Clinical trial NCT03627065
Conditions: Primary Sjögren's Syndrome
Keywords: Primary Sjögren's syndrome PI3Kδ inhibitor
Sponsor: Incyte Corporation
Start date: 2019-02-28; Completion date: 2020-01-02
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to assess the impact of parsaclisib on the signs and symptoms of Sjögren's syndrome (SS).

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Parsaclisib
Intervention descriptions: intervention 1: Parsaclisib administered orally once daily at the protocol-defined dose.

Protocol documents:
Prot_001.pdf: 
Incyte Corporation 
 
Page 1 of 65 
Protocol INCB 50465-207 
Version 0 
12 JUN 2018 
 
Clinical Study Protocol 
 
 
INCB 50465-207 
 
An Open-Label Phase 2 Study of INCB050465 in Participants With 
Primary Sjögren's Syndrome 
 
Product: 
INCB050465 
IND Number: 
 
Phase of Study: 
2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
12 JUN 2018 
 
 
 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws 
and country-specific regulations in which the study is being conducted. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without prior 
written consent. 
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Page 2 of 65 
Protocol INCB 50465-207 
Version 0 
12 JUN 2018 
INVESTIGATOR'S AGREEMENT 
I have read the INCB 50465-207 Protocol (Version 0 dated 12 JUN 2018) 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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Page 3 of 65 
Protocol INCB 50465-207 
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12 JUN 2018 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................10 
2. 
INTRODUCTION ......................................................................................................14 
2.1. 
Background .................................................................................................................14 
2.1.1. 
Sjögren's Syndrome ....................................................................................................14 
2.1.2. 
Diagnosis of Sjögren's Syndrome ...............................................................................15 
2.2. 
Current Treatment and Unmet Needs for Sjögren's Syndrome ..................................16 
2.3. 
PI3Kδ in Autoimmune Diseases .................................................................................16 
2.3.1. 
PI3Kδ in Sjögren's Syndrome .....................................................................................17 
2.3.2. 
INCB050465 ...............................................................................................................17 
2.4. 
Study Rationale ...........................................................................................................18 
2.4.1. 
Scientific Rationale for Study Design ........................................................................18 
2.4.2. 
Nonclinical Toxicology and Safety Margins ..............................................................18 
2.4.3. 
Justification for Dose ..................................................................................................19 
 
 
2.5.1. 
Potential Risks of INCB050465 Based on Preclinical Safety ....................................19 
2.5.2. 
Potential Risks of INCB050465 Based on Clinical Safety .........................................21 
2.5.3. 
Potential Benefits of INCB050465 in Sjögren's Syndrome ........................................22 
2.5.4. 
Overall Risk/Benefit Statement ..................................................................................22 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................23 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.2. 
Overall Study Duration ...............................................................................................25 
4.3. 
Study Termination ......................................................................................................25 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................29 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................29 
5.4. 
Screen Failures ............................................................................................................29 
5.5. 
Replacement of Participants .......................................................................................29 
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Protocol INCB 50465-207 
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6. 
STUDY TREATMENT ..............................................................................................30 
6.1. 
Study Treatment Administered ...................................................................................30 
6.2. 
Preparation, Handling, and Accountability ................................................................30 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding .......................................31 
6.4. 
Study Treatment Compliance .....................................................................................31 
6.5. 
Dose Modifications .....................................................................................................31 
6.5.1. 
Management of  Urgent Toxicities .............................................................................31 
6.5.2. 
Criteria and Procedures for Dose Interruptions and Adjustments of Study 
Drug ............................................................................................................................31 
6.5.3. 
Criteria for Permanent Discontinuation of INCB050465 ...........................................32 
6.6. 
Concomitant Medications and Procedures .................................................................32 
6.6.1. 
Permitted Medications and Procedures ......................................................................33 
6.6.1.1. 
Prophylaxis for Pneumocystis jirovecii Pneumonia ...................................................33 
6.6.1.2. 
Nonprescription Therapies for Sjögren's Syndrome ...................................................33 
6.6.2. 
Restricted Medications and Procedures ......................................................................33 
6.6.3. 
Prohibited Medications and Procedures .....................................................................34 
6.7. 
Treatment After the End of the Study .........................................................................34 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................35 
7.1. 
Discontinuation of Study Treatment ...........................................................................35 
7.1.1. 
Reasons for Discontinuation .......................................................................................35 
7.1.2. 
Discontinuation Procedures ........................................................................................35 
7.2. 
Participant Withdrawal From the Study .....................................................................36 
7.3. 
Lost to Follow-Up.......................................................................................................36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................37 
8.1. 
Administrative and General Procedures .....................................................................37 
8.1.1. 
Informed Consent Process ..........................................................................................37 
8.1.2. 
Screening Procedures ..................................................................................................38 
8.1.3. 
Interactive Response Technology Procedure ..............................................................38 
8.1.4. 
Distribution of Reminder Cards and/or Diaries ..........................................................38 
8.1.5. 
Demography and Medical History ..............................................................................39 
8.1.5.1. 
Demographics and General Medical History .............................................................39 
8.1.5.2. 
Disease Characteristics and Treatment History ..........................................................39 
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8.2. 
Efficacy Assessments .................................................................................................39 
8.2.1. 
Ultrasound of Salivary Glands ....................................................................................39 
8.2.2. 
EULAR Sjögren's Syndrome Disease Activity Index ................................................39 
8.2.3. 
Salivary Flow ..............................................................................................................39 
8.2.4. 
Patient-Reported Outcomes ........................................................................................40 
8.2.4.1. 
Dryness Questionnaire ................................................................................................40 
8.2.4.2. 
EULAR Sjögren's Syndrome Patient Reported Index ................................................40 
8.2.4.3. 
Patient Global Impression of Change Questionnaire ..................................................40 
8.2.4.4. 
Female Sexual Function Index ...................................................................................40 
8.2.4.5. 
PROMIS Fatigue Short Form .....................................................................................40 
8.2.4.6. 
European Quality Of Life 5 Dimensions Questionnaire .............................................40 
8.2.5. 
Health Economics .......................................................................................................40 
8.3. 
Safety Assessments .....................................................................................................40 
8.3.1. 
Adverse Events ...........................................................................................................41 
8.3.2. 
Physical Examinations ................................................................................................41 
8.3.3. 
Vital Signs ..................................................................................................................41 
8.3.4. 
Electrocardiograms .....................................................................................................42 
8.3.5. 
Laboratory Assessments .............................................................................................42 
8.3.5.1. 
Pregnancy Testing ......................................................................................................43 
8.3.5.2. 
Serology and Virology ................................................................................................44 
8.3.5.3. 
Tuberculosis Testing ...................................................................................................44 
 
 
 
 
 
 
 
 
 
 
8.6. 
End of Treatment ........................................................................................................46 
8.7. 
Safety Follow-Up ........................................................................................................46 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING ......................46 
9.1. 
Definition of Adverse Event .......................................................................................46 
9.2. 
Definition of Serious Adverse Event ..........................................................................47 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse Events .........48 
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9.4. 
Reporting of Serious Adverse Events .........................................................................50 
9.5. 
Adverse Events of Special Interest .............................................................................51 
9.6. 
Emergency Unblinding of Treatment Assignment .....................................................51 
9.7. 
Pregnancy ...................................................................................................................52 
9.8. 
Warnings and Precautions ..........................................................................................52 
9.9. 
Product Complaints ....................................................................................................52 
9.10. 
Treatment of Overdose ...............................................................................................53 
10. 
STATISTICS ..............................................................................................................53 
10.1. 
Sample Size Determination ........................................................................................53 
10.2. 
Populations for Analysis .............................................................................................53 
10.3. 
Level of Significance ..................................................................................................53 
10.4. 
Statistical Analyses .....................................................................................................53 
10.4.1. 
Efficacy Analysis ........................................................................................................54 
10.4.2. 
Safety Analyses ..........................................................................................................54 
 
 
 
 
10.5. 
Interim Analysis ..........................................................................................................55 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................55 
11.1. 
Investigator Responsibilities .......................................................................................55 
11.2. 
Data Management .......................................................................................................56 
11.3. 
Data Privacy and Confidentiality of Study Records ...................................................57 
11.4. 
Financial Disclosure ...................................................................................................58 
11.5. 
Publication Policy .......................................................................................................58 
11.6. 
Study and Site Closure................................................................................................59 
12. 
REFERENCES ...........................................................................................................60 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS ...............................................................................63 
APPENDIX B. DRYNESS QUESTIONNAIRE ........................................................................64 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ............................65 
 
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LIST OF TABLES 
Table 1: 
Primary and Key Secondary Objectives and Endpoints .............................................10 
Table 2: 
Key Study Design Elements .......................................................................................10 
Table 3: 
Schedule of Activities .................................................................................................12 
Table 4: 
Schedule of Laboratory Assessments .........................................................................13 
Table 5: 
Objectives and Endpoints ...........................................................................................23 
Table 6: 
Exclusionary Laboratory Values ................................................................................29 
Table 7: 
Study Treatment Information .....................................................................................30 
Table 8: 
Criteria for Interrupting, Restarting, or Discontinuing Study Drug ...........................32 
Table 9: 
Electrocardiogram Schedule .......................................................................................42 
Table 10: Required Laboratory Analytes ....................................................................................43 
 
 
 
 
 
LIST OF FIGURES 
 
 
 
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LIST OF ABBREVIATIONS 
Abbreviations and 
Special Terms 
Definition 
AE 
adverse event 
AECG 
American−European Consensus Group 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
 
 
 
 
AST 
aspartate aminotransferase 
AUC 
area under the plasma or serum concentration curve 
BTK 
Bruton's tyrosine kinase 
CAML 
calcium-modulating ligand 
CD 
cluster of differentiation 
Cmin 
minimum observed plasma or serum concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXCL13 
CXC motif chemokine ligand 13 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicity 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOT 
end of treatment 
EQ-5D 
European Quality Of Life 5 Dimensions questionnaire 
ESSDAI 
EULAR Sjögren's Syndrome Disease Activity Index 
ESSPRI 
EULAR Sjögren's Syndrome Patient Reported Index 
EULAR 
European League Against Rheumatism 
FAS 
full analysis set 
FSFI 
Female Sexual Function Index 
FSH 
follicle-stimulating hormone 
GLP 
Good Laboratory Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IB 
Investigator's Brochure 
IC50 
concentration that results in 50% inhibition 
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Abbreviations and 
Special Terms 
Definition 
IC90 
concentration that results in 90% inhibition 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
independent ethics committee 
 
 
IL 
interleukin 
IRB 
institutional review board 
IRT 
interactive response technology 
IV 
intravenous 
JAK 
Janus kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
PBMC 
peripheral blood mononuclear cells 
PD 
pharmacodynamic  
PGIC 
Patient Global Impression of Change questionnaire 
PI3Kδ 
phosphatidylinositide 3-kinase delta isoform 
PJP 
Pneumocystis jirovecii pneumonia 
 
 
PROMIS 
Patient-Reported-Outcomes Measurement Information System 
QD 
once daily 
QTcF 
QT interval corrected for heart rate using Fridericia's formula 
RA 
rheumatoid arthritis 
RNA 
ribonucleic acid 
SGUS 
salivary gland ultrasound 
SLE 
systemic lupus erythematosus 
SoA 
schedule of activities 
SS 
Sjögren's syndrome 
T3, T4 
triiodothyronine and thyroxine (thyroid hormones) 
TB 
tuberculosis  
TEAE 
treatment-emergent adverse event, AEs reported for the first time or worsening of 
a pre-existing event after first dose of study treatment 
TNF 
tissue necrosis factor 
Treg 
regulatory T cell 
ULN 
upper limit of normal 
 
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Table 3: 
Schedule of Activities 
 
Screening 
(Day -28 
to Day -1) 
Day 1 
Week 2 
(± 3 Days) 
Week 4 
(± 7 Days) 
Week 8 
(± 7 Days) 
Week 12/ 
EOT 
(± 7 Days) 
Safety Follow-Up 
(30 Days [+7 Days] 
After Last Dose of 
Study Drug) 
Comments 
Administrative Procedures 
Informed consent 
X 
 
 
 
 
 
 
 
Contact IRT 
X 
X 
X 
X 
X 
X 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
Medical and medication history 
X 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
 
Dispense reminder card 
 
X 
X 
X 
X 
 
 
 
