A Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of XmAb®5871 on Systemic Lupus Erythematosus Disease Activity
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: Xencor, Inc.

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
Page 1 of 132 
29 July 2016 
Clinical Study Protocol 
A Randomized, Double-Blinded, Placebo-Controlled Study of the 
Effect of XmAb®5871 on Systemic Lupus Erythematosus Disease 
Activity  
Sponsor: 
Xencor, Inc. 
111 West Lemon Avenue 
Monrovia, CA 91016 
Clinical Research Organization: 
Pharmaceutical Product Development, LLC 
929 N Front St  
Wilmington, NC 28401 
Coordinating Investigator: 
Joan T. Merrill, MD 
Sponsor Protocol No.: 
XmAb5871-04 
IND No.: 
125,319 
IMP Name: 
XmAb5871 
Development Phase: 
Phase 2 
Version, Date: 
Version 2.0 Amendment 1 
29 July 2016 
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 XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
Page 3 of 132 
29 July 2016 
SIGNATURE PAGE 
Declaration of the Principal Investigator 
Protocol Title: A Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of 
XmAb®5871 on SLE Disease Activity 
This clinical study protocol was subjected to critical review and has been released by the 
Sponsor.  I have read this protocol and agree that the information it contains is consistent with 
current risk and benefit evaluation of the investigational medicinal product (IMP), as well as 
with the moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki (Version 2008), and the current guidelines on Good Clinical Practices 
(GCP) applicable to this clinical study.  
I will provide copies of the protocol and of the clinical and preclinical information on the 
investigational product, which was furnished to me by the Sponsor, to all members of the study 
team responsible to me who participate in the study.  I will discuss this material with them to 
assure that they are fully informed regarding the study drug and the conduct of the study. 
I will perform the study according to specifications outlined in the protocol and agree to 
implement protocol requirements only after this protocol version and the patient 
information/informed consent forms have been approved by the Institutional Review Board 
(IRB).  I will not modify this protocol without obtaining the prior approval of the Sponsor and of 
the IRB. I will submit any protocol modifications (amendments) and/or any informed consent 
form modifications to the Sponsor and the IRB, and approval will be obtained before any 
modifications are implemented. 
I understand that the information presented in this study protocol is confidential, and I hereby 
assure that no information based on the conduct of the study will be released without prior 
consent from the Sponsor Xencor, Inc., unless this requirement is superseded by a regulatory 
authority, e.g., FDA. 
I agree to conduct the study as outlined in this Clinical Study Protocol dated 27 July 2016.  Any 
modification of the Clinical Study Protocol must be agreed upon by the Sponsor and the 
Investigator(s) and must be documented in writing. 
Principal Investigator 
Signature 
Date 
Printed name 
Institution 
August 2, 2016
Joan T. Merrill, M.D.                                                         Oklahoma Medical Research Foundation

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
Page 4 of 132 
29 July 2016 
PROTOCOL SYNOPSIS 
Protocol Title: 
A Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of XmAb®5871 
on Systemic Lupus Erythematosus  Disease Activity 
Protocol Short Title 
Phase 2 Study of XmAb5871 in Patients with SLE 
Study Number: 
Sponsor Protocol No.:  XmAb5871-04 
Investigational 
Product 
XmAb®5871 
IND Number 
125,319 
Development Phase: 
Phase 2 
Indication 
Systemic Lupus Erythematosus (SLE) 
Sponsor: 
Xencor, Inc. 
Coordinating 
Investigator: 
Joan T. Merrill, MD 
Study Center(s): 
Up to 25 sites  
Study Objectives: 
Primary Objective 
•
 To determine the ability of  XmAb5871 to maintain SLE disease activity improvement
achieved by a brief course of disease-suppressing intramuscular (IM) steroid therapy in
SLE patients
Secondary Objective 
•
To evaluate time to loss of SLE disease activity improvement achieved by a brief
course of  disease-suppressing IM steroid therapy in SLE patients 
•
To evaluate the safety and tolerability of every other week intravenous (IV)
administration of XmAb5871 in patients with SLE 
•
To evaluate the pharmacokinetics (PK) and immunogenicity of every other week IV
administration of XmAb5871 in patients with SLE 
Exploratory Objectives  
•
To characterize the pharmacodynamics (PD) of every other week IV administration of
XmAb5871 in patients with SLE as follows:
•
To evaluate the effect of XmAb5871 on changes in the absolute B Cell count
(ABC)
•
 To characterize the effect of XmAb5871 on SLE disease activity over time
•
To evaluate the effect of XmAb5871 on autoantibody, complement and cytokine
levels
Study Design: 
This is a randomized double-blind, placebo-controlled study of approximately 90 patients 
with SLE.  Participants will receive 5 mg/kg XmAb5871 or placebo (randomized 1:1) by 
IV infusion every other week for up to a total of 16 infusions.   
Investigational 
Medicinal 
Product(s); IMP, 
Dose and Route of 
Administration: 
XmAb5871 drug product is a liquid product supplied in single-use glass vials.  Each 10 mL 
glass vial is filled with 10.5 mL of drug product containing 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.   
Dose and route of administration: Every other week administration of XmAb5871 at 
5.0 mg/kg by IV infusion over 1-2 hours 
Placebo to match XmAb5871, administered by IV infusion over 1-2 hours 
Number of Patients: 
Approximately 90 patients with active SLE 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
Page 5 of 132 
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Study Population: 
Male and female patients ages 18 to 65 inclusive with active SLE at screening 
Study Duration 
After up to a 4-week screening period, participants will receive XmAb5871 or placebo IV 
every other week for up to a total of 16 doses (30 weeks) and will be followed for 6 weeks 
following the last dose for a total study period of up to 40 weeks. 
Study Procedures: 
Eligible patients must have moderate to severe, non-organ threatening, SLE activity defined 
as a SELENA SLEDAI of ≥6 (≥4 points of which must come from non-serological 
findings) OR ≥1 BILAG B score OR ≥1 BILAG A score.  Patients must be able and willing 
to discontinue background immunosuppressive medications and to receive a brief course of 
IM steroid therapy to enter screening.   
After obtaining informed consent, 160 mg of IM depomedrol will be administered and 
screening studies will be performed.  Over the 2-4 week period following the initial IM 
depomedrol, per investigator discretion, patients may receive additional IM depomedrol (up 
to an additional 320 mg during screening) to treat their SLE symptoms to a target of disease 
activity improvement defined as a SELENA SLEDAI decrease of ≥4 points OR a decrease 
in BILAG of ≥1 severity grade in at least one organ system that began with A or B (clinical 
criteria without requiring temporal criteria).  Immunosuppressive therapy will be stopped or 
tapered off over the 2-4 week screening period and must be discontinued by randomization 
on Day 1.  Patients on anti-malarial therapy may continue on their usual dose.  Patients 
entering the study on oral doses of ≤15 mg of prednisone per day (or the equivalent) will 
taper their oral steroids to 10 mg per day or less by randomization (Day 1) and then may 
continue on a ≤10 mg daily dose through the study.  Patients who do not meet the disease 
activity improvement criteria during the 2-4 week screening period will not be randomized 
into the study and their participation will end. 
Patients must have documented disease activity improvement following the brief course of 
IM steroid therapy during the screening period to be randomized into the study on Day 1.  
Those patients who achieve the required disease activity improvement from the screening 
baseline will be randomized to receive either XmAb5871 (5 mg/kg) or matching placebo by 
IV administration (double-blinded) over 1-2 hours every 2 weeks from Day 1 through Day 
211 for a total of up to 16 infusions.  Disease activity (SELENA SLEDAI, BILAG) on Day 
1 will be considered the baseline disease activity for determination of the efficacy 
endpoints.  On Day 1, 80 mg of IM depomedrol will be administered and baseline 
procedures including physical exam, blood and urine samples for laboratory assessments, 
PK and PD samples will be performed.  The first infusion of XmAb5871 or placebo will be 
given IV over a period of 2 hours.  Patients will be observed for at least 2 hours after 
completion of the first study drug administration during which time safety assessments will 
be performed.   
All patients will return to the research facility on Day 8 for safety, PK and PD assessments.  
On study Day 15, patients will receive 80 mg of IM depomedrol in addition to the 
procedures scheduled for that day and will receive the second IV infusion of XmAb5871 or 
placebo.  Patients will return on study Days 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 
183, 197 and 211 for XmAb5871 or placebo administration IV over 1-2 hours and for 
safety, PK and PD assessments.  Patients will be required to remain at the study site for 
observation for at least 1 hour after the completion of each infusion.  
Patients will be followed for the loss of disease activity improvement (LOI) as defined by: 
I. 
The assessment by the investigator that SLE disease activity is appropriate for an 
increase in therapy (including addition of another lupus therapy, except for 
adjustments in NSAIDs) AND 
II. There has been one of the following compared to baseline (Day 1):
1) a SELENA SLEDAI increase of ≥4 points from maximal improvement OR
2) a worsening of at least 1 BILAG A or B score OR
3) the appearance of a new BILAG A or B score.
Patients who meet the criteria for loss of disease activity improvement at any timepoint up 
to and including Day 211 will not receive further infusions of XmAb5871 or placebo and 
may receive any appropriate SLE therapy at the discretion of the principal 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 6 of 132 
29 July 2016 
 
