An Open-label, Single-arm, Pilot Study to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients With IgG4-Related Disease
Phase: PHASE2
Conditions: IgG4-RD
Sponsor: Xencor, Inc.

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
           31 Jan 2017                     CONFIDENTIAL 
Page 1 of 92 
31 Jan 2017 
Clinical Study Protocol 
An Open-label, Single-arm, Pilot Study to Evaluate the Effect of 
XmAb®5871 on Disease Activity in Patients with IgG4-Related 
Disease 
Sponsor: 
Xencor, Inc. 
111 West Lemon Avenue 
Monrovia, CA 91016 
Clinical Research Organization: 
The Translational Medicine Group 
Massachusetts General Hospital 
Richard B. Simches Research Center 
185 Cambridge Street, MCPZN 7205 
Boston, MA 02114 
Phone: 617-643-9351 
Principal Investigator: 
John H. Stone, MD, MPH 
Sponsor Protocol No.: 
XmAb5871-03 
IND No.: 
125,319 
IMP Name: 
XmAb5871 
Development Phase: 
Phase 2 
Version, Date 
Version 3.0 Amendment 2, 31 Jan 2017 
This clinical study will be conducted according to the protocol and in compliance with Good Clinical 
Practice (GCP) as outlined in CPMP/ICH/135/95, with the Declaration of Helsinki (Version 2008) and 
with other applicable regulatory requirements. 
Confidentiality Statement 
This document contains confidential information of Xencor, Inc.  Do not copy or distribute without 
written permission from the Sponsor. 

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
           31 Jan 2017                     CONFIDENTIAL 
 
  
 
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PROTOCOL SYNOPSIS 
Protocol Title: 
An Open-label, Single-arm Pilot Study to Evaluate the Effect of XmAb®5871 on Disease 
Activity in Patients with IgG4-Related Disease 
Protocol Short Title 
XmAb5871 Phase 2 Open-label Multiple-Dose Study in Patients with IgG4-RD 
Study Number: 
Sponsor Protocol No.:  XmAb5871-03 
Investigational 
Product 
XmAb5871 
IND Number 
125,319 
Development Phase: 
Phase 2 
Indication 
IgG4-Related Disease (IgG4-RD) 
Sponsor: 
Xencor, Inc. 
Principal 
Investigator: 
John H. Stone, MD, MPH 
Study Center(s): 
The study will be conducted at the Massachusetts General Hospital (Boston, MA) and up to 
2 additional sites.   
Study Objectives: 
Primary Objective  
• 
To evaluate the effect of every other week intravenous (IV) administration of  
XmAb5871 on the IgG4-RD Responder Index (RI) in patients with active IgG4-RD 
Secondary Objective  
• 
To evaluate the safety and tolerability of every other week IV administration of 
XmAb5871 in patients with active IgG4-RD 
• 
To evaluate the pharmacokinetics (PK) and immunogenicity of every other week IV 
administration of XmAb5871 in patients with active IgG4-RD 
Exploratory Objectives  
• 
To characterize the pharmacodynamics (PD) of every other week IV administration of 
XmAb5871 in patients with active IgG4-RD as follows: 
• 
To evaluate the effect of XmAb5871 on changes in the absolute B cell count 
(ABC) 
• 
To evaluate the effect of XmAb5871 on changes in serum IgG4 and IgE 
concentrations 
• 
To evaluate the effect of XmAb5871 on changes in the circulating plasmablast 
count, changes in plasmablast markers of apoptosis and changes in plasmablast 
gene expression 
• 
To evaluate the effect of XmAb5871 on changes in 18F FDG PET/CT imaging in 
patients with active IgG4-RD  
Study Design: 
This is an open-label, single-arm study of up to 21 patients with active IgG4-RD.  
Participants will receive XmAb5871 by IV infusion every other week for up to a total of 12 
infusions.   
Investigational 
Medicinal 
Product(s); IMP, 
Dose and Route of 
Administration: 
XmAb5871 drug product is a sterile liquid product supplied in single-use glass vials. Each 
10 mL glass vial is filled with 10.5 mL of drug product that contains 10.0 (+/- 5%) mg/mL 
of XmAb5871, 10 mM sodium phosphate, 150 mM sodium chloride and 0.01% (w/v) 
polysorbate 20 at pH 7.2.   

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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Dose and route of administration: Every other week administration of XmAb5871 at 5.0 
mg/kg by IV infusion over 1-2 hours for the first 15 patients, then up to 6 patients treated 
with either 90 mg fixed dose or 180 mg fixed dose by IV infusion every other week. 
Number of Subjects: 
Up to 21 patients with active IgG4-RD 
Study Population: 
Male and female patients with histopathologically proven IgG4-RD with active disease as 
defined by disease activity in one or more organ systems AND an IgG4-RD RI of ≥3. 
Patients are not required to have failed prior therapy for their disease to be eligible for this 
study. Patients with disease in only one organ system whose primary manifestation is 
fibrosis will be excluded. 
Study Duration 
After a screening period of up to 28-days, eligible patients will receive XmAb5871 IV 
every other week for a total of up to 12 doses (22 weeks).  Patients will be followed on 
study for 6 weeks following the last dose for a total study period of up to 32 weeks.  
Study Procedures: 
After obtaining informed consent, all screening procedures and tests establishing eligibility 
will be performed within a period of 28 days before dosing.  Patients determined to be 
eligible at screening will return to the study site on study Day 1 at which time baseline 
procedures and tests will be performed.  Following baseline assessments, patients will be 
administered XmAb5871 as an IV infusion over a 2 hour infusion period at a dose of 5 
mg/kg.  Patients will be observed for at least 2 hours after the completion of the first 
administration during which time safety assessments will be performed.   
All patients will return to the study site on Day 8 for safety, PK and PD assessments.  
Patients will return on study Days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141 and 155 for 
XmAb5871 (5 mg/kg) administration over a 1-2 hour infusion period, as well as for safety, 
PK, PD and disease response assessments.  Patients will be required to remain at the study 
site for observation for at least 1 hour after the completion of each infusion, during which 
time safety assessments will be performed.  
All patients completing the treatment period will be followed through at least Day 
197/EOS.  Safety, PK, PD and disease response assessments will be collected on both Day 
169 and Day 197/EOS.  Patient participation will be considered complete once EOS study 
procedures have been performed.  All AE(s) (including serious AEs and deaths) and use of 
concomitant medication information will be collected throughout the study from screening 
through the EOS visit.  Patients developing treatment-emergent AEs or clinically 
significant safety lab abnormalities will be followed until resolution or until stabilization of 
the AEs/abnormalities.  
Based on preliminary data in this study showing reduction of IgG4-RD disease activity 
following treatment with XmAb5871 at 5 mg/kg every 2 weeks and based on data from a 
previous study in patients with active rheumatoid arthritis suggesting disease response 
activity at doses as low as 0.3 mg/kg, the study has been amended in this protocol version 
in order to explore the treatment effect of lower doses of XmAb5871. Following enrollment 
of the  first 15 patients (treated at 5 mg/kg every other week), approximately 3 additional 
patients will be treated with a fixed dose of 90 mg of XmAb5871 given IV every other 
week. A second set of up to 3 additional patients may be treated with either 90 mg or 180 
mg of XmAb5871. At the discretion of the Investigator and Sponsor, subjects dosed at 90 
mg of XmAb5871 may have their dose increased to 180 mg if there has been an inadequate 
clinical response to therapy. All study procedures will remain the same for these patients 
except for the administration of a lower dosage of XmAb5871.  The dose for the 90 and 
180 mg dose subjects will be administered over a 1 hour period at a constant rate. 
Criteria for 
Evaluation: 
Disease Activity: 
The following disease activity parameters will be recorded at scheduled intervals 
throughout the study: 
• 
IgG4-RD RI score  

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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• 
Physician Global Assessment of Disease Activity (Visual Activity Score) 
• 
Patient Global Assessment of Disease Activity (Visual Activity Score) 
• 
18F FDG PET/CT imaging  
 
Safety: 
The following safety parameters will be recorded at regular intervals during the study: 
• 
Adverse events (CTCAE V4.03) 
• 
Physical examinations 
• 
Vital signs (supine blood pressure [BP], heart rate [HR], oral body temperature, 
respiratory rate [RR]) 
• 
Twelve-lead electrocardiogram (ECG) 
• 
Clinical laboratory testing (clinical chemistry, hematology, coagulation and urinalysis) 
• 
Serum immunoglobulin (Ig) levels (IgG, IgM, IgE, IgA, IgG1-4) 
• 
B cell and T cell quantification by flow cytometry 
• 
Concomitant medications 
 
Immunogenicity: 
The following immunogenicity parameter will be recorded during the study: 
• 
Anti-XmAb5871 antibodies [anti-drug antibodies (ADA)] 
 
Pharmacokinetics: 
Serum XmAb5871 concentration will be measured at pre-dose (trough) and end-of-infusion 
(peak) for selected infusions.  In addition, levels will be obtained on Days 8, 169 and 
197/EOS.  Peak and trough concentration-time profiles will be compared to biomarker-time 
profiles to explore the relationship between XmAb5871 serum concentration and biomarker 
response.  Peak and trough concentrations will be evaluated to determine if they differ in 
patients with different FcγRIIa and FcγRIIb receptor genotypes. 
 
Pharmacodynamics: 
• 
Circulating ABC count 
• 
Serum IgG4 
• 
Serum IgE 
• 
Circulating plasmablast count 
• 
Circulating plasmablast markers of apoptosis 
• 
Circulating plasmablast gene expression 
 
Pharmacogenomics: 
• 
FcγRIIa R131H polymorphism 
• 
FcγRIIb I232T polymorphism 
Statistical Methods: 
Sample size considerations: 
The sample size chosen for this study was based upon precedent set by other pilot studies 
of similar nature and was not based on power calculations.  The sample size is based 
primarily on feasibility and the desire to gain disease response information and safety 
information to support further clinical studies.  A total of approximately 15 patients are 
considered suitable to achieve the study objectives.   
 
Data Presentation/Descriptive Statistics: 
Since this is an open label, single-arm clinical trial, descriptive statistics will be employed 

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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to analyze the data.  Summary statistics for continuous variables will include the mean, 
standard deviation, median, and range (minimum/maximum).  Categorical variables will be 
presented as frequency counts and percentages.  Time-to-event variables (if any) will be 
summarized by Kaplan-Meier medians and Kaplan-Meier plots.  Data listings will be 
created to support each table and to present all data. 
 
The data will be tabulated with respect to patient enrollment, subject disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
efficacy, and safety measures.  The efficacy and safety analysis will be performed on the 
ITT/Safety Population, defined as all patients who received any amount of XmAb5871.  PK 
and PD data will also be displayed graphically, as appropriate.   
 
Any deviations from the planned analyses will be described and justified in the final 
integrated clinical study report.  

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
           31 Jan 2017                     CONFIDENTIAL 
 
  
 
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LIST OF STUDY STAFF 
Sponsor: 
Xencor, Inc. 
Medical Monitor 
Debra Zack, MD, PhD 
12770 High Bluff Dr., Suite 260 
San Diego, CA 92130 
Telephone number: 858-480-3893 
Email: dzack@xencor.com 
Adverse Event 
Reporting: 
Vigilare International 
150 N. Radnor Chester Road 
Suite F200 
Radnor, PA 19087 
Telephone number: 610-977-0899 
Email: angela.pitwood@vigilareintl.com 
Contract Research 
Organization: 
The Translational Medicine Group 
Massachusetts General Hospital 
Richard B. Simches Research Center 
185 Cambridge Street, MCPZN 7205 
Boston, MA 02114 
Telephone number: 617-643-9351 
Principal Investigator: 
John H. Stone, MD, MPH 
Massachusetts General Hospital  
Rheumatology Associates, Yawkey 2 
55 Fruit St. 
Boston, MA 02114 
Telephone number: 617-643-5385 (OFFICE) 
Email: JHSTONE@mgh.harvard.edu 
Clinical Laboratories: 
Massachusetts General Hospital (clinical chemistry, hematology, coagulation, 
urinalysis, pregnancy tests, IgG, IgG1-4, IgM, IgE, IgA, screening absolute B cell count 
when indicated, hepatitis and HIV serologies):  
MGH Pathology Core Laboratory  
55 Fruit Street 
Boston, MA 02114, USA 
Telephone number: 617-724-5227 
Clinical Site: 
Massachusetts General Hospital  
Clinical Research Center  
55 Fruit Street 
Boston, MA 02114, USA 
Telephone number: 617-726-3294 
Bioanalytical 
Laboratory (PK): 
Cynthia Wydysh  
ICON Laboratory Services, Inc.  
8282 Halsey Road 
Whitesboro, NY 13492 
Telephone number: 315-768-2527 
Fax number: 315-736-2460 
Email: Cynthia.Wydysh@iconplc.com 

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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Genotyping Laboratory: 
 
Ryan Newman 
Cancer Genetics, Inc. 
133 Southcenter Court, Suite 400 
Morrisville, NC 27560 
Telephone number: 919-653-5532 
Fax number: 919-653-5542 
Email: Ryan.Newman@cgix.com  
Immunogenicity (ADA) 
Assessment Laboratory: 
 
Mallika Kopalle 
ICON Laboratory Services, Inc.  
8282 Halsey Road 
Whitesboro, NY 13492 
Telephone number: 315-768-2834 
Email: Mallika.Kopalle@iconplc.com  
Mechanistic Studies 
Laboratory: 
 
Shiv Pillai, MD, PhD  
Ragon Institute of MGH, MIT and Harvard 
400 Tech Square  
Cambridge MA 02139 
Telephone number: 857-268-7005 
Email: pillai@helix.mgh.harvard.edu 
18F FDG PET/CT 
Imaging Assessment 
Laboratory: 
 
Dushyant Sahani, MD 
Massachusetts General Hospital 
Department of Radiology 
55 Fruit Street 
Boston, MA 02114, USA 
Telephone number: 617-726-8396 
Fax number: 617-726-4891 
Email: dsahani@partners.org 
Flow Cytometry B Cell 
and T Cell Assessment 
Laboratory: 
 
Alisa Euler  
ICON Laboratory Services, Inc.  
123 Smith Street 
Farmingdale, NY  11735 
Telephone number: 631-306-9676 
Email: Alisa.euler@iconplc.com  
 
 

Xencor, Inc. 
Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
           31 Jan 2017                     CONFIDENTIAL 
 
  
 
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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ............................................................................................................... 4 
LIST OF STUDY STAFF ............................................................................................................... 8 
TABLE OF CONTENTS .............................................................................................................. 10 
LIST OF TABLES ........................................................................................................................ 13 
SUMMARY OF CHANGES – VERSION 2 TO VERSION 3 .................................................... 17 
1 
INTRODUCTION ........................................................................................................... 21 
1.1 
Background......................................................................................................... 21 
1.1.1 
Role of B Cells in Autoimmunity ................................................................... 21 
1.1.2 
XmAb5871 ..................................................................................................... 21 
1.1.3 
IgG4-Related Disease ..................................................................................... 22 
1.1.4 
Current Treatment of IgG4-RD ...................................................................... 23 
1.2 
Non-Clinical Studies .......................................................................................... 24 
1.2.1 
Pharmacology of XmAb5871 ......................................................................... 24 
1.2.2 
Secondary Pharmacology: Off Target Receptor Binding Studies .................. 25 
1.2.3 
Nonclinical Pharmacokinetics and Toxicology of XmAb5871 ...................... 27 
1.3 
Clinical Studies ................................................................................................... 29 
1.3.1 
A Randomised, Blinded, Placebo-Controlled, Single Ascending Dose 
Study of the Safety, Tolerability, and Pharmacokinetics of XmAb5871 in 
Healthy Adult Volunteers ............................................................................... 29 
1.3.2 
A 
Randomized, 
Placebo-Controlled, 
Double-Blinded, 
Ascending 
Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of XmAb5871 in Patients with Rheumatoid Arthritis .... 31 
1.4 
Rationale for the Clinical Study ......................................................................... 33 
1.4.1 
Risk-Benefit Assessment ................................................................................ 34 
1.4.2 
Potential Risks ................................................................................................ 35 
1.4.3 
Potential Benefits ............................................................................................ 38 
1.4.4 
Conclusion ...................................................................................................... 38 
2 
STUDY OBJECTIVES ................................................................................................... 39 
2.1 
Primary Objective ............................................................................................... 39 
2.2 
Secondary Objective ........................................................................................... 39 
2.3 
Exploratory Objectives ....................................................................................... 39 
3 
INVESTIGATIONAL PLAN .......................................................................................... 39 
3.1 
Overall Study Design and Plan........................................................................... 39 
3.2 
Discussion of Study Design................................................................................ 41 
3.3 
Selection of Patient Population .......................................................................... 42 
3.4 
Endpoints ............................................................................................................ 42 
3.4.1 
Disease Activity .............................................................................................. 42 
3.4.2 
Mechanistic Studies ........................................................................................ 42 
3.4.3 
Safety Endpoints ............................................................................................. 43 
3.4.4 
Immunogenicity Endpoint .............................................................................. 43 
3.4.5 
Pharmacokinetic Endpoints ............................................................................ 43 

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Clinical Study Protocol V3.0 , Amendment 2 
       
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3.4.6 
Pharmacodynamic Endpoints ......................................................................... 44 
3.4.7 
Pharmacogenomics Endpoints ........................................................................ 44 
3.5 
Stopping Criteria for the Clinical Study ............................................................. 44 
3.6 
Dose Delay and Dose Modification in Patients Who Experience Toxicity ....... 44 
4 
STUDY POPULATION .................................................................................................. 45 
4.1 
Number of Patients ............................................................................................. 45 
4.2 
Inclusion Criteria ................................................................................................ 45 
4.3 
Exclusion Criteria ............................................................................................... 46 
4.4 
Subject Withdrawal and Replacement ................................................................ 47 
4.5 
Termination of the Clinical Study ...................................................................... 48 
5 
INVESTIGATIONAL MEDICINAL PRODUCT .......................................................... 49 
5.1 
Identity of the Investigational Medicinal Products ............................................ 49 
5.2 
Drug Storage and Handling Requirements ......................................................... 49 
5.3 
Drug Administration ........................................................................................... 50 
5.4 
Dose Rationale.................................................................................................... 51 
5.5 
Supply, Packaging, and Labeling ....................................................................... 51 
5.6 
Drug Accountability, Dispensing, and Destruction ............................................ 52 
5.7 
Subject Identification.......................................................................................... 52 
5.7.1 
Screening Numbers ......................................................................................... 52 
5.7.2 
Enrollment Numbers ....................................................................................... 52 
5.8 
Administration of Investigational Medicinal Product ........................................ 53 
5.9 
Compliance ......................................................................................................... 53 
5.10 
Concomitant Medications ................................................................................... 53 
5.10.1 
Previous/Concomitant Medication ................................................................. 53 
5.10.2 
Contraception .................................................................................................. 54 
6 
VARIABLES AND METHODS OF ASSESSMENT .................................................... 55 
6.1 
Safety Variables.................................................................................................. 55 
6.1.1 
Medical History, Demographic, and Other Baseline Information .................. 55 
6.1.2 
Adverse Events ............................................................................................... 55 
6.1.3 
Vital Signs ...................................................................................................... 67 
6.1.4 
12-lead Electrocardiograms ............................................................................ 67 
6.1.5 
Physical Examinations .................................................................................... 68 
6.1.6 
Clinical Laboratory Assessments .................................................................... 68 
6.2 
Pharmacokinetic Variables ................................................................................. 71 
6.3 
Pharmacodynamic Variables .............................................................................. 71 
6.4 
Pharmacogenomics Variables ............................................................................ 72 
6.4.1 
Efficacy Measurements................................................................................... 72 
7 
STUDY CONDUCT ........................................................................................................ 73 
7.1 
Schedule of Assessments .................................................................................... 73 
7.1.1 
Assessments by Visit ...................................................................................... 77 
7.1.2 
Early Termination Visit .................................................................................. 77 
7.1.3 
End-of-Study ................................................................................................... 77 

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8 
STATISTICAL METHODS ............................................................................................ 77 
8.1 
Study Population ................................................................................................ 77 
8.1.1 
Disposition of Patients .................................................................................... 77 
8.1.2 
Protocol Deviations ........................................................................................ 77 
8.1.3 
Analysis Populations ...................................................................................... 77 
8.2 
General Considerations ...................................................................................... 78 
8.3 
Determination of Sample Size ............................................................................ 79 
8.4 
Treatment Assignment and Blinding .................................................................. 79 
8.5 
Study Endpoints and Statistical Analyses .......................................................... 79 
8.5.1 
Primary Efficacy Endpoint (Disease Activity) ............................................... 79 
8.5.2 
Secondary Efficacy Endpoint (Disease Activity) ........................................... 79 
8.5.3 
Safety and Tolerability Endpoints .................................................................. 80 
8.6 
Pharmacokinetic Analyses .................................................................................. 81 
8.7 
Pharmacodynamic Analyses ............................................................................... 81 
8.8 
Pharmacokinetic/Pharmacodynamic Analyses ................................................... 81 
8.9 
Data Quality Assurance ...................................................................................... 81 
8.10 
Immunogenicity Analysis ................................................................................... 81 
8.11 
Interim Analyses ................................................................................................. 81 
9 
ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS .......................................... 82 
9.1 
Data Quality Assurance ...................................................................................... 82 
9.2 
Access to Source Data/Documents ..................................................................... 82 
9.3 
Archiving Study Documents .............................................................................. 83 
9.4 
Good Clinical Practice ........................................................................................ 83 
9.5 
Informed Consent ............................................................................................... 83 
9.6 
Protocol Approval and Amendment(s) ............................................................... 84 
9.7 
Confidentiality Data Protection .......................................................................... 84 
9.8 
Publication Policy ............................................................................................... 85 
10 
REFERENCE LIST ......................................................................................................... 86 
11 
APPENDICES ................................................................................................................. 89 
11.1 
Efficacy Assessments ......................................................................................... 89 
11.1.1 
IgG4-RD Responder Index (IgG4-RD RI) ..................................................... 89 
11.1.2 
Physician and Patient Global Assessment of Disease Activity (VAS) ........... 92 
 