Administer study drug during visit 
 
X 
X 
X 
X 
 
 
 
Dispense study drug 
 
X 
X 
X 
X 
 
 
 
Drug accountability and compliance 
assessment 
 
 
X 
X 
X 
X 
 
 
Administer PJP prophylaxis if 
needed* 
 
X 
X 
X 
X 
X 
X 
From Day 1 to at least 30 days after 
last dose of study drug. 
*See Section 6.6.1.1. 
Safety Assessments 
AE assessment 
X 
X 
X 
X 
X 
X 
X 
 
Comprehensive physical examination 
X 
 
 
 
 
 
X 
 
Targeted physical examination 
 
X 
X 
X 
X 
X 
 
Body systems with symptoms should 
be physically examined. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
Measure height at screening only. 
12-lead ECG 
X 
X 
X 
 
 
X 
X* 
*Standard ECG. 
Efficacy Assessments 
Ultrasound of parotid and 
submandibular salivary glands 
 
X* 
 
X 
 
X 
 
*Schedule ultrasound 2 weeks before 
Day 1 to ensure results availability. 
Measurement of total unstimulated 
salivary flow 
X 
X 
 
X 
X 
X 
 
 
Measurement of total stimulated 
salivary flow 
X* 
X 
 
X 
X 
X 
 
*Documented measurement within 
12 weeks before screening visit. 
Questionnaire for dryness of eyes, 
mouth, and (females only) vagina 
X 
X 
 
X 
X 
X 
 
 
ESSDAI assessment 
X 
X 
 
X 
X 
X 
 
 
ESSPRI questionnaire 
X 
X 
 
X 
X 
X 
 
 
PGIC questionnaire 
X 
X 
 
X 
X 
X 
 
 
FSFI questionnaire  
X 
X 
 
X 
X 
X 
 
Female participants only. 
PROMIS Fatigue questionnaire 
X 
X 
 
X 
X 
X 
 
 
EQ-5D questionnaire 
X 
X 
 
X 
X 
X 
 
 
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Table 4: 
Schedule of Laboratory Assessments 
 
Screening 
(Day -28 to 
Day -1) 
Day 1 
Week 2 
(± 3 days) 
Week 4 
(± 7 Days) 
Week 8 
(± 7 Days) 
Week 12/EOT 
(± 7 Days) 
Safety Follow-Up 
(30 Days [+ 7 Days] 
After Last Dose of 
Study Drug) 
Comments 
Clinical Laboratory Assessments 
Serum chemistries 
X 
X 
X 
X 
X 
X 
X 
 
Hematology 
X 
X 
X 
X 
X 
X 
X 
 
Serum pregnancy test 
X 
 
 
 
 
 
X 
All female participants of 
childbearing potential. 
FSH 
X 
 
 
 
 
 
 
To document hormonal 
menopause defined as 
amenorrhea of at least 
12 months before screening 
Urine pregnancy test 
 
X 
X 
X 
X 
X 
 
Female participants of 
childbearing potential only. 
Thyroid function 
X 
 
 
 
 
 
 
 
Serology – HIV, HBV, and HCV, 
viral load reflex if required 
X 
 
 
 
 
 
 
 
TB test 
X 
 
 
 
 
 
 
QuantiFERON-TB Gold test or 
T-spot.TB. 
Urinalysis 
X 
 
 
 
 
X 
X 
 
 
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3. 
OBJECTIVES AND ENDPOINTS 
Table 5 presents the objectives and endpoints. 
Table 5: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To determine the impact of INCB050465 on 
salivary gland echostructure. 
• 
Proportion of participants with a 1 point or greater 
improvement on the SGUS score for parotid and 
submandibular glands at Week 4 and Week 12. 
Secondary 
To assess the impact of INCB050465 on 
salivary CXCL13 
• 
Change and percent change from baseline in 
salivary CXCL13 levels at Week 4 and Week 12. 
To assess the efficacy of INCB050465  
• 
Change and percent change in stimulated and 
unstimulated whole salivary flow from baseline at 
Weeks 4, 8, and 12. 
• 
Change and percent change in ESSDAI at Week 12. 
• 
Change and percent change in ESSPRI at Weeks 4, 
8, and 12. 
• 
Change and percent change in symptom scores for 
dryness of eyes, mouth, and vagina at Weeks 4, 8, 
and 12. 
• 
Proportions of participants in each PGIC category 
at Weeks 4, 8, and 12. 
• 
Change and percent change in PROMIS Fatigue 
short form at Weeks 4, 8, and 12. 
• 
Change and percent change in FSFI at Weeks 4, 8, 
and 12 (female participants only). 
• 
Change and percent change in EQ-5D at Weeks 4, 
8, and 12. 
To evaluate the safety and tolerability of 
INCB050465 
• 
Frequency, duration, and severity of AEs, clinical 
laboratory test results, vital sign results, ECGs, and 
physical examination findings. 
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Table 5: 
Objectives and Endpoints (Continued) 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a single group, open-label study of the impact of PI3Kδ inhibitor INCB050465 on signs 
and symptoms of SS.  Twelve participants meeting the inclusion criteria and none of the 
exclusion criteria will be enrolled.  Participants will receive treatment with INCB050465 
 
QD for 12 weeks and undergo ultrasound measurement of salivary glands, measurements of 
salivary flow, collection of symptom questionnaires, and PD 
 blood sampling to allow 
studies of cytokine levels, gene expression levels, and other PD markers. 
Participants will have regularly scheduled study visits at screening, Day 1 (baseline; first day of 
dose administration), and at the end of Weeks 4, 8 and 12, where laboratory and other 
assessments will be performed.  There will also be a laboratory-only visit at the end of Week 2 to 
collect safety laboratory assessments 
. Participants will complete 
questionnaires regarding signs and symptoms of disease at each study visit. 
Ultrasound measurement of the parotid and submandibular glands will be performed on Day 1 
(before the first dose) and after 4 and 12 weeks of treatment.  Ultrasound of glands will be 
performed in the longitudinal and transverse planes with participants in a supine position.  The  
ultrasound images will be evaluated for quality then transmitted to a central vendor for reading 
and data summarization.   
The echostructure of each gland on B-mode images will be graded on a 5-point scale (0 to 4):   
• Grade 0:  normal homogeneous gland. 
• Grade 1:  small hypoechoic areas with hyperechoic bands. 
• Grade 2:  multiple hypoechoic areas less than 2 mm. 
• Grade 3:  multiple hypoechoic areas 2 to 6 mm.  
• Grade 4:  multiple hypoechoic areas larger than 6 mm.   
For each timepoint, 4 grades will be obtained, one for each parotid and submandibular gland.  
The SGUS score is the numeric sum of the 4 individual grades (maximum score of 16).  
Instructions for conducting and transmitting ultrasound measurements will be provided in the 
Study Manual. 
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Stimulated and unstimulated salivary flow will be performed at baseline and after 4, 8, and 
12 weeks of treatment.  Instructions for performing salivary flow measurements will be provided 
in the Study Manual. 
PJP prophylaxis:  Prior treatment with prednisone or equivalent may represent a risk factor for 
PJP in combination with other immunosuppressants.  Participants who have received prednisone 
≥ 20 mg per day (or equivalent) within 60 days before baseline are excluded.  Participants 
receiving ≥ 10 mg to < 20 mg of prednisone (or equivalent) may be at increased risk for PJP, and 
prophylaxis should be considered for these participants, particularly if they have a history of PJP 
or have recently received any immunosuppressive therapy that may represent and increased risk.  
Participants receiving < 10 mg of prednisone or equivalent have some potential risk.  PJP 
prophylaxis is not required for these participants but should be considered by the investigator 
only in exceptional circumstances in consultation with the medical monitor as needed. 
Examples of standard PJP prophylaxis therapies include trimethoprim-sulfamethoxazole, 
atovaquone, dapsone with or without pyrimethamine, and pentamidine (Baden et al 2012).  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.  Prophylaxis should be given while participants are receiving 
study drug and should continue for at least 30 days after the last dose of study drug. 
In addition to these study visits, there will be laboratory-only visits at the end of Week 2 to 
collect safety laboratory assessments 
. 
Week 12 will correspond to the EOT.  A safety follow up visit will occur 30 (+7) days after the 
last dose of study drug. 
4.2. 
Overall Study Duration 
Individual participants will participate for a duration of up to 21 weeks (4 weeks screening, 
12 weeks treatment, 4-5 weeks safety follow-up; see Figure 1). 
The study begins when the first participant signs the ICF.  The end of the study is defined as the 
date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if he/she has completed all study visits, 
including the follow-up visit. 
The investigator will be expected to monitor for and report any SAEs, AEs of special interest, 
and pregnancies as detailed in Section 9.  The remaining participants are considered to be on 
study until a discontinuation criterion is met and written notification is provided to the sponsor. 
4.3. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the IRB/IEC in writing of the 
study's completion or early termination, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, or if required by regulatory agency.  If the study 
is terminated prematurely, the sponsor or designee will notify the investigators, the IRBs and 
IECs, and regulatory bodies of the decision and reason for termination of the study. 
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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Diagnosis of secondary SS according to the revised AECG criteria (eg, the presence of a 
previously diagnosed or a present diagnosis of RA, SLE, systemic sclerosis, mixed 
connective tissue disease, polymyositis, dermatomyositis, immunoglobulin G4-related 
disorder, sarcoidosis, or any other defined autoimmune rheumatologic disorder). 
a. NOTE:  Nonrheumatologic autoimmune disorders (eg, Hashimoto thyroiditis, 
alopecia, vitiligo, Type 1 diabetes mellitus) do not constitute an exclusion; the 
medical monitor should be consulted if there are questions regarding a specific 
participant's disease history or diagnosis. 
2. Concurrent conditions and history of other diseases: 
a. History or clinical manifestations of significant unstable metabolic, hepatic, renal, 
hematologic, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or 
psychiatric disorders. 
b. Clinically significant cardiac disease, including unstable angina, acute myocardial 
infarction, and or cardiac conduction issues within 180 days of the date of study drug 
administration. 
c. Current New York Heart Association Class II to IV congestive heart failure or 
uncontrolled arrhythmia. 
d. History of osteomyelitis, PJP, or bronchiectasis. 
e. Active bacterial, fungal, parasitic, or viral infection that requires antibiotic therapy.  
Participants with acute infections requiring treatment should delay 
screening/enrollment until the course of therapy has been completed and the event is 
considered resolved.  Prophylactic antibiotics will be permitted if they have been 
started at least 28 days before the screening visit. 
f. History within 6 months before screening, or current presence at screening, of poorly 
healing wound and/or cutaneous ulcers. 
g. Prior head or neck irradiation. 
h. History of or ongoing serious illness or medical, physical, or psychiatric condition(s) 
that, in the investigator's opinion, would 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. 
3. Positive test results for TB from the QuantiFERON-TB Gold test or T-spot.TB test at 
screening.  If a result is indeterminate, the test should be repeated.  If the repeat test result 
is positive, the participant is excluded.  If the repeat test result is indeterminate, a purified 
protein derivative skin test should be done, and if there is < 5 mm of induration, the 
participant can be enrolled. 
4. Positive serology test results for HIV antibody, hepatitis B surface antigen, hepatitis B 
surface antigen antibody, HBV core antibody, or HCV (HCV antibody with positive 
HCV-RNA) at screening. 
5. Severely impaired liver function (Child-Pugh Class C). 
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6. Prior or ongoing therapy with: 
a. Any drug that inhibits PI3K (examples of drugs targeting this pathway include but 
are not limited to leniolisib, seletalisib, INCB040093, idelalisib, and duvelisib) at 
any time before baseline or during study. 
b. Immunologic or other immunosuppressive therapy, or B-cell targeted therapy (eg, 
rituximab, other anti-CD20 agents, anti-CD19 agents, anti-CD22 agents, 
anti-CD52 agents) or LyS-targeted therapy (eg, belimumab, CAML interactor) or 
other biologic investigational agent (eg, CD40L antibody) or cyclophosphamide 
within the prior 365 days before baseline or during study. 
c. BTK inhibitors (examples of drugs targeting this pathway include but are not 
limited to ibrutinib and PCI32765) within 90 days before baseline or during study. 
d. Use of anti-TNFα therapy, IL-1−receptor antagonist, monoclonal antibody to 
IL-1, costimulation modulator, monoclonal antibody to IL-6 or IL-6−receptor, 
monoclonal antibody to IL-17, monoclonal antibody to IL-23, JAK inhibitor, 
IV immunoglobulin, plasmapheresis, or Staph protein A column within 90 days 
before baseline or during study. 
e. Use of any experimental drug therapy for SS within 90 days before baseline or 
during study. 
f. Use of nutraceuticals, ayurvedic, herbal, and other nonprescription therapies used 
for SS are permitted with investigator review, provided the participant has been 
taking the therapy for at least 60 days as a stable regimen and agrees to continue 
taking the same preparation at the same dose regimen during the course of the 
study. 
g. Antimalarials, if ongoing, should be stable within 60 days of baseline and be 
anticipated to remain stable throughout the 12-week study assessment period. 
h. Glucocorticoids at doses ≥ 20 mg prednisone equivalents per day within 60 days 
before baseline or during study.  Administration of glucocorticoids at doses of 
20 mg or less must be stable within 30 days of baseline and be anticipated to 
remain stable throughout the 12-week study assessment period. 
i. Use of anticholinergics within 30 days before baseline or during study. 
j. Use of any potent cytochrome CYP3A4 inhibitors or inducers within 14 days or 
5 half-lives (whichever is longer) before baseline or anticipated during the study. 
k. Use of cholinergic agents such as pilocarpine within 12 hours of salivary flow 
visits at Day 1 and Weeks 4, 8, and 12. 
7. Receipt of any live vaccine in the 30 days before screening.  NOTE:  Participants will not 
be allowed to receive live or attenuated vaccines during their participation in the study or 
until 30 days after the last dose of study medication with the exception of influenza 
vaccine. 
8. No major surgery within 30 days before screening.  Inadequate recovery from toxicity 
and/or complications from a major surgery before starting therapy. 
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9. 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. 
10. Laboratory values at screening defined in Table 6. 
Table 6: 
Exclusionary Laboratory Values 
Laboratory Parameter 
Exclusion Criterion 
Hematology 
Platelets 
≤ 100 × 109/L 
ANC 
≤ 1.5 × 109/L 
Hepatic 
ALT 
>2 x ULN 
AST 
>2 x ULN 
Renal 
eGFR 
Participants with inadequate renal function defined as eGFR 
≤ 50 mL/min 
11. Women who are pregnant or breastfeeding. 
12. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug/treatment and attending required 
study visits; pose a significant risk to the participant; or interfere with interpretation of 
study data. 
13. Inability of the participant (or parent, guardian, or legally authorized representative) to 
comprehend the ICF or unwillingness to sign the ICF. 
5.3. 
Lifestyle Considerations 
No restrictions are required. 
5.3.1. 
Meals and Dietary Restrictions 
Not applicable. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. 
Tests with results that fail eligibility requirements may be repeated once during screening if the 
investigator believes the result to be not consistent with the participant's clinical status.  
Additionally, a participant who fails screening may repeat the screening process 1 time if the 
investigator believes that there has been a change in eligibility status.  Participants who rescreen 
must reconsent and be assigned a new participant number. 
5.5. 
Replacement of Participants 
Participants will not be replaced during the study. 
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6. 
STUDY TREATMENT 
6.1. 
Study Treatment Administered 
Information regarding study drug and administration is provided in Table 7.  Participants will 
record study drug administration daily in a diary. 
Table 7: 
Study Treatment Information 
Study treatment name: 
INCB050465 
Dose formulation: 
Tablet 
Unit dose strength/dose level: 
 