investigator.  
The effect of XmAb5871 on loss of improvement of SLE disease activity will be evaluated 
as the percentage of patients without loss of disease activity improvement at Day 225 
(primary endpoint) and Day 169 (secondary endpoint).  Patients with loss of disease 
activity improvement at any time-point up to and including Day 225 will be considered 
non-responders for the primary endpoint.  Patients who discontinue the study early either 
because of loss of improvement or for other reasons will be followed for a further period of 
6 weeks after their last dose of XmAb5871 or placebo.   
All patients completing the treatment period should be followed through Day 253(EOS).  
Patient participation is complete once EOS study procedures are 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 (TEAEs) or clinically significant safety lab abnormalities will be 
followed until resolution or until the TEAEs/abnormalities are stabilized.  
Criteria for 
Evaluation: 
Disease Activity: 
The following disease activity parameters will be recorded at scheduled intervals 
throughout the study: 
• 
SELENA SLEDAI using the SELENA SLEDAI hybrid version with the SELENA 
SLEDAI Flare Index 
• 
BILAG using the BILAG 2004 
• 
Physician’s Global Assessment VAS 
Safety: 
The following safety parameters will be recorded at regular intervals during the study: 
• 
Adverse events (CTCAE v 4.03) 
• 
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) 
• 
B cell and T cell quantification by flow cytometry 
• 
Concomitant medications 
• 
Physical examinations 
Immunogenicity: 
The following immunogenicity parameter will be recorded during the study: 
• 
Anti-XmAb5871 antibodies (anti-drug antibodies [ADA]) 
Pharmacokinetics: 
Serum XmAb5871 peak and trough serum concentrations will be measured in this study.  
Pharmacodynamics: 
• 
Circulating ABC count 
• 
SLE autoantibody panel, complement levels and cytokine profile 
Pharmacogenomics: 
• 
FcγRIIa R131H polymorphism 
• 
FcγRIIb I232T polymorphism 
Statistical Methods: 
Sample size considerations: 
Sample size is based on a previously completed study of SLE patients treated with disease-
suppressing IM depomedrol therapy for up to 2 weeks following cessation of background 
immunosuppressant therapy.  In that study, by month 6, 40/41 patients lost the disease 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 7 of 132 
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activity improvement achieved following IM steroid therapy; a 2.4% placebo response.  
Assuming a placebo response of 10% and a 38% XmAb5871 response in preventing loss of 
disease activity improvement, the number of patients needed for 80% power and 5% 
significance would be approximately 40 per arm.  Adding approximately 10% for 
unevaluable patients, the total number per arm is calculated as 45. 
Statistics: 
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 will be summarized using 
Kaplan-Meier methods (median, 95% CI, number of events, number censored, 
Kaplan-Meier figures).  Data listings will be created to support each table and to present all 
data.   
The primary efficacy endpoint will be evaluated as the percentage of patients without loss 
of disease activity improvement on Day 225. The percentage of patients without loss of 
disease activity improvement on Day 169 will be a secondary endpoint.  Loss of 
improvement (LOI) will be defined as worsening of disease activity that: 
In the opinion of the principal investigator requires change in treatment (exclusive of a 
decrease in oral steroid use) AND one of  
1) A SELENA SLEDAI increase of ≥4 points from maximal improvement OR  
2) A worsening of at least 1 BILAG A or B score OR  
3) A new BILAG A or B score. 
The Fishers exact test will be performed on the Efficacy Evaluable Population to test for 
treatment group differences.  The same analysis on the ITT Population will also be utilized 
for sensitivity analysis.    
In addition to the percentage of patients without loss of disease activity improvement on 
Day 169, the time to loss of SLE disease activity improvement achieved by a short period 
of IM steroid therapy in SLE patients will be a secondary endpoint. This endpoint will be 
summarized by treatment arm using Kaplan-Meier methods (median, 95% CI, number of 
events, number censored, etc.) and Kaplan-Meier plots. The log-rank test will be used to 
test for treatment group differences on the Efficacy Evaluable and ITT populations.  
All safety data will be based on the Safety 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 by treatment arm.  Treatment-emergent 
adverse events will also be tabulated according to intensity and causality by treatment arm. 
Clinical laboratory tests, vital signs, and ECG data will be summarized by treatment arm 
using descriptive statistics. 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 8 of 132 
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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: 
Justine Bucholz 
PPD 
3900 Paramount Parkway  
Morrisville, NC 27560-7200 
Telephone number: 910-558-4994 
Cell: 234-788-3475 Email: Justine.Bucholz@ppdi.com 
Coordinating 
Investigator: 
Joan T. Merrill, MD 
Oklahoma Medical Research Foundation 
825 NE 13th St. 
Oklahoma City, Oklahoma 73104 
Telephone number: 405-271-7805 
Fax number: 405-271-8793 
Email: Joan-Merrill@omrf.org 
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 
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 

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Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
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Email: Mallika.Kopalle@iconplc.com 
Clinical Laboratory 
(including Flow 
Cytometry B- 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  
Biomarker and 
Mechanistic Study 
Laboratory 
Judith James, MD, PhD 
Oklahoma Medical Research Foundation 
825 NE 13th St. 
Oklahoma City, Oklahoma 73104 
Telephone number: 405-271-4987 
Email: Judith-James@omrf.org 
 
 
 
 

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Protocol Number XmAb5871-04 
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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ................................................................................................................4 
LIST OF STUDY STAFF ................................................................................................................8 
LIST OF ABBREVIATIONS ........................................................................................................15 
SUMMARY OF CHANGES – VERSION 1 TO VERSION 2 .....................................................18 
1. 
INTRODUCTION ......................................................................................................31 
1.1. 
Background .................................................................................................................31 
1.1.1. 
Role of B Cells in Autoimmunity ...............................................................................31 
1.1.2. 
XmAb5871 .................................................................................................................31 
1.1.3. 
Systemic Lupus Erythematosus (SLE) .......................................................................32 
1.1.4. 
Current Treatment of SLE ..........................................................................................34 
1.2. 
Non-Clinical Studies ...................................................................................................34 
1.2.1. 
Pharmacology of XmAb5871 .....................................................................................34 
1.2.1.1. 
In Vitro Pharmacology ...............................................................................................34 
1.2.1.2. 
In Vivo Pharmacology ................................................................................................36 
1.2.2. 
Secondary Pharmacology: Off Target Receptor Binding Studies ..............................36 
1.2.3. 
Nonclinical Pharmacokinetics and Toxicology of XmAb5871 ..................................38 
1.2.3.1. 
Tissue Cross-Reactivity Studies .................................................................................38 
1.2.3.2. 
Non-GLP and GLP Toxicology Studies in Cynomolgus Monkey .............................38 
1.3. 
Clinical Studies ...........................................................................................................40 
1.3.1. 
A Randomised, Blinded, Placebo-Controlled, Single Ascending Dose Study 
of the Safety, Tolerability, and Pharmacokinetics of XmAb®5871 in Healthy 
Adult Volunteers .........................................................................................................40 
1.3.2. 
A Randomized, Placebo-Controlled, Double-Blinded, Ascending 
Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of XmAb®5871 in Patients with Rheumatoid Arthritis ..............41 
1.4. 
Rationale for the Clinical Study .................................................................................44 
1.4.1. 
Risk-Benefit Assessment ............................................................................................45 
1.4.2. 
Potential Risks ............................................................................................................46 
1.4.2.1. 
Infusion-Related Reactions .........................................................................................46 
1.4.2.2. 
Infusion-Associated Gastrointestinal-Related Toxicity ..............................................47 
1.4.2.3. 
B-Cell Lymphopenia ..................................................................................................48 
1.4.2.4. 
Infections ....................................................................................................................48 
1.4.3. 
Potential Benefits ........................................................................................................49 

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1.4.4. 
Conclusion ..................................................................................................................49 
2. 
STUDY OBJECTIVES ..............................................................................................49 
2.1. 
Primary Objective .......................................................................................................49 
2.2. 
Secondary Objective ...................................................................................................49 
2.3. 
Exploratory Objectives ...............................................................................................50 
3. 
INVESTIGATIONAL PLAN .....................................................................................50 
3.1. 
Overall Study Design and Plan ...................................................................................50 
3.2. 
Discussion of Study Design ........................................................................................52 
3.3. 
Selection of Patient Population ...................................................................................53 
3.4. 
Endpoints ....................................................................................................................53 
3.4.1. 
Disease Activity ..........................................................................................................53 
3.4.2. 
Mechanistic Studies ....................................................................................................53 
3.4.3. 
Safety Endpoints .........................................................................................................54 
3.4.4. 
Immunogenicity Endpoint ..........................................................................................54 
3.4.5. 
Pharmacokinetic Endpoints ........................................................................................54 
3.4.6. 
Pharmacodynamic Endpoints .....................................................................................55 
3.4.7. 
Pharmacogenomics Endpoints ....................................................................................55 
3.5. 
Stopping Criteria for the Clinical Study .....................................................................55 
3.6. 
Dose Delay and Dose Modification in Patients Who Experience Toxicity ................55 
4. 
STUDY POPULATION .............................................................................................56 
4.1. 
Number of Patients .....................................................................................................56 
4.2. 
Inclusion Criteria ........................................................................................................56 
4.3. 
Exclusion Criteria .......................................................................................................58 
4.4. 
Patient Withdrawal and Replacement .........................................................................59 
4.5. 
Termination of the Clinical Study ..............................................................................60 
5. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................60 
5.1. 
Identity of the Investigational Medicinal Products .....................................................60 
5.2. 
Drug Storage and Handling Requirements .................................................................61 
5.3. 
Drug Administration ...................................................................................................62 
5.4. 
Dose Rationale ............................................................................................................62 
5.5. 
Supply, Packaging, and Labeling ...............................................................................63 
5.6. 
Drug Accountability, Dispensing and Destruction .....................................................63 

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5.7. 
Patient Identification ...................................................................................................64 
5.7.1. 
Screening and Randomization Numbers ....................................................................64 
5.8. 
Administration of Investigational Medicinal Product ................................................64 
5.9. 
Compliance .................................................................................................................64 
5.10. 
Concomitant Medications ...........................................................................................65 
5.10.1. 
Previous / Concomitant Medication ...........................................................................65 
5.10.1.1. 
Disallowed previous or concomitant medications: .....................................................65 
5.10.2. 
Contraception ..............................................................................................................66 
6. 
VARIABLES AND METHODS OF ASSESSMENT ...............................................66 
6.1. 
Safety Variables ..........................................................................................................66 
6.1.1. 
Medical History, Demographic and Other Baseline Information ...............................66 
6.1.2. 
Adverse Events ...........................................................................................................67 
6.1.2.1. 
Definitions ..................................................................................................................67 
6.1.2.2. 
Recording of Adverse Events .....................................................................................68 
6.1.2.3. 
Assessment of Adverse Events ...................................................................................68 
6.1.2.4. 
Reporting of Serious Adverse Events .........................................................................76 
6.1.2.5. 
Follow-up of Adverse Events .....................................................................................78 
6.1.2.6. 
Pregnancy ...................................................................................................................78 
6.1.3. 
Vital Signs ..................................................................................................................79 
6.1.4. 
12-lead Electrocardiograms ........................................................................................79 
6.1.5. 
Physical Examinations ................................................................................................80 
6.1.6. 
Clinical Laboratory Assessments ...............................................................................80 
6.2. 
Pharmacokinetic Variables .........................................................................................83 
6.3. 
Pharmacodynamic Variables ......................................................................................83 
6.4. 
Pharmacogenomics Variables .....................................................................................83 
6.4.1. 
Efficacy Measurements ..............................................................................................84 
7. 
STUDY CONDUCT ...................................................................................................85 
7.1. 
Schedule of Assessments ............................................................................................85 
7.1.1. 
Assessments by Visit ..................................................................................................85 
7.1.2. 
Early Termination Visit ..............................................................................................86 
7.1.3. 
End-of-Study ...............................................................................................................86 
8. 
STATISTICAL METHODS .......................................................................................90 