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Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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LIST OF TABLES 
Table 1: Prednisone Equivalence .................................................................................................. 54 
Table 2: Severity Grading Scale ................................................................................................... 57 
Table 3: Causality Grading Scale ................................................................................................. 58 
Table 4: Definition of Anaphylaxis .............................................................................................. 61 
Table 5: Infusion-Related Reaction and Cytokine Release Syndrome ......................................... 62 
Table 6: Schedule of Assessments ................................................................................................ 74 

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Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
       
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
Ab 
Antibody 
ABC 
Absolute B cell count 
ADA 
Antidrug antibody 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AP 
Alkaline phosphatase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AUC 
The area under the serum concentration-time curve from time zero to time 
point at a later time x (AUCx), time point of the last measurable concentration 
(AUClast), or extrapolated to time infinity (AUC∞) 
BCR 
B cell receptor 
BP 
Blood pressure 
bpm 
Beats per minute 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CL 
Clearance of drug 
Clast 
Last measurable concentration 
Cmax 
Maximum observed concentration 
CPK 
Creatine phosphokinase 
CRF 
Case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
D5W 
5% dextrose 
DNA 
Deoxyribonucleic acid 
DP 
Drug product 
ECG 
Electrocardiogram 
EOI 
End of infusion 
EOS 
End-of-study 
Fc 
Fragment, crystalizable 
FcγRIIb 
Fcγ receptor IIb 
FDA 
Food and Drug Administration 
FIH 
First in human 

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FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
H 
Histidine 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
HCO3 
Bicarbonate 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
IC 
Immune complex 
IC50 
Median inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IFNγ 
Interferon gamma 
Ig 
Immunoglobulin 
IL-4 
Interleukin-4 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IU 
International units 
IUD 
Intrauterine device 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
mAb 
Monoclonal antibody 
mmHg 
Millimeters of mercury 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NIAID 
National Institute of Allergy and Infectious Diseases 
NK 
Natural killer 
NOAEL 
No observable adverse effect level 

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Protocol Number XmAb5871-03 
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OTC 
Over-the-counter 
PBMC 
Peripheral blood mononuclear cell 
PD 
Pharmacodynamic 
PEF 
Peak expiratory flow 
PI 
Principal investigator 
PK 
Pharmacokinetic 
PT 
Prothrombin time 
R 
Arginine 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCID 
Severe combined immunodeficiency 
SD 
Standard deviation 
SID 
Subject identification 
SOP 
Standard Operating Procedure 
T1/2 
Terminal phase half-life of drug 
TEAE 
Treatment-emergent adverse event 
TNFα 
Tumor necrosis factor alpha 
ULN 
Upper limit of normal 
 

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Protocol Number XmAb5871-03 
Clinical Study Protocol V3.0 , Amendment 2 
               
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PROTOCOL NO. XmAb5871-03 
AMENDMENT 2 - 31 JANUARY 2017 
“An Open-label, Single-arm, Pilot Study to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients with IgG4-Related Disease” 
SUMMARY OF CHANGES – VERSION 2 TO VERSION 3 
Page 
Section 
Change (bolded text added; strikethrough text deleted) 
Justification 
4 
Protocol Synopsis 
(Study Design) 
Changed the following stricken text and added the following bold 
text:  
1521 
• 
Add up to 6 additional patients to be treated in the 
current protocol 
5 
Protocol Synopsis 
(Administration) 
Added the following bolded text: 
Dose and route of administration: Every other week administration of 
XmAb5871 at 5.0 mg/kg by IV infusion over 1-2 hours for the first 15 
patients, then up to 6 patients treated with either 90 mg fixed dose or 
180 mg fixed dose by IV infusion every other week. 
• 
Allow up to 6 additional patients to be treated with 
one of two fixed doses of XmAb5871 at dosages 
lower than 5.0 mg/kg used in the first 15 patients 
5  
Protocol Synopsis 
(Number of Subjects) 
Changed the following stricken text and added the following bold 
text:  
1521 
• 
Add up to 6 additional patients to be treated in the 
current protocol 
5  
Protocol Synopsis 
(Study Duration) 
Added the following bolded text: 
Patients will be followed on study for 6 weeks following the last dose 
for a total study period of up to 32 weeks. 
• 
Clarification of follow-up period while on study 
5  
Protocol Synopsis 
(Study Procedures) 
Added the following bolded text: 
Based on preliminary data in this study showing reduction of IgG4-
RD disease activity following treatment with XmAb5871 at 5 mg/kg 
every 2 weeks and based on data from a previous study in patients 
with active rheumatoid arthritis suggesting activity at doses as low as 
0.3 mg/kg, the study has been amended in this protocol version in 
order to explore the treatment effect of lower doses of XmAb5871. 
Following enrollment of the first 15 patients (treated at 5 mg/kg 
every other week), approximately 3 additional patients will be treated 
• 
Addition of 6 patients to be treated with one of two 
fixed doses of XmAb5871 at dosages lower than 
5.0 mg/kg used in the first 15 patients  

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Page 
Section 
Change (bolded text added; strikethrough text deleted) 
Justification 
with a fixed dose of 90 mg of XmAb5871 given IV every other week. 
A second set of up to 3 additional patients may be treated with either 
90 mg or 180 mg of XmAb5871. At the discretion of the Investigator 
and Sponsor, subjects dosed at 90 mg of XmAb5871 may have their 
dose increased to 180 mg if there has been an inadequate clinical 
response to therapy. All study procedures will remain the same for 
these patients except for the administration of a lower dosage of 
XmAb5871.  The dose for the 90 and 180 mg subjects will be 
administered over a 1 hour period at a constant rate. 
31 
1.3.2.A Randomized, 
Placebo-
controlled 
double-blinded 
ascending 
multiple-dose 
study of the 
safety, 
tolerability, 
pharmacokinetics 
and 
pharmacodynami
cs of XmAb5871 
in patients with 
rheumatoid 
arthritis 
Added the following bolded text: 
In Part A of the study, all cohorts treated with XmAb5871 at any 
dose tested (0.3, 1.0, 3.0, or 10.0 mg/kg) achieved higher percentages 
of DAS-CRP low disease or remission at Day 85 than did the 
placebo-treated patients. For example, in the 0.3 mg/kg group (n=3), 
there were 33% DAS28-CRP remissions, 100% ACR20, 33% ACR50 
and 33% ACR70 responses vs 14%, 29%, 14% and 0% in the placebo 
group (Part A).   
• 
Justifying the use of lower dosages 
39 
3.1 Overall Study 
Design and Plan 
Changed the following stricken text and added the following bold 
text:  
The first 15 patients enrolled All patients will receive 5.0 mg/kg of 
XmAb5871 infused IV over 1-2 hours on an every other week dosing 
schedule for up to a total of 12 doses.  Up to six additional patients 
may be enrolled and treated with either 90 mg fixed dose or 180 mg 
fixed dose by IV infusion every other week. Patients will be followed 
for 6 weeks after the final infusion.  Up to 1521 patients will be 
enrolled. 
• 
Adjusting language to add up to 6 patients at one 
or two fixed dosages lower than 5 mg/kg 

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Justification 
40 
3.1 Overall Study 
Design and Plan 
Added the following bolded text: 
Based on preliminary data in this study showing reduction of IgG4-
RD disease activity following treatment with XmAb5871 at 5 mg/kg 
every 2 weeks and based on data from a previous study in patients 
with active rheumatoid arthritis suggesting activity at doses as low as 
0.3 mg/kg, the study has been amended in this protocol version in 
order to explore the treatment effect of lower doses of XmAb5871. 
Following enrollment of the first 15 patients (treated at 5 mg/kg 
every other week), approximately 3 additional patients will be treated 
with a fixed dose of 90 mg of XmAb5871 given IV every other week. 
A second set of up to 3 additional patients may be treated with either 
90 mg or 180 mg of XmAb5871. At the discretion of the Investigator 
and Sponsor, subjects dosed at 90 mg of XmAb5871 may have their 
dose increased to 180 mg if there has been an inadequate clinical 
response to therapy All study procedures will remain the same for 
these patients except for the administration of a lower dosage of 
XmAb5871.  The dose for the 90 and 180 mg  dose subjects will be 
administered over a 1 hour period at a constant rate. 
• 
Adjusting language to add up to 6 patients at one 
or two fixed dosages lower than 5 mg/kg 
42 
3.3 Selection of 
Patient 
Population 
Changed the following stricken text and added the following bold 
text:  
1521 
• 
Add up to 6 additional patients to be treated in the 
current protocol 
45 
4.1 Number of Patients Changed the following stricken text and added the following bold 
text:  
1521 
• 
Add up to 6 additional patients to be treated in the 
current protocol 
49 
5.2 Drug Storage and 
Handling 
Requirements 
Changed the following stricken text and added the following bold 
text:  
For the first 15 patients, the full calculated dose 
• 
Clarification of dose 
50 
5.2 Drug Storage and 
Handling 
Requirements 
Added the following bolded text: 
After the first 15 patients, the next up to 6 patients will be dosed with 
fixed doses of either 90 mg or 180 mg per dose. The XmAb5871 will 
be diluted as for the 5.0 mg/kg dose, but instead of weight-based 
• 
Adjusting language to add up to 6 patients at one 
or two fixed dosages lower than 5 mg/kg 

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dosing, either 18 mL or 36 mL of the solution will be given as a fixed 
dose. 
51 
5.4 Dose Rationale 
Added the following bolded text: 
This protocol has been amended in order to explore the treatment 
effect of lower doses of XmAb5871. After the first 15 patients are 
enrolled, approximately 3 additional patients will be treated with a 
fixed dose of 90 mg of XmAb5871 given IV every other week instead 
of 5 mg/kg. A second set of up to 3 additional patients may be treated 
with either 90 mg or 180 mg XmAb5871 instead of 5 mg/kg.  These 
two doses represent approximately 1 mg/kg and 2 mg/kg for a 75 kg 
person and are well within the ranges previously studied. 
• 
Adjusting language to add up to 6 patients at one 
or two fixed dosages lower than 5 mg/kg 
77 
7.1.3 End-of-Study 
Added the following bolded text: 
In addition, the PI and/or study site will contact all patients 
approximately every 6 months following EOS and will keep a log of 
when (if) the patient has recurrent symptoms and when (if) new 
medications for IgG4-RD treatment have been added since the end of 
study.  This information will be provided to the sponsor periodically 
following the completion of the study. 
• 
Adding off-study followup 
79 
8.3 Determination of 
Sample Size 
Changed the following stricken text and added the following bold 
text:  
1521 
• 
Add up to 6 additional patients to be treated in the 
current protocol 

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1 
INTRODUCTION 
1.1 
Background 
1.1.1 Role of B Cells in Autoimmunity 
Autoimmune diseases, including connective tissue diseases and bullous diseases, may be 
life-threatening.  Recent clinical and experimental approaches have demonstrated that B cells 
play critical roles in the pathophysiology of autoimmune disease.  They do so not only by 
well-established autoantibody-mediated mechanisms but also by a variety of other functions 
including interactions with dendritic cells and T cells.  B cell activation and autoantibody 
production therefore offer an important therapeutic target mechanism for the management of 
immune-mediated conditions.  B cell directed therapies are approved for both the treatment of 
rheumatoid arthritis (RA) (rituximab) and systemic lupus erythematosus (SLE) (belimumab).  In 
IgG4-related disease (IgG4-RD), an open-label pilot study has also shown evidence of an effect 
on disease activity with B cell depletion therapy (Carruthers et al., 2015). 
B cells are activated through a number of cell surface receptors including the B cell receptor 
(BCR).  The BCR, once coupled with cognate antigen, induces a complex signaling pathway that 
results in B cell activation, proliferation and differentiation.  The BCR response to antigen is 
modulated by a number of specialized cell surface co-receptors, or response regulators, which 
inform B cells of their microenvironment.  These response regulators include cluster of 
differentiation 19 (CD19) and CD22.  In addition, B cells have Fcγ receptor IIb (FcγRIIb) on 
their surface.  Activation of FcγRIIb results in the down-regulation of BCR signaling and 
decreased B cell function.  FcγRIIb has also been shown to play a crucial role in suppressing 
autoimmunity (Nimmerjahn et al. 2008, McGaha et al. 2005, Taransenko et al. 2007, Brownlie et 
al. 2008).   
1.1.2 XmAb5871 
XmAb®5871 is a humanized monoclonal antibody (mAb) being developed by Xencor Inc. for 
the treatment of B cell mediated autoimmune disorders such as IgG4-RD, SLE and RA. 
XmAb5871 is a humanized Fc (fragment, crystallizable) engineered mAb that binds to the 
human B cell restricted surface antigen CD19 and has enhanced Fc binding to FcγRIIb.  The 
antibody variable region of XmAb5871 has been engineered to increase affinity to human CD19, 
while the constant region is engineered to increase affinity for the inhibitory FcγRIIb (Chu et al. 
2008, Horton et al. 2011).  

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FcγRIIb is the only Fc receptor (FcR) on B cells and serves as an antibody sensing 
down-regulator of humoral immunity that is naturally engaged by immune complexes (Smith et 
al. 2010).  When sufficient antibody is raised against a given antigen, specific immune 
complexes form and co-engage FcγRIIb and the BCR with high avidity, selectively suppressing 
only the B cells that recognize cognate antigen.  In addition, FcγRIIb regulates the activity of 
other B cell stimulators including IL-4, lipopolysaccharide (LPS), and B cell activating factor 
(BAFF) that amplify BCR-driven B cell proliferation and differentiation (Crowley et al. 2009).   
By simultaneously binding CD19 and FcγRIIb, XmAb5871 mimics the action of 
antigen-antibody complexes and down-regulates B cell activity.  The proposed mechanism of 
action of XmAb5871 of simultaneously binding CD19 and FcγRIIb and down regulating B cell 
activity has been demonstrated in vitro and in vivo, including in classical animal models of 
autoimmune disease.    
1.1.3 IgG4-Related Disease 
IgG4-RD is a chronic fibro-inflammatory condition that can affect a variety of organs including 
the pancreas, biliary tract, salivary and lacrimal glands, orbits, lungs, kidneys, meninges, 
pituitary gland, prostate and thyroid among others.  It may also involve the retroperitoneum.  
This multi-organ immune-mediated condition was previously regarded as a group of isolated 
single organ diseases but has recently been recognized as a unifying entity linked by common 
histopathological and immunohistochemical features.  The histopathological features include a 
dense lymphoplasmacytic infiltrate consisting of T cells and IgG4+ plasma cells, storiform 
fibrosis and obliterative phlebitis.  Immunoperoxidase staining of affected tissues generally 
demonstrate a ratio of ≥40% IgG4/IgG+ plasma cells (Deshpande et al. 2012).  Serum IgG4 
concentrations are elevated in at least 50-60% of cases before the initiation of treatment (Wallace 
et al. 2015).  
Several B cell subsets have recently been described by flow cytometry to be elevated in the 
peripheral blood of IgG4-RD patients.  Circulating IgG4+ plasmablasts (CD19lowCD38+CD20-
CD27+) have been shown to be elevated in active disease as compared to individuals with other 
diseases and normal controls, even in IgG4-RD patients with normal IgG4 serum levels.  Total 
plasmablasts can be utilized both as a diagnostic feature of IgG4-RD as well as a biomarker of 
treatment response (Wallace et al. 2014, Mattoo et al. 2014).  CD4+ T cells have been putatively 
implicated in the pathogenesis of IgG4-RD as well, but the precise type(s) and function(s) of this 
population have yet to be clarified (Kamisawa et al. 2014).   

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The frequency of IgG4-RD is unknown in most countries other than Japan, where it is thought to 
affect at least 8000 individuals (Uchida et al. 2012).  However, because this disease has only 
been recognized and described in the last 10 years, recognition of the disease is growing in other 
parts of the world, including the US and Europe.  IgG4-RD appears to have a modest 
predilection for affecting men more often than women, and tends to afflict middle-aged to 
elderly individuals.  Although IgG4-RD can affect a single organ at presentation, it is not 
uncommon for patients to present with or develop multi-organ disease.  As the disease 
progresses, additional organs develop lesions and the cellular inflammation characterizing early 
disease moves toward a more fibrotic stage, causing major tissue damage, dysfunction and 
ultimately organ failure. 
1.1.4 Current Treatment of IgG4-RD 
IgG4-RD is currently incurable.  The goals of treatment are to reduce inflammation and swelling 
in the organs, prevent or reverse (if possible) fibrosis and increase glandular secretion.  
Aggressive treatment is warranted to prevent organ failure when vital organs are involved.  For 
example, cholangitis due to IgG4-RD can lead to hepatic failure, IgG4-related (type 2) 
autoimmune pancreatitis can lead to failure of either or both the endocrine and exocrine 
pancreas, and IgG4-related aortitis can lead to aneurysms and/or aortic dissection.  At the present 
time, glucocorticosteroids at daily doses of 0.6 mg/kg daily for 2 to 4 weeks followed by tapering 
to low doses (or discontinuing altogether) over 3-6 months is the first line of therapy.  Although 
this approach is effective initially in most patients, the relapse rate upon tapering or 
discontinuation is high (Khosroshahi et al. 2015).  In addition, the long term use of 
glucocorticosteroids in older populations such as that affected by IgG4-RD can lead to many 
untoward 
side 
effects 
such 
as 
osteoporosis, 
high 
blood 
pressure 
and 
diabetes.  
Immunosuppressive medications such as azathioprine, mycophenolate mofetil and methotrexate 
have been used as glucocorticosteroid-sparing agents, with no clear indication of efficacy (Stone 
et al. 2012, Yamamoto et al. 2014, Khosroshahi et al. 2015).  A high disease response rate has 
been observed in one small open-label trial with rituximab, utilizing an IgG4-RD Responder 
Index (RI) as a measure of disease response (Khosroshahi et al. 2010, Carruthers et al. 2015).  
The presumed role of B cells and plasmablasts in IgG4-RD and the preliminary observation of an 
effect on IgG4-RD disease activity by B cell depletion therapy support the evaluation of other 
non-depleting B cell directed therapies such as XmAb5871.  

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1.2 
Non-Clinical Studies 
1.2.1 Pharmacology of XmAb5871 
1.2.1.1 
In Vitro Pharmacology  
XmAb5871 has two key functional attributes: binding to human CD19 (hCD19) and binding to 
human FcγRIIb.  The EC50 of binding of XmAb5871 to an hCD19 expressing cell line (Ramos) 
is 0.3 nM.  The EC50 of binding to human primary B cells is 1.4 nM when measured under 
similar assay conditions.  Human B cells express both CD19 and FcγRIIb, so the EC50 of 1.4 nM 
represents the avidity of XmAb5871 for the human B cell surface.  The affinity of XmAb5871 to 
the CD19 of the relevant toxicology species, the cynomolgus monkey, is approximately 6 fold 
lower than the affinity for the human CD19.  No appreciable XmAb5871 binding has been 
detected with B cells from the mouse, rat, rabbit, or dog.  
The second functional attribute important for the pharmacology of XmAb5871 is its enhanced 
binding to FcγRIIb relative to binding to other FcγRs.  FcγRs, expressed on a wide variety of 
immune cells, bind to the Fc portion of immunoglobulin G (IgG) to mediate a range of 
immunological functions.  FcγRI (CD64), FcγRIIa (CD32a), and FcγRIIIa (CD16a) are all 
activating receptors that signal through the intracellular immunoreceptor known as the 
tyrosine-based activation motif (ITAM).  In contrast, FcγRIIb (CD32b) signals via the 
immunoreceptor tyrosine-based inhibitory motif (ITIM), leading to the down-regulation of 
immune responses.  
The affinity of XmAb5871 for human FcγRIIb is approximately 8 nM, representing an increase 
of approximately 225-fold relative to human native IgG1.  The binding affinity of XmAb5871 
for the human activating FcγRs is reduced or unchanged except for one allele of a commonly 
occurring polymorphism in FcγRIIa, the R131 allele.  The affinity of XmAb5871 for the R131 
allele of the activating receptor FcγRIIa (~3 nM) is increased over 150-fold relative to native 
IgG1.  In contrast, a slight decrease in affinity was observed for the H131 allele of FcγRIIa, 
implicating the arginine at position 131 as a key amino acid residue for the capacity of the 
XmAb5871 Fc to improve FcγRIIb affinity.  FcγRIIb contains an arginine residue at the 
analogous amino acid position and there are no known polymorphisms at this amino acid 
position in human FcγRIIb. 
The binding affinities of XmAb5871 to activating FcγRs in humans and cynomolgus monkeys 
were similar.  However, the significant increase in affinity for the human inhibitory receptor 
FcγRIIb was not observed with the analogous cynomolgus monkey inhibitory receptor FcγRIIb 