Route of administration:  
Oral 
Administration instructions: 
INCB050465 will be taken QD, orally with water and without regard 
to food. 
Packaging and labeling: 
INCB050465 will be packaged in high-density polyethylene bottles. 
Storage: 
Ambient (15°C-30°C/59°F-86°F) 
6.2. 
Preparation, Handling, and Accountability 
Only participants enrolled in the study may receive study treatment, and only authorized site 
staff may supply or administer study treatment.  All study treatment must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff. 
The investigator (or designee) is responsible for study treatment accountability, reconciliation, 
and record maintenance (ie, receipt, reconciliation, and final disposition records).  Inventory and 
accountability records must be maintained and readily available for inspection by the study 
monitor and are open to inspection at any time by any applicable regulatory authorities.  The 
investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Participant use of the study drug, including pill count from each supply dispensed. 
• Return of study drug to the investigator or designee by participants. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the participants were provided the 
specified study drug.  These records should include dates, quantities, and any available batch or 
serial numbers or unique code numbers assigned to the investigational product and study 
participants. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
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conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
Further guidance and information for the final disposition of unused study treatments are 
provided in the study materials provided to sites. 
6.3. 
Measures to Minimize Bias:  Randomization and Blinding 
Not applicable. 
6.4. 
Study Treatment Compliance 
Compliance with study drug should be emphasized to the participant by the site personnel, and 
appropriate steps should be taken to optimize compliance during the study.  Compliance with 
INCB050465 will be calculated by the sponsor based on the drug accountability documented by 
the site staff and monitored by the sponsor/designee (tablet counts).  Participants will be 
instructed to bring all study drug with them to the study visits in order for site personnel to 
conduct tablet counts to assess study drug accountability.  The drug accountability 
documentation will be used by the sponsor to calculate treatment compliance. 
6.5. 
Dose Modifications 
6.5.1. 
Management of  Urgent Toxicities  
Investigators may employ any measures or concomitant medications necessary to optimally treat 
the participant after discussion with the sponsor (whenever possible). 
6.5.2. 
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. 
There are no dose modifications in this study.  In some circumstances, it may be necessary to 
temporarily interrupt treatment with INCB050465 as a result of AEs or laboratory abnormalities 
that have an unclear relationship to the study drug (see Table 8).  Except in cases of emergency, 
it is recommended that any laboratory findings be confirmed and that the investigator consult 
with the sponsor's medical monitor (or other representative of the sponsor) before temporarily 
interrupting study drug.  Participants who experience a recurrence of the AEs or laboratory 
abnormalities upon restarting the study drug may have the study drug permanently discontinued. 
Instructions for dose interruptions for INCB050465 are outlined in Table 8.  Individual decisions 
regarding dose interruptions should be made using clinical judgment in consultation with the 
medical monitor (whenever possible), taking into account relatedness of the AE to the study 
treatment and the participant's underlying condition.  Adverse events that have a clear alternative 
explanation, or transient (≤ 72 hours) abnormal laboratory values without associated clinically 
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significant signs or symptoms, may be exempt from dose interruption.  Dose interruptions may 
occur at any time during the 12 weeks of administration. 
Table 8: 
Criteria for Interrupting, Restarting, or Discontinuing Study Drug 
ADVERSE EVENT 
ACTION TAKEN 
Chemistry 
• AST and/or ALT is > 3.0 × ULN. 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until the 
toxicity has resolved to ≤ Grade 1 except by approval of the 
medical monitor. 
Step 2:  Restart study drug and monitor as clinically indicated.   
• AST and/or ALT is > 5.0 × ULN 
Discontinue study drug administration and follow-up per Protocol.   
Hematology 
• ANC ≤ 1.0 × 109/L, unless due to 
underlying disease. 
• Platelet count is 50 × 109/L to < 75 × 109/L, 
unless due to underlying disease. 
Step 1:  Interrupt study drug up to 2 weeks (14 days) until the 
toxicity has resolved to ≤ Grade 1 or pretherapy baseline. 
Step 2:  Restart study drug and monitor as clinically indicated. 
• Grade 4 ANC (< 0.5 × 109/L). 
• ≥ Grade 3 ANC with an oral temperature of 
at least 38.5°C OR with ≥ Grade 3 infection. 
• Platelet count is < 50 × 109/L. 
Discontinue study drug administration and follow-up per Protocol.   
Other toxicities 
• Any Grade 1 or Grade 2 toxicity. 
Continue study drug administration and treat the toxicity; monitor 
as clinically indicated. 
• Any Grade 3 toxicity, if clinically 
significant and not manageable by 
supportive care. 
Step 1:  Interrupt study drug up to 2 weeks (14 days), until 
toxicity resolves to ≤ Grade 1. 
Step 2:  Restart study drug and monitor as clinically indicated.   
• Any recurrent Grade 3 toxicity after dose 
restart. 
Discontinue study drug administration and follow-up per Protocol.   
• Any other Grade 4 toxicity. 
Discontinue study drug administration and follow-up per Protocol. 
6.5.3. 
Criteria for Permanent Discontinuation of INCB050465 
The occurrence of unacceptable toxicity not caused by the underlying disease will be presumed 
to be related to study drug treatment and will require that the study drug be permanently 
discontinued.  Unacceptable toxicity is defined as follows: 
• Occurrence of an AE that is related to treatment with the study drug that, in the judgment 
of the investigator or the sponsor's medical monitor, compromises the participant's ability 
to continue study-specific procedures or is considered to not be in the participant’s best 
interest.  
• Persistent AE requiring a delay of therapy for more than 2 weeks without resolution of 
the AE.  A greater treatment delay requires approval by the sponsor's medical monitor. 
6.6. 
Concomitant Medications and Procedures 
All concomitant medications and treatments (including over-the-counter or prescription 
medicines, vitamins, vaccines, and/or herbal supplements) must be recorded in the eCRF.  Any 
prior medication received up to 28 days before the first dose of study treatment and 30 days after 
the last dose of study treatment will be recorded in the eCRF.  A detailed history of prior 
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medications use related to SS in the year before screening will be also be collected, as well as 
response to each treatment and reason for discontinuation. 
Any addition, deletion, or change in the dose of these medications will also be recorded.  
Concomitant medications administered after 30 days after the last dose of study treatment should 
be recorded for SAEs as defined in Section 9.3.  Concomitant treatments/procedures that are 
required to manage a participant's medical condition during the study will also be recorded in the 
eCRF.  The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6.1. 
Permitted Medications and Procedures 
6.6.1.1. 
Prophylaxis for Pneumocystis jirovecii Pneumonia 
Prior treatment with prednisone or equivalent may represent a risk factor for PJP in combination 
with other immunosuppressants.  Participants who have received prednisone ≥ 20 mg per day (or 
equivalent) within 60 days before baseline are excluded.  Participants receiving ≥ 10 to < 20 mg 
of prednisone (or equivalent) may be at increased risk for PJP, and prophylaxis should be 
considered for these participants, particularly if they have a history of PJP or have recently 
received any immunosuppressive therapy that may represent an increased risk.  Participants 
receiving < 10 mg of prednisone or equivalent have some potential risk; however, PJP 
prophylaxis is not generally required for these participants and should be considered only in 
exceptional circumstances and in consultation with the medical monitor as needed. 
Examples of standard PJP prophylaxis therapies include trimethoprim-sulfamethoxazole, 
atovaquone, dapsone with or without pyrimethamine, and pentamidine (Baden et al 2012).  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.  Prophylaxis should be given while participants are receiving 
study drug and should continue for at least 30 days after the last dose of study drug. 
6.6.1.2. 
Nonprescription Therapies for Sjögren's Syndrome 
Use of nutraceuticals, ayurvedic, herbal, and other nonprescription therapies used for SS are 
permitted with investigator review provided the participant has been taking the therapy for at 
least 60 days as a stable regimen and agrees to continue taking the same preparation at the same 
dose during the course of the study. 
6.6.2. 
Restricted Medications and Procedures 
• Inducers of CYP3A4 (see Study Manual) are discouraged, and investigators should seek 
other options if available. 
• Moderate CYP3A4 inhibitors (see Study Manual) are discouraged, and investigators 
should seek other options if available. 
• Administration of glucocorticoids at doses of 20 mg or less must be stable within 30 days 
of Day 1 and be anticipated to remain stable throughout the 12-week study assessment 
period. 
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• Antimalarials, if ongoing, should be stable within 60 days of Day 1 and be anticipated to 
remain stable throughout the 12-week study assessment period. 
6.6.3. 
Prohibited Medications and Procedures 
The following medications and procedures are prohibited during the study from screening 
through the follow-up visit and before the study as indicated for individual medications: 
At any time before baseline (Day 1): 
• Any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not 
limited to leniolisib, seletalisib, INCB040093, idelalisib, and duvelisib). 
Within 1 year (365 days) before baseline (Day 1): 
• Immunologic or other immunosuppressive therapy, or B-cell targeted therapy (eg 
rituximab, other anti-CD-19 agents, anti-CD-20 agents, anti-CD-22 agents, anti CD52 
agents) or LyS-targeted therapy (eg, belimumab, CAML interactor) or other biologic 
investigational agent (eg, CD-40L antibody) or cyclophosphamide. 
• Anti-TNFα therapy, IL-1−receptor antagonist, monoclonal antibody to IL-1, 
costimulation modulator, monoclonal antibody to IL-6 or IL-6−receptor, monoclonal 
antibody to IL-17, monoclonal antibody to IL-23, JAK inhibitor, IV immunoglobulin, 
plasmapheresis, or Staph protein A column. 
Within 3 months (90 days) before baseline (Day 1): 
• Any experimental drug therapy for SS. 
• BTK inhibitors (examples of drugs targeting this pathway include but are not limited to 
ibrutinib and PCI32765). 
Within 2 months (60 days) before baseline (Day 1): 
• Glucocorticoids at doses > 20 mg prednisone equivalents. 
Within 1 month (30 days) before baseline (Day 1): 
• Anticholinergics. 
• Receipt of any live vaccine.  Note participants will not be allowed to receive live or 
attenuated vaccines during their participation in the study or until 30 days after the last 
dose of study medication with the exception of influenza vaccine. 
Within 2 weeks (14 days) before baseline (Day 1): 
• Any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is 
longer) before the first dose of INCB050465 or anticipated during the study. 
Within 12 hours (< 1 day) before baseline (Day 1): 
• Cholinergic agents such as pilocarpine. 
6.7. 
Treatment After the End of the Study 
There is no treatment after the end of the study. 
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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
7.1.1. 
Reasons for Discontinuation 
Participants must be discontinued from study treatment for the following reasons: 
• The participant becomes pregnant. 
• Consent is withdrawn.   
Note:  Consent withdrawn means that the participant has explicitly indicated that they 
do not want to be followed any longer; in this case no further data, except data in 
public domain, may be solicited from or collected on the participant.  
• 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 6.5.3. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
A participant may be discontinued from study treatment as follows: 
• If, during the course of the study, a participant is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the participant should be withdrawn from study treatment. 
• If a participant is noncompliant with study procedures or study drug administration in 
the investigator's opinion, the sponsor should be consulted for instruction on handling 
the participant. 
7.1.2. 
Discontinuation Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the EOT 
visit should be conducted.  Reasonable efforts should be made to have the participant return for a 
follow-up visit.  These visits are described in Table 3 and Table 4.  The last date of the last dose 
of study drug(s)/treatment and the reason for discontinuation of study treatment will be recorded 
in the eCRF. 
If a participant is discontinued from study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal must be documented in the participant's medical record 
and the primary reason for withdrawal must be included in the eCRF. 
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the eCRF. 
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• Participants must be followed for safety until the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longest. 
If the participant discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up) 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 assessments. 
7.2. 
Participant Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. 
If 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. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
See Table 3 and Table 4 for data to be collected at the time of study discontinuation and 
follow-up and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant's last known mailing address 
or local equivalent methods).  These contact attempts should be documented in the 
participant's medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Administrative and General Procedures 
8.1.1. 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the participant.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to participant records. 
− The ICF must contain all required elements and describe the nature, scope, and 
possible consequences of the study in a form understandable to the study 
participant. 
• Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent that meets the applicable requirements and regulations for the IRB/IEC or 
study center. 
• The participant must be informed that his/her personal study-related data will be used 
by the sponsor in accordance with local data protection laws.  The level of disclosure 
must also be explained to the participant. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained.  The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must provide consent to the most current version of the ICF(s) during 
their participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant's legally 
authorized representative. 
Participants who are rescreened are required to sign a new ICF. 
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8.1.2. 
Screening Procedures 
Screening is the interval between signing the ICF and the day the participant is enrolled in the 
study (Day 1).  Screening may not exceed 28 days.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
Procedures conducted as part of the participant's routine clinical management (eg, blood count, 
imaging study) and obtained before signing of informed consent may be used for screening or 
baseline purposes provided the procedure meets the Protocol-defined criteria and has been 
performed in the timeframe of the study (ie, within 28 days of Day 1).  For participants who are 
enrolled in the study, information associated with eligibility requirements must be entered into 
the appropriate eCRF pages. 
Results from the screening visit evaluations will be reviewed to confirm eligibility before 
enrollment or the administration of study drug.  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 
treatment assignment will be used to determine eligibility.  Treatment should start as soon as 
possible, but within 3 days after the date of enrollment. 
See Sections 5.4 and 5.5 for information regarding screen failures and replacement of 
participants, respectively. 
8.1.3. 
Interactive Response Technology Procedure 
Each participant will be identified in the study by a participant ID number, which is a 
combination of the site ID and participant number.  Site staff should contact the IRT to obtain the 
participant ID number during screening.  Upon determining that the participant is eligible for 
study entry, the IRT will be contacted to obtain the study medication bottle or kit assignment.  
Additionally, the IRT will be contacted at each regular study visit to update the study drug 
supply.  Additional details are provided in the IRT manual. 
8.1.4. 
Distribution of Reminder Cards and/or Diaries 
Participants will be provided with a reminder card on Day 1 and Weeks 2, 4, and 8.  The 
reminder card will indicate the date/time of the next visit and will also remind the participant that 
they should not take their morning dose of study drug on the day of each study visit as they will 
take it after blood draws for safety evaluation have been completed.  The reminder cards for each 
visit will have an area on which the date and time of the last dose taken (from the previous 
evening) and the time of their last meal before the visit should be recorded. 
Participants will also be provided with a diary on Day 1 in order to record study drug 
administration daily.  The date and time of the last dose of study drug 
 