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8.1. 
Study Population .........................................................................................................90 
8.1.1. 
Disposition of Patients ................................................................................................90 
8.1.2. 
Protocol Deviations ....................................................................................................90 
8.1.3. 
Analysis Populations ..................................................................................................90 
8.2. 
General Considerations ...............................................................................................91 
8.3. 
Determination of Sample Size ....................................................................................91 
8.4. 
Treatment Assignment and Drop-Outs .......................................................................91 
8.5. 
Blinding ......................................................................................................................92 
8.6. 
Study Endpoints and Statistical Analyses ...................................................................92 
8.6.1. 
Primary Efficacy Endpoint (Loss of Improvement at Day 225) .................................93 
8.6.2. 
Secondary Efficacy Endpoints ....................................................................................93 
8.6.3. 
Exploratory Efficacy Endpoints .................................................................................93 
8.6.4. 
Safety and Tolerability Endpoints ..............................................................................94 
8.7. 
Pharmacokinetic Analyses ..........................................................................................94 
8.8. 
Pharmacodynamic Analyses .......................................................................................95 
8.9. 
Pharmacokinetic/Pharmacodynamic Analyses ...........................................................95 
8.10. 
Data Quality Assurance ..............................................................................................95 
8.11. 
Immunogenicity Analysis ...........................................................................................95 
8.12. 
Interim Analyses .........................................................................................................95 
9. 
ETHICAL, LEGAL AND ADMINISTRATIVE ASPECTS .....................................95 
9.1. 
Data Quality Assurance ..............................................................................................95 
9.2. 
Access to Source Data/Documents .............................................................................96 
9.3. 
Archiving Study Documents .......................................................................................97 
9.4. 
Good Clinical Practice ................................................................................................97 
9.5. 
Informed Consent .......................................................................................................97 
9.6. 
Protocol Approval and Amendment(s) .......................................................................98 
9.7. 
Confidentiality Data Protection ..................................................................................98 
9.8. 
Publication Policy .......................................................................................................99 
10. 
REFERENCE LIST ..................................................................................................100 
11. 
APPENDICES ..........................................................................................................102 
11.1. 
Efficacy Assessments ...............................................................................................102 
11.1.1. 
Hybrid SELENA SLEDAI and SELENA SLEDAI Flare Index ..............................102 

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11.1.2. 
BILAG2004 ..............................................................................................................105 
11.1.3. 
Physician Global Assessment of Disease Activity (VAS) .......................................106 
11.1.4. 
BILAG2004 and SELENA SLEDAI Instructions ....................................................106 
 
LIST OF TABLES 
Table 1: Prednisone Equivalence ...................................................................................................65 
Table 2: Severity Grading Scale ....................................................................................................69 
Table 3: Causality Grading Scale ..................................................................................................70 
Table 4: Definition of Anaphylaxis ...............................................................................................73 
Table 5: Infusion-Related Reaction and Cytokine Release Syndrome ..........................................74 
Table 6: Schedule of Assessments [a] .............................................................................................87 
 
 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 15 of 132 
29 July 2016 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
Ab 
Antibody 
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 
BILAG 
British Isles Lupus Activity Group, in this protocol, version BILAG2004 
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 
ECG 
Electrocardiogram 
ELISA 
Enzyme-linked immunosorbant assay 
EOI 
End of infusion 
EOS 
End-of-study 
Fc 
Fragment, crystallizable 
FcγRIIb 
Fcγ receptor IIb 
FDA 
Food and Drug Administration 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 16 of 132 
29 July 2016 
 
FIH 
First in human 
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 
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 
kD 
Dissociation constant 
LDH 
Lactate dehydrogenase 
LOI 
Loss of disease activity improvement 
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 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 17 of 132 
29 July 2016 
 
NK 
Natural killer 
NOAEL 
No observable adverse effect level 
NSAID 
Nonsteroidal anti-inflammatory drug 
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 
SELENA 
SLEDAI 
SLE disease activity index as modified in the SELENA study 
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 
URI 
Upper respiratory infection 
 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 18 of 132 
29 July 2016 
 
 
PROTOCOL NO. XmAb5871-04AMENDMENT 1 - 27 JULY 2016 
“A Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of XmAb®5871 on Systemic Lupus Erythematosus Disease Activity”  
SUMMARY OF CHANGES – VERSION 1 TO VERSION 2 
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:  
Participants will receive 5 mg/kg XmAb5871 or placebo (randomized 
1:1) by IV infusion every other week for up to a total of 16 12 
infusions.  
• 
Adding 4 additional infusions for a total of 16 
5  
Protocol Synopsis 
(Study Duration) 
Changed the following stricken text and added the following bold 
text:  
After up to a 4-week screening period, participants will receive 
XmAb5871 or placebo IV every other week for up to a total of 1612 
doses (3022 weeks) and will be followed for 6 weeks following the last 
dose for a total study period of up to 4032 weeks. 
• 
Incorporating the additional 8 weeks of dosing 
5-6  Protocol Synopsis 
(Study 
Procedures) 
Changed the following stricken text and added the following bold 
text:  
Those patients who achieve the required disease activity improvement 
from the screening baseline will be randomized to receive either 
XmAb5871 (5 mg/kg) or matching placebo by IV administration 
(double-blinded) over 1-2 hours every 2 weeks from Day 1 through 
Day 211155 for a total of up to 16 12 infusions. 
Patients will return on study Days 29, 43, 57, 71, 85, 99, 113, 127, 
141, and 155, 169, 183, 197 and 211 for XmAb5871 or placebo 
administration IV over 1-2 hours and for safety, PK and PD 
assessments.   
Patients who meet the criteria for loss of disease activity improvement 
at any timepoint up to and including Day 211155 will not receive 
further infusions of XmAb5871 or placebo 
The effect of XmAb5871 on loss of improvement of SLE disease activity 
will be evaluated as the percentage of patients without loss of disease 
activity improvement at Day 225169 (primary endpoint) and Day 169 
(secondary endpoint).  Patients with loss of disease activity 
• 
Incorporating the additional 8 weeks of dosing 
 
 
 
 
• 
The new primary endpoint will be at 2 weeks after 
the last infusion, with the previous Day 169 
evaluation becoming a secondary endpoint. 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 19 of 132 
29 July 2016 
 
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Justification 
improvement at any time-point up to and including Day 225169 will be 
considered non-responders for the primary endpoint.   
All patients completing the treatment period should be followed 
through Day 253197(EOS). 
7  
Protocol Synopsis 
(Statistical 
Methods) 
Changed the following stricken text and added the following bold 
text:  
The primary efficacy endpoint will be evaluated as the percentage of 
patients without loss of disease activity improvement on Day 225 169. 
The percentage of patients without loss of disease activity 
improvement on Day 169 will be a secondary endpoint.   
In addition to the percentage of patients without loss of disease 
activity improvement on Day 169, . The secondary efficacy endpoint 
will beof the time to loss of SLE disease activity improvement achieved 
by a short period of IM steroid therapy in SLE patients will be a 
secondary endpoint. This endpoint will be summarized by treatment 
arm using Kaplan-Meier methods 
• 
Adjusts the primary endpoint to Day 225, with 
percentage of patients without loss of disease 
activity improvement on Day 169 made a 
secondary endpoint. 
8 
List of Study Staff 
(Contract 
Research 
Organization) 
Updated the name and contact information for the following staff: 
Justine Bucholz Cherie Young 
PPD 
3900 Paramount Parkway 929 N Front St  
MorrisvilleWilmington, NC 27560-720028401 
Telephone number: 910-558-4994 
Cell: 234-788-3475 512-284-4927 
Email: Justine.Bucholz@ppdi.com Cherie.Young@ppdi.com 
• 
Updated to reflect personnel changes 
8  
List of Study Staff 
(Bioanalytical 
Laboratory – PK) 
Updated the name and contact information for the following staff: 
Deborah P. Candido Cynthia Wydysh 
ICON Laboratory Services, Inc. Development Solutions, LLC  
8282 Halsey Road 
Whitesboro, NY 13492 
Telephone number: 315-768-2527 
• 
Updated to reflect personnel and address changes 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 20 of 132 
29 July 2016 
 
Page 
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Justification 
Fax number: 315-736-2460 
Email: Cynthia.Wydysh@iconplc.com 
Telephone number: 315-768-2554 
Email: Deborah.Candido@iconplc.com 
8  
List of Study Staff 
(Genotyping 
Laboratory) 
Updated the name of the Genotyping Laboratory: 
Ryan Newman 
Cancer Genetics, Inc.Gentris Corporation 
133 Southcenter Court, Suite 400 
Morrisville, NC 27560 
Telephone number: 919-653-5532 
Fax number: 919-653-5542 
Email: Ryan.Newman@cgix.Gentris.com 
• 
Updated to reflect changed company name and 
emails 
8-9  List of Study Staff 
(Immunogenicity 
Laboratory – 
ADA) 
Updated the name and contact information for the following staff: 
Melissa Mitchell Mallika Kopalle 
ICON Laboratory Services, Inc. Development Solutions, LLC 
8282 Halsey Road 
Whitesboro, NY 13492 
Telephone number: 315-768-2834  
Telephone number: 315-768-2800 
Email: Melissa.Mitchell Mallika.Kopalle@iconplc.com 
• 
Updated to reflect personnel and address changes 
9 
List of Study Staff 
(Clinical 
Laboratory 
including Flow 
Lab) 
Updated the name and contact information for the following staff: 
Alisa Euler  
ICON Laboratory Services, Inc. Central Laboratory  
• 
Updated to reflect address changes 
37-
39 
3.1 Overall Study 
Design and Plan 
Added the following bolded text and deleted the stricken text: 
All patients will receive 5.0 mg/kg of XmAb5871 or matched placebo 
over 1-2 hours IV on an every other week dosing schedule for a total of 
• 
Extending the number of infusions to 16 and 
updating the visit dates accordingly. 
 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 21 of 132 
29 July 2016 
 
Page 
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Justification 
up to 16 12 doses.   
Those patients who achieve the required disease activity improvement 
from the screening baseline will be randomized to receive either 
XmAb5871 (5 mg/kg) or placebo by IV administration (double-
blinded) over 1-2 hours every 2 weeks from Day 1 through Day 
211155 for a total of up to 16 12  infusions. 
On Day 15 and on study Days 29, 43, 57, 71, 85, 99, 113, 127, 141, 
and 155, 169, 183, 197, and 211 patients will return for XmAb5871 (5 
mg/kg) or placebo administration IV over 1-2 hour 
Patients who meet the criteria for loss of disease activity improvement 
at any timepoint up to and including Day 211155 will not receive 
further infusions of XmAb5871 or placebo 
Patients who discontinue the study early either because of loss of 
improvement or for other reasons will be followed for safety for a 
further period of 6 weeks after their last dose of XmAb5871 or placebo 
(completing assessments in schedule of events listed as Day 225169 as 
the LOI visit and Day 253197[EOS] visit 4 weeks later) at which time 
their participation is completed. 
All patients completing the treatment period should be followed 
through Day 253197(EOS).  
The effect of XmAb5871 on maintenance of improvement of SLE 
disease activity will be evaluated as the percentage of patients without 
loss of improvement at Day 225169 (primary endpoint) and Day 169 
(secondary endpoint).  
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
Updating primary endpoint to 2 weeks after final 
infusion and adding the Day 169 (after 12 
infusions) 
efficacy 
evaluation 
as 
previously 
planned as a secondary endpoint.  
39 
3.2 Discussion of 
Study Design 
Added the following bolded text: 
The protocol has been amended to change the time of the primary 
endpoint from 6 months to 8 months to account for the more 
prolonged initial course of IM steroid therapy being given in this 
study relative to the BOLD study. 
• 
Explanation for the addition of 4 more infusions 
and longer time to primary endpoint. 
40 
3.4.1 Disease Activity Added the following bolded text and deleted the stricken text: 
The primary endpoint will be evaluated as the percentage of patients 
without loss of disease activity improvement at Day 253169.   The 
percentage of patients without loss of disease activity improvement 
on Day 169 and Ttime to loss of disease activity improvement will be 
• 
Updated to reflect longer dosing period.   