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(250 fold less).  This is probably due to the absence of an arginine amino acid residue at position 
131 in the FcγRIIb of the cynomolgus monkey. 
The co-engagement of CD19 and FcγRIIb is the presumed mechanism by which excess 
antigen-antibody complexes down regulate B cell activity.  XmAb5871 also binds these 2 
receptors simultaneously, thereby inhibiting B cell activation.  In vitro co-engagement of CD19 
and FcγRIIb by XmAb5871 was shown to inhibit BCR-induced calcium release in human B 
cells.  The effect is dependent on binding to both CD19 and FcγRIIb binding and cannot be 
mimicked by control antibodies that bind to only one of these targets or the other.  Similarly, 
control antibodies directed against the two targets individually are ineffective in downregulating 
B cell activity, even if such antibodies were used in combination. 
1.2.1.2 
In Vivo Pharmacology 
In vivo, XmAb5871 inhibits human B cell function in a model of human peripheral blood 
mononuclear cell (PBMC) xenografts in severe combined immunodeficient (SCID) mice.  In 
these studies, the engrafted human B cell response to an in vivo tetanus toxoid antigen challenge 
can be blocked by XmAb5871.  Tetanus toxoid-specific human IgG production was inhibited by 
XmAb5871, whereas negative control antibodies (e.g., those that bind human CD19 but not 
human FcγRIIb) did not differ from buffer alone.  These studies show an inhibitory effect on 
specific B cell activation by XmAb5871. 
A murine pharmacology model was also developed in which the murine Fc receptor gene was 
removed and the human FcγRIIb gene inserted.  These transgenic mice were then used to 
demonstrate the protective effect of a surrogate antibody that recognizes human FcγRIIb and 
murine CD19 in a collagen-induced arthritis model of polyarticular disease.  Treatment with the 
surrogate antibody successfully blocked both the incidence and severity of the disease (for more 
details, see Investigator Brochure). 
1.2.2 Secondary Pharmacology: Off Target Receptor Binding Studies 
The binding affinity of XmAb5871 for FcγRIIb is increased approximately 225-fold compared to 
native human IgG1 Fc.  Moreover, its binding affinity to the activating receptor FcγRIIIa, 
involved in antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, is reduced 
approximately 20-fold compared to the same native human IgG1 Fc (Chu et al. 2008).  
ADCC-mediated killing of B cells is an important mechanism of depletion of mature B cell 
populations in humans by the anti-CD20 mAb rituximab (Reff et al. 1994).  In ex vivo human 
PBMC cultures, XmAb5871 did not stimulate B cell depletion.  In contrast, two known depleting 

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antibodies, rituximab (anti-CD20; Reff et al. 1994) and XmAb5574 (an anti-CD19 antibody with 
the Fc engineered to enhance FcγRIIIa binding; Horton et al. 2008) depleted B cells in a 
dose-dependent manner.  
FcγRIIa, a low affinity, activating FcγR present on human platelets and myeloid cells 
(monocytes, dendritic cells, macrophages), is important in the antibody-dependent cell-mediated 
phagocytosis (ADCP) function of macrophages.  Two alleles of the gene encoding FcγRIIa 
generate 2 variants that differ at amino acid position 131.  The histidine (H131) and arginine 
(R131) alleles are distributed roughly equally in humans, with some ethnic variation.  The 
affinity of XmAb5871 for FcγRIIa R131 is increased 150-fold relative to that of wild type IgG1 
binding, but the affinity for the H131 allotype is slightly decreased relative to IgG1.  The 
potential implications of this increased binding to FcγRIIa R131 (i.e., ADCP) have been 
examined.  In vitro phagocytosis experiments demonstrate that monocyte-derived macrophages 
from R131 positive donors phagocytose Ramos cells (CD19+ B cell line) and purified human B 
cells in the presence of XmAb5871.  Very little phagocytosis was observed with 
monocyte-derived macrophages from H131 homozygous donors.  These observations raise the 
possibility of B cell reduction or depletion in R131-positive patients.  However, data from the 
first-in-human (FIH) study in healthy volunteers as well as data from the multiple ascending dose 
study in RA patients, both described below, have not shown an association of the R131 allele 
with the extent of B cell count reduction following dosing with XmAb5871. 
In the human FcγRIIb transgenic mouse model, a surrogate antibody that recognizes human 
FcγRIIb and murine CD19 did not cause B cell depletion.  A small reduction in the B cell count 
was observed, possibly due to inhibition of BCR-mediated proliferation signals.  Interestingly, 
the surrogate antibody did produce B cell depletion in the same strain of mice that lacks the 
human FcγRIIb transgene, suggesting that the presence of human FcγRIIb may be protective 
against B cell depletion mediated by activating FcRs. 
FcγRIIa is the sole FcγR expressed on human platelets.  Cross-linking of FcγRIIa by 
platelet-antigen associated immune complexes has been demonstrated to activate platelets fully 
for secretion and aggregation.  The potential for platelet interaction was evaluated even though 
neither CD19 nor FcγRIIb are platelet-associated antigens.  In an ex vivo study, the addition of 
XmAb5871 to samples from human donors did not induce platelet activation.  Moreover, in the 
completed human studies in healthy subjects and in RA patients, no changes in platelet count 
were observed. 

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Whole blood assays were also used to monitor for possible cytokine release in response to 
XmAb5871.  No XmAb5871-mediated release of TNF-α or interferon-γ (IFN-γ) was observed.  
In the completed FIH, single ascending dose study, no signs or symptoms consistent with either 
cytokine release syndrome or immunologically-mediated infusion-related reactions were 
observed.  In the Phase 2a study in RA patients, two of 40 XmAb5871-treated patients (5%) 
experienced an infusion-related reaction with hypotension, both at a dose of 10 mg/kg.  One 
occurred at the time of the first infusion and the other during the second infusion. It is possible 
the infusion-related reactions were mediated by cytokine release. 
1.2.3 Nonclinical Pharmacokinetics and Toxicology of XmAb5871 
The cynomolgus monkey was found to be the single most relevant common toxicology species 
based on the binding of XmAb5871 to lymphocytes in flow cytometric analyses.  XmAb5871 
cross reacted with B cells from cynomolgus monkey but failed to bind to cells from mouse, rat, 
rabbit or dog.  Human and cynomolgus monkey binding affinities were similar for most of the 
FcγRs, however, the binding affinity to the FcγRIIb of the cynomolgus monkey was 
approximately 250-fold lower than that observed for the corresponding human receptor.  
However, ex vivo studies have confirmed that FcγRIIb was engaged by XmAb5871 on 
cynomolgus monkey B cells and was capable of inducing pharmacologically measurable 
consequences despite the 250-fold lower FcγRIIb binding affinity. 
1.2.3.1 
Tissue Cross-Reactivity Studies 
The CD19 antigen is restricted to B cell lineages (Nadler et al. 1983, Meeker et al. 1984).  In a 
cross-reactivity study with a normal human tissue panel, fluorescein-XmAb5871 stained 
mononuclear leukocytes and lymphocytes that were judged to be B cells based on their 
morphology and/or localization.  Some staining (weak to moderate) was noted in a variety of 
human cell types that are presumed not to express CD19.  The staining in these tissues was often 
observable only at the higher concentration of antibody tested and not observed in the analogous 
monkey tissues.  The tissues include Kupffer cells and endothelium of the liver. Endothelium, 
Hofbauer cells and spindloid cells of placental sections and spindloid cells and Leydig cells of 
the testes showed weak to moderate staining. 
A companion study with cynomolgus monkey tissues also stained mononuclear leukocytes and 
lymphocytes and bone marrow precursor cells judged to be of B cell origin.  No other binding 
was observed in the monkey tissues. 

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1.2.3.2 
Non-GLP and GLP Toxicology Studies in Cynomolgus Monkey 
In an exploratory non-good laboratory practice (GLP) PK/toxicity study in 12 cynomolgus 
monkeys (two/gender/group), XmAb5871 or vehicle was administered as a single 1 hour IV 
infusion at doses of 3 or 30 mg/kg.  Necropsies were performed in 6 monkeys (1 of each sex per 
group) on study days 30 and 92. There were no mortalities in that study, and single IV 
administration of XmAb5871 in cynomolgus monkey was tolerated well at both 3 and 30 mg/kg.  
There were no test article-related changes identified in clinical observations, food consumption, 
body weights, hematology, serum chemistry, gross or microscopic anatomical pathology 
parameters.  
A GLP 12-week repeat-dose toxicity study was completed in cynomolgus monkey of both 
genders.  XmAb5871 was administered via 1 hour IV infusion at doses of 0, 2, 10 or 50 mg/kg 
on an every other week x 6 dosing regimen.  Exposure of cynomolgus monkeys to 6 
administrations of XmAb5871 at 14-day intervals was well-tolerated, with all animals surviving 
to scheduled sacrifice.  No test article-related changes were observed in clinical observations, 
food consumption, body weight, electrocardiography, ophthalmology, hematology, serum 
chemistry, coagulation, urinalysis, organ weight, gross observations, or histopathology.  
Dose-dependent decreases in the mean absolute and relative B cell (CD3-CD20+) counts were 
observed, relative to baseline levels, on Days 15 and 43; however, recovery of B cell counts to at 
least 75% of baseline occurred during the dosing period for all groups.  The reduction in B cell 
count to less than 75% of baseline levels (Day -1) did not occur at any time during dosing for the 
2 mg/kg and 10 mg/kg groups.  In the 50 mg/kg group, the B cell count was reduced to 
approximately 45% of baseline on Day 15 (pre-dose infusion #2) and Day 43 (pre-dose infusion 
#4) and recovered to within 75% of baseline counts on Day 71 (pre-dose infusion #6).  No test 
article-related effects were noted in T lymphocyte counts or total lymphocyte counts, and no 
microscopic changes were observed in lymphoid tissues.  Because no related effects were 
observed in other endpoints, these changes were not considered to be adverse. 
Anti-drug antibodies (ADA) were detected in animals during the dosing period only in the two 
lowest dose groups, eight in the 2 mg/kg group, and two in the 10 m/kg group.  
A 6-month GLP pharmacokinetic/toxicity study has also been performed in cynomolgus 
monkey.  Animals of both sexes were dosed IV with XmAb5871 or vehicle control every other 
week for a total of 13 doses at 0, 10, 50, or 200 mg/kg. No mortalities occurred in the study and 
no test article-related effects were identified in clinical observations, body weight, 
electrocardiography and ophthalmology assessments, urinalysis, hematology, serum chemistry 

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and coagulation parameters, or gross and microscopic anatomic evaluations.  Test article-related 
effects were limited to dose-related reductions in B cells (CD3-CD20+) observed from Day 15 
through Day 183.  At all doses, the reduction observed after the first dose was maintained 
throughout the dosing period with no notable further reduction with subsequent doses.  The B 
cell count was reduced to approximately 45-50%, 30-35% and 25-30% of baseline values in the 
10 mg/kg, 50 mg/kg and 200 mg/kg groups.  At all doses, evidence of recovery was observed by 
Day 281 (3 months after the last infusion) with levels recovering to within 80% of baseline levels 
by the end of the study (Day 358).  These effects were considered not adverse as no related 
changes were observed in other endpoints.   
In summary, no adverse test article-related effects have been seen in cynomolgus monkey 
following IV infusions of up to 200 mg/kg XmAb5871 every 14 days for up to 6 months.  These 
studies identified a no observed adverse effect level (NOAEL) of 200 mg/kg, the highest dose 
studied.  A detailed description of the non-clinical studies is presented in the XmAb5871 
Investigator’s Brochure.  
1.3 
Clinical Studies 
A FIH, single ascending dose study with XmAb5871 (XmAb5871-01) in healthy volunteers and 
a multiple ascending dose study in RA patients (XmAb5871-02) have been completed. 
1.3.1 A Randomised, Blinded, Placebo-Controlled, Single Ascending Dose 
Study of the Safety, Tolerability, and Pharmacokinetics of XmAb5871 
in Healthy Adult Volunteers 
In the FIH study, 48 healthy male subjects were enrolled and were randomized 3:1 
(XmAb5871:placebo) in a double-blind manner to receive a single IV infusion of XmAb5871 or 
matching placebo administered over a 2 hour period.  Thirty-six subjects received single IV 
infusions of XmAb5871 at dose levels of 0.03 mg/kg (N=3), 0.1 mg/kg (N=3), 0.2 mg/kg (N=7), 
0.6 mg/kg (N=6), 2.0 mg/kg (N=6), 5.0 mg/kg (N=6) and 10.0 mg/kg (N=5).  Twelve subjects 
received placebo.  All completed the study. 
XmAb5871 was generally well-tolerated at the doses investigated.  No subjects experienced a 
serious adverse event (SAE) or dose limiting toxicity and no subjects discontinued the study 
prematurely.  A total of 32/36 XmAb5871 subjects (88.9%) reported at least 1 
treatment-emergent adverse event (TEAE).  The percentage of patients who experienced TEAEs 
in the active treatment groups was similar to that of the subjects in the placebo group (11/12 
subjects [91.7%]).  The most common TEAEs were gastrointestinal-related: nausea, vomiting, 

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abdominal pain, abdominal discomfort, epigastric discomfort and diarrhea.  Such 
gastrointestinal-related TEAEs were reported by 14/36 (38.9%) XmAb5871 subjects, but no 
placebo subjects.  Symptoms were assessed as mild or moderate in severity in all except one 
subject, a subject in the 10.0 mg/kg XmAb5871 cohort who reported nausea of severe intensity.  
Eight subjects (22%) had their XmAb5871 IV infusion temporarily interrupted as a result of the 
infusion-related gastrointestinal symptoms.  These temporary suspensions occurred at doses of 
0.2 to 10.0 mg/kg.  All subjects were able to continue the infusion after a short interruption and 
symptoms did not recur.  No concomitant medication was required for relief of symptoms.  
There were no consistent trends in hematology, coagulation, clinical chemistry, immunoglobulin 
levels, electrocardiogram (ECG), or vital sign parameters reported. 
Pharmacokinetic analysis indicated that serum concentrations of XmAb5871 increased in an 
approximately dose-proportional manner and declined monophasically.  Clearance decreased 
with increasing dose approaching a constant value at the higher dose levels (0.6-10.0 mg/kg).  
The volume of distribution decreased with dose increment approaching a value that was similar 
to physiologic serum volume.  The half-life tended to increase with dose but was relatively 
constant at the four highest dose levels, averaging 3.63 +/- 1.24 days.  Circulating B cell CD19 
was completely saturated at all dose levels and there was a strong relationship between dose and 
time to recovery. 
Sixteen of 36 (44%) XmAb5871-treated subjects had at least one sample positive for ADA.  
Distinct evidence of ADA-mediated clearance of XmAb5871 occurred in only one ADA-positive 
subject (in the 5 mg/kg cohort) in whom an accelerated decline in XmAb5871 concentration was 
observed in the terminal portion of the concentration time curve.  All positive ADA samples 
were negative in a bioassay to detect neutralizing antibodies against XmAb5871. 
A dose-related reduction of CD20+ B cells followed XmAb5871 administration.  The nadir mean 
CD20+ B cell count, approximately 40% to 50% of baseline cell counts, occurred roughly 
between Day 4 and Day 8.  The degree of CD20+ B cell count reduction did not increase 
significantly as the dose of XmAb5871 increased.  The recovery of the B cell count 
approximated the observed kinetics of XmAb5871 clearance.  No association between the 
presence of the FcγRIIa R131 polymorphic allele and the CD20+ B cell count at nadir was 
observed.   
The expression of CD86 on B cells is a signaling pathway event downstream of the BCR.  At all 
doses evaluated, XmAb5871 suppressed the expression of CD86 in ex vivo stimulated B cells.  
This observation is consistent with the proposed mechanism of action of XmAb5871; namely, 

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down-regulation of the BCR signaling pathway.  XmAb5871 also attenuated the mean 
anti-tetanus toxoid (TT) response in subjects after a single administration at doses of ≥ 0.2 
mg/kg.  Additional information on the FIH study can be found in the Investigator Brochure. 
1.3.2 A 
Randomized, 
Placebo-Controlled, 
Double-Blinded, 
Ascending 
Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of XmAb5871 in Patients with Rheumatoid 
Arthritis 
A multiple ascending dose Phase 2a study has also been completed using investigational sites in 
Hungary, Poland, Slovakia and the Czech Republic.  This study enrolled RA patients who had 
active disease despite the use of disease modifying anti-rheumatic agents (DMARDS).  The 
completed Phase 2a study was enrolled in two parts:  
• Part A administered doses of XmAb5871 at 0.3, 1.0, 3.0 or 10.0 mg/kg or matching 
placebo (double-blind) by a 2-hour infusion for up to 6 consecutive doses given at 
2-week intervals.   
• Part B was an extension cohort of 10.0 mg/kg or placebo (2:1 randomization), 
administered up to 6 times at 2-week intervals.   
A total of 57 RA patients were enrolled in the study, 30 in Part A and 27 in Part B.  One patient 
discontinued the study before being dosed.  Twenty-two patients received XmAb5871 in Part A.  
Three patients received 6 doses of 0.3 mg/kg XmAb5871, 6 patients at each dose level received 6 
doses of 1.0, 3.0, and 10.0 mg/kg and one additional patient received 2 doses of 10.0 mg/kg 
before discontinuing the study.   
In Part B, 15 patients received 6 doses of 10.0 mg/kg XmAb5871 and 3 patients received 1-3 
doses each before discontinuing the study.  Across the study, a total of 223 doses of active drug 
were administered, of which 3 were partial infusions that were not completed.     
XmAb5871 was generally well-tolerated at doses investigated.  A total of 103 TEAEs were 
reported in 30/40 (75.0%) of the XmAb5871-treated patients.  Of these, 49 of the 103 TEAEs 
(47.6%) were regarded as unrelated or unlikely to be related to administration of XmAb5871.  
As seen in the FIH study, the most common treatment-related AEs in the XmAb5871 groups 
were nausea, vomiting and diarrhea that occurred during the first infusion in 10 of the 40 
XmAb5871-treated patients (25%).  The gastrointestinal symptoms were generally mild to 
moderate, with vomiting of severe intensity reported by only one patient (10.0 mg/kg 
XmAb5871).  Nine patients (23%) had their first XmAb5871 IV infusion temporarily interrupted 

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as a result of the infusion-related gastrointestinal symptoms (vomiting/nausea or diarrhea).  
Seven of the 9 (78%) occurred in the 10.0 mg/kg cohort.  In all cases, the patients were able to 
continue the infusion after a short interruption (5-31 minutes) and symptoms did not in general 
recur on continuation of the infusion or during subsequent infusions.  There were no consistent 
trends in hematology, coagulation, clinical chemistry, immunoglobulin levels, electrocardiogram 
(ECG), or vital sign parameters reported.  
A total of two XmAb5871 treatment-emergent SAEs in 2 patients were reported during the phase 
2a study, both in the 10.0 mg/kg XmAb5871 group.  One case of lower extremity deep venous 
thrombosis occurred during the follow-up period, 22 days after the last infusion.  The SAE was 
considered to be possibly related to XmAb5871 by the investigator, but because the onset of the 
event occurred more than 6 half-lives after the last infusion of study drug, the Sponsor 
considered the event unlikely to be related to XmAb5871.  The other SAE was a case of 
infusion- related reaction that occurred at the time of the second infusion of XmAb5871 and was 
assessed to be definitely related to the administration of XmAb5871 by the investigator.  A 
second patient also experienced an infusion-related reaction with hypotension (non-SAE) of 
moderate severity during the first infusion.  Both were on the 10.0 mg/kg dose and were 
discontinued from the study.  The nature and severity of these infusion-related reactions were 
consistent with those reported for other monoclonal antibody therapies.  
Pharmacokinetic analysis indicated that serum concentrations of XmAb5871 decreased roughly 
monophasically over time.  The Cmax for the first and last dose increased in a manner slightly 
greater than proportional to the dose.  The AUC for the first and last dose increased 
proportionally to the dose increment.  At the dose levels studied, neither clearance nor volume of 
distribution showed any significant dependence on dose following either the first or last 
administration.  There was little accumulation between the first and last doses with the 2-week 
dosing interval. 
Across all 4 dose levels, last dose clearance averaged 15.16 ± 3.68 mL/day/kg.  The last dose 
volume of distribution averaged 49.27 ± 14.17 mL/kg.  This figure is close to the literature value 
for physiological serum volume.  The last dose half-life averaged 3.51 ± 1.06 days.  There was 
no statistically significant difference in clearance or volume of distribution between any of the 
receptor alleles for either FcγRIIa or FcγRIIb. 
Complete CD19 receptor occupancy was seen at doses of 1.0, 3.0, and 10.0 mg/kg from first 
dose through the completion of dosing.  The peripheral B cell count decreased in all cohorts 
following the first dose, with cohort mean levels in the range of 52-79% of baseline.  The level 

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of reduction did not increase with increasing dose or with subsequent doses and recovered to a 
mean cohort level of ≥ 80% of baseline levels occurred during the post-treatment period. 
Samples positive for anti-drug antibodies (ADA) were found in 7 of 40 (17.5%) XmAb5871-
treated patients and in 1 of 16 (6.25%) placebo-treated patients.  With the exception of the 
placebo-treated patient, all of the ADA were observed in the 10.0 mg/kg group.  Only 2 of the 7 
patients had positive ADA samples that remained positive after a >2-fold dilution (i.e., most 
were of low titer).  One of these 2 patients experienced apparent hypersensitivity reactions with 
vomiting, fever and chills during the second infusion and vomiting, fever, and erythema during 
the third infusion.  This was associated with the development of ADA at the time of second 
infusion with increasing titer ADA thereafter.  There was no distinct evidence of ADA-mediated 
clearance of XmAb5871 in any ADA positive patient. 
In Part B of the study, more patients treated with XmAb5871 (10.0 mg/kg) achieved 
DAS28-CRP low disease or remission at Day 85 than did the placebo treated patients (5/15 vs 
0/8; 33% vs 0%).  In addition, 40% (6/15) of the XmAb5871-treated patients achieved an 
ACR50 and 20% (3/15) achieved an ACR70.  By comparison, only 12.5% (1/8) and 0% (0/8) of 
the placebo treated patients achieved ACR50 and ACR70 responses, respectively.  
In Part A of the study, all cohorts treated with XmAb5871 at any dose tested (0.3, 1.0, 3.0, or 
10.0 mg/kg) achieved higher percentages of DAS-CRP low disease or remission at Day 85 than 
did the placebo-treated patients. For example, in the 0.3 mg/kg group (n=3), there were 33% 
DAS28-CRP remissions, 100% ACR20, 33% ACR50 and 33% ACR70 responses vs 14%, 29%, 
14% and 0% in the placebo group (Part A).   
Data collected during the Phase 2a study confirms that XmAb5871 binds as intended to the 
circulating B cell CD19 receptor and a beneficial trend towards reducing RA disease activity was 
observed.   
The Sponsor will immediately notify the Principal Investigator if any additional safety or 
toxicology information becomes available during the study.  A detailed description of the 
completed clinical studies is presented in the XmAb5871 Investigator’s Brochure. 
1.4 
Rationale for the Clinical Study 
The presumed role of B cells and plasmablasts in IgG4-RD and the preliminary observation of an 
effect on IgG4-RD disease activity by B cell depletion therapy support the evaluation of 
non-depleting B cell-directed therapies such as XmAb5871.  The proposed dose and dosing 

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regimen is based on available data from the non-clinical pharmacology and toxicology studies 
and available data from the completed human studies.  
The GLP 6-month, repeat-dose toxicity study in cynomolgus monkeys consisted of 13 infusions 
administered every other week, a dosing schedule and duration matching that of the proposed 
pilot study of XmAb5871 in human patients with IgG4-RD.  The maximum dose administered 
and the NOAEL in the cynomolgus monkey study was 200 mg/kg.  XmAb5871 was generally 
well-tolerated when given at doses up to 10.0 mg/kg every other week for 6 doses in patients 
with RA (see above), and there was no evidence of any cumulative toxicity over the 6 doses.  
Complete CD19 receptor occupancy was observed in the repeat dose RA study at doses of 1.0, 
3.0, and 10.0 mg/kg from first dose through the completion of dosing.  Trends in improvement in 
RA clinical disease activity were seen at all doses, particularly at 3.0 and 10.0 mg/kg.  Based on 
the observed safety and tolerability profile, the effects on CD19 receptor occupancy and effects 
on disease activity in the RA trial, a dose of 5 mg/kg has been selected for this study.  
1.4.1 Risk-Benefit Assessment 
The risks and benefits for the use of XmAb5871 are currently assessed by the available 
non-clinical data and the information from studies completed in humans.  The preclinical data to 
date indicate that XmAb5871 was well-tolerated in the cynomolgus monkey, the most relevant 
single toxicology species.  Both 12-week and 6-month repeat dose GLP toxicity evaluations have 
been performed in cynomolgus monkey.  No deaths occurred and no test article-related effects 
were identified in clinical observations, body weight, electrocardiography and ophthalmology 
assessments, urinalysis, hematology, serum chemistry and coagulation parameters, or  in 
anatomic evaluations (gross and microscopic).  At doses up to 200 mg/kg in the 6-month study, 
mean absolute and relative counts of B lymphocytes were observed to be decreased, relative to 
baseline levels, in a dose-related manner.  B cell counts demonstrated recovery at day 281, and 
this recovery was sustained at day 358.  
The differences between the binding affinities for XmAb5871 to human and cynomolgus 
monkey FcγRs should be considered in light of the toxicology results.  The affinity of 
XmAb5871 for cynomolgus monkey FcγRIIb is approximately 250-fold less than that for human 
FcγRIIb.  Although the desired pharmacologic effect was observed in cynomolgus monkey (i.e., 
down-regulation of BCR mediated B cell signaling), target-mediated toxicity may be more 
difficult to observe in the cynomolgus monkey than in humans.  No significant toxicities have 
been observed in either of the two completed human studies, however, suggesting that the 
toxicology species is informative.  