 will be recorded in the diary and 
eCRF.  Daily study drug administration (see Section 6.1) will also be recorded in the diary. 
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8.2.4. 
Patient-Reported Outcomes 
Patient-reported outcome instruments will be given to participants for completion at study visits 
indicated in Table 3.  Site staff will enter completed questionnaires into the eCRF database. 
8.2.4.1. 
Dryness Questionnaire 
The dryness questionnaire will ask participants to rate the dryness of eyes, mouth, or vagina 
(female participants only) with 24-hour recall using an 11-point numerical rating system ranging 
from 0 (no dryness) to 10 (worst imaginable; see Appendix B). 
8.2.4.2. 
EULAR Sjögren's Syndrome Patient Reported Index 
The ESSPRI consists of 3 items, each with a 0 (no symptom) to 10 (maximum imaginable 
symptom) scale.  The 3 items are dryness, fatigue, and pain.  The recall period is 2 weeks. 
8.2.4.3. 
Patient Global Impression of Change Questionnaire 
The PGIC asks a single question regarding how the patient is feeling since beginning new 
therapy.  The questionnaire uses a 7 point scale ranging from "very much worse" to "very much 
improved," with the midpoint as no change. 
8.2.4.4. 
Female Sexual Function Index 
The FSFI is a brief, self-report measure of female sexual function (female participants only).  
The questionnaire contains 19 items covering 6 domains of sexual function.  The recall period is 
4 weeks. 
8.2.4.5. 
PROMIS Fatigue Short Form 
The PROMIS fatigue short form includes 7 items with a rating sale of 1 to 5.  The recall period is 
7 days. 
8.2.4.6. 
European Quality Of Life 5 Dimensions Questionnaire 
The EQ-5D is a standardized measure of health status.  It consists of 5 questions, each with a 5-
item rating scale plus a visual analog scale rating from 1 to 100 for overall health status.  The 
questionnaire probes the participants responses for the current day. 
8.2.5. 
Health Economics 
Not applicable. 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in Table 3. 
See Section 6.5 for guidelines regarding the management of relevant laboratory or other safety 
assessment abnormalities. 
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8.3.1. 
Adverse Events 
Adverse events will be monitored from the time the participant signs the ICF until at least 
30 days after the last dose of study drug.  Adverse events that begin or worsen after informed 
consent should be recorded on the Adverse Events Form in the eCRF regardless of the 
assumption of a causal relationship with 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, 
considered related to the study treatment/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 recorded and reported to the sponsor or designee within 24 hours.  The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
8.3.2. 
Physical Examinations 
Physical examinations will be conducted at the timepoints listed in Table 3. 
A comprehensive physical examination will include height and body weight and assessment 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.  A brief 
neurological examination will also be performed. 
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 are to be reported as AEs. 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits. 
8.3.3. 
Vital Signs 
Vital sign measurements (to be taken before blood collection for laboratory tests) include blood 
pressure, pulse, respiratory rate, and oral body temperature.  Blood pressure and pulse will be 
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taken with the participant in the sitting position after 5 minutes of rest.  Abnormal vital sign 
results identified after the first dose of study treatment constitute an AE if they are considered 
clinically meaningful, induce clinical signs or symptoms, or require concomitant therapy. 
8.3.4. 
Electrocardiograms 
Single 12-lead ECGs will be obtained as outlined in the SoA (see Table 3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals.  All 12-lead ECGs will be performed as indicated in Table 9 with the participant in a 
recumbent or semirecumbent position after 5 minutes of rest. 
The 12-lead ECGs will be interpreted by the investigator at the site to be used for immediate 
participant management and care.  Additional 12-lead ECGs may be performed as clinically 
indicated to manage participant safety.  The decision to include or exclude a participant or 
withdraw a participant from the 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. 
Table 9: 
Electrocardiogram Schedule 
Study Visit 
Timing of Electrocardiogram Relative to Administration of Study Drug 
Not Applicable 
Predose (Trough) ECG 
Postdose ECG 
Screening
a 
Single → Triple
b 
 
 
Day 1
c 
 
Triple 
Single → Tripleb 
Week 2c 
 
Single → Tripleb 
Single → Tripleb 
Week 12
d 
 
 
Single → Tripleb 
a Prolonged QTcF values (> 470 milliseconds for males or > 480 milliseconds for females) at screening are to be confirmed by 
performing 2 additional ECGs and averaging the results to determine whether the averaged value meets the exclusion criterion. 
b Single → Triple:  Single ECG will be performed first.  If prolonged QTcF intervals (defined as > 470 milliseconds for males or 
> 480 milliseconds for females) are observed, an additional 2 ECGs will be measured within the next 5 minutes. 
c Day 1 and Week 2 postdose ECGs will be performed after participants complete all of the study assessments 
 
 
d Week12 postdose ECGs will be performed after participants complete all of the study assessments. 
All ECG measurements should be performed before blood draws for laboratory 
 