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 22 of 132 
29 July 2016 
 
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Justification 
evaluated as a secondary endpoints. 
40 
3.4.2 Mechanistic 
Studies 
Added the following bolded text and deleted the stricken text: 
Blood will be collected and analyzed at Screening, Day 1, Day 29 and 
either at the first visit with loss of disease activity improvement (LOI) 
or 2 weeks after the last infusion (Day 225169), whichever comes first. 
• 
Updated to reflect longer dosing period.   
42 
3.5 Stopping Criteria 
for the Clinical 
Study 
Added the following bolded text and deleted the stricken text: 
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.  In addition, unblinded aggregate safety information will be 
reviewed by the an external Safety Review Committee (SRC) after 
approximately 15 patients have completed the study, and after 
approximately 45 patients have completed the study, and afterand 75 
patients have completed the study.  The SRC will consist of, at a 
minimum, two rheumatologists with SLE expertise and a 
biostatistician who will review the data in an unblinded manner.  
Tthe coordinating investigator and the medical representatives of the 
Sponsor (Xencor) and the CRO (PPD) will review blinded data only. 
The principal investigators and/or their delegates from each actively 
enrolling investigational site will be allowed to participate.  All 
patients in the study will receive appropriate SLE rescue therapy at the 
discretion of the principal investigator and discontinue study drug 
infusions at the time of loss of disease activity improvement., however 
the SRC blinded study team may request an unblinded review of safety 
data by the SRCan independent review committee should there be a 
trend in either an increased frequency of early SLE disease flares or 
the occurrence of organ-threatening SLE disease flares.   
• 
Updated to reflect the addition of an unblinded 
external safety committee. 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 23 of 132 
29 July 2016 
 
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Justification 
44 
4.2 Inclusion Criteria 
Added the following bolded text: 
3. Patients have a history of a (+) ANA, (+) ENA (anti-RNP or anti-
Smith) or a (+) anti-dsDNA serology documented by laboratory report 
within the year prior to randomization. 
• 
Clarification of ENA for sites 
47 
4.4 Patient Withdrawal 
and Replacement 
Added the following bolded text and deleted the stricken text: 
At the time that a patient withdrawals prematurely for any reason, all 
assessments as listed for the Day 225169 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 253197 (EOS) visit should be 
performed. 
• 
Changed to reflect longer trial period 
52 
5.8 Administration of 
Investigational 
Medicinal 
Product 
Added the following bolded text: 
For the initial infusion, pPatients 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. 
• 
Fasting periods have been relaxed following the 
first 
infusion 
since 
the 
infusion-related 
gastrointestinal symptoms occur primarily during 
the first infusion. 
62 
6.1.2.3.6 Adverse 
Events of Special 
Interest 
(Management of 
Infusion-Related 
Reactions & 
Cytokine Release 
Syndrome) 
Added the following bolded text: 
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). 
• 
Added as per FDA’s request in the comments on 
the IND filing 
66 
6.1.2.4 Reporting of 
Serious Adverse 
Events 
Added the following bolded text and deleted the stricken text:  
SERIOUS ADVERSE EVENT REPORTING INSTRUCTIONS 
SAEXmAb5871-04@vigilareintl.com 
• 
Update to reflect updated SAE reporting procedure 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 24 of 132 
29 July 2016 
 
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Change (bolded text added; strikethrough text deleted) 
Justification 
24 hour telephone number: 610-977-0899 x4801 
Emergency contact number: 917-741-5205 
Portal url: https://vigilareintl.sharepoint.com/xencor  
1. E-mail your SAE form to the study specific e-mail address above.  
Telephone Vigilare to state that you are forwarding an SAE form.  If 
Vigilare is not available, leave a message in the voice mailbox, and 
call the emergency contact number. 
67 
6.1.2.6 Pregnancy 
Added the following bolded text: 
Each pregnancy notification must be reported by the Investigator to 
the Sponsor and Vigilare within 30 days after becoming aware of the 
pregnancy.  In the event of pregnancy in a female participant, no 
more study drug will be given.  However, tThe Investigator must 
follow-up 
• 
Clarification that in the event of a patient’s 
pregnancy, no further drug should be given. 
67 
6.1.3 Vital Signs 
Added the following bolded text and deleted the stricken text:  
Vital signs will be assessed at Screening and on Days 1, 8, 15, 29, 43, 
57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225 and 253197 
(EOS).   
• 
Addition of extra infusion days 
68 
6.1.4 12-lead 
Electrocardiogra
ms 
Added the following bolded text and deleted the stricken text:  
Standard safety 12-lead ECGs will be performed at Screening and on 
Days 1, 29, 127, 183, and 253197 (EOS).   
• 
Addition of extra infusion days 
68 
6.1.5 Physical 
Examinations 
Added the following bolded text and deleted the stricken text:  
Physical examinations will be performed at Screening and on Days 1, 
8, 29, 57, 85, 113, 141, 169, and 197, 225 and 253 (EOS). 
• 
Update to account for additional infusions 
68-
70 
6.1.6 Clinical 
Laboratory 
Assessments 
Added the following bolded text and deleted the stricken text:  
Genotyping will be performed by Cancer Genetics Inc.Gentris, 
Morrisville, NC.  
•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, 183, 197, 211, 225 and 253197(EOS) 
•Clinical chemistry: The following clinical chemistry parameters will 
be assessed at Screening and at Day 1, 8, 29, 57, 85, 113, 141, 169, 
 
• 
Company has changed its name. 
• 
Updated all assessments to add additional visit 
dates 
 
 
 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 25 of 132 
29 July 2016 
 
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Justification 
and 197, 225 and 253(EOS) 
•Immunoglobulin: Serum IgG, IgE, and IgM will be assessed at 
Screening and on Days 1, 15, 71, 127, 155, 183, 211 and 
253197(EOS). 
•Complement levels:  C3 and C4 levels will be assessed at Screening 
and on Days 1, 29, 57, 85, 113, 141, 169, and 197, 225 and 253(EOS). 
•Coagulation: The following coagulation parameters will be assessed 
on Screening, and Days 1, 29, 85, 141, and 197 and 253(EOS) 
•Urinalysis: The following urinalysis parameters will be assessed at 
Screening, and on Days 1, 29, 57, 85, 113, 141, 169, and 197, 225 and 
253(EOS) 
•Urine pregnancy test: Urine pregnancy testing will be performed in 
female patients at Screening, Days 1, 15, 43, 71, 99, 127, 155, 183, 
211 and 253197(EOS). 
•Immunogenicity: The presence of human anti-human antibodies 
(ADA) will be assessed on Days 1, 15, 43, 85, 127, 18369, 225 and 
253197(EOS). 
•Flow Cytometry B Cell and T Cell Assessment:  
CD20+ B cells and T cells will be quantified at Screening and on Days 
1, 8, 15, 29, 57, 85, 113, 141, 169, and 197, 225 and 253(EOS).   
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 at 
Screening and on Days 1, 8, 15, 29, 57, 85, 113, 141, 169, and 197, 
225 and 253(EOS).      
Mechanistic studies:  
For randomized patients, mechanistic studies that will be performed 
on Days 1, 29, and at the LOI visit (either at the visit at which loss of 
response is noted or on Day 225169 
Additional samples will be collected at screening and on Days 8, 15, 
57, 71, 99, 113, 127, 141, 155, and 169, 183, 197, 211 and 253 197 (or 
EOS 6 weeks after loss of improvement, whichever comes first) and 
stored for potential mechanistic studies.  Screening samples for all 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
Requirements for the RNA PAX gene tubes are 7 
mL instead of 18 mL.  Clarification of type of PAX 
gene tube. 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 26 of 132 
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Page 
Section 
Change (bolded text added; strikethrough text deleted) 
Justification 
patients will be analyzed for ANA with pattern and anticardiolipin 
antibodies, with a repeat anticardiolipin antibody panel at LOI or Day 
225169, whichever comes first.   
Blood requirements 
•Mechanistic Studies: Blood (2536 mL) will be collected into one 10 
mL SST tube, one 10 mL green top (heparin) tube and 2 RNA PAX 
gene tubes. 
72 
6.2 Pharmacokinetic 
Variables 
Added the following bolded text and deleted the stricken text:  
prior to the start of the infusion and at EOI on Study Days 1, 15, 29, 
57, 85, 113, 141, and 155 and at visit time on Days 8, 225169 and 
253197(EOS).   
• 
Correction for addition of extra infusion days 
72 
6.4 
Pharmacogenomi
cs Variables 
Added the following bolded text and deleted the stricken text:  
Cancer Genetics Inc.Gentris Corporation 
• 
Correction to updated company name 
72 
6.4.1 Efficacy 
Measurements 
Added the following bolded text and deleted the stricken text:  
Disease activity will be measured at Screening and on Days 1, 29, 57, 
85, 113, 141, 169, and 197, 225 and 253 (EOS).   
• 
Addition of measurements to account for extra 
infusion days 
74 
7.1 Schedule of 
Assessments 
Added the following bolded text and deleted the stricken text:  
The study consists of a Screening visit (Day -28 to Day -1) followed by 
twelve sixteen infusions of XmAb5871 given every two weeks (Days 1, 
15, 29, 43, 57, 71, 85, 99, 113, 127, 141, and 155, 169, 183, 197 and 
211) with collection of disease activity assessments, safety data, 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 
225169 and 253197[EOS]). 
Assessments listed for the Day 225169 visit should be performed at the 
time of loss of disease activity improvement (LOI).  Assessments listed 
for the Day 253197(EOS) visit should be performed at the follow-up 
visit 6 weeks from the time of the last study drug infusion.  The 
maximal study duration for an individual patient will be 253197 days 
after the first infusion.   
• 
Corrections to account for increase in number 
of infusions 
74 
7.1.2 Early 
Termination 
Added the following bolded text and deleted the stricken text:  
If a patient withdraws prematurely after dosing, assessments listed for 
• 
Updated to account for increase in length of 
study 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 27 of 132 
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Justification 
Visit 
the Day 225169 visit should be performed at the time of loss of disease 
activity improvement or time of discontinuation for other reasons.  
Assessments listed for the Day 253197(EOS) visit should be performed 
at the follow-up visit 6 weeks from the time of the last study drug 
infusion as a final safety check. 
74 
7.1.3 End-of-Study 
The following bolded text has been added and stricken text 
deleted: 
End-of-Study is defined as completion of the End-of Study Visit on Day 
253197.   
• 
Updated to account for increase in study duration.   
75 
Table 6: Schedule of 
Assessments 
The following bolded text has been added: 
Study Day 8 +/-1 
Immunogenicity (ADA) [k,l] 
 
• 
Windows for Day 8 added (correction) 
• 
Footnotes for followup of positive ADA added  
76  Table 6: Schedule of 
Assessments 
The following addition to Table 6 has been added: 
 
• 
Addition 
of 
4 
extra 
infusion 
days 
with 
accompanying safety and efficacy labs and 
assessments 
 