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The observed reduction in absolute B cell count (ABC) in both the human studies may have 
occurred from the result of redistribution of B cells from the circulation to central compartments, 
from direct anti-proliferative effect of CD19 engagement, or from the inhibition of the B cell 
pro-survival effects induced by BCR signaling.  These possibilities are not mutually exclusive.  
B cell counts can be monitored readily in clinical laboratories and the safety impact of even a 
substantial B cell reduction is considered minimal given the degree to which complete B cell 
depletion with rituximab is tolerated.  The toxicity and pharmacologic action of B cell depletion 
is now understood well from years of clinical experience with primary B cell- depleting agents 
such as rituximab.  Even the complete absence of detectable circulating B cells is regarded as a 
manageable safety risk in humans.  Both the toxicology and human studies of XmAb5871 have 
indicated the reductions in B cell concentration are reversible following discontinuation of the 
study drug.  
Both clinical studies completed to date have been randomized, double-blinded, placebo 
controlled studies with a primary endpoint of safety and tolerability.  Therefore, the clinical 
benefit of XmAb5871 has not been established.  The Phase 2a trial in RA was not powered for 
efficacy, but trends in improvement in RA disease activity among the XmAb5871-treated 
patients compared to those treated with placebo were observed. 
1.4.2 Potential Risks 
Based on preclinical toxicology studies, experience in human studies to date and class effects of 
immunomodulating monoclonal antibodies, patients receiving XmAb5871 may be at risk for the 
following adverse events: 
1.4.2.1 
Infusion-Related Reactions 
All monoclonal antibody therapeutics are associated with the risk of both allergic 
(hypersensitivity) and non-allergic (cytokine release syndrome) infusion-related reactions.  Most 
infusion-related reactions are mild and may be alleviated by interruption of the infusion and 
reinitiating the infusion at a slower infusion rate after symptoms abate.  
No signs or symptoms of infusion-related reaction were observed in the FIH study.  Two subjects 
in the multiple dose Phase 2a study, both of whom had received XmAb5871 at 10.0 mg/kg, 
experienced infusion-related reactions with hypotension and were discontinued from the study.  
The first patient experienced a severe infusion-related reaction on the second infusion; the 
second patient’s infusion-related reaction was considered moderate and occurred during the first 
infusion.  In both cases, the infusion was stopped and symptomatic therapy given.  The 

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symptoms responded quickly and there were no sequelae.  The nature and severity of the 
infusion reactions were consistent with those reported for other monoclonal antibody therapies.  
In addition, a third patient developed signs and symptoms of a hypersensitivity reaction during 
the second and third infusions, associated with the development of an ADA response with titers 
that increased over time.  This patient was also discontinued from the study and also recovered 
without sequelae. 
Although observed rarely, severe infusion-related reactions, including deaths following the 
administration of otherwise well-tolerated monoclonal antibody therapies, have been reported.  
Patients should be closely monitored during and after all infusions as specified in the study 
protocol.  In the case of an infusion reaction, the infusion should be stopped immediately and the 
patient managed as per the treatment guidelines listed in Section 6.1.2.3.6.   
All investigators should be well trained in the management of acute infusion-related events 
including administration of epinephrine and other therapeutic modalities.  Emergency 
resuscitation equipment and medications should be present for immediate use in the area where 
patients are receiving their infusions.   
Patients should be monitored closely during and after infusion.  XmAb5871 should be 
administered intravenously at a constant rate over a 2 hour period for the first infusion and over a 
1-2 hour period for subsequent infusions.  Patients will be assessed continuously during the 
infusion and for at least 1 hour following the end of infusion (2 hours following the first 
infusion).  During the first infusion, vital signs including blood pressure, heart rate, respiratory 
rate and temperature assessments will be performed within 2 hours before the infusion, at 15, 30, 
60 and 120 minutes after the start of infusion, and at the end of infusion (if different than 120 
minutes from start of infusion).  In addition, vital signs will be performed 15, 30, 60 and 120 
minutes after end of the first infusion.  
The frequency of vital sign monitoring will be modified slightly at subsequent infusions if the 
first infusion is tolerated well.  At all subsequent infusions,  vital signs will be assessed within 2 
hours before the infusion, at 30 and 60 minutes after the start of infusion, at the end of infusion 
(if different than 60 minutes from start of infusion), and at 30 and 60 minutes after end of the 
infusion. 
1.4.2.2 
Infusion Associated Gastrointestinal-Related Toxicity 
The most common XmAb5871 AEs reported in both clinical studies have been the occurrence of 
nausea, vomiting, or diarrhea during the first XmAb5871 infusion.  In the FIH study, 8 patients 

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(over the dose range 0.2 mg/kg to 10.0 mg/kg) had their XmAb5871 IV infusion interrupted 
temporarily because of the self-limited gastrointestinal-related symptoms of short duration 
(abdominal discomfort, abdominal pain, epigastric discomfort, nausea and vomiting).  In all 
cases, the patients were able to continue the infusion after a short interruption (maximum total 
infusion duration was 2 hours and 54 minutes) and symptoms did not recur.  No concomitant 
medication was required for alleviation of symptoms. 
In the Phase 2a study, 9 patients (23%) had their first XmAb5871 IV infusion temporarily 
interrupted as a result of the gastrointestinal-related symptoms (nausea, vomiting or diarrhea).  
Seven of the 9 (78%) occurred in the 10.0 mg/kg cohorts.  In all cases, the patients were able to 
continue the infusion after a short interruption (5-31 minutes) and symptoms did not generally 
recur on continuation of the infusion or during subsequent infusions.  No concomitant 
medication was required for alleviation of symptoms. 
The etiology of these symptoms is not clear.  There are no known associations of CD19 or 
FcγRIIb and the gastrointestinal tract.  Mild to moderate nausea, vomiting or diarrhea may occur 
during the first infusion of XmAb5871 and should be treated by interrupting the infusion for 15-
30 minutes.  The infusion may be restarted at the original rate once symptoms have resolved.  
Medication for symptomatic relief may be administered if required.  
1.4.2.3 
B-Cell Lymphopenia 
B cell lymphopenia, with no notable effect on the total lymphocyte count, was observed in both 
nonclinical toxicology and clinical studies.  In cynomolgus monkey, reversible reductions in B 
cell levels were observed in the two repeat-dose GLP toxicology studies performed to date.  In 
both the 12-week (six infusions at doses up to 50 mg/kg) and 6-month (13 infusions at doses up 
to 200 mg/kg) toxicology studies in which XmAb5871 was administered IV every two weeks, 
reductions in cohort mean B cell count were observed. In the 12-week study, the B cell count 
was reduced to approximately 45-50%, 30-35% and 25-30% of baseline values in the 10 mg/kg, 
50 mg/kg and 200 mg/kg groups.  At all doses, evidence of recovery was observed by Day 281 
(3 months after the last infusion).   
In both clinical studies performed to date, reversible reductions in ABCs were observed.  The 
ABCs declined to 50-60% of baseline levels, with a maximum individual subject reduction to 
22% of baseline.  In both studies, the reductions in ABC were not associated with the presence of 
the FcγRIIa R131 genotype and were not associated with clinical adverse events.  

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The recovery of B cell counts after a single dose or multiple doses of XmAb5871 approximated 
the kinetics of the clearance of XmAb5871 from serum in the clinical studies.  Prolonged 
reductions in B cell counts to the extent seen with B cell depleting therapies have not been 
observed and are not expected with XmAb5971.  B cell depleting therapies have been widely 
used both in hematologic malignancies and in autoimmune diseases.  Toxicity and 
pharmacologic action of B cell depletion is well understood and is a manageable risk in humans.  
Patients will be monitored with quantitation of B cell counts during the trial.  
1.4.2.4 
Infections 
XmAb5871 is an immunomodulating agent by virtue of its effect on down regulation of B cell 
function.  No severe or opportunistic infections have been observed in cynomolgus monkey 
toxicology studies or in the XmAb5871 clinical program to date.  However, all patients receiving 
any immunomodulating agent should be monitored for the development of infections, including 
those caused by bacterial, viral and fungal pathogens. 
1.4.3 Potential Benefits 
The primary purpose of the study is to evaluate the effect of XmAb5871 on the disease activity 
of IgG4-RD.  Based on the effect of XmAb5871 on B cell function observed in in vitro, in vivo, 
and clinical studies and on the trends in improvement in RA disease activity observed, some 
IgG4-RD patients may experience improvement in disease activity. 
1.4.4 Conclusion 
XmAb5871 is being developed for the treatment of autoimmune disease including IgG4-RD.  An 
open-label pilot trial to evaluate effects on disease activity is proposed.  Given the established 
role of B cells in the pathogenesis of IgG4-RD and the effects of XmAb5871 on B cell function, 
XmAb5871 may provide an attractive therapeutic option for this condition.  There is presently no 
FDA-approved therapy for the treatment of IgG4-RD.    
The design of the proposed trial contains measures appropriate to the mitigation of risk factors 
for adverse events.  Furthermore, frequent safety monitoring is an inherent part of the protocol.  
In summary, the benefits and risk assessment for the application of XmAb5871 appears 
favorable and supportive for initiation of the proposed clinical trial. 
This study will be performed in compliance with the protocol, International Conference on 
Harmonization (ICH) Good Clinical Practice (GCP) and applicable regulatory requirements.  

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Aspects of the study concerned with the investigational medicinal product(s) (IMPs) will meet 
the requirements of standard Good Manufacturing Practice (GMP). 
2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
• To evaluate the effect of every other week intravenous (IV) administration of  XmAb5871 on 
the IgG4-RD Responder Index (RI) in patients with active IgG4-RD 
2.2 
Secondary Objective 
• To evaluate the safety and tolerability of every other week IV administration of XmAb5871 
in patients with active IgG4-RD  
• To evaluate the pharmacokinetics (PK) and immunogenicity of every other week IV 
administration of XmAb5871 in patients with active IgG4-RD  
2.3 
Exploratory Objectives 
• To characterize the pharmacodynamics (PD) of every other week IV administration of 
XmAb5871 in patients with active IgG4-RD, as follows: 
 To evaluate the effect of XmAb5871 on changes in the absolute B cell count (ABC) 
 To evaluate the effect of XmAb5871 on changes in serum IgG4 and IgE concentration 
 To evaluate the effect of XmAb5871 on changes in the circulating plasmablast count, 
changes in plasmablast markers of apoptosis, and changes in plasmablast gene expression 
 To evaluate the effect of XmAb5871 on changes in 18F FDG PET/CT imaging in patients 
with active IgG4-RD 
3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
This is an open-label, single-arm, multiple-dose study to investigate the effect of XmAb5871 on 
disease activity, safety, tolerability, PK, immunogenicity and PD of XmAb5871 in patients with 
active IgG4-RD.  The study will be conducted in centers with expertise in this disease.    
The first 15 patients enrolled will receive 5.0 mg/kg of XmAb5871 infused IV over 1-2 hours on 
an every other week dosing schedule for up to a total of 12 doses.  Up to six additional patients 

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may be enrolled and treated with either 90 mg fixed dose or 180 mg fixed dose by IV infusion 
every other week. Patients will be followed for 6 weeks after the final infusion.  Up to 21 
patients will be enrolled. 
After obtaining informed consent, all screening procedures and tests establishing eligibility will 
be performed within a period of 28 days before dosing.  Patients determined to be eligible at 
screening will return to the study site on Day 1, at which time baseline procedures such as 
physical examination and the collection of blood and urine samples will be performed.  Eligible 
patients will be administered XmAb5871 as an IV infusion over a 2 hour infusion period at a 
dose of 5 mg/kg.  Patients will be observed for at least 2 hours after the first administration, 
during which time safety assessments will be performed.   
All patients will return to the study site on Day 8 for safety, PK and PD assessments.  Patients 
will return on study Days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141 and 155 for XmAb5871 (5 
mg/kg) administration over a 1-2 hour infusion period and for safety, PK and PD assessments as 
outlined in Table 6: Schedule of Assessments.  Patients will be required to remain at the study 
site for observation for at least 1 hour after the completion of each infusion.  Post-treatment visits 
for safety, PK and PD will occur on Days 169 and 197/EOS. 
Based on preliminary data in this study showing reduction of IgG4-RD disease activity following 
treatment with XmAb5871 at 5 mg/kg every 2 weeks and based on data from a previous study in 
patients with active rheumatoid arthritis suggesting activity at doses as low as 0.3 mg/kg, the 
study has been amended in this protocol version in order to explore the treatment effect of lower 
doses of XmAb5871. Following enrollment of the first 15 patients (treated at 5 mg/kg every 
other week), approximately 3 additional patients will be treated with a fixed dose of 90 mg of 
XmAb5871 given IV every other week. A second set of up to 3 additional patients may be 
treated with either 90 mg or 180 mg of XmAb5871. At the discretion of the Investigator and 
Sponsor, subjects dosed at 90 mg of XmAb5871 may have their dose increased to 180 mg if 
there has been an inadequate clinical response to therapy. All study procedures will remain the 
same for these patients except for the administration of a lower dosage of XmAb5871.  The dose 
for the 90 and 180 mg dose subjects will be administered over a 1 hour period at a constant 
rate.All patients completing the treatment period will be followed through at least D197/EOS (or 
for 6 weeks following the last infusion for early termination).  Patient participation is complete 
once EOS study procedures are performed.  
Signs and symptoms of IgG4-RD disease activity will be measured periodically throughout the 
study using a modification of the IgG4-RD RI (Carruthers et al. 2012).  The IgG4-RD RI is 

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based on the Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (Stone et al. 
2001) utilized for the evaluation and licensure of rituximab in ANCA-associated vasculitis 
(Stone et al. 2010).  The IgG4-RD RI is an instrument designed to detect change in disease 
activity and identify improvements and worsening in the same or different organ systems and has 
been used in a prior clinical trial to monitor IgG4-RD disease activity (Khosroshahi et al. 2010, 
Carruthers et al. 2015).  18FDG PET/CT imaging, which has been reported to have disease 
activity monitoring utility in IgG4-RD (Matsubayashi et al. 2009), will be obtained at baseline 
and after 3 and 6 months of therapy as an exploratory measure of disease activity. 
All AEs, including serious AEs and deaths and information about concomitant medication use, 
will be collected throughout the study from screening through the EOS visit.  Patients developing 
treatment-emergent AEs or clinically significant safety lab abnormalities will be followed until 
such abnormalities have resolved or stabilized.  
Assessments will include AE assessment, physical examination, vital signs, ECG, clinical 
laboratory tests (hematology, clinical chemistry, B cell and T cell levels, immunoglobulin levels, 
urinalysis, coagulation, PK, PD and immunogenicity).   
Pharmacodynamics of XmAb5871 will be evaluated by serial measurements of IgG and IgE, by 
enumeration of circulating B cells and plasmablasts, and by evaluation of markers of plasmablast 
apoptosis and gene expression.  
In addition, FcγRIIa and FcγRIIb genotypes will be determined. 
Patients may also consent to optional predose and/or postdose biopsy of involved tissue(s). 
Please refer to Table 6: Schedule of Assessments for a detailed list of procedures performed on 
each study day/visit.  
3.2 
Discussion of Study Design 
In this study, all patients will receive the active investigational medicinal product XmAb5871.  
Because this is an open-label pilot Phase 2 study to investigate the effect of XmAb5871 on 
IgG4-RD disease activity, an appropriate sample size cannot be determined on a statistical basis, 
owing to the absence of adequate information to perform formal sample size calculations.  The 
sample size has been selected to provide information on safety, tolerability, PK, efficacy and PD 
following multiple doses of XmAb5871.  The study is designed to obtain preliminary 
information on the effect of XmAb5871 on IgG4-RD disease activity and safety of XmAb5871 
in IgG4-RD before the initiation of a randomized, double blind placebo controlled study in this 
disease. 

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3.3 
Selection of Patient Population 
Up to 21 evaluable patients will be enrolled in the study.  The sample size chosen for this study 
was based upon precedent set by other pilot studies of similar nature and was not based on power 
calculations.  The sample size is based primarily on feasibility and the desire to gain efficacy and 
safety information to support the design of randomized, placebo-controlled trials. 
3.4 
Endpoints 
The study involves assessments of disease activity, safety, immunogenicity, PK, PD and 
pharmacogenomics.  The specific endpoints are listed below. 
3.4.1 Disease Activity 
Primary outcome measure will be the proportion of patients on Day 169 with an improvement of 
disease activity as defined by a decrease of IgG4-RD RI ≥ 2 points from Day 1 pre-dose disease 
activity score.  
 In addition, the proportion of patients with 1) a decline of the IgG4-RD RI of ≥ 2 points 
compared to baseline (Day 1), 2) no disease flares during the study, and 3) no glucocorticoid use 
between months 2 and 6 will be determined.  Disease flare is defined as increase in the IgG4-RD 
RI of ≥ 2 and/or the need for increase in steroids or institution of additional therapy for IgG4-
RD.  
The proportion of patients with disease improvement at any time and the duration and the degree 
of improvement in IgG4-RD RI will also be examined.   
The following disease parameters will be measured: 
• IgG4-RD Responder Index (RI)  
• Physician Global Assessment of Disease Activity (Visual Activity Score)  
• Patient Global Assessment of Disease Activity (Visual Activity Score) 
• 
18F FDG PET/CT imaging  
3.4.2 Mechanistic Studies 
Blood will be collected for mechanistic studies at pre-dose baseline and at multiple time points 
during the treatment and follow-up phases.  These studies may include the following: 
enumeration of plasmablast levels; quantification of levels of B cell activation markers on B 

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cells; total multi-parametric peripheral blood white cell population analysis by Cytof mass 
cytometry (at the Ragon Institute); analysis of plasmablasts for markers of apoptosis and 
activation by flow cytometry and by RNA-seq before and after therapy.  The results from these 
studies may be reported separately from the clinical study report. 
3.4.3 Safety Endpoints 
Secondary outcome measures will include patient incidence of TEAEs and clinically significant 
changes in safety laboratory tests, physical examination findings, vital signs, and ECGs. 
Safety and tolerability will be assessed with the following: 
• Adverse event assessments 
• Vital signs (supine blood pressure [BP], heart rate, oral body temperature, respiratory rate 
[RR]).  During the infusion of XmAb5871, vital signs will be obtained in the semi-supine 
siting position 
• Twelve-lead electrocardiograms (ECG): PR interval, QRS interval, RR interval, QT 
interval, and QTc interval (Bazett’s correction [QTcB] and Fridericia’s correction 
[QTcF])  
• Clinical laboratory testing (hematology, coagulation, clinical chemistry, and urinalysis) 
• B cell and T cell quantification by flow cytometry 
• Concomitant medication assessments 
• Physical examinations 
• Serum immunoglobulin (Ig) levels (IgG, IgM, IgE, IgA, IgG1-4) 
• Complement levels C3 and C4 
• Monitoring for pregnancy in women of child-bearing age only 
3.4.4 Immunogenicity Endpoint 
Frequency and titer of anti-XmAb5871 antibodies (anti-drug antibodies [ADA]) 
3.4.5 Pharmacokinetic Endpoints 
Pre-dose (trough) and end-of-infusion (peak) XmAb5871 serum concentrations will be measured 
on selected study days.  No PK parameters will be computed because no extensive serial post-
dose sampling will be done in this study. 