assessments, and all predose (trough) ECG measurements should be taken before the participant 
takes study drug for that day. 
8.3.5. 
Laboratory Assessments 
See Table 10 for the list of clinical laboratory tests to be performed and the Schedule of 
Laboratory Assessments (Table 4) for the timing and frequency.  A central laboratory will 
perform all clinical laboratory assessments for safety (ie, blood chemistries, hematology 
assessments, thyroid function, and urinalysis) and will store the samples for 
 PD.  
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 the Schedule of Laboratory Assessments (Table 4).  Information regarding collection, 
processing, and shipping of laboratory assessments is provided in the Laboratory Manual. 
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If the serum pregnancy test is negative after a urine test was positive, the investigator will assess 
the potential benefit/risk to the participant and determine whether it is in the participant's best 
interest to resume study drug and continue participation in the study. 
If a pregnancy is confirmed by a serum pregnancy test, see Section 9.6 for reporting 
requirements. 
8.3.5.2. 
Serology and Virology 
Hepatitis and HIV assessments will be performed at the screening visit to rule out hepatitis or 
HIV infection; required analytes are shown in Table 10.  Serology and virology 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. 
8.3.5.3. 
Tuberculosis Testing 
Tuberculosis B assessments will be performed at the screening visit.  Test must be performed 
using the QuantiFERON-TB Gold test or T-SPOT.TB test.  If there are 2 indeterminate tests, 
evaluation by a purified protein derivative test with a result of < 5 mm of induration must be 
conducted within 3 months of screening. 
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8.5. 
Pharmacodynamic and Translational Assessments 
Peripheral blood samples (eg, serum, PBMC, RNA), tear samples, and saliva samples will be 
collected from participants at timepoints outlined in Table 4.  All samples for PD and 
translational assessments will be collected before INCB050465 administration. 
 All analyses will be conducted by 
Incyte Corporation (Wilmington, DE) or Incyte's designee.  Information regarding 
handling/shipping of specimens will be provided in the Laboratory Manual. 
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8.6. 
End of Treatment 
If a decision is made that the participant permanently discontinues study drug (early termination) 
or has completed the Protocol-specified duration of treatment, then an EOT visit should be 
conducted.  If the EOT visit coincides with a regular study visit, the EOT evaluations will 
supersede those of that scheduled visit, and the data should be entered in the EOT visit in the 
eCRF.  The participant should be encouraged to return for the safety follow-up visits. 
8.7. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 to 37 days after the EOT visit (or after the last dose of study 
drug/treatment if the EOT visit was not performed. 
Adverse events and SAEs must be reported up until at least 30 days after the last dose of study 
drug, the date of the follow-up visit, or until toxicities resolve, return to baseline, or are deemed 
irreversible, whichever is longer.  Reasonable efforts should be made to have the participant 
return for the follow-up visit and report any AEs that may occur during this period. 
9. 
ADVERSE EVENTS:  DEFINITIONS AND PROCEDURES FOR 
RECORDING, EVALUATING, FOLLOW-UP, AND REPORTING 
9.1. 
Definition of Adverse Event 
Adverse Event Definition 
• An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not 
considered drug-related. 
• An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
Events Meeting the Adverse Event Definition  
• Any safety assessments (eg ECG, vital signs measurements), including those that worsen from baseline, 
considered clinically significant in the medical and scientific judgment of the investigator (ie, not 
related to progression of underlying disease). 
• Abnormal laboratory test results constitute an AE if they are considered clinically meaningful, induce 
clinical signs or symptoms, require concomitant therapy, or require changes in study drug.  Whenever 
possible, a diagnosis (eg, anemia, thrombocytopenia) should be recorded in the eCRF rather than the 
abnormal lab result (eg, low hemoglobin, platelet count decreased). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even though they may have 
been present before the start of the study. 
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• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication.  Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent.  Such overdoses should be reported 
regardless of sequelae. 
Events NOT Meeting the Adverse Event Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety assessments that are 
associated with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant's condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder 
being studied, unless more severe than expected for the participant's condition or considered to be 
treatment-related by the investigator. 
• Efficacy endpoints as outlined in Section 3 will not be reported as AE/SAEs, specifically, any event 
that is related to disease progression of the cancer under study.  Unblinded aggregated efficacy endpoint 
events and safety data will be monitored to ensure the safety of the participants in the study.  Any 
suspected endpoint that upon review is not progression of the cancer under study will be forwarded to 
Incyte Pharmacovigilance as a SAE within 24 hours of determination that the event is not progression 
of the cancer under study. 
• Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that leads to the 
procedure is the AE if it occurred after signing informed consent.  If present before entering the study, 
the condition should be captured as medical history. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the 
start of the study that do not worsen. 
9.2. 
Definition of Serious Adverse Event 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A Serious Adverse Event is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an adverse drug experience that places the 
participant, in the opinion of the initial reporter, at immediate risk of death from the adverse experience as 
it occurred.  This does not include an adverse drug experience that, had it occurred in a more severe form, 
might have caused death. 
c.  Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician's office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether "hospitalization" occurred or was necessary, the AE 
should be considered serious. 
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Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person's ability to conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor medical significance, such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained 
ankle), that may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
e.  Is a congenital anomaly/birth defect 
f. Other situations (Important Medical Event) 
An event that may not result in death, be immediately life-threatening, or require hospitalization, but may 
be considered serious when, based on appropriate medical judgment, the event may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the outcomes listed in the 
above definition.  Examples of such events include invasive or malignant cancers (excluding the 
disease[s] under study in oncology protocols), intensive treatment in an emergency department or at home 
for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
9.3. 
Recording and Follow-Up of Adverse Events and/or Serious Adverse 
Events 
Adverse Event and Serious Adverse Event Recording 
• An AE/SAE that begins or worsens after informed consent is signed should be recorded on the Adverse 
Event Form in the eCRF.  Conditions that were present at the time informed consent was given should 
be recorded on the Medical History Form in the eCRF. 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation (eg, 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• The investigator (or delegate) will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant's medical records in lieu 
of completing the AE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested.  In this case, all 
participant identifiers, with the exception of the participant number, will be redacted on the copies of 
the medical records before submission. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information.  Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE.  When a clear diagnosis cannot be identified, each sign or symptom 
should be reported as a separate AE/SAE. 
To the extent possible, each AE/SAE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 5).  See below for further instructions on the assessment of 
intensity. 
• Whether there is at least a reasonable possibility that the AE is related to the study 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 final follow-up. 
• The action taken with regard to study drug as a result of the AE/SAE(s). 
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• The event outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per the SAE definition provided in Section 9.2. 
• The action taken with regard to the event.  Note:  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event Form and the treatment should be 
specified on the appropriate eCRF (eg, Prior/Concomitant Medications, Procedures and Non-Drug 
Therapy). 
Assessment of Intensity 
The severity of AEs will be assessed using CTCAE v4.03 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to estimate the 
grade of severity: 
The investigator will make an assessment of intensity for each AE and SAE reported during the study and 
assign it to 1 of the following categories: 
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment 
not indicated. 
• Grade 2:  Moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate 
activities of daily living. 
• Grade 3:  Severe or medical significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
• Grade 4:  Life-threatening consequences; urgent treatment indicated. 
• Grade 5:  Fatal. 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment and each occurrence of 
each AE/SAE.   
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or arguments to 
suggest a causal relationship, rather than that a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• The investigator will also consult the RSI in the IB and/or Product Information, for marketed products, 
in his/her assessment. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as 
the temporal relationship of the event to study treatment administration, will be considered and 
investigated. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• With regard to assessing causality of SAEs: 
− There may be situations in which an SAE has occurred and the investigator has minimal information 
to include in the initial report.  However, the causality assessment is one of the criteria used when 
determining regulatory reporting requirements.  Therefore, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE. 
− The investigator may change his/her opinion of causality in light of follow-up information and send a 
follow-up SAE report with the updated causality assessment. 
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Follow-Up of Adverse Events and Serious Adverse Events 
• The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor to elucidate the nature and/or 
causality of the AE or SAE as fully as possible.  This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care professionals. 
• 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. 
• New or updated information will be recorded in the originally completed eCRF. 
• Any updated SAE data will be submitted to the sponsor (or designee) within 24 hours of receipt of the 
information. 
• Once an AE is detected, it should be followed until it has resolved or until it is judged to be permanent; 
assessment should be made at each visit (or more frequently if necessary) of any changes in severity, 
the suspected relationship to the study drug, the interventions required to treat the event, and the 
outcome. 
• When the severity of an AE changes over time for a reporting period (eg, between visits), each change 
in severity will be reported as a separate AE until the event resolves. 
9.4. 
Reporting of Serious Adverse Events 
All SAEs, regardless of suspected causality (eg, relationship to study drug, or study 
procedure[s]), occurring after the participant has signed the ICF through the last study visit or 
30 + 7 days after the last dose of study drug, whichever occurs later, must be reported to the 
sponsor (or designee) within 24 hours of learning of its occurrence, unless otherwise specified 
by the Protocol.  The investigator will submit any updated SAE data to the sponsor (or designee) 
within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE information after conclusion of the 
study participation.  However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study treatment or study participation, the investigator must notify the 
sponsor (or designee) within 24 hours of becoming aware of the event. 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification to inform all investigators involved in any study 
with the same drug that this SAE has been reported.  Suspected Unexpected Serious Adverse 
Reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC, or as per national regulatory requirements 
in participating countries. 
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The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected adverse reactions 
according to local regulatory requirements and sponsor policy and forwarded to investigators as 
necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg summary or listing of SAEs) from the sponsor will review and then file it 
along with the Investigator's Brochure 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 also complete the Incyte Serious Adverse Event Report Form, in English.  Refer 
to the Incyte Reference Guide for Completing the Serious Adverse Event Report Form. 
• Facsimile or email transmission of the Serious Adverse Event Report Form is the preferred method to 
transmit this information to Pharmacovigilance/designee (eg, C3i/Telerx).  The contact information of 
the sponsor's study-specific representatives is listed in the Study Manual provided to each site.  The 
original copy of the Serious Adverse Event Report Form and the confirmation sheet must be kept at the 
study site. 
• 
 
