REFERENCES 
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. 
Birgens H, Frederiksen H, Hasselbalch HC, et al. A Phase III randomized trial comparing 
glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune 
haemolytic anaemia. Br J Haematol 2013;163:393-399. 
Lechner K, Jäger U. How I treat autoimmune hemolytic anemias in adults. Blood 
2010;116:1831-1838. 


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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. 
Shells are provided in a separate document for tables that are not in the most current Standard 
Safety Tables v1.13. 
The list of tables and listings are to be used as guidelines. Modifications of the lists that do not 
otherwise affect the nature of the analysis will not warrant an amendment to the SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
Baseline and Demographic Characteristics 
1.1 Disposition 
1.1.1 
Analysis Populations 
Safety 
X 
1.1.2 
Summary of Participant Disposition  
Safety 
X 
1.2 Demography 
1.2.1 
Summary of Demographics 
Safety 
X 
1.3 Baseline Characteristics 
1.3.1 
Summary of Baseline Disease Characteristics 
Safety 
X 
1.4 Prior Medication and Concomitant Medication 
1.4.1 
Summary of Prior Medications 
Safety 
X 
1.4.2 
Summary of Prior Medications for wAIHA 
Safety 
X 
1.4.3 
Summary of Concomitant Medications 
Safety 
X 
1.5 Others 
1.5.1 
Summary of General Medical History 
Safety 
X 
1.5.2 
Summary of wAIHA History 
Safety 
X 
1.5.3 
Summary of Protocol Deviations by Category 
Safety 
X 
Efficacy 
2.1 Primary and Key Secondary Efficacy 
2.1.1 
Summary of Participants With Hemoglobin ≥ 10 g/dL With an 
Increase From Baseline of ≥ 2 g/dL 
Safety 
 
2.1.2 
Summary of Participants With a ≥ 3-Point Increase From Baseline 
in FACIT-F Score at Week 24 
Safety 
 
Safety 
3.1 Study Drug Exposure 
3.1.1 
Summary of Drug Compliance 
Safety 
X 
3.1.2 
Summary of Study Drug Exposure 
Safety 
X 
3.1.3 
Summary of Daily Usage of Prednisone  
Safety 
X 
3.2 Adverse Events 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA 
Preferred Term in Decreasing Order of Frequency 
Safety 
X 
3.2.4 
Summary of Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 


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Table No. 
Title 
Population 
Standard 
3.2.5 
Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.6 
Summary of Treatment-Emergent Adverse Events With a Fatal 
Outcome by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.7 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.8 
Summary of Treatment-Emergent Adverse Events Leading to Dose 
Interruption by MedDRA System Organ Class and Preferred Term 
Safety 
X 
3.2.9 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study Drug by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
3.3 Laboratory 
3.3.1 
Summary of Laboratory Values - Hematology 
Safety 
X 
3.3.2 
Summary of Laboratory Values - Chemistry  
Safety 
X 
3.4 Vital Signs 
3.4.1 
Summary of Systolic Blood Pressure 
Safety 
X 
3.4.2 
Summary of Diastolic Blood Pressure  
Safety 
X 
3.4.3 
Summary of Pulse  
Safety 
X 
3.4.4 
Summary of Respiratory Rate 
Safety 
X 
3.4.5 
Summary of Body Temperature 
Safety 
X 
3.5 ECG 
3.5.1 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.2 
Summary of QRS Interval (ms) From 12-Lead ECG  
Safety 
X 
3.5.3 
Summary of QT Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.4 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.5 
Summary of RR Interval (ms) From 12-Lead ECG 
Safety 
X 
3.5.6 
Summary of Clinically Significant ECG Abnormality 
Safety 
X 
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  
1.2.2 
Baseline Disease Characteristics 
1.3.1 
General Medical History 
1.3.2 
wAIHA History 
1.4.1 
Prior and Concomitant Medications 
1.4.2 
Prior Medications for AIHA 
1.5 
Study Drug Exposure and Compliance  
Efficacy 
2.1 
FACIT-F 
2.2 
6MWT 


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Listing No. 
Title 
2.3 
Transfusion 
2.4 
Daily Corticosteroid Dose 
2.5 
Rescue Therapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events and Exposure 
3.2.1 
Adverse Events 
3.2.2 
Serious Adverse Events 
3.2.3 
Grade 3 or Higher 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  
3.5.2 
Clinically Significant ECG Abnormality