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3.4.6 Pharmacodynamic Endpoints 
• Absolute B cell counts (ABC)  
• Serum IgG4 and IgE concentration 
• Number of circulating plasmablasts 
• Markers of plasmablast apoptosis and gene expression 
3.4.7 Pharmacogenomics Endpoints 
• FcγRIIa R131H polymorphism 
• 
FcγRIIb I232T polymorphism 
3.5 
Stopping Criteria for the Clinical Study 
Participation for any individual patient will be stopped if the patient experiences a possibly 
drug-related serious adverse event (SAE) or a possibly drug-related significant non-serious AE, 
which in the opinion of the PI or Sponsor’s medical representative, warrants discontinuation of 
the patient in the study in the interest of that patient’s well-being.  Discontinuation of the patient 
from the study will be discussed with the Sponsor. 
The Investigator will make all appropriate safety assessments on an ongoing basis.  The 
Sponsor’s medical representative will review individual safety information as it becomes 
available throughout the study.   
Enrollment will be suspended if ANY of the criteria listed below are met.  If the study is 
suspended due to meeting any of the criteria below, it may only be restarted after review and 
agreement by the PI and Sponsor.  
• The occurrence of 2 or more SAEs that are assessed as drug-related  
• The occurrence of a severe AE, assessed as related to the study drug, of similar origin in 3 or 
more patients   
3.6 
Dose Delay and Dose Modification in Patients Who Experience Toxicity 
Patients experiencing a ≥Grade 2 drug-related hematologic or non-hematologic toxicity will have 
subsequent dosing held until recovery to baseline or ≤Grade 1 values following the AE.  Patients 
who enter the study with pre-existing disease-related abnormalities of >Grade 1 will have 
subsequent dosing held if there is drug-related worsening to Grade 3 until recovery to baseline or 
≤Grade 1 values following the worsening.  

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In the event that drug-related toxicity persists for >21 days or such that two consecutive doses 
are missed, the subject will be permanently discontinued from the study drug treatment.   
There will be no dose level modification in this study.  
4 
STUDY POPULATION 
The study population will consist of male and female patients with histopathologically proven 
IgG4-RD and activity in one or more organ systems AND with an IgG4-RD RI of ≥3.  Patients 
are not required to have failed prior therapy for their disease to be eligible for this study. 
Patients with disease in only one organ system whose primary manifestation is fibrosis will be 
excluded.  Patients must be able to provide written informed consent and meet all the inclusion 
criteria and none of the exclusion criteria. 
4.1 
Number of Patients 
Up to 21 evaluable patients will be enrolled in the study.  The sample size is based on practical 
considerations and is consistent with the goals of this phase 2 pilot study. 
4.2 
Inclusion Criteria 
Patients who meet the following criteria will be considered eligible to participate in the clinical 
study if they: 
1. Are male or female between 18 to 80 years of age, inclusive. 
2. Have active disease based on an IgG4-RD RI ≥3 and may or may not have received prior 
IgG4-RD therapy. 
3. Have a compatible pattern of organ involvement consistent with IgG4-RD that cannot be 
attributed to other causes. 
4. Have a histopathologically-proven diagnosis of IgG4-RD: at least two out of the three major 
features of lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis.  
5. Have a peripheral blood plasmablast count of > 900 cells/mL and/or an elevated IgG4 level 
during screening. 
6. Are judged by the investigator as likely to be able to discontinue any baseline prednisone 
within two months of enrollment.  

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7. History of a negative test result for HIV I and II antibody, hepatitis B surface antigen, 
hepatitis B core antibody and hepatitis C antibody within 60 days before first dose of 
XmAb5871.   
8. Are able and willing to complete the entire study according to the study schedule. 
9. Are willing to forego other forms of experimental treatment during the study. 
10. Are able to provide written informed consent. 
4.3 
Exclusion Criteria 
Patients who meet one or more of the following criteria will not be considered eligible to 
participate in the clinical study: 
1. History or evidence of a clinically unstable/uncontrolled disorder, condition or disease 
(including but not limited to cardiopulmonary, oncologic, renal, hepatic, metabolic, 
hematologic or psychiatric) other than IgG4-RD that, in the opinion of the Investigator would 
pose a risk to patient safety or interfere with the study evaluation, procedures or completion. 
2. Malignancy within 5 years (except successfully treated in situ cervical cancer, resected 
squamous cell or basal cell carcinoma of the skin, or prostate cancer with no recurrence 
≥3 years following prostatectomy). 
3. Presence of recurrent or chronic infections, defined as ≥3 infections requiring antimicrobials 
over the past 6 months prior to screening. 
4. Active infection requiring hospitalization or treatment with parenteral antimicrobials within 
the 60 days prior to randomization or oral antimicrobials  within the 21 days prior to 
enrollment. 
5. Patient is taking > 40 mg of prednisone QD (or the equivalent, refer to Table 1) 
6. Prior use of rituximab (or other B cell depleting agents) within 3 months of enrollment.  Prior 
use of any B cell depleting agent greater than 3 months from enrollment is allowed if 
circulating plasmablasts are ≥ 900 cells/mL. 
7. Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life 
is unknown) prior to enrollment. 
8. Immunosuppressive agent use within the three months prior to enrollment (e.g. methotrexate, 
mycophenolate mofetil, 6-mercaptopurine, tacrolimus, cyclophosphamide or azathioprine).  
9. White blood cell count < 2.5 x 103/µL. 

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10. Absolute neutrophil count (ANC) < 1.0 x 103/µL. 
11. Elevated serum creatinine > 1.5 x ULN, unless the decline in renal function is known to be 
caused by IgG4-related renal disease in which case serum creatinine must not be 
>2.0 x ULN.  
12. Hemoglobin < 10 g/dL. 
13. Platelet count < 75,000 x 109/L. 
14. Has received live vaccines within 2 months of enrollment. 
15. Inability to communicate reliably with the investigator. 
16. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the 
study, up to EOS visit. 
17. Positive pregnancy test at screening or during the study. 
18. Subjects who do not agree to use medically acceptable methods of contraception (as defined 
in Section 5.10.2). 
19. Male patient with a pregnant partner who is not willing to use a condom during the treatment 
and up to EOS visit.  
20. Known or suspected sensitivity to mammalian cell-derived products or any components of 
the study drug. 
21. History of alcohol and/or substance abuse within 12 months prior to screening. 
22. Unable or unwilling to partake in follow-up assessments or required protocol procedures. 
4.4 
Subject Withdrawal and Replacement 
Patients are encouraged to complete all study evaluations.  However, they may withdraw from 
the study at any time and for any reason.  Every effort will be made to determine why any 
subject withdraws from the study prematurely.  All patients who withdraw from the study with 
an ongoing AE must be followed until the event is resolved or deemed stable.  At the time that a 
patient withdraws prematurely for any reason, all assessments as listed for the Day 169 visit 
should be performed. In addition, the patient should be scheduled for a follow-up visit 6 weeks 
from the time of the last infusion of study drug, at which time all assessments as listed for the 
Day 197/EOS visit should be performed. If a subject withdraws prematurely after dosing, all data 
to be collected prior to discharge from the clinical site will be collected at the time of premature 

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discontinuation or at the scheduled end of study visit.  Subject participation may be terminated 
prior to completing the study and the reason recorded as follows:  
1. Adverse event 
2. Protocol violation 
3. Loss to Follow-up 
4. Subject withdrew consent  
5. Other 
A comprehensive effort must be made to determine the reason(s) why a subject fails to return for 
the necessary visits or is discontinued from the study.  If the subject is unreachable by telephone, 
a registered letter, at the minimum, should be sent to the subject requesting him/her to contact the 
study site.   
Patients withdrawn due to AEs considered to have a possible relationship to study drug will not 
be replaced.  Patients withdrawn for a non-drug related reason will be replaced if deemed 
necessary by the Sponsor.  The decision regarding the replacement of patients will be 
documented. 
4.5 
Termination of the Clinical Study 
If the Investigator or the Sponsor becomes aware of conditions or events that suggest a possible 
hazard to patients if the clinical study continues, then the clinical study may be terminated after 
appropriate consultation among the involved parties.  The clinical study may be terminated at the 
Sponsor’s discretion also in the absence of such a finding. 
Conditions that may warrant termination of the clinical study include, but are not limited to: 
• The discovery of an unexpected, relevant, or unacceptable risk to the patients enrolled in the 
clinical study; 
• Failure to enroll patients at the required rate; 
• A decision of the Sponsor to suspend or discontinue development of the IMP.   
Should the study be terminated and/or the site closed for whatever reason, all documentation 
pertaining to the study and IMP must be returned to the Sponsor.  Any actions required for 
assessing or maintaining study patient safety will continue as required, despite termination of the 
study by the Sponsor. 

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5 
INVESTIGATIONAL MEDICINAL PRODUCT 
5.1 
Identity of the Investigational Medicinal Products 
XmAb5871, the IMP, is an Fc engineered humanized mAb that binds to human CD19.  
XmAb5871 contains a modified IgG1 heavy chain Fc region that contains two amino acid 
substitutions in the Fc portion of the heavy chain that results in an increase in affinity to FcγRIIb 
binding relative to the native IgG1 Fc.  
XmAb5871 drug product (DP) will be a sterile liquid product supplied in single-use glass vials.  
Each 10 mL glass vial is filled with 10.5 mL of drug product that contains 10 (+/-5%) mg/mL of 
XmAb5871, 10 mM sodium phosphate, 150 mM sodium chloride and 0.01% (w/v) polysorbate 
20 at pH 7.2.   
Active substance: XmAb5871 
Activity: Humanized anti-CD19, Fc (fragment, crystallizable) engineered mAb with enhanced 
binding to FcγRIIb 
Tested indication: IgG4-RD 
Strength: 10 (+/-5%) mg/mL 
Dosage form: Solution for infusion  
Route of administration: IV infusion 
5.2 
Drug Storage and Handling Requirements 
All study medication should be maintained in a storage area of the Pharmacy in a secure, 
temperature controlled, locked environment with restricted access.  XmAb5871 DP must be 
stored under refrigeration at 2 to 8oC (+/- 5oC).  Prior to administration, XmAb5871 DP should 
be removed from storage temperature conditions and allowed to equilibrate to room temperature.  
Undiluted XmAb5871 is stable for up to 24 hours at room temperature; however Xencor must be 
notified if the drug product is left at room temperature for more than 8 hours.  XmAb5871 should 
be mixed by swirling the vial gently before diluting to the dosing solution.  DO NOT SHAKE; 
excess agitation may cause aggregate formation and foaming.   
For the first 15 patients, the full calculated dose will be administered based on the patient’s Day 
1 weight.  The administered dose will be adjusted on subsequent infusion days ONLY if the 

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weight on the infusion day differs more than 10% from the weight on Day 1.  The XmAb5871 
dose for patients whose weight exceeds 100 kg will be calculated based on a weight of 100 kg. 
After the first 15 patients, the next up to 6 patients will be dosed with fixed doses of either 90 mg 
or 180 mg per dose. The XmAb5871 will be diluted as for the 5.0 mg/kg dose, but instead of 
weight-based dosing, either 18 mL or 36 mL of the solution will be given as a fixed dose. 
XmAb5871 will be diluted to a final concentration of 5.0 mg/mL in an infusion bag containing 
0.9% sodium chloride for injection, USP.  Prior to dilution, the parenteral drug product (DP) 
should be inspected visually.  XmAb5871 DP should appear clear to slightly opalescent, 
colorless to yellow; practically free of particulates.  If particulate matter and/or discoloration are 
noted, the drug should NOT be administered.  XmAb5871 should not be mixed or diluted with 
other drugs or diluents such as 5% dextrose in water (D5W). 
The bag should be gently inverted 2 or 3 times to mix the solution.  The bag must not be shaken; 
excess agitation may cause aggregate formation.   
Administration of XmAb5871 will be performed as described in the Pharmacy Manual, which 
will be provided to the sites. 
Diluted XmAb5871 should be administered IV at a constant rate over a 1-2 hour period.  
XmAb5871 SHOULD NOT BE ADMINISTERED AS AN INTRAVENOUS PUSH OR 
BOLUS.  
Vials are single-use containers.  All unused supplies of XmAb5871 will either be destroyed or 
returned to the study Sponsor at the end of the study in accordance with instruction by the 
Sponsor. 
5.3 
Drug Administration 
Administration of XmAb5871 should take place as soon as possible following dilution.  If a 
delay is anticipated, diluted XmAb5871 may be stored at 2 to 8oC for no more than 24 hours or 
at room temperature for no more than 8 hours prior to infusion.  Diluted XmAb5871 should be 
administered intravenously at a constant rate over a 2 hour period for the first infusion and over a 
1-2 hour period for subsequent infusions.  XmAb5871 SHOULD NOT BE ADMINISTERED 
AS AN INTRAVENOUS PUSH OR BOLUS.   

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5.4 
Dose Rationale 
The proposed dose and dosing regimen is based on available data from the non-clinical 
pharmacology and toxicology studies with XmAb5871 and available data from the completed 
human studies.  
The maximum dose administered and the NOAEL in the GLP 6-month, repeat-dose toxicity 
study in cynomolgus monkey (IV infusion every other week X 13 infusions) was 200 mg/kg.  
The dosing schedule and duration of the toxicity study provides support for the dose/schedule of 
the proposed pilot study.  The completed FIH study examined single doses from 0.03 mg/kg, a 
dose predicted to result in a Cmax about 5-fold below the estimated biological effect level, to 
10.0 mg/kg, a maximum dose based on predicted human PK and PD profiles, adequate safety 
margins, and practical considerations.  These doses were generally well tolerated in the single 
ascending dose study as well as in the 3-month multiple ascending dose study (QOW dosing X 6 
doses) in RA patients.  Complete CD19 receptor occupancy was seen in the repeat dose RA 
study at doses of 1.0, 3.0, and 10.0 mg/kg from first dose through the completion of dosing.  A 
trend towards beneficial effects on RA disease activity could be seen in both the 3.0 and 10.0 
mg/kg cohorts as well as in the comparison of XmAb5871 treated (all doses) vs all placebo 
treated patients.  Based on the observed safety and tolerability profile, the effects on CD19 
receptor occupancy and effects on disease activity in the RA trial, a dose of 5 mg/kg has been 
selected for this study.  
This protocol has been amended in order to explore the treatment effect of lower doses of 
XmAb5871. After the first 15 patients are enrolled, approximately 3 additional patients will be 
treated with a fixed dose of 90 mg of XmAb5871 given IV every other week instead of 5 mg/kg. 
A second set of up to 3 additional patients may be treated with either 90 mg or 180 mg 
XmAb5871 instead of 5 mg/kg.  These two doses represent approximately 1 mg/kg and 2 mg/kg 
for a 75 kg person and are well within the ranges previously studied. 
5.5 
Supply, Packaging, and Labeling 
XmAb5871 DP will be supplied by Almac.  Investigational medicinal products will be packaged 
and labeled according to applicable local and regulatory requirements. 
XmAb5871 DP will be a sterile liquid product supplied in single-use glass vials.  Each 10 mL 
glass vial is filled with 10.5 mL of drug product that contains 10 (+/-5%) mg/mL of XmAb5871, 
10 mM sodium phosphate, 150 mM sodium chloride and 0.01% (w/v) polysorbate 20 at pH 7.2.  

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Each product vial is intended to deliver at least 10 mL of drug solution or 100 mg (+/- 5%) of 
XmAb5871. 
All supplies of IMPs must be stored in accordance with the manufacturer’s instructions.  The 
IMPs will be stored in a secured area, accessible to authorized persons only, until needed for 
dosing. 
5.6 
Drug Accountability, Dispensing, and Destruction 
The Investigator or designee is responsible for maintaining accurate accountability records of the 
IMPs throughout the clinical study.  The drug accountability log includes information such as, 
random number, amount dispensed and amount returned to the pharmacy (if any).   
All dispensing and accountability records will be available for Sponsor review after database 
lock.  When the Study Monitor visits the site, he or she will review the drug accountability log 
provided by the site pharmacy.  
The site pharmacist (or designee under the direction of the pharmacist) will dispense IMP for 
each patient according to the protocol and pharmacy manual, if applicable.  
After receiving Sponsor approval in writing, the site is responsible for returning all unused or 
partially used IMP to the Sponsor or designated third party or for preparing the IMP for 
destruction according to locally compliant procedures.   
5.7 
Subject Identification  
5.7.1 Screening Numbers 
All screened patients will be assigned a unique subject identification (SID) number.  The SID 
numbers are consecutive 4-digit numbers that identify patients from time of Screening until time 
of enrollment (i.e., time at which the patient has been determined to meet all inclusion criteria 
and no exclusion criteria).  Each SID will start with a 9 in the first digit position.  The first 
subject screened will be assigned the SID 9001, the second 9002, the third 9003 etc.  Patients 
who drop out of the clinical study before enrollment will retain their SID number. 
5.7.2 Enrollment Numbers 
At enrollment, patients will be assigned consecutive 4-digit enrollment numbers.  The first 
subject randomized will be assigned 1001, the second 1002, the third 1003 and so forth.   

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5.8 
Administration of Investigational Medicinal Product 
XmAb5871 will be administered as an intravenous infusion over 1-2 hours (first infusion over 
2 hours; subsequent infusions over 1-2 hours). 
Study medication will be administered with the patient in a semi-supine position with the head of 
the bed at an elevation of 0 to 90 degrees.  For the initial infusion, patients are to remain fasted 
for at least 3 hours before starting the infusion until at least 1 hour after end of infusion.  During 
pre-infusion fasting, no fluids are allowed except small amounts of water.  During the post-dose 
fasting period, small amounts of clear liquids will be allowed.  At subsequent infusions, patients 
should fast for 1 hour prior, may have clear liquids during and after the infusion, and may 
resume their normal diet 1 hour later. 
5.9 
Compliance 
Dosing will be performed by trained, qualified personnel designated by the PI.  The date and 
time of dosing will be documented on each dosing day.  Comments will be recorded if there are 
any deviations from the planned dosing procedures.   
5.10 Concomitant Medications 
5.10.1 Previous/Concomitant Medication  
Disallowed previous or concomitant medications: 
• Prior use of rituximab (or other B cell depleting agents) within 3 months of enrollment.  Prior 
use of any B cell depleting agent greater than 3 months from enrollment is allowed if 
circulating plasmablasts are ≥ 900 cells/mL.  
• Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-life is 
unknown) prior to enrollment. 
• Received live vaccines within 2 months of enrollment. 
• Immunosuppressive agents (e.g. methotrexate, azathioprine, mycophenolate mofetil, 
cyclophosphamide, tacrolimus, 6-mercaptopurine) within 3 months of enrollment. 
• Patient is taking > 40 mg of prednisone QD (or the equivalent, refer to Table 1) 
 
 

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Table 1: Prednisone Equivalence 
 
 
 
 
 
 
 
 
 
 
Details of all prior and concomitant medication must be recorded at study entry (i.e., at the first 
visit) including prior treatment for IgG4-RD, prior IgG4-RD clinical trial participation and prior 
monoclonal antibody use.  All therapies (prescriptions or over-the-counter medications, 
including vitamins and herbal supplements) different from the study drug must be recorded in the 
eCRF.  Any medicinal product, prescribed or OTC, including herbal and other non-traditional 
remedies, is considered a concomitant medication.  Any changes in concomitant medication must 
be recorded at each visit.  If the change influences the subject’s eligibility to continue in the 
study, the Sponsor must be informed.  Concomitant medication use may be warranted for the 
treatment of AEs.  In the interests of subject safety and acceptable standards of medical care the 
Investigator will be permitted to prescribe treatment(s) at his/her discretion.  All treatments must 
be recorded in the patients’ case report form (CRF); medication, dose, treatment duration and 
indication. 
The information collected for each concomitant medication includes, at a minimum, start date, 
end date or ongoing, dose and unit, frequency, route of administration and indication. 
5.10.2 Contraception  
Women of childbearing potential must have a negative pregnancy test during screening and at 
baseline (Day 1) and must use 1 highly effective method of birth control during the study and for 
3 months following last dose of XmAb5871.  Highly effective methods of birth control include 
hormonal birth control, intrauterine devices (IUDs), or any barrier methods (sponges, female 
condoms) used by the woman in addition to contraception used by their male partner such as 
vasectomy or condom supplemented with spermicide. 
Women of non-childbearing potential must have a documented reason (i.e., postmenopausal by 
history with no menses for one year and confirmed by FSH [using local reference ranges], OR 
Prednisone 
40 
mg 
Hydrocortisone 
160 
mg 
Prednisolone 
40 
mg 
Triamcinolone 
32 
mg 
Methylprednisolone 
32 
mg 
Dexamethasone 
6 
mg 
Betamethasone 
4.8 
mg 
Cortisone acetate 
200 
mg 

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history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral 
oophorectomy). 
Male patients of childbearing potential must be willing to practice a highly effective method of 
birth control for the duration of the study and continuing for 3 months after the last dose of 
XmAb5871.  Highly effective methods of birth control include vasectomy or a condom in 
combination with barrier methods, hormonal birth control or IUD used by the woman. 
6 
VARIABLES AND METHODS OF ASSESSMENT 
6.1 
Safety Variables 
6.1.1 Medical History, Demographic, and Other Baseline Information 
The medical history comprises: 
• General medical history including IgG4-RD history 
• Medication history 
• Reproductive history 
The following demographic information will be recorded: 
• Age 
• Gender 
• Ethnic origin (Hispanic/Latino or not Hispanic/not Latino) 
• Race (White, American Indian/Alaska Native, Asian, Native Hawaiian or other Pacific 
Islander, Black/African American) 
• Height, without shoes (in cm) 
• Body weight, without shoes (in kg) 
• Body mass index 
6.1.2 Adverse Events 
Adverse event (AE) reporting will begin with the signing of the informed consent document 
(Screening) and will continue until the last study visit. 