• Follow-up information is recorded on an amended or new Serious Adverse Event Report Form, with an 
indication that it is follow-up to the previously reported SAE and the date of the original report.  The 
follow-up report should include information that was not provided on the previous Serious Adverse 
Event Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment provided, 
action taken with study drug because of the SAE (eg, dose reduced, interrupted, or discontinued), or 
participant disposition (eg, continued or withdrew from study participation).  Each recurrence, 
complication, or progression of the original event should be reported as follow-up to that event, 
regardless of when it occurs. 
• In rare circumstances, and in the absence of facsimile or computer equipment, notification by telephone 
is acceptable with a copy of the Incyte Serious Adverse Event Report Form sent by overnight mail or 
courier service.  Initial notification via telephone does not replace the need for the investigator to 
complete and sign the Serious Adverse Event Report Form within the designated reporting time frames. 
• Contacts for SAE reporting can be found in the Study Manual. 
9.5. 
Adverse Events of Special Interest 
Adverse events of special interest are defined as occurrences of PJP or other serious infections 
due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens; colitis; 
and exfoliative dermatitis. 
9.6. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
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9.7. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a participant during maternal or paternal exposure to study 
drug, the following procedures should be followed in order to ensure safety: 
• The study drug must be discontinued immediately. 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy Form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
Data on fetal outcome are collected for regulatory reporting and drug safety evaluation.  
Follow-up should be conducted for each pregnancy to determine outcome, including spontaneous 
or voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications, by following until the first 
well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported 
by the investigator to the sponsor or its designee.  Pregnancy follow-up information should be 
recorded on the same form and should include an assessment of the possible causal relationship 
to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the first well-baby 
visit or the duration specified in local regulations, whichever is later.  Refer to the Incyte 
Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy of a study participant must be recorded on the 
Serious Adverse Event Report Form and submitted to the sponsor or designee. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, or ectopic pregnancy) are considered SAEs (if occurring in the study participant) and 
must be reported as described in Section 9.4.  If an abnormal pregnancy outcome is reported in a 
study participant's partner, the event should be reported to the sponsor on the Clinical Trial 
Pregnancy Form. 
9.8. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the IB.  Additional safety information collected 
between IB updates will be communicated in the form of Investigator Notifications.  Any 
important new safety information should be discussed with the participant during the study, as 
necessary.  If new significant risks are identified, they will be added to the ICF. 
9.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
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10.4.1. 
Efficacy Analysis 
Efficacy assessments will be summarized using descriptive statistics at each visit. 
For the primary endpoint, proportion of participants with 1 point or greater improvement on the 
SGUS for parotid and submandibular glands, as well as the secondary endpoint of PGIC, 
summary statistics will include sample size, frequency, and percentages. 
For all other measurements in the secondary endpoints, which are continuous, summary statistics 
will include sample size, mean, median, standard deviation, standard error of the mean, 
minimum, maximum, and the 95% confidence interval where appropriate.  Summary statistics 
will be provided for baseline, the actual measurements at each visit, and the change and percent 
change from baseline at each visit, if applicable.  All analyses will be implemented using SAS 
version 9.1 or higher. 
10.4.2. 
Safety Analyses 
Safety analyses will be conducted for the FAS 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. 
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The secondary endpoint of change and percent change from baseline in salivary CXCL13 levels 
at Week 4 and 12 will be determined from saliva samples for each participant.   
All analyses will be conducted by Incyte Corporation (Wilmington, DE) or Incyte's designee, 
and information regarding handling/shipping of specimens will be provided in the Laboratory 
Manual. 
10.5. 
Interim Analysis 
No formal interim analysis is planned in this study. 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Investigator Responsibilities 
• The Protocol, Protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements, the 
policies and procedures established by the IRB/IEC, and institutional requirements. 
• Any amendments to the Protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to GCP, 
IRB/IEC requirements, institutional requirements, and applicable laws and 
country-specific regulations. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling participants who have met 
the specified eligibility criteria. 
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• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
11.2. 
Data Management 
Data management will be performed in a validated EDC system.  The investigator will be 
provided with access to an EDC system so that an eCRF can be completed for each participant. 
The site will be provided eCRF completion guidelines for instructions on data entry in the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 
is appropriately documented, reported, and resolved in a timely manner in accordance with the 
plan's requirements. 
The sponsor (or designee) will be responsible for: 
• The data management of this study including quality checking of the data. 
• Ensuring that study monitors perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
The investigator will be responsible for: 
• Ensuring participant data relating to the study is recorded in the eCRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, diary data) 
or as otherwise specified in the Protocol.  The investigator is responsible for verifying 
that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
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• Maintaining accurate documentation (source data) that supports the information 
entered in the eCRF. 
− Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator's site. 
− Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained.  The 
investigator may need to request previous medical records or transfer records, 
depending on the study.  Also, current medical records must be available. 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
participant records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all participants. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
11.3. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor or its designee are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
Participant names will not be supplied to the sponsor or its designee.  Only the participant 
number will be recorded in the eCRF, where permitted; if the participant's name appears on any 
other document (eg laboratory report), it must be obliterated on the copy of the document to be 
supplied to the sponsor or its designee.  Study findings stored on a computer will be stored in 
accordance with local data protection laws. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 10 years after study completion unless local regulations or 
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institutional policies require a longer retention period.  No records may be destroyed during the 
retention period without the written approval of the sponsor.  No records may be transferred to 
another location or party without written notification to the sponsor. 
11.4. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to Food 
and Drug Administration Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical 
Investigators (ie, "covered studies") are required to submit a completed Clinical Investigator 
Financial Disclosure form that sufficiently details any financial interests and arrangements that 
apply.  For the purpose of this regulation, "clinical investigator" is defined as any investigator or 
subinvestigator who is directly involved in the treatment or evaluation of research participants, 
including the spouse and each dependent child of the clinical investigator or subinvestigator.  
These requirements apply to both US and foreign clinical investigators conducting covered 
clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
11.5. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Corporation, for the purposes of national and 
international registration, publication, and information for medical and pharmaceutical 
professionals.  Study results will be published in accordance with applicable local and national 
regulations.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  A signed agreement will 
be retained by the sponsor or its designee. 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements. 
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11.6. 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 
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12. 
REFERENCES 
Baden LR, Bensinger W, Angarone M, et al. Prevention and treatment of cancer-related 
infections. J Natl Compr Canc Netw 2012;10:1412-1445. 
Bilancio A, Okkenhaug K, Camps M, et al. Key role of the p110δ isoform of PI3K in B-cell 
antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic 
interference with p110δ function in B cells. Blood 2006;107:642-650. 
Bombardieri M, Lewis M, Pitzalis C.  Ectopic lymphoid neogenesis in rheumatic autoimmune 
diseases. Nat Rev Rheumatol 2017;13:141-154. 
Brito-Zerón P, Ramos-Casals M; EULAR-SS task force group. Advances in the understanding 
and treatment of systemic complications in Sjögren's syndrome. Curr Opin Rheumatol 
2014;26:520-527. 
Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-1657. 
Carsons SE, Bhimji SS. Sjogren Syndrome. StatPearls [Internet]. Treasure Island (FL): 
StatPearls Publishing; 2017 Jun-. 2017 Oct 1. 
Clinical Trial Facilitation Group. Recommendations related to contraception and pregnancy 
testing in clinical trials. 2014. http://www.hma.eu/ctfg.html. Accessed MAR 20, 2018.  
Fazaa A, Bourcier T, Chatelus E, et al. Classification criteria and treatment modalities in primary 
Sjögren's syndrome. Expert Rev Clin Immunol 2014;10:543-551. 
Foulks GN, Forstot SL, Donshik PC, et al. Clinical guidelines for management of dry eye 
associated with Sjögren disease. Ocul Surf 2015;13:118-132. 
Fung-Leung WP. Phosphoinositide 3-kinase delta (PI3Kδ) in leukocyte signaling and function. 
Cell Signal 2011;23:603-608. 
Gazeau P, Cornec D, Jousse-Joulin S, Guellec D, Saraux A, Devauchelle-Pensec V. Time-course 
of ultrasound abnormalities of major salivary glands in suspected Sjogren’s syndrome. Joint 
Bone Spine 2018;85:227-232. 
Henley T, Kovesdi D, Turner M. B-cell responses to B-cell activation factor of the TNF family 
(BAFF) are impaired in the absence of PI3K delta. Eur J Immunol 2008;38:3543-3548. 
INCB050465 Investigator's Brochure. Wilmington, DE: Incyte Corporation. 
Jin L, Yu D, Li X, Yu N, et al. CD4+CXCR5+ follicular helper T cells in salivary gland promote 
B cells maturation in patients with primary Sjogren’s syndrome. Int J Clin Exp Pathol 
2014;7:1988-1996. 
Kang HI, Fei HM, Saito I, et al. Comparison of HLA class II genes in Caucasoid, Chinese, and 
Japanese patients with primary Sjögren's syndrome. J Immunol 1993;150:3615-3623. 
Kasperkiewicz M, Ellebrecht CT, Takahashi H, et al. Pemphigus. Nat Rev Dis Primers 
2017;3:17026. 
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Lessard CJ, Li H, Adrianto I, et al. Variants at multiple loci implicated in both innate and 
adaptive immune responses are associated with Sjögren’s Syndrome. Nat Genet 2013;34:1284-
1292. 
Maehara T, Moriyama M, Hayashida JN, et al. Selective localization of T helper subsets in labial 
salivary glands from primary Sjögren’s syndrome patients. Clin Exp Immunol 2012;169:89-99. 
Marone R, Cmiljanovic V, Giese B, Wymann MP. Targeting phosphoinositide 3-kinase – 
moving towards therapy. Biochim Biophys Acta 2008;1784:159-185. 
Mayne CG, Williams CB. Induced and natural regulatory T cells in the development of 
inflammatory bowel disease. Inflamm Bowel Dis 2013;19:1772-1788. 
Patton DT, Garden OA, Pearce WP, et al. Cutting edge: the phosphoinositide 3-kinase p110δ is 
critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J Immunol 2006;177:6598-
6602. 
Pertovaara M, Korpela M, Uusitalo H, et al. Clinical follow up study of 87 patients with sicca 
symptoms (dryness of eyes or mouth, or both). Ann Rheum Dis 1999;58:423-427. 
Phillips TJ, Ramchandren R, Wertheim MS, et al. An ongoing open-label phase 1/2 study of 
INCB050465, a selective PI3Kδ inhibitor, in patients with previously treated B-cell 
malignancies. Blood 2016;128:4195. 
Pillai S, Cariappa A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat 
Rev Immunol 2009;9:767-777. 
Pillemer SR, Matteson EL, Jacobsson LT, et al. Incidence of physician-diagnosed primary 
Sjögren syndrome in residents of Olmsted County, Minnesota. Mayo Clin Proc 2001;76:593-
599. 
Puri KD, Gold MR. Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell 
function with potential for treating autoimmune inflammatory diseases and B-cell malignancies. 
Front Immunol 2012;3:256. 
Qin B, Wang J, Yang Z, et al. Epidemiology of primary Sjögren's syndrome: a systematic review 
and meta-analysis. Ann Rheum Dis 2015;74:1983-1989. 
Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X, Tzioufas AG. Topical and systemic 
medications for the treatment of primary Sjögren's syndrome. Nat Rev Rheumatol 2012;8:399-
411. 
Ramos-Casals M, Tzioufas AG, Font J. Primary Sjögren's syndrome: new clinical and 
therapeutic concepts. Ann Rheum Dis 2005;64:347-354. 
Ramos-Casals M, Tzioufas AG, Stone JH, Sisó A, Bosch X. Treatment of primary Sjögren 
syndrome: a systematic review. JAMA 2010;304:452-460. 
Reif K, Okkenhaug K, Sasaki T, Penninger JM, Vanhaesebroeck B, Cyster JG. Cutting edge: 
differential roles for phosphoinositide 3-kinases, p110γ and p110δ, in lymphocyte chemotaxis 
and homing. J Immunol 2004;173:2236-2240. 
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Risselada AP, Kruize AA, Goldschmeding R, Lafeber FP, Bijlsma JW, van Roon JA. The 
prognostic value of routinely performed minor salivary gland assessments in primary Sjögren's 
syndrome. Ann Rheum Dis 2014;73:1537-1540. 
Rolf J, Bell SE, Kovesdi D et al. Phosphoinositide 3-kinase activity in T cells regulates the 
magnitude of the germinal center reaction. J Immunol 2010;185:4042-4052. 
Salomonsson S, Jonsson MV, Skarstein K, et al. Cellular basis of ctopic germinal center 
formation and autoantibody production in the target organ of patients with Sjögren’s syndrome. 
Arthritis Rheum 2003;48:3187-3201. 
Saraux A, Pers JO, Devauchelle-Pensec V. Treatment of primary Sjögren syndrome. Nat Rev 
Rheumatol 2016;12:456-471. 
Seror R, Theander E, Brun JG, et al. Validation of EULAR primary Sjögren's syndrome disease 
activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis 2015;74:859-866. 
Szabo K, Papp G, Dezso B and Zeher M.  The histopathology of labial salivary glands in primary 
Sjögren’s syndrome: focusing on follicular helper T cells in the inflammatory infiltrates.  
Mediators Inflamm 2014;2014:631787. DOI:10.1155/2014/631787. 
Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. 
Semin Arthritis Rheum 2008;37:273-292. 
Theander E, Vasaitis L, Baecklund E, et al. Lymphoid organisation in labial salivary gland 
biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's 
syndrome. Ann Rheum Dis 2011;70:1363-1368. 
Vigorito E, Bardi G, Glassford J, Lam EW, Clayton E, Turner M. Vav-dependent and 
vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the 
nature of the stimulus. J Immunol 2004;173:3209-3214. 
Vitali C. Classification criteria for Sjögren's syndrome. Ann Rheum Dis 2003;62:94-95. 
Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren's syndrome: a 
revised version of the European criteria proposed by the American-European Consensus Group. 
Ann Rheum Dis 2002;61:554-558. 
Vivino FB, Carsons SE, Foulks G, et al. New Treatment Guidelines for Sjögren's Disease. 
Rheum Dis Clin North Am 2016;42:531-551. 
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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For male participants in the study: 
Male participants should use a condom during treatment and through 90 days after the end of systemic 
exposure.  If the male participant has a partner that is of child-bearing potential, the partner should also 
use contraception through 93 days after the end of relevant systemic exposure.  In addition, male 
participants must refrain from donating sperm during the study through 90 days after the end of 
relevant systemic exposure.  Males who have had a vasectomy qualify as having met the requirement 
for a highly effective birth control method. 
For female participants in the study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods: 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation
a 
− 
oral 
− 
intravaginal 
− 
transdermal 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulationa 
− 
oral 
− 
injectable 
− 
implantable
b 
• 
Intrauterine deviceb 
• 
Intrauterine hormone-releasing systemb 
• 
Bilateral tubal occlusionb 
• 
Vasectomized partnerb 
c 
• 
Sexual abstinence
d 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• 
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary 
mode of action 
• 
Male or female condom with or without spermicide
e 
• 
Cap, diaphragm or sponge with spermicidee 
• 
Tubal ligation 
a Hormonal contraception may be susceptible to interaction with the investigational medicinal product, which may 
reduce the efficacy of the contraception method. 
b Contraception methods that in the context of this guidance are considered to have low user dependency. 
c Vasectomized partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the vasectomized partner has received 
medical assessment of the surgical success. 
d In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the 
preferred and usual lifestyle of the participant. 
e A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) 
are also considered acceptable, but not highly effective, birth control methods. 
Source:  Clinical Trials Facilitation Group 2014. 
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APPENDIX B. DRYNESS QUESTIONNAIRE 
1. During the past 24 hours, how severe was the worst dryness 
of your mouth? 
0-10 scale 
0 = No dryness, 
10 = Worst Imaginable 
2. During the past 24 hours, how severe was the worst dryness 
of your eyes? 
0-10 scale 
0 = No dryness, 
10 = Worst Imaginable 
FOR FEMALE PARTICIPANTS ONLY 
3. During the past 24 hours, how severe was the worst dryness 
of your vagina? 
0-10 scale 
0 = No dryness, 
10 = Worst Imaginable 
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APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Not applicable. 
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TABLE OF CONTENTS 
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 .........................................................................................................8 
3.1. 
Randomization ..............................................................................................................8 
3.2. 
Control of Type I Error .................................................................................................8 
3.3. 
Sample Size Considerations .........................................................................................8 
3.4. 
Schedule of Assessments ..............................................................................................8 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ....................................9 
4.1. 
Scheduled Study Evaluations .......................................................................................9 
4.1.1. 
Day 1 .............................................................................................................................9 
4.1.2. 
Study Day .....................................................................................................................9 
4.1.3. 
Baseline Value ..............................................................................................................9 
4.1.4. 
Last Available Value ....................................................................................................9 
4.1.5. 
Handling of Missing and Incomplete Data ...................................................................9 
4.2. 
Variable Definitions ......................................................................................................9 
4.2.1. 
Age ................................................................................................................................9 
4.2.2. 
Body Mass Index ........................................................................................................10 
4.2.3. 
Prior and Concomitant Medication .............................................................................10 
5. 
STATISTICAL METHODOLOGY ...........................................................................10 
5.1. 
General Methodology .................................................................................................10 
5.2. 
Treatment Groups .......................................................................................................10 
5.3. 
Analysis Populations ..................................................................................................10 
5.3.1. 
Full Analysis Set .........................................................................................................10 
 