 
Study Phase 
 
EOS 
Visit Number 
15 
16 
17 
18 
19[b] 
20[b] 
Study Week 
25 
27 
29 
31 
33[b] 
37[b] 
Study Day 
169 
+/-2 
183 
+/-2 
197 
+/-2 
211 
+/-2 
225[b]   
+/-3 
253[b] 
+/-3 
Informed consent 
 
 
 
 
 
 
Withdraw immuno-
suppressant  
 
 
 
 
 
 
Depomedrol IM 
 
 
 
 
 
 
Improvement 
 
 
 
 
 
 

Xencor, Inc. 
Protocol Number XmAb5871-04 
Clinical Study Protocol V 2.0 dated 29 July 2016 
CONFIDENTIAL 
 
 
Page 28 of 132 
29 July 2016 
 
Page 
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Justification 
assessment 
Study drug 
administration  
X 
X 
X 
X 
 
 
AE Assessment 
X 
X 
X 
X 
X 
X 
Medical history 
 
 
 
 
 
 
Physical exam 
X 
 
X 
 
X 
X 
Vital signs[e] 
X 
X 
X 
X 
X 
X 
Electrocardiogram 
(ECG) 
 
X 
 
 
 
X 
CBC, differential, 
platelets 
X 
X 
X 
X 
X 
X 
Chemistry panel 
X 
 
X 
 
X 
X 
PT/INR and APTT 
 
 
X 
 
 
X 
Urinalysis 
X 
 
X 
 
X 
X 
HBsAg, HCV Ab, HBc 
Ab 
 
 
 
 
 
 
Pregnancy test[g] 
 
X 
 
X 
 
X 
FSH[h] 
 
 
 
 
 
 
FcγR polymorphisms[i]  
 
 
 
 
 
 
T and B cell 
X 
 
X 
 
X 
X 

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Page 
Section 
Change (bolded text added; strikethrough text deleted) 
Justification 
enumeration, CD19RO 
and B cell subsets  
SELENA SLEDAI 
X 
 
X 
 
X 
X 
BILAG 2004 
X 
 
X 
 
X 
X 
SLE Autoantibody 
Panel 
X 
 
X 
 
X 
X 
C3 and C4 
X 
 
X 
 
X 
X 
PGA 
X 
 
X 
 
X 
X 
Serum IgM, IgG, IgE 
 
X 
 
X 
 
X 
PK blood[j] 
X 
 
X 
X 
X 
X 
Immunogenicity (ADA) 
[k] 
 
X 
 
 
X 
X 
Mechanistic studies 
X 
X 
X 
X 
X 
X 
77  Table 6: Schedule of 
Assessments 
The following bolded text has been added and stricken text deleted 
in the footnotes of Table 6: 
[b]If a patient experiences a loss of disease activity improvement (LOI), 
they will receive no more infusions of study drug.  Assessments listed 
above under Day 169 225 should be performed at the time of loss of 
disease activity improvement and assessments for Day 253197 (EOS) 
should be performed at a visit 6 weeks from the time of the last study 
drug infusion. 
[k]ADA sample should be drawn at the time of any suspected 
immunological related AE and at the time of each subsequent visit  X 
4.  
 
• 
Updated to account for longer study duration 
 
 
 
• 
Aligns Table 6 with the previous section changes 

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Page 
Section 
Change (bolded text added; strikethrough text deleted) 
Justification 
78 
8.1.3 Analysis 
Populations 
Added the following bolded text and deleted the stricken text: 
•Efficacy Evaluable Population:  All patients who: 
Complete study through Day 225169 assessments 
• 
Correction for addition of study days 
81 
8.6.1 Primary Efficacy 
Endpoint 
Added the following bolded text and deleted the stricken text: 
(Loss of Improvement at Day 225) 
The primary endpoint will be evaluated as the percentage of SLE 
patients without loss of disease activity improvement from Day 1 to 
Day 225169 (i.e., responders).   
The primary efficacy analysis will employ the Fisher’s Exact Test 
testing for differences in treatment response rate (patients without loss 
of disease activity improvement from Day 1 to Day 225169) between 
the two treatment groups.   
• 
Clarification of dates  
• 
Correction for addition of study days 
81 
8.6.2 Secondary 
Efficacy 
Endpoint 
Added the following bolded text and deleted the stricken text: 
8.6.2Secondary Efficacy Endpoints (Time to Loss of Improvement) 
The percentage of SLE patients without loss of disease activity 
improvement from Day 1 to Day 169 (i.e., responders) will be 
evaluated as above. 
• 
Addition of another secondary endpoint 
 
 
Add BOLD reference if available 
 
 

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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, confer high risk 
of chronic symptoms, poor quality of life and progressive disability, and 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 erythematosis (SLE) (belimumab).  
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 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, Tarasenko 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 SLE, RA and IgG4 Related 
Disease (IgG4-RD). 
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 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 inhibition of peripheral B cells 
from SLE patients (Horton et al 2011) and in classical animal models of autoimmune disease.    
1.1.3. 
Systemic Lupus Erythematosus (SLE) 
SLE is the prototypic autoimmune disease, with many immunological abnormalities including 
the presence of a plethora of autoantibodies, hyperactive B cells, activated T cells, increased 
cytokines and increased innate immune function.  Hyperactive B cells may play a role both as 
the precursors to autoantibody-producing cells and as antigen presenting cells to other cells of 
the immune system such as T cells.  Autoantibodies complexed with their autoantigens stimulate 
plasmacytoid dendritic cells and neutrophils.  Several groups have shown down-regulation of the 
inhibitory Fc receptor, FcγRIIb, in mouse models of SLE and on memory B cells and 
plasmablasts from SLE patients.  This correlated with a decreased suppression of BCR induced 
responses in those B cells and suggested that a critical checkpoint in memory B cell regulation, 
FcγRIIb, might be impaired (Mackay et al 2006, Su et al 2007).  Therefore, targeting this 
receptor to restore a more normal level of suppressive function could potentially help to reduce 
the activation of the immune system in SLE.   
SLE is a chronic systemic autoimmune disease that may affect multiple organs.  The ACR 
Classification criteria for SLE (Tan et al, 1982) include malar rash, discoid rash, 
photosensitivity, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, 
immunologic disorder (autoantibodies), and antinuclear antibody (ANA), of which any 4 of the 
11 can be present to classify a patient as having SLE.  SLE is typically a disease of young 
women ages 15-45, with a 10-fold greater incidence in women than in men.  There are some 
ethnic differences, with greater prevalence and severity of disease in persons of African, 
Hispanic, Asian and Native American descent.  While the risk of mortality has decreased to 
5-10% at 10 years, patients still die of active disease, infection, cardiovascular causes, and 

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treatment associated effects.  Despite improved survival, it is estimated that only 15% of patients 
have good to excellent disease control sustained for 1 year (http://www.niams.nih.gov/ 
Health_Info/Lupus/default.asp).  
The frequent remissions and flares that characterize the disease have made development of 
assessment tools and the design of clinical studies difficult.  The confounding effects of 
concomitant medications have often been considered to be a major reason for the inability to 
show efficacy of potential new therapeutics (Bruce et al 2010, Thanou et al 2014).  Trial designs 
other than the frequently utilized model of adding a new drug or placebo on top of standard of 
care have been needed.  Recently, a Biomarker of Lupus Disease study (BOLD, NCT 00987831) 
was completed at Oklahoma Medical Research Foundation that used a design that, by reducing 
potential for placebo response, could allow proof-of-concept for new therapeutic agents with 
enrollment of a much smaller number of patients.  Forty-one SLE patients with active, non-organ 
threatening disease had a brief course of IM depomedrol substituted for their ineffective SLE 
medications.  All achieved disease activity improvement following 1-4 injections of 160 mg of 
IM depomedrol given over 2 weeks, with 360 mg the mean amount of steroid given.  The 
investigator then monitored the patients until they required additional therapy for loss of disease 
activity improvement.  Forty of the 41 required the addition of other therapy within 6 months 
with the overall median time to loss of disease activity improvement of 56 days.  This suggested 
that the effect of the brief course of IM depomedrol therapy gradually wore off over the first few 
months.  The patients received rescue therapy as soon as disease activity improvement was lost 
and there was a quick response to rescue therapy.  There were no SAEs from disease flares and 
patients did not have disease flares of manifestations that were worse than their previous disease 
activity (Merrill et al 2011).  In addition, a predictive model using biomarkers of disease 
(Guthridge et al 2014) indicated the likelihood of an early flare was drastically reduced in the 
absence of activated monocytes (activated CD11bhi) and activated naïve B cells (CD86hi).  
Conclusions from the study were that patients with moderately severe, non-organ threatening 
SLE can tolerate withdrawal of their ineffective treatments for periods of time and that their 
disease activity can be controlled with a short period of IM steroid therapy.  The design was 
thought to reflect clinical practice and to support a trial design with disease amelioration 
(steroids) at baseline and immediate treatment if disease activity returns (Merrill 2013).  
Therefore, this design has the potential to study investigational agents that could be added at the 
time of improvement with IM steroid therapy.  An effective agent would be expected to reduce 
the number of patients who would require additional therapy, and should be able to do so within 
a reasonably short period of study time (6 months).  Using the BOLD study design, the present 
study proposes to test if XmAb5871 can improve on the proportion of patients at 6 months that 

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maintain disease activity improvement induced by IM steroid therapy after ineffective (and 
potentially confounding) agents are discontinued.  This is particularly interesting given the 
demonstrated ability of XmAb5871 to suppress the expression of CD86 on stimulated SLE and 
normal human B cells. 
1.1.4. 
Current Treatment of SLE 
SLE is currently incurable.  The goals of treatment are to reduce inflammation and damage to the 
organs and to prevent or reverse disease exacerbations.  Therapy is tailored to the organ systems 
involved and the amount of inflammation, but most of the agents used are non-specific 
immunosuppressants that are frequently used in combination.  For milder forms of SLE 
involving skin and/or joints, topical or low dose oral steroids, hydroxychloroquine, NSAIDs 
and/or methotrexate are often the mainstay of therapy.  Involvement of other organ systems often 
warrants higher doses of oral steroids together with agents such as azathioprine, mycophenolate 
mofetil, or belimumab.    
Aggressive treatment is warranted when vital organs are involved to prevent organ damage or 
failure.  High dose oral or IV corticosteroids with cyclophosphamide, azathioprine, or 
mycophenolate mofetil may be used for organ threatening disease in the kidneys, CVS, and 
hematopoetic systems.  Many of the therapeutics are less than optimal therapies particularly for 
young women because of their long term safety profiles.  For example, long term corticosteroid 
use can lead to hypertension, diabetes, osteoporosis, and infection risk, whereas 
cyclophosphamide may lead to sterility and bladder cancer.  Only one new therapy for SLE, 
belimumab, has been approved in over 50 years. 
Therefore, there is a need for more targeted agents to control the disease long-term.  Because of 
the presumed role of B cells in SLE, the effect of a B cell inhibitor might provide a more 
long-term solution to disease control.  
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 
cynomolgus monkey (the relevant toxicology species) CD19 is approximately 6 fold lower than 

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its affinity for human CD19.  No appreciable XmAb5871 binding was detected with B cells from 
mouse, rat, rabbit, or dog.  
The second functional attribute important for the pharmacology of XmAb5871 is the 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 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 bind to FcγRIIb with increased 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 human and cynomolgus monkey 
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 
(250 fold less).  This is probably due to the absence of an arginine amino acid residue at position 
131 in the FcγRIIb of cynomolgus monkey. 
XmAb5871 inhibits B cell activation by binding to CD19 and FcγRIIb simultaneously.  The 
co-engagement of these 2 receptors is the presumed mechanism by which excess antigen-
antibody complexes down-regulate B cell activity.  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 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 down-regulating B cell activity, even if such 
antibodies were used in combination. 