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6.1.2.1 
Definitions 
An AE is any untoward medical occurrence in a study subject administered an IMP.  The AE 
does not necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an IMP, whether or not considered 
related to the IMP.  Adverse events may include the onset of new illness and the exacerbation of 
pre-existing conditions. 
Other untoward events occurring in the framework of a clinical study will be recorded as AEs, 
e.g., those occurring during treatment-free periods (including Screening or post-treatment 
Follow-up periods), in association with study-related procedures and assessments, or under 
placebo.  For IMPs, lack of efficacy may be an expected potential outcome and should not be 
reported as an AE unless the event is unusual in some way, e.g., greater in severity.   
Concomitant illnesses, which existed prior to entry into the clinical study, will not be considered 
AEs unless they worsen during the treatment period.  Pre-existing conditions will be recorded as 
part of the subject’s medical history. 
Clinically significant abnormal laboratory results which are not caused by the underlying disease 
or are not consistent with the patient’s medications will be recorded as AEs and the relationship 
to the study drug will be indicated as in Table 3.  Laboratory values outside the normal range 
will be assigned one of the following categories by the Investigator or designee: 
1. Not clinically significant, minor out of range value/finding.  AE - No  
2. Not clinically significant, out of range value/finding explainable by anticipated or known 
effect of study drug or concomitant drugs.  AE - No  
3. Clinically significant but consistent with the patient’s underlying disease.  AE - No 
4. Clinically significant out of range value/finding.  AE - Yes 
6.1.2.2 
Recording of Adverse Events 
Adverse events should be collected and recorded for each subject from the date the informed 
consent form (ICF) was signed until the end of their participation in the study, i.e., the subject 
has discontinued or completed the study.   
Adverse events may be volunteered spontaneously by the study subject, or discovered by the 
study staff during physical examinations or by asking an open, non-leading question such as 

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‘How have you been feeling since you were last asked?’  All AEs and any required remedial 
action will be recorded.  The nature of AE, date (and time, if known) of AE onset, date (and 
time, if known) of AE outcome to date, severity, and action taken of the AE will be documented 
together with the Investigator’s assessment of the seriousness of the AE and causal relationship 
to study drug and/or study procedure. 
All AEs should be recorded individually in the study subject’s own words (verbatim) unless, in 
the opinion of the Investigator, the AEs constitute components of a recognized condition, disease 
or syndrome.  In the latter case, the condition, disease or syndrome should be named rather than 
each individual symptom.  The date (and time, if known) that the investigator or study site is first 
made aware of the AE (or any subsequent follow up information is received) will be 
documented.  The AEs will be coded using the current version of the Medical Dictionary for 
Regulatory Activities (MedDRA). 
6.1.2.3 
Assessment of Adverse Events 
Each AE will be assessed by the Investigator with regard to the categories discussed in the 
sections below. 
6.1.2.3.1 
Intensity 
The Investigator will assess all AEs for severity utilizing the National Cancer Institute’s 
Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale (V 4.03).  AEs 
not contained within CTCAE version 4.3 will be rated on a five-point scale (Table 2): 
Table 2: Severity Grading Scale 
Mild  
(Grade 1) 
Mild events are those which are easily tolerated with no disruption of normal daily 
activity. 
Moderate  
(Grade 2) 
Moderate events are those which cause sufficient discomfort to interfere with daily 
activity. 
Severe  
(Grade 3) 
Severe events are those which incapacitate and prevent usual activity. 
Life-threatening  
(Grade 4) 
An adverse event that has life-threatening consequences; for which urgent 
intervention is indicated; that puts the subject at risk of death at the time of the 
event if immediate intervention is not undertaken; or that causes blindness or 
deafness. 
Fatal  
(Grade 5)   
The termination of life as a result of an adverse event. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the event should be noted for that day.  Any change in severity of signs and 

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symptoms over a number of days will be captured by recording a new AE, with the amended 
severity grade and the date (and time, if known) of the change. 
6.1.2.3.2 
Causality 
The Investigator will assess the causality/relationship between the IMP and the AE.  One of the 
following categories should be selected based on good medical and scientific judgment, 
considering the definitions in Table 3 and all contributing factors. 
Table 3: Causality Grading Scale 
Related 
 
A clinical event, including laboratory test abnormality, occurs in a plausible 
time relationship to treatment administration, and which concurrent disease or 
other drugs or chemicals cannot explain.  The response to withdrawal of the 
treatment (dechallenge*) should be clinically plausible.  The event must be 
definitive pharmacologically or phenomenologically, using a satisfactory 
rechallenge† procedure if necessary. 
Probably Related 
 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and which follows a clinically 
reasonable response on withdrawal (dechallenge).  Rechallenge information is 
not required to fulfill this definition. 
Possibly Related 
 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, but which could also be explained 
by concurrent disease or other drugs or chemicals.  Information on treatment 
withdrawal may be lacking or unclear. 
Unlikely Related 
 
A clinical event, including laboratory test abnormality, with a temporal 
relationship to treatment administration which makes a causal relationship 
improbable, and in which other drugs, chemicals or underlying disease provide 
plausible explanations. 
Not Related 
 
A clinical event, including laboratory test abnormality, with little or no temporal 
relationship with treatment administration.  May have negative dechallenge and 
rechallenge information.  Typically explained by extraneous factors (e.g. 
concomitant disease, environmental factors or other drugs or chemicals) 
* Dechallenge is when a drug suspected of causing an AE is discontinued.  If the symptoms of the AE disappear partially or 
completely, within a reasonable time from drug discontinuation, this is termed a positive dechallenge.  If the symptoms 
continue despite withdrawal of the drug, this is termed a negative dechallenge.  Note that there are exceptions when an AE 
does not disappear upon discontinuation of the drug, yet drug-relatedness clearly exists (for example, as in bone marrow 
suppression, fixed drug eruptions, or tardive dyskinesia). 
† Rechallenge is when a drug suspected of causing an AE in a specific subject in the past is readministered to that subject.  If the 
AE recurs upon exposure, this is termed a positive rechallenge.  If the AE does not recur, this is termed a negative rechallenge. 
 
6.1.2.3.3 
Action Taken 
Action taken will be defined as: 
• None; 
• Infusion interrupted; 
• Infusion discontinued; 

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• Medication given (details to include medication name, start date and time, stop date and 
time, dose, route, frequency and reason for administration); 
• Other (details of other to be specified) 
6.1.2.3.4 
Outcome 
Outcome will be defined as: 
• Death related to adverse event; 
• Not recovered or not resolved; 
• Recovered or resolved; 
• Recovered or resolved with sequelae; 
• Recovering or resolving; 
• Unknown. 
6.1.2.3.5 
Seriousness 
An SAE is defined as any untoward medical occurrence at any dose if it: 
• Results in death; 
• Is life-threatening; this means that the subject was at immediate risk of death at the time of 
the event; it does not mean that the event hypothetically might have caused death if it were 
more severe; 
• Requires hospitalization or prolongation in existing hospitalization; 
• Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions; 
• Is a congenital anomaly or birth defect; 
• Is an important medical event (see below). 
Important medical events that do not result in death, are not life-threatening, or do not require 
hospitalization may be considered SAEs when, based on appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed above.  Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or in a physician’s office, blood dyscrasias 
or seizures that do not result in in-patient hospitalization, and the development of drug 
dependency or drug abuse. 

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A distinction should be drawn between serious and severe AEs.  Severity is a measure of 
intensity whereas seriousness is defined by the criteria above.  For example, a mild degree of 
gastrointestinal bleeding requiring an overnight hospitalization for monitoring purposes would be 
considered an SAE, but is not necessarily severe.  Similarly, an AE that is severe in intensity is 
not necessarily an SAE.  For example, alopecia may be assessed as severe in intensity but would 
not be considered an SAE. 
Medical and scientific judgment should be exercised in deciding if an AE is serious and if 
expedited reporting is appropriate. 
6.1.2.3.6 
Adverse Events of Special Interest 
Infusion-Related Reactions 
All monoclonal antibody therapeutics are associated with the risk of both non-allergic (cytokine 
release syndrome) and allergic (hypersensitivity) infusion-related reactions.  
A. Non-allergic reactions (cytokine release): Most infusion-related reactions are mild and 
non-allergic in etiology and may be alleviated by interruption of the infusion and 
reinitiating the infusion at the same of slower infusion rate after symptoms abate.  
Signs/symptoms may include: arthralgia (joint pain);  cough; dizziness; dyspnea 
(shortness of breath); fatigue (asthenia, lethargy, malaise); fever; headache; hypertension; 
hypotension; myalgia (muscle pain); nausea;  rash/desquamation; rigors/chills; sweating 
(diaphoresis); tachycardia;  vomiting.  
B. Allergic (hypersensitivity) reactions and anaphylaxis: The Immune System Disorders 
section of NCI-CTCAE 4.03 should be used to help characterize AEs related to 
hypersensitivity and immunogenicity.  To identify cases of anaphylaxis in this study, the 
National Institute of Allergy and Infectious Diseases (NIAID) definition of anaphylaxis 
(Sampson et al. 2006) will be used (see Table 4: Definition of Anaphylaxis below). 

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Table 4: Definition of Anaphylaxis 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., 
generalized hives, pruritus or flushing, swollen lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, 
incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to 
several hours): 
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula) 
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP* 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
PEF = Peak expiratory flow; BP = blood pressure. 
*Low systolic blood pressure for children is defined as less than 70 mmHg from 1 month to 1 year, less than (70 mmHg + [2 X 
age]) from 1 to 10 years, and less than 90 mmHg from 11 to 17 years. 
 
Monitoring During Infusions 
Patients should be closely monitored during and after infusion.  XmAb5871 should be 
administered intravenously at a constant rate over a 1-2 hour period (2 hours for first infusion, 
1-2 hours for subsequent infusions).  Patients will be continuously assessed during the 1-2 hour 
infusion and for 1 hour following the end of infusion (2 hours following the first infusion).  Vital 
signs including blood pressure, heart rate, respiratory rate and temperature assessments will be 
made within 2 hours prior to infusion, 30, 60 and 120 minutes from the start of infusion, at the 
end of infusion (if different than 120 minutes from start of infusion) and 30 and 60 minutes after 
end of infusion.  During the first infusion, an additional measurement of vital signs should be 
made at 15 minutes after the start of infusion and after the end. 
Severe infusion-related reactions, including deaths following the administration of otherwise 
well-tolerated monoclonal antibodies, have been reported rarely.  As with all monoclonal IV 
antibody therapies, XmAb5871 should only be administered by healthcare providers and in 
healthcare settings that are prepared to recognize and to manage severe infusion-related reactions 
and/or anaphylaxis that can be life-threatening.  All investigators should be well trained in the 
management of anaphylaxis (and other acute infusion-related events) including administration of 
epinephrine and other therapeutic modalities.  Medications and equipment for the treatment of 
life-threating anaphylaxis should be available in the immediate area of treatment. 

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Management of Infusion-Related Reactions & Cytokine Release Syndrome 
Infusion-related reactions and cytokine release syndrome will be toxicity graded according to the 
NCI-CTCAE, Version 4.3, as defined in Table 5. 
Table 5: Infusion-Related Reaction and Cytokine Release Syndrome 
Adverse 
Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Infusion related 
reaction 
Mild transient 
reaction; 
infusion 
interruption 
not 
indicated; 
intervention 
not 
indicated 
Therapy or infusion 
interruption indicated but 
responds promptly to 
symptomatic treatment 
(e.g., 
antihistamines, NSAIDS, 
narcotics, IV fluids); 
prophylactic medications 
indicated for ≤24 hrs 
Prolonged (e.g., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for 
clinical sequelae 
Life-
threatening 
consequences; 
urgent 
intervention 
indicated 
Cytokine release 
syndrome 
Mild reaction; 
infusion 
interruption 
not indicated; 
intervention 
not indicated 
Therapy or infusion 
interruption indicated but 
responds promptly to 
symptomatic treatment 
(e.g., 
antihistamines, NSAIDS, 
narcotics, IV fluids); 
prophylactic medications 
indicated for ≤24 hrs 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for 
other clinical sequelae (e.g., 
renal impairment, pulmonary 
infiltrates) 
Life-
threatening; 
consequences; 
pressor or 
ventilatory 
support 
indicated 
REMARK:  An acute infusion-related reaction may occur with an agent that causes cytokine release (e.g., monoclonal 
antibodies or other biological agents).  Signs and symptoms usually develop during or shortly after drug infusion and 
generally resolve completely within 24 hrs of completion of infusion.  Signs/symptoms may include: Allergic 
reaction/hypersensitivity (including drug fever); Arthralgia (joint pain); Bronchospasm; Cough; Dizziness; Dyspnea 
(shortness of breath); Fatigue (asthenia, lethargy, malaise); Headache; Hypertension; Hypotension; Myalgia (muscle 
pain); Nausea; Pruritis/itching; Rash/desquamation; Rigors/chills; Sweating (diaphoresis); Tachycardia; Urticaria 
(hives, welts, wheals); Vomiting. 
The Xencor Medical Monitor should be contacted immediately if questions arise concerning the 
grade of the infusion-related reaction. 
An ADA sample should be drawn at the time of any suspected immunological related AE and at 
the time of each subsequent visit X 4 (and as per pre-specified sampling schedule). 
The following are treatment guidelines for XmAb5871 treatment-related infusion-related 
reactions: 
Grade 1 or 2: 
• Discontinue the infusion and administer acetaminophen and/or diphenhydramine 
and/or dexamethasone to treat signs and symptoms if clinically indicated.  Once 
symptoms have resolved, slow the infusion rate by 50% of the baseline rate.  If, 

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after one hour, the patient’s symptoms do not return and vital signs are stable, the 
infusion rate may be increased every 30 minutes as tolerated to the baseline rate; 
• Vital signs should be measured every 15 minutes or less as clinically indicated.  
For patients who are able to tolerate an increase in the infusion rate back to 
baseline and maintain normal blood pressure for 30 minutes after the rate increase 
then, at the discretion of the investigator, the frequency of vital sign assessment 
may be reduced to every 30 minutes during the infusion;  
• Monitor the patient for worsening of condition; if severity of event increases to a 
higher Grade (Grade 3, or 4) stop the infusion, administer appropriate treatment, 
and refer to guidelines below for Grades 3 or 4 infusion-related reactions; 
• Patients with maximum Grade 2 infusion-related reaction may continue on study 
and should receive prophylactic pre-medication with acetaminophen 650 mg po 
and diphenhydramine hydrochloride 25-50 mg IV and dexamethasone 10 mg IV 
(or equivalent) prior to all subsequent XmAb5871 infusions.  
Grade 3 and 4: 
• Stop the infusion and disconnect the infusion tubing from the patient; 
• Administer diphenhydramine hydrochloride 50 mg IV, dexamethasone 10-20 mg 
IV (or equivalent), and other medications/treatment as medically indicated; 
• Give epinephrine or bronchodilators as indicated; 
• Hospital admission for observation may be indicated; 
• Patients with Grade 3 or 4 infusion-related reaction or with anaphylaxis should 
not receive further XmAb5871 treatment, but will continue to be followed on the 
protocol; 
• Obtain blood sample for cytokine analysis during the event and approximately 
24 hours later. 
• Notify the Xencor Medical Monitor immediately; 
Infusion Associated Gastrointestinal-Related Symptoms 
In the completed XmAb5871 FIH single-dose study, the most frequently reported treatment-
related AEs were:  nausea (7/36 subjects [19.4%]), vomiting (5/36 subjects [13.9%]), diarrhea 
(4/36 subjects [11.1%]) and abdominal pain (3/36 subjects [8.3%]) which typically occurred 
during the infusion.  Symptoms were reported over the dose range of 0.2 to 10.0 mg/kg and at a 
similar overall level in each dose group.  In the 8 cases of nausea and vomiting in which the IMP 
infusion was interrupted, the symptoms responsible for the interruption resolved quickly and no 
concomitant medication was required for relief of symptoms.  When vomiting occurred, 

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symptoms resolved very rapidly following the vomiting episode (1-3 minutes).  The planned 
infusion was completed without recurrence of symptoms.  No subject was withdrawn and none 
self-withdrew. 
In the Phase 2a study in RA patients, 9 patients (23%) had their XmAb5871 IV infusion 
temporarily interrupted as a result of the gastrointestinal symptoms (vomiting/nausea or 
diarrhea).  Seven of the 9 (78%) occurred in the 10.0 mg/kg cohorts.  In all but one episode, the 
symptoms were mild to moderate (one episode of severe vomiting).  In all cases, the patients 
were able to continue the infusion after a short break (5-31 minutes) and symptoms did not recur 
on continuation of the infusion or during subsequent infusions.  No concomitant medication was 
required for alleviation of symptoms. 
There is no known mechanism of action by which a mAb with enhanced binding to FcγRIIb 
would result in the infusion-associated, transient GI toxicity seen.  There is also no known 
mechanism of action by which targeting CD19, a B cell restricted antigen, would produce such 
toxicity.  
Mild to moderate nausea, vomiting or diarrhea may occur during the first infusion of 
XmAb5871.  The subject should be monitored during the infusion and at the first sign of 
abdominal distress be allowed to elevate the head of the bed to up to a 90 degree position.  
Should nausea occur and become significant and/or vomiting occurs, the IV infusion should be 
interrupted.  After a 15-30 minute interruption and if the subject’s symptoms have substantially 
resolved, the infusion may be restarted at the original infusion rate.  
6.1.2.4 
Reporting of Serious Adverse Events 
The Investigator will review each potential SAE and evaluate the intensity and the causal 
relationship of the event to IMP.  All potential SAEs will be recorded from signing of informed 
consent until EOS.  Serious AEs occurring after EOS and coming to the attention of the 
Investigator must be reported only if there is (in the opinion of the Investigator) reasonable 
causal relationship with the IMP. 
The Investigator is responsible for providing notification to Vigilare of any potential SAE, 
whether deemed IMP-related or not, that a subject experiences during their participation in study 
within 24 hours of becoming aware of the event.  Vigilare will provide the information to the 
Sponsor.  
 

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As a minimum requirement, the initial notification should provide the following information: 
• Study number 
• Patient number 
• Gender 
• Date of birth 
• Name of PI and full clinical site address 
• Name of the reporter 
• Details of SAE 
• Criterion for classification as ‘serious’ 
• Study drug name, dose and treatment start date 
• Date of SAE onset 
• Date of SAE first awareness (by Investigator or study site staff) 
• Causality assessment  
Vigilare will request clarification of omitted or discrepant information from the initial 
notification.  The PI or an authorized delegate is responsible for providing the requested 
information to Vigilare within 24 hours of the request. 
Initial reports of SAEs must be followed up as soon as possible with detailed descriptions; this 
may include clear photocopies of other documents as necessary (e.g., hospital reports, consultant 
reports, autopsy reports, etc.), with the study subject’s personal identifiers removed.  All relevant 
information obtained by the Investigator through review of these documents will be recorded and 
forwarded to Vigilare within 24 hours of receipt of the information.  If a new SAE Report Form 
is completed, then the PI must sign and date the form.  Vigilare and/or the Sponsor may also 
request additional information on the SAE in order to obtain the full clinical picture, to which the 
PI or an authorized delegate must respond to Vigilare within 24 hours of the request. 

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SERIOUS ADVERSE EVENT REPORTING INSTRUCTIONS 
SAEXmAb5871-03@vigilareintl.com 
24 hour telephone number: 610-977-0899 x4801 
Emergency contact number: 917-741-5205 
1. E-mail your SAE form to the study specific e-mail address above.  . 
2. Provide Vigilare with the name of the PI, your name, the telephone number where you can be 
reached and the protocol number and title. 
3. Immediately forward the SAE form and any supporting documentation to Vigilare: this must 
be done within 24 hours of becoming aware of the event. 
6.1.2.5 
Follow-up of Adverse Events 
All AEs experienced by a subject, irrespective of the suspected causality, will be monitored until 
the event has resolved or stabilized, until any abnormal laboratory values have returned to 
baseline or stabilized at a level acceptable to the Investigator and Sponsor medical 
representative, until there is a satisfactory explanation for the changes observed, or until the 
subject is lost to Follow-up. 
6.1.2.6 
Pregnancy 
The Investigator and Sponsor have a responsibility to monitor the outcome of all pregnancies, 
including pregnancies in partners of male participants, reported during the clinical study. 
Pregnancy alone is not regarded as an AE unless there is a suspicion that the IMP may have 
interfered with the effectiveness of a contraceptive medication.  Elective abortions without 
complications should not be regarded as AEs, unless they were therapeutic abortions (see 
below).  Hospitalization for normal delivery of a healthy newborn should not be considered an 
SAE.  All notifications of pregnancy should be documented and reported whether or not there is 
an associated AE or SAE. 
Each pregnancy notification must be reported by the Investigator to the Sponsor and Vigilare 
within 30 days after becoming aware of the pregnancy.  The Investigator must follow-up and 
document the course and the outcome of all pregnancies even if the subject was withdrawn from 
the clinical study or if the clinical study has finished.  The follow-up period will be deemed to 
have ended when the health status of the child has been determined on its birth. 