 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................11 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............11 
6.1.1. 
Demographics .............................................................................................................11 
6.1.2. 
Baseline Disease Characteristics ................................................................................11 
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6.1.3. 
Prior Therapy ..............................................................................................................11 
6.1.4. 
General Medical History .............................................................................................12 
6.2. 
Disposition of Participants ..........................................................................................12 
6.3. 
Protocol Deviations ....................................................................................................12 
6.4. 
Exposure .....................................................................................................................12 
6.5. 
Study Drug Compliance .............................................................................................12 
6.6. 
Prior and Concomitant Medication .............................................................................12 
7. 
EFFICACY .................................................................................................................13 
7.1. 
Efficacy Parameters ....................................................................................................13 
7.1.1. 
Ultrasound of Salivary Glands ....................................................................................13 
7.1.2. 
EULAR Sjögren's Syndrome Disease Activity Index ................................................13 
7.1.3. 
Salivary Flow ..............................................................................................................13 
7.1.4. 
Patient-Reported Outcomes ........................................................................................13 
7.1.4.1. 
Dryness Questionnaire ................................................................................................13 
7.1.4.2. 
EULAR Sjögren's Syndrome Patient Reported Index ................................................13 
7.1.4.3. 
Patient Global Impression of Change Questionnaire ..................................................13 
7.1.4.4. 
Female Sexual Function Index ...................................................................................14 
7.1.4.5. 
PROMIS Fatigue Short Form .....................................................................................14 
7.1.4.6. 
European Quality of Life 5 Dimensions Questionnaire .............................................14 
7.2. 
Analysis of Efficacy Endpoints ..................................................................................14 
 
 
 
 
8. 
SAFETY AND TOLERABILITY ..............................................................................15 
8.1. 
General Considerations ...............................................................................................15 
8.2. 
Adverse Events ...........................................................................................................15 
8.2.1. 
Adverse Event Definitions ..........................................................................................15 
8.2.2. 
Adverse Event Summaries ..........................................................................................16 
8.3. 
Clinical Laboratory Tests ...........................................................................................17 
8.3.1. 
Laboratory Value Definitions .....................................................................................17 
8.3.2. 
Laboratory Value Summaries .....................................................................................17 
8.4. 
Vital Signs ..................................................................................................................17 
8.5. 
Electrocardiograms .....................................................................................................18 
9. 
INTERIM ANALYSES ..............................................................................................18 
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10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................19 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................19 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................19 
11. 
REFERENCES ...........................................................................................................20 
APPENDIX A. PLANNED TABLES AND LISTINGS ............................................................21 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................7 
Table 2: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................18 
Table 3: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................18 
Table 4: 
Statistical Analysis Plan Versions ..............................................................................19 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ANC 
absolute neutrophil count 
 
 
 
 
 
 
BMI 
body mass index 
 
 
CRF 
case report form 
CTC 
Common Terminology Criteria 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXCL13 
CXC motif chemokine ligand 13 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EQ-5D 
European Quality Of Life 5 Dimensions questionnaire 
ESSDAI 
EULAR Sjögren's Syndrome Disease Activity Index 
ESSPRI 
EULAR Sjögren's Syndrome Patient Reported Index 
EULAR 
European League Against Rheumatism 
FAS 
full analysis set 
FSFI 
Female Sexual Function Index 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
PD 
pharmacodynamic  
PGIC 
Patient Global Impression of Change questionnaire 
PI3Kδ 
phosphatidylinositide 3-kinase delta isoform 
 
 
PROMIS 
Patient-Reported-Outcomes Measurement Information System 
PT 
preferred term 
QD 
once daily 
QTcF 
QT interval corrected for heart rate using Fridericia's formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SGUS 
salivary gland ultrasound 
SOC 
system organ class 
SS 
Sjögren's syndrome 
 
 
TEAE 
treatment-emergent adverse event 
WHO 
World Health Organization 
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1. 
INTRODUCTION 
This is a single-group, open-label study of the impact of PI3Kδ inhibitor INCB050465 on signs 
and symptoms of SS.  Twelve participants meeting the inclusion criteria and none of the 
exclusion criteria will be enrolled.  Participants will receive treatment with INCB050465 
 
 for 12 weeks and undergo ultrasound measurement of salivary glands, measurements of 
salivary flow, collection of symptom questionnaires, and PD 
 blood sampling to allow 
studies of cytokine levels, gene expression levels, and other PD markers. 
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCB 50465-207 Protocol. 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 50465-207 Protocol dated 12 JUN 2018 and CRFs approved 
11 OCT 2018.  Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and CRF versions. 
2.2. 
Objectives and Endpoints 
Table 1 presents the objectives and endpoints. 
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Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• To determine the impact of INCB050465 
on salivary gland echostructure. 
• Proportion of participants with a 1 point or greater 
improvement on the SGUS score for parotid and 
submandibular glands at Week 4 and Week 12. 
Secondary 
• To assess the impact of INCB050465 on 
salivary CXCL13. 
• Change and percent change from baseline in salivary 
CXCL13 levels at Week 4 and Week 12. 
• To assess the efficacy of INCB050465. 
• Change and percent change in stimulated and 
unstimulated whole salivary flow from baseline at 
Weeks 4, 8, and 12. 
• Change and percent change in ESSDAI at Week 12. 
• Change and percent change in ESSPRI at Weeks 4, 8, 
and 12.  
• Change and percent change in symptom scores for 
dryness of eyes, mouth, and vagina at Weeks 4, 8, and 
12. 
• Proportions of participants in each PGIC category at 
Weeks 4, 8, and 12. 
• Change and percent change in PROMIS Fatigue short 
form at Weeks 4, 8, and 12. 
• Change and percent change in FSFI at Weeks 4, 8, 
and 12 (female participants only). 
• Change and percent change in EQ-5D at Weeks 4, 8, 
and 12.  
• To evaluate the safety and tolerability of 
INCB050465. 
• Frequency, duration, and severity of AEs, clinical 
laboratory test results, vital sign results, ECGs, and 
physical examination findings. 
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3. 
STUDY DESIGN 
This is a single-group, open-label study of the impact of PI3Kδ inhibitor INCB050465 on signs 
and symptoms of SS.  Twelve participants meeting the inclusion criteria and none of the 
exclusion criteria will be enrolled.  Participants will receive treatment with INCB050465 
 