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Because FcγRIIb has been shown to be dysregulated in SLE patients (Mackay et al, 2006), 
B cells from SLE donors were studied in vitro to determine whether they would respond to 
XmAb5871 in a similar fashion to normal healthy volunteers.  As with the normal B cells, 
XmAb5871 was able to stimulate FcγRIIb and suppress BCR-induced calcium mobilization, 
B cell proliferation and expression of costimulatory molecules (CD86) on SLE-derived B cells.  
In addition, B cell proliferation induced by any of the B cell stimuli LPS, IL-4, and BAFF was 
suppressed by XmAb5871 in SLE B cells, just as in normal (Horton et al 2011).  This suggests 
that even though SLE patients may have less expression of FcγRIIb, their cells are still able to 
respond to XmAb5871. 
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, 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 (CIA) 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 
Although the binding affinity of XmAb5871 for FcγRIIb is approximately 225 fold increased, 
the binding affinity to the activating receptor FcγRIIIa, involved in antibody-dependent 
cell-mediated cytotoxicity (ADCC) by NK cells, was reduced approximately 20-fold relative to 
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, while 2 known depleting 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.  

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FcγRIIa, a low affinity, activating FcγR present on human platelets and myeloid cells 
(monocytes, dendritic cells, macrophages), is important in macrophage mediated antibody-
dependent cell-mediated phagocytosis (ADCP).  Two alleles of the gene encoding FcγRIIa 
generate 2 variants differing at amino acid position 131.  The histidine (H131) and arginine 
(R131) alleles are reported to be roughly equally distributed 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.  Potential 
implications of this increased binding to FcγRIIa R131 (i.e., ADCP) were examined in vitro.  In 
vitro phagocytosis experiments demonstrate that monocyte-derived macrophages from R131 
positive donors will, in the presence of XmAb5871, phagocytose Ramos cells (CD19+ B cell 
line) and purified human B cells.  Very little phagocytosis was observed with monocyte-derived 
macrophages from H131 homozygous donors, but these observations raise the possibility of 
B cell reduction or depletion in R131 positive patients.  However, neither data from the 
first-in-human (FIH) study in healthy volunteers nor data from the multiple ascending dose study 
in RA patients have shown an association of the presence 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 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 lacking 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 fully activate platelets 
for secretion and aggregation.  While neither CD19 nor FcγRIIb are platelet-associated antigens, 
the potential for platelet interaction was evaluated.  In an ex vivo study, the addition of 
XmAb5871 to samples from human donors did not induce platelet activation.  Additionally, in 
the completed human studies in healthy subjects and in RA patients, no changes in platelet count 
were observed. 
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, there were no signs or symptoms consistent 
with cytokine release syndrome or immunologically mediated infusion-related reactions.  In the 
Phase 2a study in RA patients, two of 40 patients (5%) experienced an infusion-related reaction 

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with hypotension, both at a dose of 10.0 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 flow cytometric analysis of XmAb5871 binding to lymphocytes from different species.  
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 FcγRIIb of the cynomolgus monkey was 
approximately 250-fold less strong 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 which 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 which 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. 
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 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.  

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A GLP 12-week repeat-dose toxicity study was completed in cynomolgus monkeys of both 
genders.  XmAb5871 was administered via a one hour IV infusion at doses of 0, 2, 10 or 
50 mg/kg on an every other week × 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-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. 
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 the 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 
and coagulation parameters, and 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.   

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In summary, no adverse test article-related effects have been seen in cynomolgus monkeys 
following IV infusions of up to 200 mg/kg XmAb5871 every 14 days for up to 6 months.  These 
studies therefore 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 XmAb®5871 in Healthy Adult 
Volunteers 
In the FIH study, 48 healthy male subjects were enrolled and were randomized 3:1 
(XmAb5871:placebo) to receive a single IV infusion of XmAb5871 or matching placebo 
administered over a 2 hour period in a double-blinded manner.  Thirty-six subjects received 
single IV infusions of XmAb5871 at 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) dose levels. Twelve 
subjects received placebo.  All completed the study. 
XmAb5871 was moderately 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 subjects who experienced TEAEs 
in the active group 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, abdominal 
pain, abdominal discomfort, epigastric discomfort and diarrhea.  Such gastrointestinal-related 
TEAEs were reported by 14/36 XmAb5871 subjects (38.9%), 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 cohort, who reported nausea of severe intensity.  Eight subjects (22%), at doses 
of 0.2 to 10.0 mg/kg, had their XmAb5871 IV infusion temporarily interrupted as a result of the 
infusion-related gastrointestinal symptoms; 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 in an apparent mono-phasic manner.  

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Clearance decreased with increasing dose approaching a constant value at the higher dose levels.  
Volume of distribution decreased with dose increment approaching a value that was similar to 
physiologic serum volume.  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 CD19 desaturation. 
Sixteen of 36 (44%) XmAb5871 treated subjects had at least one sample positive for ADA.  
There was no distinct evidence of ADA mediated clearance of XmAb5871 in any ADA positive 
subject other than one subject (5 mg/kg) 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 cell count followed XmAb5871 administration.  The nadir 
mean CD20+ B cell counts of roughly 40% to 50% of baseline cell counts occurred between 
approximately Day 4 and Day 8.  The degree of the CD20+ B cell count reduction at nadir did 
not significantly increase as dose of XmAb5871 increased.  The recovery of the B cell count 
approximated the observed kinetics of XmAb5871 clearance.  There was no association observed 
between the presence of the FcγRIIa R131 polymorphic allele and the CD20+ B cell count at 
nadir.   
Expression of CD86 on B cells is induced by 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, 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 
XmAb®5871 in Patients with Rheumatoid Arthritis 
A randomized, double-blinded, ascending multiple-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 on stable non-biologic disease modifying anti-
rheumatic drug (DMARD) therapy.  The completed Phase 2a study was enrolled in two parts:  

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• 
Part A administered doses of XmAb5871 at 0.3, 1.0, 3.0 or 10.0 mg/kg or matching 
placebo (3:1 randomization) 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) given up to 
6 times at 2 week intervals.   
A total of 57 RA patients (41 XmAb5871, 16 placebo) were enrolled in the study, 30 in Part A 
and 27 in Part B.  One patient randomized to XmAb5871 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 2 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 (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 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 generally 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 2 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, the Sponsor considered the event 
unlikely to be related to XmAb5871.  The other SAE was a case of infusion-related reaction that 

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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 in an 
apparent mono-phasic manner over time.  Cmax for the first and last dose increased in a slightly 
greater than proportional manner with dose while the AUC for the first and last dose increased in 
a manner proportional with dose increment.  At the dose levels studied, neither clearance nor 
volume of distribution showed any significant dose dependence, either for the first or last dose.  
There was little accumulation between the first and last doses with the every 14-day dosing 
interval. 
Across all 4 dose levels, last dose clearance averaged 15.16 ± 3.68 mL/day/kg.  Last dose 
volume of distribution averaged 49.27 ± 14.17 mL/kg.  This figure is close to the literature value 
for physiological serum volume.  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.  Peripheral B cell count decreased in all cohorts 
following the first dose, with cohort mean levels of approximately 52-79% of baseline.  The 
level of reduction did not increase with increasing dose or with subsequent doses and recovered 
to a mean cohort level of ≥ 80% of baseline levels 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., the 
majority 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 an ADA 
response with titers that increased over time.  There was no distinct evidence of ADA mediated 
clearance of XmAb5871 in any ADA positive patient. 

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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, 12.5% (1/8) and 0% (0/8) of the placebo-
treated patients achieved ACR50 and ACR70 responses, respectively.  
The Sponsor will immediately notify the Principal Investigators 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 
Although glucocorticoids are effective in SLE, long term use of these agents is not optimal and 
disease exacerbations are common as the therapy is tapered.  There is a clear need for ongoing 
development of new drugs with different modes of action, different pathways, improved safety 
profiles and quality of life benefits.  Therapy to reduce B cell proliferation by depleting a needed 
growth factor, BAFF or BLyS, (belimumab) has been licensed as a therapy for SLE and it stands 
to reason that other therapies directed at B cell function by a different mechanism of action may 
also be shown to be efficacious, potentially even in non-overlapping subsets of patients.  
FcγRIIb has been shown to play a crucial role in suppressing autoimmunity.  For example, 
autoimmune disease is exacerbated in mice lacking FcγRIIb (Nimmerjahn et al, 2008), and its 
restoration rescues mice in SLE, arthritis, and asthma models (Brownlie et al 2008, Dharajiya et 
al 2010, McGaha et al 2005).  Moreover, FcγRIIb polymorphisms affecting activity or 
expression are associated with human autoimmunity (Floto et al 2005, Tsuchiya et al 2006, 
Tarasenko et al 2007) and B cell expression of FcγRIIb is dysregulated in SLE (Mackay et al 
2006).  Despite the dysregulation of FcγRIIb in SLE, XmAb5871 was able to inhibit human SLE 
B cells in vitro (Horton et al 2011).  The presumed role of B cells and plasmablasts in SLE and 
the observations of beneficial effects on SLE disease activity by B cell directed therapies support 
the evaluation of non-depleting B cell directed therapies such as XmAb5871 in patients with 
SLE.  The proposed dose and dosing 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 SLE.  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 

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(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 the completed human studies.  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, suggesting that the toxicology 
species is informative.  
The observed reduction in absolute B cell count 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 

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such as rituximab.  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.  In the 
multiple dose Phase 2a study, two patients, 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 
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 ADA prior to the second 
infusion with increasing titers thereafter.  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 antibodies, 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.   

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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 continuously assessed 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 the end of the first infusion.  
The frequency of vital sign monitoring will be modified 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 subjects 
(over the dose range 0.2 mg/kg to 10.0 mg/kg) had their XmAb5871 IV infusion interrupted 
temporarily as a result of the self-limiting gastrointestinal-related symptoms of short duration 
(abdominal discomfort, abdominal pain, epigastric discomfort, nausea and vomiting).  In all 
cases, the subjects 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. 