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All outcomes of pregnancy must be reported by the Investigator to the Sponsor and Vigilare on 
the pregnancy outcome report form within 30 days after he/she has gained knowledge of the 
normal delivery or elective abortion. 
Any SAE that occurs during pregnancy must be recorded on the SAE report form (e.g., maternal 
serious complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, birth defect) and reported within 24 hours of awareness in accordance with 
the procedure for reporting SAEs. 
6.1.3 Vital Signs 
Vital signs will be assessed at Screening and on Days 1, 8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 
141, 155, 169 and 197. On Day 1, vital sign assessments will be made immediately prior to 
infusion, 15, 30, 60, and 120 minutes after the start of the infusion (±5 minutes), immediately 
before the EOI (if different than 120 minutes from start of infusion), and at 15, 30, 60 and 
120 minutes after EOI.  During subsequent infusions, vital signs will be measured immediately 
prior to infusion, 30 and 60 minutes after the start of the infusion (±5 minutes), immediately 
before the EOI (if different than 60 minutes from start of infusion), and at 30 and 60 minutes 
after EOI.  On non-dosing days vital signs should be measured prior to blood sampling.  During 
the infusion of XmAb5871, vital signs will be obtained in the semi-supine siting position.  The 
following vital signs will be measured:  
Blood pressure (systolic and diastolic [mmHg]); 
Heart rate (beats per minute [bpm]); 
Oral body temperature (°C); 
Respiratory rate (breaths per minute). 
Supine BP and heart rate recordings will be made after the study subject has been recumbent and 
at rest ≥ 5 minutes.   
6.1.4 12-lead Electrocardiograms 
Standard safety 12-lead ECGs will be performed at Screening and on Days 1, 29, 57, 113, 155, 
and 197.  On Day 1, supine ECGs will be performed immediately prior to the infusion and 
2 hours after EOI.  On all other visit days, ECGs will be performed only pre-dose.  
The 12-lead ECGs will be performed after the subject has been resting supine for ≥ 5 minutes.  
The ECG will include all 12 standard leads and a Lead II rhythm strip on the bottom of the 

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tracing.  The ECG will be recorded at a paper speed of 25 mm/sec.  The following ECG 
parameters will be collected:  PR interval, QRS interval, RR interval, QT interval, and QTc 
interval (QTcB and QTcF).   
All ECGs must be evaluated by a qualified physician for the presence of abnormalities.   
6.1.5 Physical Examinations 
Complete physical examinations will be performed at Screening and on Days 1 and 169.  
Abbreviated, symptom directed PE will be performed on Days 8, 15, 29, 57, 85, 113, 141, and 
197 (EOS). 
The physical examination includes an assessment of general appearance and a review of systems 
(dermatologic, head, eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, respiratory, 
cardiovascular, gastrointestinal, extremities, musculoskeletal, neurologic, and psychiatric 
systems). 
6.1.6 Clinical Laboratory Assessments 
Safety clinical laboratory assessments will be performed by the Pathology Core Laboratory of 
the Massachusetts General Hospital, Boston, MA.  Flow cytometry for B cell and T cell 
quantitation and for CD19 RO will be performed by ICON Central Laboratories, Farmingdale, 
NY.  PK and immunogenicity laboratory assessments will be performed by ICON Development 
Solutions, LLC, Whitesboro, NY.  Genotyping will be performed by Gentris, Morrisville, NC.  
Plasmablast and mechanistic studies will be done at Ragon Institute, Cambridge, MA. 
Blood samples should be taken using standard venipuncture techniques.  Blood sampling will be 
performed according to MGH SOPs. 
The following laboratory variables will be determined as outlined below:   
Hematology: The following hematology parameters will be assessed at Screening and at Days 1, 
8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, and 197:  hemoglobin, hematocrit, red 
blood cell count, white blood cell count with differential (% and derived absolute values), mean 
corpuscular 
volume, 
mean 
corpuscular 
hemoglobin, 
mean 
corpuscular 
hemoglobin 
concentration, and absolute platelet count. 
Clinical chemistry: The following clinical chemistry parameters will be assessed at Screening 
and at Day 1, 15, 29, 57, 85, 113, 141, 169, and 197.  Tube 1:  total protein, sodium, potassium, 
calcium, chloride, bicarbonate (HCO3), albumin, glucose, blood urea nitrogen (BUN), creatinine, 

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total bilirubin, alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine 
aminotransferase (ALT).  Tube 2:  gamma-glutamyl transferase (GGT), lactate dehydrogenase 
(LDH), amylase and lipase.  Tube 3:  uric acid, inorganic phosphate and creatine phosphokinase 
(CPK). 
Immunoglobulin: Serum IgG, IgE, IgM, IgA and IgG1-4 will be assessed at Screening and on 
Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 197. 
Complement levels:  C3 and C4 levels will be assessed at Screening and on Days 1, 15, 29, 57, 
85, 113, 141, 169, and 197. 
Coagulation: The following coagulation parameters will be assessed on Screening, and Days 1, 
8, 29, 85, 141, and 197:  international normalized ratio (INR), prothrombin time (PT), and 
activated partial thromboplastin time (aPTT). 
Urinalysis: The following urinalysis parameters will be assessed at Screening, and on Days 1, 
29, 85, 141, and 197: pH, glucose, ketones, specific gravity, nitrite, protein, bilirubin, 
urobilinogen, leukocytes and blood.  Microscopic urinalysis will be performed if clinically 
indicated. 
Serology: Anti-HIV Type I and II Ab, HBsAg, HBcAb, and HCV Ab will be performed at 
Screening.   
Urine Pregnancy Test: Urine pregnancy testing will be performed in female patients on the first 
Screening Day and at Days 1, 71 and 197(EOS). 
Serum Pregnancy Test: A stat serum pregnancy test for women of child-bearing age will be 
obtained and a negative result verified before each of the 18F FDG PET/CT scans (during the 
screening period immediately prior to the PET/CT scan and on Day 85).   
Follicle Stimulating Hormone (FSH) will be performed in women of non-childbearing 
potential at Screening.   
Immunogenicity: The presence of human anti-human antibodies (ADA) will be assessed at 
Screening and on Days 1, 29, 71, 99, 155, 169, and 197. 
Flow Cytometry B Cell and T Cell Assessment:  
For any patients with a history of rituximab or other anti-CD20 therapy, an initial B cell count 
will be performed during Screening to ensure that the patient’s B cell level has returned to 
normal levels. 

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For enrolled patients, CD20+ B cells, T cells, and NK cells will be quantified on Days 1, 8, 15, 
29, 57, 85, 113, 141, 169, and 197.   
CD19 RO (as CD19+ geometric mean of all CD20+ [MFI]) and B cell subsets (CD20+, 
CD20+/IgD+CD27-,  CD20+/IgD+CD27+, CD20+/IgD-CD27+-,  CD20+/IgD-CD27-) will be 
quantified on Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 197.  
Plasmablast Assessment and Mechanistic Studies:  
Plasmablasts will be enumerated at the Screening visit. 
For those enrolled in the study, mechanistic studies that will be performed on Days 1, 8, 43, and 
85 may include one or more of the following studies: plasmablast population quantification, total 
multi-parametric PBMC population analysis using Cytof mass cytometry, analysis of markers of 
plasmablast apoptosis in flow cytometry and RNA-seq experiments before and after IMP 
therapy.  Additional samples will be collected on Days 15, 29, 57, 71, 99, 113, 127, 141, 155, 
169, and 197 and stored for potential mechanistic studies. 
Blood Requirements: 
Blood will be collected for clinical laboratory testing as outlined below:  
Hematology: Blood (3 mL) will be collected into a lavender-top tube. 
Chemistry: Blood (9 mL) will be collected into 3 green-top tubes of 3 mL each. 
Serology: Blood (3.5 mL) will be collected into a gold-top tube. 
Serum pregnancy (3 mL) will be collected into a lavender-top tube. 
Follicle Stimulating Hormone: Blood (3 mL) will be collected into a lavender-top tube. 
Coagulation panel: Blood (5 mL) will be collected into a blue top tube. 
Immunoglobulins (IgG, IgM, IgA, IgE, IgG1-4): Blood (5 mL) will be collected into a serum gel 
(STT) tube. 
Complement C3 and C4: Blood (5 mL) will be collected in a gold-top tube on ice. 
XmAb5871 drug levels (PK; see Section 6.2 below): Blood (5.0 mL) will be collected into a 
serum gel (SST) tube. 
Immunogenicity (ADA): Blood (5.0 mL) will be collected into a serum gel (SST) tube. 
Genotyping: Blood (8.5 mL) will be collected into a PAXgene™ Blood DNA collection tube 
(see Section 6.4 below). 

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Flow Cytometry B Cell and T Cell Assessment, CD19 RO: Blood (3 mL) will be collected into a 
lavender-top tube and blood (5 mL) will be collected in a Cyto-Chex BCT glass streck CE 
marked tube. 
Plasmablast Assessment and Mechanistic Studies: Blood (25.5 mL) will be collected into 
3 yellow-top ACD tubes. 
The total blood volume collected for clinical labs (including PK samples) over the duration of 
the study will be approximately 920 mL collected on 16 different days with volumes ranging 
from 33.5 to 89 mL at time of blood draw.  Women of child-bearing potential will have an 
additional 6 mL drawn for pre-PET scan stat serum pregnancy tests. 
Laboratory Values Outside Normal Range: 
Any value outside the normal range will be flagged for the attention of the Investigator or 
designee at the site.  The Investigator or designee will indicate whether or not the value is of 
clinical significance as in Section 6.1.2.1.  Laboratory values that are clinically significant and 
that are not explained by the patient’s underlying disease or medications should be entered as 
AEs and the relationship to study drug assigned.  Additional testing during the study may be 
done if medically indicated.  The study patient will be followed until the test(s) has (have) 
normalized or stabilized. 
6.2 
Pharmacokinetic Variables 
Blood (approximately 5.0 mL) will be collected at the following time points relative to IMP 
dosing:  prior to the start of the infusion and at EOI on Study Days 1, 15, 29, 43, 71, 99, 127, and 
155 and at visit time on Days 8, 169 and 197.  The blood volume collected during the study for 
PK assessments will be approximately 95 mL.  Blood sample collection, processing, and 
shipping details will be outlined in a separate laboratory manual.  Samples will be processed and 
serum analyzed by a validated method for concentrations of XmAb5871.  The PK parameters 
listed in Section 3.4.4 will be calculated from the serum concentration-actual time profiles.   
6.3 
Pharmacodynamic Variables 
Pharmacodynamics of XmAb5871 will be evaluated by serial measurements as outlined in 
Table 6: Schedule of Assessments, of absolute B cell counts (ABC) and B cell subsets, number 
of circulating IgG4+ plasmablasts and total plasmablasts, and serum IgG4 and IgE 
concentrations.   

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6.4 
Pharmacogenomics Variables 
Blood will be collected as outlined as in Table 6: Schedule of Assessments, on Day 1 (pre-dose) 
for the assessment of FcγR genotype testing (FcγRIIa R131H and FcγRIIb I232T 
polymorphisms).  The blood volume collected on Day 1 for the FcγR genotyping will be 
approximately 8.5 mL.  Blood sample collection, processing, and shipping details will be 
outlined in a separate laboratory manual.  In brief, blood will be processed and the 
deoxyribonucleic acid (DNA) from the white blood cells will be analyzed for the FcγRIIa and 
FcγRIIb polymorphic alleles. 
6.4.1 Efficacy Measurements 
The following efficacy assessments will be performed according to the time points defined in 
Table 6: Schedule of Assessments. 
6.4.1.1 
IgG4-RD Responder Index 
Disease activity will be measured at Screening and on Days 1, 15, 29, 57, 85, 113, 141, 169, and 
197 (EOS).  For determination of the IgG4-RD responder index as described in the schedules of 
assessments (IgG4-RD RI), the following criteria will be used (modified after Carruthers et al. 
2012): 
Organ site, symptomatic, urgent disease (as per IgG4-RD RI) over the previous 28 days 
The original IgG4-RD RI has been modified to include the full spectrum of organs affected most 
frequently by IgG4-RD and to eliminate serum IgG4 concentrations as part of the instrument.  In 
addition, an assessment of damage caused by IgG4-RD in each affected organ is included.  A 
sample assessment form is included in Appendix 11.1.1. 
6.4.1.2 
Disease Activity VAS 
The physician’s and patient’s overall assessment of the patient’s current disease activity will be 
recorded on a 100 mm linear horizontal VAS, where the left hand extreme of the line is 
considered “non” (symptom free and no IgG4-RD symptoms) and the right hand extreme is 
considered “maximum” (maximum IgG4-RD activity).  Assessments will be performed at 
Screening and on Days 1, 15, 29, 57, 85, 113, 141, 169, and 197 (EOS).   
Details on the efficacy assessments can be found in Appendix 11.1.2. 

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6.4.1.3 
18F FDG PET/CT Imaging 
18F FDG PET/CT imaging has been used as an exploratory measure of activity and inflammation 
in IgG4-RD patients.  Baseline images will be obtained within 28 days before the first infusion 
of XmAb5871 and compared to images obtained at Day 85 (+/- 3 days) and at Day 169 (+/- 3 
days). Stat serum pregnancy testing will be done on the day of the PET scan (during the 
screening period and at Days 85 and 169) and negative result documented prior to beginning the 
radiological procedure in women of child-bearing potential. PET will be performed with full 
diagnostic CT, and low-dose CT attenuation correction. The dosing of 18F FDG will follow 
current clinical BMI-based protocol: 15mCi standard, 20mCi for BMI greater than 35, and 
25mCi for BMI greater than 45. 
6.4.1.4 
Optional Tissue Biopsy 
Patients may consent to an optional predose biopsy of involved tissue for pathology, 
immunohistology and potentially mechanistic studies prior to study drug administration. Patients 
may also elect to undergo an optional biopsy of involved tissues at any timepoint in the study 
after treatment begins if clinically indicated based on clinical response to treatment, i.e., 
improvement or worsening.  
7 
STUDY CONDUCT 
7.1 
Schedule of Assessments 
The study consists of a Screening visit (Day -28 to Day -1) followed by twelve infusions of 
XmAb5871 given every two weeks (Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141 and 155) 
with collection of safety, PK, and PD.  Patients will be seen on Day 8 for safety monitoring, PK 
and PD and will be followed for 6 weeks after the final infusion (Days 169 and 197[EOS]).  The 
maximal study duration for an individual subject will be 197 days after the first infusion.   
Please see Table 6 for the schedule of assessments:  

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Table 6: Schedule of Assessments  
Study Phase  
Screening 
Treatment 
EOS 
VISIT NUMBER 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
WEEK 
 
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
29 
DAY 
-28  
to -1 
1 
8 
15   
+/-1 
29   
+/-1 
43   
+/-1 
57   
+/-1 
71  
+/-1 
85 
+/-3 
99  
+/-2 
113 
+/-2 
127 
+/-2 
141 
+/-2 
155 
+/-2 
169  
+/-3 
197  
+/-3 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration1 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination2 
X3 
X3 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X3 
X 
Adverse Event assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead electrocardiogram5 
X 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
CBC w/ differential, platelet 
count 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry Panel Tube 1-3 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
PT/INR and APTT 
X 
X 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
Urinalysis 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
Urine Pregnancy test6 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
HBsAg, HBcAb, HCV, HIV I 
and II Ab7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum follicle stimulating 
hormone (FSH; (postmenopausal 
females only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum immunoglobulin levels 
(IgM, IgE, IgG, IgA, IgG1-4 
subclasses) 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
C3 and C4 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
B and T cell quantitation; CD19 
RO  
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Absolute B cell count 8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasmablast enumeration and 
mechanistic studies 
X 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study Phase  
Screening 
Treatment 
EOS 
VISIT NUMBER 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
WEEK 
 
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
25 
29 
DAY 
-28  
to -1 
1 
8 
15   
+/-1 
29   
+/-1 
43   
+/-1 
57   
+/-1 
71  
+/-1 
85 
+/-3 
99  
+/-2 
113 
+/-2 
127 
+/-2 
141 
+/-2 
155 
+/-2 
169  
+/-3 
197  
+/-3 
FcγR polymorphism genotyping 
(FcγRIIa  R131H and FcγRIIb 
I232T)  
 
X10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic blood sampling 
 
X11 
X 
X11 
X11 
X11 
 
X11 
 
X11 
 
X11 
 
X11 
X 
X 
Immunogenicity (ADA) blood 
sampling12 
X 
X 
 
 
X 
 
 
X 
 
X 
 
 
 
X 
X 
X13 
IgG4-RD RI 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Physician and patient Global 
Activity VAS 
X 
X 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Stat serum pregnancy test 14 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
18F FDG PET/CT imaging  
X14 
 
 
 
 
 
 
 
X14 
 
 
 
 
 
X14 
 
Tissue Biopsy (optional)15 
X 
 
 
 
 
 
 
 
 
X15 
 
 
 
 
 
 
1 XmAb5871 to be given over 2 hours for the first infusion, then over 1-2 hours for subsequent infusions. 
2 Include height at screening only and weight on all dosing days. 
3 Complete physical examinations will be performed at Screening and on Days 1 and 169. Abbreviated, symptom directed PE will be performed on Days 8, 15, 
29, 57, 85, 113, 141, and 197 (EOS). 
4 Supine blood pressure and heart rate, body temperature, respiratory rate.  On Day 1, vital sign assessments will be made immediately prior to infusion, 15, 30, 
60, and 120 minutes after the start of the infusion (±5 minutes), immediately before the EOI (if different than 120 minutes from start of infusion [±5 minutes]), 
and at 15, 30, 60 and 120 minutes after EOI (±5 minutes).  During subsequent infusions, vital signs will be measured immediately prior to infusion, 30 and 60 
minutes after the start of the infusion (±5 minutes), immediately before the EOI (if different than 60 minutes from start of infusion [±5 minutes]), and at 30 and 
60 minutes after EOI(±5 minutes). On non-dosing days vital signs should be measured prior to blood sampling. 
5 Supine ECG immediately prior to infusion and 2 hours after end-of-infusion on Day 1.  All others to be done pre-dose. 
6 Pregnancy test only for women of child-bearing potential (urine)  
7 If the patient has a documented negative result within 60 days before the first dose of XmAb5871, this item may be omitted. 
8 Only for patients with a history of rituximab (or other anti-CD20 mAb) use 
9 Mechanistic study sample predose, 2 hours and 24 hours (optional) after end-of-infusion.  
10 Sample to be collected pre-dose. 

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11 PK pre-infusion and at end of infusion 
12ADA sample should be drawn at the time of any suspected immunological related AE and at the time of each subsequent visit  X 4.  
13Patients with a positive ADA at EOS (or early termination) will be followed every 28 days (± 3 days) until ADA is negative. 
14 Stat serum pregnancy testing will be done on the day of the PET scan (during the screening period and at Days 85 and 169) and negative result documented 
prior to beginning the radiological procedure in women of child-bearing potential.  
15An optional biopsy of clinically involved tissue may be performed during screening or up to predose Day 1. Patients may also elect to undergo an optional 
repeat of the involved tissues at any time point in the study after treatment begins if clinically indicated based on clinical response to treatment, i.e., improvement 
or worsening.  

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7.1.1 Assessments by Visit 
Please refer to Table 6: Schedule of Assessments for a description of the assessments to be 
performed at each study visit.  
7.1.2 Early Termination Visit 
If a subject withdraws prematurely, all assessments as listed for the Day 169 visit should be 
performed. In addition, the patient should be scheduled for a follow-up visit 6 weeks from the 
time of the last infusion of study drug, at which time all assessments as listed for the Day 
197/EOS visit should be performed.   
7.1.3 End-of-Study 
End-of-Study is defined as completion of the End-of Study Visit on Day 197.  Patients with a 
positive ADA at end-of-study will be followed every 28 days (± 3 days) until ADA is negative.   
For those patients that withdraw prematurely see Section 7.1.2.  In addition, the PI and/or study 
site will contact all patients approximately every 6 months following EOS and will keep a log of 
when (if) the patient has recurrent symptoms and when (if) new medications for IgG4-RD 
treatment have been added since the end of study.  This information will be provided to the 
sponsor periodically following the completion of the study. 
8 
STATISTICAL METHODS 
Before database lock, a statistical analysis plan (SAP) will be issued as a separate document, 
providing detailed methods for the analyses outlined below.  Any deviations from the planned 
analyses will be described and justified in the final integrated clinical study report. 
8.1 
Study Population 
8.1.1 Disposition of Patients 
The number and percentage of patients completing the clinical study will be presented. 
8.1.2 Protocol Deviations 
Protocol deviations will be listed by patient.   
8.1.3 Analysis Populations 
The definitions of study populations are as follows: 

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• Enrolled Population: All patients who were enrolled in the study (signed informed 
consent, met inclusion and exclusion criteria and were assigned an enrollment number), 
whether or not the study drug was administered. 
• Intent to Treat (ITT) Population: All patients who have received at least a partial dose of 
XmAb5871.  All efficacy and safety analyses will utilize the intent-to-treat analysis 
dataset.  
• Safety Population: All patients who receive at least a partial dose of XmAb5871.  In this 
study, this was equivalent to the ITT population. 
• Pharmacokinetic/Immunogenicity Population: All patients who received XmAb5871 and 
for whom the PK data are considered to be sufficient and interpretable will be included in 
the PK population.  All patients who received XmAb5871 and have at least 1 post-IMP 
dosing ADA sample drawn will be included in the immunogenicity population. 
• Pharmacodynamic Population: All patients who have received XmAb5871 and for whom 
the PD data are considered to be sufficient and interpretable will be analyzed in the PD 
analyses.   
8.2 
General Considerations 
Since this is an open-label, single-arm clinical trial, descriptive statistics will be employed to 
analyze the data.  Summary statistics for continuous variables will include the mean, standard 
deviation, median, and range (minimum/maximum); categorical variables will be presented as 
frequency counts and percentages; and time-to-event variables (if any) will be summarized by 
Kaplan-Meier medians and Kaplan-Meier plots.  Data listings will be created to support each 
table and to present all data. 
The data will be tabulated with respect to patient enrollment, patient disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
efficacy, and safety measures.  The efficacy and safety analysis will be performed on the 
ITT/Safety Population which is defined as all patients who received any amount of XmAb5871. 
Prior to database lock, a statistical analysis plan (SAP) will be issued as a separate document that 
will provide additional detailed methods and mock table shells for the analyses outlined below.  
Any deviations from the planned analyses will be described and justified in the final integrated 
clinical study report.  