for 12 weeks and undergo ultrasound measurement of salivary glands, measurements of 
salivary flow, collection of symptom questionnaires, and PD 
 blood sampling to allow 
studies of cytokine levels, gene expression levels, and other PD markers. 
3.1. 
Randomization 
Not applicable. 
3.2. 
Control of Type I Error 
All statistical analyses are exploratory in nature.  No alpha control will be implemented.  Unless 
otherwise specified, all confidence intervals provided will be at the 95% confidence level. 
3.3. 
Sample Size Considerations 
The sample size is based on the demonstration of preliminary findings of efficacy, which also 
depends on the occurrence of safety findings.  Approximately 12 participants will be enrolled, 
which will provide > 90% chance of detecting at least 1 AE of interest (eg, platelets, 
hemoglobin, ANC, liver functions, and infections) if the underlying AE rate is 20%. 
3.4. 
Schedule of Assessments 
Refer to the Protocol dated 12 JUN 2018 for a full description of all study procedures and 
assessment schedules for this study. 
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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug INCB050465 is administered to the 
participants.  
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date + 1).  
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date).  
A study day of -1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCB050465. 
When scheduled assessments and unscheduled assessments occur on the same day and time of 
the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Last Available Value 
The last available value is the last nonmissing measurement obtained after starting INCB050465 
and within 30 days after the last dose of INCB050465. 
4.1.5. 
Handling of Missing and Incomplete Data  
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in relevant sections.  
4.2. 
Variable Definitions 
4.2.1. 
Age 
Participant age will be directly copied from the Demography Form of the eCRF. 
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4.2.2. 
Body Mass Index 
Body mass index (BMI) will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2. 
4.2.3. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB050465. 
Concomitant medication is defined as any nonstudy medication that is started accordingly: 
• Before the date of first administration of INCB050465 and is ongoing throughout the 
study or ends on/after the date of first administration of INCB050465. 
• On/after the date of first administration of INCB050465 and is ongoing or ends 
during the course of study treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first administration of INCB050465.  In the listing, it will be indicated whether 
a medication is prior-only, concomitant-only, or both prior and concomitant. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 
5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS software (SAS Institute Inc, Cary, NC; Version 9.1 or later) will 
be used for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries 
for continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of participants in each category. 
5.2. 
Treatment Groups 
This is an open-label, single-arm study.  Participants will be summarized overall by total only. 
5.3. 
Analysis Populations 
5.3.1. 
Full Analysis Set 
The FAS includes all participants enrolled in the study who received at least 1 dose of study 
drug. 
The FAS will be used for the summary of demographics, baseline characteristics, participant 
disposition, and analyses of all efficacy and safety data. 
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6.1.4. 
General Medical History 
For participants in the FAS, general medical history will be summarized.  This summation will 
include the number and percentage of participants with significant medical history for each body 
system/organ class as documented on the CRF. 
6.2. 
Disposition of Participants 
The number and percentage of participants who were treated, completed study treatment, 
completed the study, discontinued study treatment with a primary reason for discontinuation, and 
discontinued from the study with a primary reason for withdrawal will be summarized for the 
FAS.  The number of participants enrolled by site will also be provided.  
6.3. 
Protocol Deviations  
Protocol deviations recorded on the CRF will be presented in the participant data listings.  A 
summary table of major protocol deviations will also be provided. 
6.4. 
Exposure 
For participants in the FAS, descriptive statistics will be provided for duration of treatment, 
average daily dose, and total dose.  Duration of treatment with INCB050465 is defined as the 
number of days from Day 1 to the date of last record of INCB050465 administration. 
6.5. 
Study Drug Compliance 
For participants in the FAS, overall compliance (%) for INCB050465 will be calculated for all 
participants as 
Compliance (%) = 100 × [total number of tablets dispensed – total number of tablets 
returned] / [total intended number of tablets]. 
The total intended number of tablets will be based on the earliest study day of permanent 
discontinuation of the study drug.  The total intended number of tablets is defined as the sum of 
the tablets prescribed by the investigator accounting both for planned dose modifications as well 
as those modifications mandated by the investigator. 
6.6. 
Prior and Concomitant Medication 
For participants in the FAS, prior medications and concomitant medications will be coded using 
the WHO Drug Dictionary and summarized by WHO drug class and WHO drug term.  Results 
will be summarized as number and percentage of participants with prior and concomitant 
medications by PT and WHO drug class. 
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8.2.2. 
Adverse Event Summaries 
An overall summary of AEs will include the following: 
• Number (%) of participants reporting any TEAEs 
• Number (%) of participants reporting any SAEs 
• Number (%) of participants reporting any Grade 3 or 4 TEAEs 
• Number (%) of participants reporting any treatment-related TEAEs 
• Number (%) of participants who temporarily interrupted study treatment because of 
TEAEs 
• Number (%) of participants who permanently discontinued study treatment because 
of TEAEs 
• Number (%) of participants who had a TEAE leading to death 
The following summaries will be produced by MedDRA term (if 2 or fewer participants appear 
in a table, a listing may be appropriate): 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of TEAEs by SOC, PT, and maximum severity 
• Summary of treatment-related AEs by SOC and PT 
• Summary of treatment-related AEs by PT in decreasing order of frequency 
• Summary of treatment-related AEs by SOC, PT, and maximum severity 
• Summary of Grade 3 or 4 AEs by SOC and PT 
• Summary of Grade 3 or 4 treatment-related AEs by SOC and PT 
• Summary of TEAEs leading to death by SOC and PT 
• Summary of treatment-emergent SAEs by SOC and PT 
• Summary of treatment-emergent SAEs by PT in descending order of frequency 
• Summary of treatment-related SAEs by SOC and PT 
• Summary of TEAEs leading to dose interruption by SOC and PT 
• Summary of TEAEs leading to discontinuation of treatment by SOC and PT 
• Summary of nonserious TEAEs by SOC and PT 
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INCB 50465-207 Statistical Analysis Plan 
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8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
Laboratory values, change from baseline values, and percentage change from baseline values 
will be summarized descriptively by visit.  Baseline values will be determined using the 
nonmissing values collected before the first administration, prioritizing scheduled assessments 
over unscheduled visits.  For baseline laboratory candidates with the same date and time in the 
same priority category, additional rules may be provided after consultation with the medical 
monitor to delineate which value will be defined as baseline. 
Laboratory test values outside the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading.  The 
incidence of abnormal laboratory values and shift tables relative to baseline will be tabulated. 
8.3.2. 
Laboratory Value Summaries 
All test results and associated normal ranges from central laboratories will be reported in SI 
units.  All tests with numeric values will have a unique unit per test. 
When there are multiple laboratory nonmissing values for a participant’s particular test at a 
scheduled postbaseline visit, use the smallest laboratory sequence number to identify the record. 
Laboratory hematology and serum chemistry parameters identified in Protocol Table 10 will be 
summarized.  Numeric laboratory values will be summarized descriptively in SI units, and 
non-numeric test values will be tabulated when necessary.  In addition, box-and-whisker plots 
may be provided for some tests if applicable. 
For test results that will be summarized with available normal ranges, the number and percentage 
of participants with the laboratory values being low, normal, high, and missing will be tabulated 
for each test and each visit. 
Shift tables will be presented showing change in CTCAE grade from baseline to worst grade 
postbaseline.  The denominator for the percentage calculation will be the number of participants 
in the baseline category. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, and body 
temperature will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 2.  The abnormal 
values for participants exhibiting clinically notable vital sign abnormalities will be listed.  Alert 
vital signs are defined as an absolute value outside the defined range and percentage change from 
baseline outside (-25%, 25%).  The abnormal values for participants exhibiting alert vital sign 
abnormalities will be listed. 
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INCB 50465-207 Statistical Analysis Plan 
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Table 2: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 
Temperature 
> 38°C 
< 35.5°C 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including PR, QRS, QT, QTcB, QTcF, and RR intervals will be obtained for 
each participant during the study.  Change and percentage change from baseline will be 
calculated at each postbaseline assessment time.  Descriptive statistics will be determined for 
each ECG parameter. 
Incidences of clinically notable ECG abnormalities are defined in Table 3.  Participants 
exhibiting clinically notable ECG abnormalities will be listed with study visit.  Abnormal values 
for participants with alert ECG values, defined as an absolute value outside the defined normal 
ranges and the percentage change from baseline outside (-25%,25%), will be identified and 
listed. 
When triple ECGs are measured, the average of the 3 ECGs will be used in the summary table, 
but all 3 of these ECGs will be listed. 
Table 3: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter  
High Threshold  
Low Threshold  
QTcF 
> 460 msec 
< 295 msec 
QTcB 
> 460 msec 
< 295 msec 
PR  
> 220 msec 
< 75 msec 
QRS  
> 120 msec 
< 50 msec 
QT  
> 500 msec 
< 300 msec 
RR  
> 1330 msec 
< 600 msec 
QTcF = Fridericia correction. 
9. 
INTERIM ANALYSES 
No formal interim analysis is planned in this study. 
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INCB 50465-207 Statistical Analysis Plan 
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10. 
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 
25 FEB 2019 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 
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11. 
REFERENCES 
Gazeau P, Cornec D, Jousse-Joulin S, Guellec D, Saraux A, Devauchelle-Pensec V. Time-course 
of ultrasound abnormalities of major salivary glands in suspected Sjögren’s syndrome. Joint 
Bone Spine 2018;85:227-232. 
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03. 2010. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf. Accessed March 20, 2018. 
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APPENDIX A. PLANNED TABLES AND LISTINGS 
This appendix provides a list of the planned tables and listings for the Clinical Study Report.  
Standard tables will follow the conventions in the Standard Safety Tables initial version.  Shells 
are provided for nonstandard tables in a separate document.  In-text tables are identical in 
structure and content as appendix tables but follow a Rich Text Format. 
The list of tables, listings, and the shells are to be used as guideline.  Modifications of the list or 
shells that do not otherwise affect the nature of the analysis will not warrant an amendment to the 
SAP. 
Tables 
Table No. 
Title 
Population 
Baseline and Demographic Characteristics 
1.1  Disposition 
1.1.1 
Analysis Populations 
FAS 
1.1.2 
Summary of Participant Disposition 
FAS 
1.1.3 
Summary of Number of Participants Enrolled by Site 
FAS 
1.2  Demography 
1.2.1 
Summary of Demographics 
FAS 
1.3  Baseline Characteristics 
1.3.1 
Summary of Baseline Disease Characteristics 
FAS 
1.4  Prior Medication and Concomitant Medication 
1.4.1 
Summary of Prior Medications 
FAS 
1.4.2 
Summary of Prior Medications for Sjögren's Syndrome 
FAS 
1.4.3 
Summary of Concomitant Medications 
FAS 
1.5  Others 
1.5.1 
Summary of General Medical History 
FAS 
Efficacy 
2.1.1.1 
Summary of Participants With 1 Point or Greater Improvement on the SGUS Score at 
Week 4 and Week 12 
FAS 
2.1.1.2 
Summary of SGUS Score From Baseline to Week 12 
FAS 
2.1.2 
Summary of Stimulated and Unstimulated  Whole Salivary Flow From Baseline to 
Week 12 
FAS 
2.1.3 
Summary of ESSDAI From Baseline to Week 12 
FAS 
2.1.4 
Summary of ESSPRI From Baseline to Week 12 
FAS 
2.1.5.1 
Summary of Symptom Scores for Dryness From Baseline to Week 12 by Subscore 
FAS 
2.1.5.2 
Summary of Total Symptom Scores for Dryness From Baseline to Week 12 for 
Female 
FAS 
2.1.6 
Summary of PGIC Category at Weeks 4, 8, and 12 
FAS 
2.1.7 
Summary of PROMIS Fatigue Short Form From Baseline to Week 12 
FAS 
2.1.8 
Summary of FSFI From Baseline to Week 12 (Females Only) 
FAS 
2.1.9 
Summary of EQ-5D From Baseline to Week 12 
FAS 
Safety 
3.1  Study Drug Exposure 
3.1.1 
Summary of Drug Compliance  
FAS 
3.1.2 
Summary of Study Drug Exposure  
FAS 
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Table No. 
Title 
Population 
3.2  Adverse Events 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
FAS 
3.2.2 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
FAS 
3.2.3 
Summary of Treatment-Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
FAS 
3.2.4 
Summary of Treatment-Emergent Adverse Events by MedDRA System Organ Class, 
Preferred Term, and Maximum Severity 
FAS 
3.2.5 
Summary of Grade 3 or Higher Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
FAS 
3.2.6 
Summary of Treatment-Related Adverse Events by MedDRA System Organ Class 
and Preferred Term  
FAS 
3.2.7 
Summary of Treatment-Related Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency  
FAS 
3.2.8 
Summary of Treatment-Related Adverse Events by MedDRA System Organ Class, 
Preferred Term, and Maximum Severity  
FAS 
3.2.9 
Summary of Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse 
Events by MedDRA Preferred Term  
FAS 
3.2.10 
Summary of Treatment-Emergent Adverse Events Leading to Death by MedDRA 
System Organ Class and Preferred Term  
FAS 
3.2.11 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA System 
Organ Class and Preferred Term  
FAS 
3.2.12 
Summary of Treatment-Emergent Serious Adverse Events by MedDRA Preferred 
Term in Decreasing Order of Frequency  
FAS 
3.2.13 
Summary of Treatment-Related Serious Adverse Events by MedDRA System Organ 
Class and Preferred Term  
FAS 
3.2.14 
Summary of Treatment-Emergent Adverse Events Leading to Dose Interruption by 
MedDRA System Organ Class and Preferred Term  
FAS 
3.2.15 
Summary of Treatment-Emergent Adverse Events Leading to Discontinuation of 
Treatment by MedDRA System Organ Class and Preferred Term  
FAS 
3.2.16 
Summary of Nonserious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term
a 
FAS 
3.3  Laboratory 
3.3.1 
Summary of Laboratory Values - Hematology 
FAS 
3.3.2 
Summary of Laboratory Values - Chemistry 
FAS 
3.3.3 
Shift Summary of Hematology Laboratory Values in CTC Grade - To the Worst 
Abnormal Value 
FAS 
3.3.4 
Shift Summary of Chemistry Laboratory Values in CTC Grade - To the Worst 
Abnormal Value 
FAS 
3.4  Vital Signs 
3.4.1 
Summary of Systolic Blood Pressure 
FAS 
3.4.2 
Summary of Diastolic Blood Pressure  
FAS 
3.4.3 
Summary of Pulse  
FAS 
3.4.4 
Summary of Respiratory Rate 
FAS 
3.4.5 
Summary of Body Temperature 
FAS 
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Table No. 
Title 
Population 
3.5  ECG 
3.5.1 
Summary of PR Interval (msec) From 12-Lead ECG 
FAS 
3.5.2 
Summary of RR Interval (msec) From 12-Lead ECG 
FAS 
3.5.3 
Summary of QT Interval (msec) From 12-Lead ECG 
FAS 
3.5.4 
Summary of QRS Interval (msec) From 12-Lead ECG 
FAS 
3.5.5 
Summary of QTcB Interval (msec) From 12-Lead ECG 
FAS 
3.5.6 
Summary of QTcF Interval (msec) From 12-Lead ECG 
FAS 
3.5.7 
Summary of Heart Rate (bpm) From 12-Lead ECG 
FAS 
3.5.8 
Summary of Outliers of QT, QTcB, and QTcF Interval Value (ms) From 12-Lead 
ECG 
FAS 
3.5.9 
Summary of Clinically Significant ECG Abnormality 
FAS 
Listings 
Listing No. 
Title 
Demographic and Baseline Characteristics  
2.1.1 
Participant Enrollment and Disposition Status 
2.1.2 
Participant Inclusion and Exclusion Criteria Violations 
2.2.1 
Protocol Deviations 
2.4.1 
Demographic  
2.4.2 
Baseline Disease Characteristics  
2.4.3 
General Medical History  
2.4.4 
Prior and Concomitant Medications  
2.4.5 
Prior Medications for Sjögren's syndrome 
2.5.1 
Study Drug Compliance  
Efficacy 
2.6.1 
SGUS Score 
2.6.2 
Stimulated and unstimulated salivary flow 
2.6.3 
ESSDAI 
2.6.4 
ESSPRI 
2.6.5 
Symptom scores for dryness of eyes, mouth, and vagina 
2.6.6 
PGIC category 
2.6.7 
PROMIS Fatigue  
2.6.8 
FSFI 
2..6.9 
EQ-5D 
Adverse Events and Exposure 
2.7.1 
Study Drug Administration 
2.7.2 
Adverse Events  
2.7.3 
Serious Adverse Events  
2.7.4 
Grade 3 and Higher Adverse Events 
2.7.5 
Adverse Events Leading to Death  
2.7.6 
Treatment-Related Adverse Events  
2.7.8 
Adverse Events Leading to Dose Interruption  
2.7.9 
Adverse Events Leading to Discontinuation  
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Listing No. 
Title 
Laboratory Data 
2.8.1 
Clinical Laboratory Values – Hematology  
2.8.2 
Clinical Laboratory Values – Serum Chemistry  
2.8.3 
Abnormal Clinical Laboratory Values – Hematology  
2.8.4 
Abnormal Clinical Laboratory Values – Serum Chemistry  
Vital Signs 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values 
ECG 
2.10.1 
12-Lead ECG Values 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.3 
Alert 12-Lead ECG Values 
 
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