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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, reductions in B cell levels 
were observed in the 2 repeat-dose GLP toxicology studies performed to date.  In both the 
12-week (6 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 2 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).   
As was the case in nonclinical toxicology studies, in both clinical studies performed to date, 
reductions in absolute B cell counts were observed with mean reductions to 50-60% of baseline 
levels and 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.  
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.  Although 
prolonged reductions in B cell counts to the extent seen with B cell depleting therapies have not 
been observed and are not expected following administration of XmAb5871, B cell depleting 
therapies have been widely used both in hematologic malignancies and in autoimmune disease 
states.  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. 

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1.4.3. 
Potential Benefits 
The primary purpose of the study is to evaluate the ability of XmAb5871 to maintain 
improvement in SLE patients following a brief course of disease-suppressing IM steroid therapy.  
Based on the effect of XmAb5871 on B cell function observed in in vitro and in vivo studies and 
on the trends in improvement in RA disease activity observed, some XmAb5871 treated patients 
may maintain the improvement in SLE disease activity induced by the brief course of IM steroid 
therapy for the 6-month duration of the study and not need to have additional therapeutics added 
for disease exacerbation.  The study will use the SELENA SLEDAI (hybrid version) with the 
SELENA SLEDAI Flare Index, BILAG (2004 version) and Physician’s Global Assessment of 
disease activity to evaluate the effect of XmAb5871 on disease activity over time. 
1.4.4. 
Conclusion 
XmAb5871 is being developed for the treatment of SLE, and a double-blind, randomized pilot 
efficacy trial is currently proposed.  Given the established role of B cells in the pathogenesis of 
SLE, the effects of XmAb5871 on B cell function in the absence of complete B cell depletion 
may provide an attractive therapeutic option for this condition. 
The trial design contains adequate measures to mitigate risk factors, and 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.  
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 determine the ability of XmAb5871 to maintain SLE disease activity improvement 
achieved by a brief course of disease-suppressing IM steroid therapy in SLE patients 
2.2. 
Secondary Objective 
• To evaluate time to loss of SLE disease activity improvement achieved by a brief course 
of disease-suppressing  IM steroid therapy in SLE patients  
• To evaluate the safety and tolerability of every other week IV administration of 
XmAb5871 in patients with SLE  

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• To evaluate the pharmacokinetics (PK) and immunogenicity of every other week IV 
administration of XmAb5871 in patients with SLE 
2.3. 
Exploratory Objectives 
• To characterize the pharmacodynamics (PD) of every other week IV administration of 
XmAb5871 in patients with SLE as follows: 
o To evaluate the effect of XmAb5871 on changes in the absolute B Cell count (ABC) 
o To characterize the effect of XmAb5871 on SLE disease activity over time  
o To evaluate the effect of XmAb5871 on autoantibody, complement and cytokine 
levels over time 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This is a double blind, randomized multiple dose pilot study to investigate the efficacy, safety, 
tolerability, PK, immunogenicity and PD of XmAb5871 in patients with SLE.  The study will be 
conducted in centers with expertise in evaluating patients with this disease.    
All patients will receive 5.0 mg/kg of XmAb5871 or matched placebo over 1-2 hours IV on an 
every other week dosing schedule for a total of up to 16 doses.  Patients will be followed for 
6 weeks after the final infusion.  Approximately 90 patients will be enrolled with a 
1:1 randomization of XmAb5871: placebo. 
Patients will enter screening with moderate to severe, non-organ threatening, SLE activity 
defined as a SELENA SLEDAI of ≥6 (≥4 points of which must come from non-serological 
findings) OR ≥1 BILAG B score OR ≥1 BILAG A score.  Patients must be able and willing to 
discontinue background immunosuppressive medications and receive a brief course of IM steroid 
therapy.  After obtaining informed consent, appropriate screening studies will be performed and 
160 mg of IM depomedrol will be administered.  Over the next 2-4 weeks of the screening 
period, per PI discretion, patients may receive additional IM depomedrol injections (up to an 
additional 320 mg during screening) to treat their SLE symptoms to a target of disease 
improvement defined as a SELENA SLEDAI decrease of ≥4 points or a decrease in BILAG of 
≥1 severity grade in at least one organ system that began with A or B (clinical criteria without 
requiring temporal criteria).  Immunosuppressive therapy will be stopped or tapered off over the 
2-4 week screening period.  Patients on anti-malarial therapy may continue on their usual dose.  
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10 mg or less per day by randomization (Day 1) and then may continue on this dose throughout 
the study.  Patients who do not meet the disease activity improvement criteria by Day 1 will not 
be randomized into the study and their participation will end. 
Patients must have documented SLE disease activity improvement following the brief course of 
IM steroid therapy to be randomized into the study on Day 1.  Those patients who achieve the 
required disease activity improvement from the screening baseline will be randomized to receive 
either XmAb5871 (5 mg/kg) or placebo by IV administration (double-blinded) over 1-2 hours 
every 2 weeks from Day 1 through Day 211 for a total of up to 16 infusions.  Disease activity 
(SELENA SLEDAI, BILAG) on Day 1 will be considered the baseline disease activity for 
determination of the primary and secondary efficacy endpoints.  On Day 1, baseline procedures 
such as physical exam, blood and urine samples for laboratory assessments, PK and PD samples 
will be collected and 80 mg of IM depomedrol will be given prior to administration of study 
drug.  The first infusion of either XmAb5871 or placebo will be given IV over a period of 
2 hours.  Patients will be observed for at least 2 hours after the completion of the first study drug 
administration during which time safety assessments will be performed.   
All patients will return to the research facility on Day 8 for safety, PK and PD assessments.  On 
Day 15, patients will receive an additional 80 mg of IM depomedrol to sustain the disease 
activity improvement long enough for XmAb5871 to reach a steady state level.  On Day 15 and 
on study Days 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, and 211 patients will 
return for XmAb5871 (5 mg/kg) or placebo administration IV over 1-2 hours and for safety, PK 
and PD assessments.  Patients will be required to remain at the study site for observation for at 
least 1 hour after the completion of each infusion.  
Patients will be followed for loss of disease improvement (LOI) as defined by: 
I. The assessment by the principal investigator that the disease activity is appropriate for an 
increase in therapy (including addition of another lupus therapy, except for adjustments 
in NSAIDs) AND 
II. There has been: 1) a SELENA SLEDAI increase of ≥4 points from maximal 
improvement; OR 2) a worsening of at least one BILAG A or B score; OR 3) the 
appearance of a new A or B.   
Patients who meet the criteria for loss of disease activity improvement at any timepoint up to and 
including Day 211 will not receive further infusions of XmAb5871 or placebo, i.e., will be 

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discontinued from the study, and may receive any appropriate SLE therapy at the discretion 
of the principal investigator.  
Patients who discontinue the study early either because of loss of improvement or for other 
reasons will be followed for safety for a further period of 6 weeks after their last dose of 
XmAb5871 or placebo (completing assessments in schedule of events listed as Day 225 as the 
LOI visit and Day 253[EOS] visit 4 weeks later) at which time their participation is completed.     
All patients completing the treatment period should be followed through Day 253(EOS).  Patient 
participation is complete once EOS study procedures are 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 the TEAEs/abnormalities are stabilized.  
The effect of XmAb5871 on maintenance of improvement of SLE disease activity will be 
evaluated as the percentage of patients without loss of improvement at Day 225 (primary 
endpoint) and Day 169 (secondary endpoint). 
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 CD19 receptor 
occupancy (RO) and by enumeration of circulating B cells and their subsets. 
FcγR polymorphisms will be assessed by FcγRIIa and FcγRIIb genotyping. 
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 the previously completed Biomarkers of Lupus Disease (BOLD) study of SLE patients in 
whom a brief course of IM steroid therapy induced SLE disease activity improvement following 
the cessation of background immunosuppressant therapy, 40/41 patients lost the disease activity 
improvement by month 6, equivalent to a 2.4% placebo response.  Assuming a 10% placebo 
response rate will be observed in this study and assuming that XmAb5871 will provide a 38% 
response rate (preventing loss of disease activity improvement), the number of patients needed 
for 80% power and 5% significance would be 40 per arm.  Adding approximately 10% for 

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drop-outs, the total number per arm is calculated as 45.  The study is designed to obtain 
information on the ability of XmAb5871 to maintain improvement of SLE disease activity after a 
brief course of IM steroid therapy.  Safety of XmAb5871 in SLE will also be evaluated.  
The protocol has been amended to change the time of the primary endpoint from 6 months to 8 
months to account for the more prolonged initial course of IM steroid therapy being given in this 
study relative to the BOLD study.  
3.3. 
Selection of Patient Population 
It is anticipated that approximately 90 SLE patients will be enrolled in the study.  Patients 
appropriate for screening will have active SLE without organ-threatening involvement, will be 
able and willing to discontinue their background ineffective immunosuppressive medications, 
and will be willing to receive a brief course of IM steroid therapy.  Those that achieve a protocol 
defined level of disease activity improvement will be randomized to receive XmAb5871 or 
placebo and will be followed for the loss of the disease activity improvement effected by the IM 
steroid therapy. 
3.4. 
Endpoints 
The study involves assessments of SLE disease activity, safety, immunogenicity, PK, PD and 
pharmacogenomics.  The specific endpoints are listed below. 
3.4.1. 
Disease Activity 
The primary endpoint will be evaluated as the percentage of patients without loss of disease 
activity improvement at Day 253.   The percentage of patients without loss of disease activity 
improvement on Day 169 and time to loss of disease activity improvement will be evaluated as 
secondary endpoints.  In addition, the following disease assessment indices may be used for 
exploratory analyses of SLE disease activity over time: 
• SELENA SLEDAI hybrid version with SELENA SLEDAI Flare index 
• BILAG 2004 
• Physician’s Global Disease activity VAS 
3.4.2. 
Mechanistic Studies 
Blood will be collected and analyzed at Screening, Day 1, Day 29 and either at the first visit with 
loss of disease activity improvement (LOI) or 2 weeks after the last infusion (Day 225), 
whichever comes first. The following biomarkers will be explored: changes in autoantibody 
profiling by BioPlex 2200, multiplex evaluation of plasma cytokines, RNA expression to 

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determine changes in selected BCR, BAFF and IL4-mediated signaling responses, and a broader, 
more exploratory evaluation of cytokine and gene expression evaluated via hierarchical 
clustering and principal component analyses.  Samples will be collected and stored from 
additional visit days as given in Table 6 to be utilized for future evaluation of additional analytes 
as deemed appropriate from initial studies.  The results from these studies may be reported 
separately from the clinical study report. 
3.4.3. 
Safety Endpoints 
• Physical examinations 
• 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 
sitting position) 
• Adverse event assessments 
• 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 
• Serum immunoglobulin (Ig) levels (IgG, IgM, IgE) 
• Complement levels C3 and C4 
• Monitoring for pregnancy in women of child-bearing potential only 
3.4.4. 
Immunogenicity Endpoint 
• Frequency and titer of anti-XmAb5871 antibodies (anti-drug antibodies [ADA]) 
3.4.5. 
Pharmacokinetic Endpoints 
Predose (trough) and end-of-infusion (peak) XmAb5871 serum concentrations will be measured 
on selected infusions, at the endpoint disease assessment timepoint and at EOS.  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)  
• Autoantibody and cytokine levels 
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 
study for 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.  In addition, unblinded aggregate safety information will be 
reviewed by an external Safety Review Committee (SRC) after approximately 15 patients have 
completed the study, and after approximately 45 and 75 patients have completed the study.  The 
SRC will consist of, at a minimum, two rheumatologists with SLE expertise and a biostatistician 
who will review the data in an unblinded manner.  The coordinating investigator and the medical 
representatives of the Sponsor (Xencor) and the CRO (PPD) will review blinded data only. All 
patients in the study will receive appropriate SLE rescue therapy at the discretion of the principal 
investigator and discontinue study drug infusions at the time of loss of disease activity 
improvement.   
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. Dose will be held until 
recovery to baseline or ≤Grade 1 values following the worsening.  
In the event that drug-related toxicity persists for >21 days or such that two consecutive doses 
are missed, the patient will be permanently discontinued from the study drug treatment.   