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8.3 
Determination of Sample Size 
Since this is an open-label pilot Phase 2 study to investigate the effect of XmAb5871 on IgG4-
RD disease activity, an appropriate sample size cannot be statistically determined since adequate 
information is not available to perform formal sample size calculations.  
The sample size chosen for this study was based upon precedent set by other pilot studies of 
similar nature and was not based on power calculations.  The sample size is based primarily on 
feasibility and the desire to gain efficacy and safety information to support further clinical 
studies.  A total of approximately 21 patients are considered suitable to achieve the study 
objectives. 
8.4 
Treatment Assignment and Blinding 
This is an open-label, single-arm, phase 2 study; thus, blinding is not part of the study design. 
8.5 
Study Endpoints and Statistical Analyses 
Efficacy analyses will be performed on ITT Population. 
8.5.1 Primary Efficacy Endpoint (Disease Activity) 
The primary endpoint will be the proportion of patients on Day 169 with an improvement of 
disease activity score as defined by a decrease of IgG4-RD RI (Total Activity Score) of ≥2 points 
from Day 1 pre-dose disease activity score.  The number of “responders” will be presented as 
frequency counts and percentages.  
8.5.2 Secondary Efficacy Endpoint (Disease Activity) 
The Total Activity Score (from the IgG4-RD RI) will be summarized at each visit using 
descriptive statistics (N, mean, standard deviation, median, minimum/maximum).  Change from 
baseline will also be tabulated at each visit using the same descriptive statistics. For those 
patients that respond (per the primary endpoint) the duration of improvement will also be 
presented.  Additional analyses on the different RI parameters will be described in the SAP. 
Physician Global Assessment of Disease Activity (Visual Activity Score) and Patient Global 
Assessment of Disease Activity (Visual Activity Score) will be summarized at each visit using 
descriptive statistics (N, mean, standard deviation, median, minimum/maximum).  Change from 
baseline will also be tabulated at each visit using the same descriptive statistics. 

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The proportion of patients with 1) a decline of the IgG4-RD RI of ≥ 2 points compared to 
baseline (Day 1), 2) no glucocorticoid use between Day 57 and Day 169, and 3) no disease flares 
during the study will be determined.  Disease flare is defined as increase in the IgG4-RD RI of ≥ 
2 and/or the need for increase in steroids or institution of additional therapy for IgG4-RD.  The 
number of patients meeting the combination of these three criteria will be presented as frequency 
counts and percentages at all timepoints.    
8.5.3 Safety and Tolerability Endpoints 
Safety analyses will be performed using the Safety population (for this study is equivalent to ITT 
population). 
• The number and percent of patients experiencing a treatment-emergent adverse event will 
be tabulated for each coded MedDRA system-organ class and preferred term.  
Treatment-emergent adverse events will also be tabulated according to intensity and 
causality. 
• All serious adverse events, discontinuations due to adverse event, or deaths occurring 
during the course of the trial will be presented in patient listings. 
• Clinical laboratory tests (observed values) will be summarized descriptively in tabular 
format.  Shift tables will be presented for select laboratory parameters.  In the patient 
listings, flags will be attached to values outside of the laboratory’s reference limits along 
with the Investigator’s assessment of clinical significance.  A list of all normal laboratory 
ranges will also be provided.  Clinically significant laboratory test abnormalities that 
were considered AEs by the Investigator will be presented in the AE listings.   
• Vital signs (blood pressure, pulse, temperature) will be summarized (observed and 
change from baseline) at each visit vital signs are collected using descriptive statistics 
and patient listings. 
• Twelve-lead ECG data (corrected QT intervals: Bazett’s correction and Fridericia’s 
correction) will be summarized (observed and change from baseline) at each visit ECGs 
are collected using descriptive statistics and patient listings.  
• Concomitant Medications will be summarized by the number and percentage of patients 
in each therapeutic class and preferred term as coded using the WHODrug dictionary. 
• Physical Examinations will be presented in patient listings.  

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8.6 
Pharmacokinetic Analyses 
The individual patient pre-dose (trough) and end-of-infusion (peak) concentration-time data will 
be listed and displayed graphically on the linear and log scales.  The concentration-time data will 
be summarized descriptively in tabular and graphical formats (linear and log scales).    
8.7 
Pharmacodynamic Analyses 
All observed PD data and change from baseline data will be summarized using descriptive 
statistics and will be listed and summarized in tabular and/or graphical form.  Descriptive 
statistics on continuous data will include mean, median, standard deviation, and range, while 
categorical data may be summarized using frequency counts and percentages. 
8.8 
Pharmacokinetic/Pharmacodynamic Analyses 
Individual and mean peak and trough serum concentrations of XmAb5871 will be plotted versus 
time on dual y-axis plots along with biomarkers CD19 RO, ABC, B cell subsets, IgG4 and IgE 
serum levels, total plasmablasts versus time.  In addition, the change in peak and trough 
concentrations from baseline will be plotted versus time along with change from baseline in the 
biomarker measurements. 
Direct comparison of PK versus PD will be done using scatterplots of peak and trough serum 
concentration versus PD biomarker value. 
The peak and trough serum concentrations of XmAb5871 will be examined by FcγRIIa R131H 
and FcγRIIb I232T polymorphisms to determine if these genetic characteristics affect 
pharmacokinetics. 
8.9 
Data Quality Assurance 
Accurate, consistent, and reliable data will be ensured through the use Good Clinical Practices 
(GCP) guidelines regarding clinical data management practices and procedures. 
8.10 Immunogenicity Analysis 
Frequency and titer of human anti-human antibodies (ADA) will be listed.  
8.11 Interim Analyses 
No formal interim analysis is planned, however as this is an open-label study, continuous review 
of safety and efficacy data will occur may be used for submission to regulatory authorities.    

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9 
ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS 
9.1 
Data Quality Assurance 
The Sponsor will conduct a study initiation visit to verify the qualifications of the Investigator, 
inspect the facilities. 
The Investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study participant.  Frequent communication 
between the clinical site and the Sponsor is essential to ensure that the safety of the study is 
monitored adequately.  The Investigator will make all appropriate safety assessments on an 
ongoing basis.  The Sponsor’s medical representative may review safety information as it 
becomes available throughout the study. 
All aspects of the study will be carefully monitored with respect to GCP and SOPs for 
compliance with applicable government regulations.  The Study Monitor will be an authorized 
individual designated by TMG.  The Study Monitor will have access to all records necessary to 
ensure integrity of the data and will periodically review the progress of the study with the PI.  
The study may be audited to assess adherence to the Clinical Study Protocol. The 
Investigator/investigational site will permit study-related monitoring, audits, Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) review and regulatory inspections by 
providing direct access to source data/documents.  Direct access includes permission to examine, 
analyze, verify, and reproduce any records and reports that are important to the evaluation of a 
clinical study. 
During the conduct of the study, process-related audits may be performed as well.  An audit 
certificate will be provided in the final study report outlining the audit performed and other 
related activities. 
9.2 
Access to Source Data/Documents 
The Investigator will ensure the accuracy, completeness, and timeliness of the data reported to 
the Sponsor.  Data collection processes and procedures will be reviewed and validated to ensure 
completeness, accuracy, reliability, and consistency.  A complete audit trail will be maintained of 
all data changes.  The Investigator or designee will cooperate with the Sponsor’s 
representative(s) for the periodic review of study documents to ensure the accuracy and 
completeness of the data capture system at each scheduled monitoring visit. 

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Electronic consistency checks and manual review will be used to identify any errors or 
inconsistencies in the data.  This information will be provided to the respective study sites by 
means of electronic or manual queries. 
The Investigator or designee will prepare and maintain adequate and accurate study documents 
(medical records, ECGs, AE and concomitant medication reporting, raw data collection forms, 
etc.) designed to record all observations and other pertinent data for each subject receiving IMP. 
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the Institutional Review Board (IRB) to have direct access to all 
documents pertaining to the study. 
9.3 
Archiving Study Documents 
According to International Conference on Harmonization (ICH) guidelines, essential documents 
should be retained for a minimum of 2 years after the last approval of a marketing application in 
an ICH region and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years have elapsed since the formal discontinuation of clinical development 
of the IMP.  However, these documents should be retained for a longer period if required by the 
applicable legal requirements. 
9.4 
Good Clinical Practice 
The procedures set out in this clinical study protocol are designed to ensure that the Sponsor and 
the Investigator abide by the principles of the ICH guidelines on Good Clinical Practice (GCP) 
as outlined in CPMP/ICH/135/95 and the Declaration of Helsinki (Version 2008).  The clinical 
study also will be carried out in keeping with national and local legal requirements (in 
accordance with United States Investigational New Drug [IND] regulations [21 CFR Parts 50, 56 
and 312]). 
The Investigator will be responsible for the care of the patients throughout the study.  If the 
Investigator is not present at the study site, he/she will leave instructions for the staff and a 
telephone number where he/she can be reached. 
9.5 
Informed Consent 
Before each patient is enrolled in the clinical study, written informed consent will be obtained 
from the patient according to the regulatory and legal requirements of the participating country.  
As part of this procedure, the Investigator must explain orally and in writing the nature, duration, 
and purpose of the study, and the action of the drug in such a manner that the study patient is 

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aware of the potential risks, inconveniences, or AEs that may occur.  The patient should be 
informed that he/she is free to withdraw from the study at any time.  He/She will receive all 
information that is required by federal regulations and ICH guidelines.  The Principal 
Investigator or designee will provide the Sponsor with a copy of the IRB-approved informed 
consent form prior to the start of the study. 
The informed consent document must be signed and dated; one copy will be given to the patient, 
and the Investigator will retain a copy as part of the clinical study records.  The Investigator will 
not undertake any investigation specifically required for the clinical study until written consent 
has been obtained.  The terms of the consent and when it was obtained must also be documented.   
If a protocol amendment is required, then the informed consent document may need to be revised 
to reflect the changes to the protocol.  If the informed consent document is revised, it must be 
reviewed and approved by the responsible IRB/Independent Ethics Committee (IEC), and signed 
by all patients subsequently enrolled in the clinical study as well as those currently enrolled in 
the clinical study. 
9.6 
Protocol Approval and Amendment(s) 
Before the start of the clinical study, the clinical study protocol and other relevant documents 
will be approved by the IRB, in accordance with local legal requirements.  The Sponsor must 
ensure that all ethical and legal requirements have been met before the first subject is enrolled in 
the clinical study. 
This protocol is to be followed exactly.  Any deviations should be agreed by both the Sponsor 
and the Investigator, with the appropriate written and approved protocol amendments made to 
reflect the changes agreed upon.  Protocol amendments must be released by the responsible staff 
and receive IRB approval prior to implementation (as appropriate).  Where the deviation occurs 
for the well-being of the subject, the Sponsor must be informed of the action agreed upon.  
Administrative changes may be made without the need for a formal amendment, but will also be 
mentioned in the integrated clinical study report.  All amendments will be distributed to all study 
protocol recipients, with appropriate instructions. 
9.7 
Confidentiality Data Protection 
All clinical study findings and documents will be regarded as confidential.  Study documents 
(protocols, IBs and other material) will be stored appropriately to ensure their confidentiality.  
The Investigator and members of his/her research team (including the IRB) must not disclose 

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such information without prior written approval from the Sponsor, except to the extent necessary 
to obtain informed consent from patients who wish to participate in the trial or to comply with 
regulatory requirements. 
The anonymity of participating patients must be maintained.  Patients will be specified on study 
documents by their subject number, initial or birth date, not by name.  Documents that identify 
the subject (e.g., the signed informed consent document) must be maintained in confidence by 
the Investigator. 
9.8 
Publication Policy 
By signing the clinical study protocol, the Investigator agrees with the use of results of the 
clinical study for the purposes of national and international registration, publication and 
information for medical and pharmaceutical professionals.  If necessary, the competent 
authorities will be notified of the Investigator’s name, address, qualifications and extent of 
involvement.  An Investigator shall not publish any data (poster, abstract, paper, etc.) without 
having consulted with the Sponsor in advance. 
 
 

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10 REFERENCE LIST 
Brownlie RJ, Lawlor KE, Niederer HA, Cutler AJ, Xiang Z, Clatworthy MR et al.. 2008. 
Distinct cell-specific control of autoimmunity and infection by FcgRIIb. J Exp Med 205:883-
895. 
 
Carruthers MN, Stone JH, Deshpande V, Khosroshahi A.  2012.  Development of an IgG4-RD 
responder Index.  Int J Rheum Volume 2012, Article ID 259408, 7 pages.   
 
Carruthers MN, Topazian MD, Khosroshahi A, et al.. 2015. Rituximab for IgG4-related disease: 
a prospective, open-label trial. Ann Rheum Dis 0:1-7, doi:10.1136/annrheumdis-2014-206605. 
 
Chu SY, Vostiar I, Karki S, Moore GL, Lazar GA, Pong E, Joyce PF, Szymkowski DE, 
Desjarlais JR. 2008. Inhibition of B cell receptor-mediated activation of primary human B cells 
by coengagement of CD19 and Fc_RIIb with Fc-engineered antibodies. Mol Immunol 45:3926–
3933. 
 
Crowley JE, Stadanlick JE, Cambier JC, Cancro MP. 2009. FcgRIIB signals inhibit BLyS 
signaling and BCR-mediated BLyS receptor up-regulation. Blood 113:1464-1473. 
 
Deshpande V, Zen Y, Chan JKC, et al..  2012.  Consensus statement on the pathology of IgG4-
related disease.  Modern Pathology 25:1181-1192. 
 
Horton HM, Bernett MJ, Pong E, Peipp M, Karki S, Chu SY, Richards JO, Vostiar I, Joyce PF, 
Repp R, Desjarlais JR, Zhukovsky EA. 2008. Potent in vitro and in vivo activity of an 
Fcengineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 
68:8049-8057. 
 
Horton HM, Chu SY, Ortiz EC, Pong E, Cemerski S, Leung IW et al.. 2011. Antibody mediated 
coengagement of FcgRIIb and B cell receptor complex suppresses humoral immunity in systemic 
lupus erythematosus. J Immunol 186:4223-4233. 
 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline, E6: Guideline for Good 
Clinical Practice (CPMP/ICH/135/95), January 1997. 
 
Kamisawa T, Zen Y, Pillai S, Stone JH.  2014. IgG4-related disease.  Lancet 
http://dx.doi.org/10.1016/S0140-6736 (14)60720-0. 
 
Khosroshahi A, Bloch DB, Deshpande V, Stone JH.  2010.  Rituximab therapy leads to rapid 
decline of serum IgG4 levels and prompt clinical improvement in IgG4-related disease.  Arthritis 
Rheumatol 62:1755-1762. 
 
Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari S,  
Della-Torre E, Frulloni L, Goto H, Hart P,  Kamisawa T, Kawa S, Kawano M, Kim MH, 
Kodama Y, Kubota K, Lerch MM, Lohr M, Masaki Y, Matsui S, Mimori T, Nakamura, 

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Nakazawa T, Ohara A, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, 
Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig T, 
Yamamoto M, Zhang W, Chiba T, and Stone JH. 2015.  International Consensus Guidance 
Statement on the Management and Treatment of IgG4-Related Disease.  Arthritis Rheumatol 
2015 (in press). 
 
Matsubayashi H, Furukawa H, Maeda A, Matsunaga K et al..  2009.  Usefulness of positron 
emission tomography in the evaluation of distribution and activity of systemic lesions associated 
with autoimmune pancreatitis.  Pancreatology 9:694-699. 
 
Mattoo H, Mahajan VS, Della Torre E, Sekigami Y, Wallace ZS, Carruthers M, Della Torre E, 
Stone JH, Pillai S. 2014. De novo oligoclonal expansions of circulating plasmablasts in active 
and relapsing IgG4-related disease.  Journal of Allergy & Clinical Immunology 134(3):679-87. 
 
McGaha TL, Sorrentino B, Ravetch JV. 2005. Restoration of tolerance in lupus by targeted 
inhibitory receptor expression. Science 307:590-3. 
 
Meeker TC, Miller RA, Link MP, Bindl J, Warnke R, Levy R. 1984. A unique human B 
lymphocyte antigen defined by a monoclonal antibody. Hybridoma. 3(4):305-320. 
 
Nadler LM, Anderson KC, Marti G, Bates M, Park E, Daley JF, et al.. 1983. B4, a human B 
lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B 
lymphocytes. J Immunol 131:244-250. 
 
Nimmerjahn F, Ravetch JV. 2008. Fcg receptors as regulators of immune responses. Nat Rev 
Immunol 8:34-47. 
 
Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, 
Anderson DR. 1994. Depletion of B Cells In Vivo by a Chimeric Mouse Human Monoclonal 
Antibody to CD20. Blood 83:435-445. 
 
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al.. 
Second symposium on the definition and management of anaphylaxis: Summary report—Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol 2006;117:391-7. 
 
Smith KG, Clatworthy MR. 2010. FcgammaRIIB in autoimmunity and infection: evolutionary 
and therapeutic implications. Nature Rev Immunol 10:328-343. 
 
Stone JH, Hoffman GS, Merkel PA, Min YI, Uhlfelder ML, Hellmann DB, Specks U, Allen NB, 
Spiera RF, Calabrese LH, Wigley FM, Davis JC, Maiden N, Valente RM, Niles JL, Fye KH, 
McCune JW, St. Clair EW, Luqmani RA.  2001. A disease-specific activity index for Wegener’s 
granulomatosis: Modification of the Birmingham Vasculitis Activity Score.  International 
Network for the Study of the Systemic Vasculitides (INSSYS).  Arthritis & Rheumatism 44: 
912-920. 
 

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Stone JH, Merkel PA, Spiera R et al..  2010.  Rituximab versus cyclophosphamide for ANCA-
associated vasculitis.  NEJM 363:221-232.  
 
Stone JH, Zen Y, Deshpande V.  2012.  IgG4-related disease.  N Engl J Med 366:539-551. 
 
Tarasenko T, Dean JA, Bolland S. 2007. FcgRIIB as a modulator of autoimmune disease 
susceptibility. Autoimmunity 40:409-17. 
 
Uchida K, Masamune A, Shimosegawa T, Okazaki. 2012.  Prevalence of IgG4-related disease in 
Japan based on nationwide survey in 2009.  Int J Rheum Volume , Article ID 358371, 5 pages. 
 
Wallace ZS, Mattoo H, Carruthers M et al..  2014.  Plasmablasts as a biomarker for IgG4-related 
disease, independent of serum IgG4 concentrations.  Ann Rheum Dis  
doi: 10.1136/annrheumdis-2014-205233 [Epub ahead of print]. 
 
Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH. 2015.  
IgG4-related disease: Baseline clinical and laboratory features in 125 patients with biopsy-
proven disease.  Arthritis & Rheumatology 2015 (in press).  
 
WMA Declaration of Helsinki (18th WMA General Assembly 1964), revised at 59th World 
Medical Association General Assembly Seoul, October 2008. 
 
Yamamoto M, Takahashi H, Shinomura Y.  2014.  Mechanisms and assessment of IgG4-related 
disease: lessons for the rheumatologist. Nat Rev Rheumatol 10:148-159. 
 
 

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11 APPENDICES 
11.1 Efficacy Assessments 
11.1.1 IgG4-RD Responder Index (IgG4-RD RI) 
The IgG4-RD RI is a tool designed to detect change in disease activity and identify 
improvements and worsening in the same or different organ systems (modified after Carruthers, 
2012).     
At each assessment, the physician enters a 0-3 score after the organ/site listed with;  
0 = Normal or resolved 
1 = Improved but still present 
2 = New or recurrent disease activity while patient is off treatment, or unchanged from previous 
visit* 
3 = Worsened or new disease manifestation despite treatment 
*Unchanged from previous visit will often refer to disease manifestations that require follow-up 
imaging to assess accurately. 
The second column is used to record symptomatic disease; yes=Y, no=N. 
The third column records whether there is urgent disease in that site; yes=Y, no=N. 
Damage in the organ/site is recorded in the fourth column; yes=Y, no=N. 
The fifth column records whether damage in the organ/site is symptomatic; yes=Y, no=N. 
 
Physician Global Assessment of disease activity is denoted on a 100 mm line as covered further 
in Appendix 11.1.2. 
 
 
 
 

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IgG4-RD Responder Index (Version 25July2016) 
Scoring Rules 
Scoring refers to manifestations of disease activity present in the last 28 days 
 
Scoring: 0 
Normal or resolved 
Improved but still present 
New / Recurrence while patient is off treatment or unchanged from previous visit* 
Worsened or new disease manifestation despite treatment 
*Unchanged from previous visit will often refer to disease manifestations that require follow-up 
imaging to assess accurately 
Definitions 
Organ/Site score: The overall level of IgG4-RD activity within a specific organ system 
Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) 

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Total activity score is calculated as given in the lower left hand corner = 
Sum of organ scores (any that are urgent are multiplied by 2).  
 
 

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11.1.2 Physician and Patient Global Assessment of Disease Activity (VAS) 
 
Patient’s Global Assessment of Disease Activity (100 mm-VAS) 
The patient will be instructed as follows: Considering all the ways in which illness and health 
conditions may affect you at this time, please make a mark between 0 and 100 mm on the line 
below to show how you are doing: 
 
VASPatient Global Assessment of Disease Activity = _______ mm 
 
Physician’s Global Assessment of Disease Activity (100 mm-VAS) 
Place a mark on the line below to indicate disease activity (independent of the patient’s self-
assessment):  
 
 
 
VASPhysician Global Assessment of Disease Activity = _______ mm 
 
Very Well 
Very Poorly 
Very Good 
Very Bad