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There will be no dose level modification in this study.  
4. 
STUDY POPULATION 
Patients eligible for screening are men and women ages 18 to 65 inclusive with active SLE, 
defined as a SELENA SLEDAI of ≥6 (≥4 points of which must come from non-serological 
findings) OR at least one BILAG A or B score. If a single BILAG B score is based on arthritis, 
there must be at least 3 tender and at least 3 swollen joints out of 28 joints counted.  If a single 
BILAG B score is based on rash, there must be involvement of at least 9% of body surface area 
for at least one week, or 5% of body surface area for discoid skin rash.  Patients must be able to 
provide written informed consent and meet all the inclusion criteria and none of the exclusion 
criteria.  They must be able and willing to stop their immunosuppressants and to be given a brief 
course of IM steroid therapy.  In the judgment of the investigator, they must have non-organ 
threatening disease (e.g. there is no active nephritis requiring either ongoing induction or 
maintenance therapy, or any other solid organ, CNS or hematologic disorder for which stopping 
SLE therapy is contraindicated).  Only patients who have protocol defined disease activity 
improvement by Day 1 will be randomized. 
4.1. 
Number of Patients 
It is anticipated that approximately 90 patients will be enrolled in the study.  In a previously 
completed study of SLE patients in whom a brief course of IM steroid therapy induced SLE 
disease activity improvement following the cessation of background immunosuppressant 
therapy, 40/41 patients lost the disease activity improvement  by month 6; equivalent to a 2.4% 
placebo response.   If we assume that XmAb5871 will provide a 38% response in preventing loss 
of disease activity improvement, the number of patients needed for 80% power and 5% 
significance would be about 40 per arm.  Adding 10% for unevaluable patients, the total number 
per arm is calculated as 45. 
4.2. 
Inclusion Criteria 
Patients who meet the following criteria will be considered eligible to participate in the clinical 
study: 
1. Able to provide written informed consent. 
2. Adult males and females aged 18 to 65 years inclusive with a diagnosis of SLE as defined 
by the ACR Criteria (≥4 criteria fulfilled). 
3. Patients have a history of a (+) ANA, (+) ENA (anti-RNP or anti-Smith) or a (+) anti-
dsDNA serology documented by laboratory report within the year prior to randomization. 

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4. The Principal Investigator has assessed the patient and in their judgment, the disease 
activity is not organ threatening (e.g. there is no active nephritis requiring either ongoing 
induction or maintenance therapy, or any other solid organ, CNS or hematologic disorder 
for which stopping SLE therapy is contraindicated).  
5. Both investigator and patient agree that it is acceptable to discontinue their current 
immunosuppressant SLE medications and receive a brief course of IM steroid therapy. 
6. Patients must have active disease at screening defined as:  
a. A SELENA SLEDAI of ≥6 (≥4 points of which must come from non-serological 
findings)  
b. OR ≥1 BILAG B score  
i. 
If a single BILAG B score is based on arthritis, there must be at least 3 tender 
and at least 3 swollen joints out of 28. 
ii. 
If a single BILAG B score is based on rash, there must be involvement of at 
least 9% of body area for at least one week, or 5% of body area for discoid skin 
rash.  
c. OR ≥1 BILAG A score  
7. To be eligible for randomization on Day 1, patients must have documented disease 
improvement defined as:  
a. SELENA SLEDAI decrease of ≥4 points OR 
b. Decrease in BILAG of ≥1 severity grade in at least one organ system that began with 
A or B (clinical criteria without temporal criteria) by Day 1.  
8. If patients are on oral steroids, they must be on the equivalent of ≤15 mg/day of 
prednisone to enter screening AND must be able to taper to ≤10 mg/day by 
randomization. 
9. Subjects must have the following laboratory parameters at screening:  
a. White blood cell count ≥1.5 × 103/µL. 
b. Absolute neutrophil count (ANC) ≥1.0 × 103/µL. 
c. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening 
≤2.5 × upper limit of normal (ULN). 
d. Serum creatinine ≤2.5 mg/dL. 

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e. Hemoglobin ≥8 g/dL. 
f. Platelet count ≥40,000 × 109/L. 
10. Subject must be able to comply with the dosing instructions for study drug administration 
and able to complete the study schedule of assessments.  
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, metabolic, hematologic 
or psychiatric) other than SLE that, in the opinion of the Principal Investigator would 
pose a risk to patient safety or interfere with the study evaluation, procedures or 
completion.  
2. Patients who have organ threatening manifestations of SLE including active Class 3 or 4 
lupus nephritis requiring induction or maintenance therapy or any other disorder for 
which stopping SLE therapy is contraindicated.  
3. Active CNS lupus such as seizures or psychosis that in the opinion of the investigator 
would preclude participation.  
4. Unstable hemolytic anemia or thrombocytopenia.   
5. Malignancy within 5 years (except successfully treated in situ cervical cancer or 
squamous or basal cell carcinoma of the skin). 
6. Active infection requiring hospitalization or treatment with parenteral antimicrobials 
within the 60 days prior to randomization, oral antimicrobials within 21 days prior to 
randomization.  
7. Patients who have received live vaccines within 2 months of randomization. 
8. Positive test for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C 
antibody.   
9. Positive urine pregnancy test (i.e., urine human chorionic gonadotropin [hCG]) at 
screening, on Day 1, or any other time during the study. 
10. Patients who do not agree to use medically acceptable methods of contraception (as 
defined in Section 5.10.2). 

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11. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in 
the study, up to End of Study (EOS) visit. 
12. Male patient with a pregnant partner who is not willing to use a condom during the 
treatment and up to EOS visit.   
13. In the judgment of the investigator any clinically-relevant drug or alcohol abuse within 
12 months of screening that may interfere with subject treatment, assessment or 
compliance with the protocol. 
14. Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-
life is unknown) prior to randomization.  
15. Use of any biologic therapy (including belimumab) within 6 months of randomization or 
prior exposure to a monoclonal antibody directed to CD20 (such as rituximab) within 
12 months of randomization. 
16. Patients with a known or suspected sensitivity to products from mammalian cell lines. 
17. Patients who cannot communicate reliably with the Investigator. 
18. Patients who are unlikely to co-operate with the requirements of the study in the opinion 
of the Investigator. 
4.4. 
Patient 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 patient 
withdraws from the study prematurely.  At the time that a patient withdrawals prematurely for 
any reason, all assessments as listed for the Day 225 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 253 (EOS) visit should be 
performed.  All patients who withdraw from the study with an ongoing AE must be followed, if 
at all possible, until the event is resolved or deemed stable by the investigator.   
Patient 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. Patient withdrew consent  

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5. Other 
A comprehensive effort must be made to determine the reason(s) why a patient fails to return for 
the necessary visits or is discontinued from the study.  If the patient is unreachable by telephone, 
a registered letter, at the minimum, should be sent to the patient 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 where the 
Sponsor deems necessary.  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 a site be closed for any 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.  
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.  

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XmAb5871 drug product will be manufactured by Catalent, Madison, Wisconsin.  The facility 
has been configured for GMP manufacture of biological products.  
XmAb5871 drug product 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: SLE 
Strength: 10 (+/-5%) mg/mL 
Dosage form: Solution for infusion  
Route of administration: IV infusion 
Matching placebo without active substance will be supplied also as a solution for 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 or placebo must 
be stored under refrigeration at 2 to 8oC (+/- 5oC).  Prior to administration, the parenteral drug 
product should be removed from storage temperature conditions and allowed to equilibrate to 
room temperature.  Undiluted XmAb5871 or placebo 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 or placebo 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.   
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 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. 
XmAb5871 or placebo 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 

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product should be inspected visually.  The drug product 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 or placebo 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 or placebo will be performed as described in the Pharmacy 
Manual, which will be provided to the sites. 
Diluted XmAb5871 or placebo 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 and placebo 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 or placebo should take place as soon as possible following 
dilution.  If a delay is anticipated, diluted XmAb5871 or placebo 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 
parenteral drug product 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.   
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 × 13 infusions) was 200 mg/kg.  
The dosing schedule and duration of the toxicity study provides support for the dose/schedule of 
the proposed 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 minimum anticipated 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 

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in the single ascending dose study as well as in the 3-month multiple ascending dose study 
(QOW dosing × 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 study, a dose of 5 mg/kg has been selected for this 
study. 
5.5. 
Supply, Packaging, and Labeling 
XmAb5871 and placebo will be supplied by Almac.  Investigational medicinal products will be 
packaged and labeled according to applicable local and regulatory requirements. 
XmAb5871 will be a 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.  Each 
product vial is intended to deliver at least 10 mL of drug solution or 100 mg (+/- 5%) of 
XmAb5871.  Matching placebo without active substance will also be supplied as a solution for 
infusion.  
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.  

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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. 
Patient Identification  
5.7.1. 
Screening and Randomization Numbers 
After obtaining oral and written informed consent, patients will be screened according to the 
inclusion and exclusion criteria.  The screening number will be used throughout the screening 
period.  Patients who meet all selection criteria including the required improvement in disease 
activity will receive a randomization number on Day 1.  The patient number (i.e. randomization 
number) will ensure identification throughout the study.  The patient number will be assigned by 
a central telephone/world wide web based randomization system.  
Patients dropping out or withdrawing, for any reason, without completing all screening 
evaluations successfully or who do not meet the requirements for improvement by Day 1 will be 
considered as “screening failures“.  Such patients will not receive a patient number, however, 
screening data will be collected in the electronic Case Report Forms (eCRFs).  The Investigator 
will keep a screening log of all patients screened in order to assess the numbers and 
characteristics of the excluded patients, and the reasons for their exclusion. 
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 elevated from 0 to 90 degrees.  If an infusion chair is used, the patient’s legs should be 
horizontal.  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 small amounts of 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.   

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5.10. 
Concomitant Medications 
5.10.1. 
Previous / Concomitant Medication  
5.10.1.1.  Disallowed previous or concomitant medications: 
• Prior use of rituximab (or other B cell depleting agents) within 12 months of 
randomization or treatment with any other biologic therapeutics (including belimumab) 
within 6 months of randomization. 
• Use of any investigational agent within 5 half-lives of the agent (or 6 months if the half-
life is unknown) prior to randomization. 
• Received live vaccines within 2 months of randomization. 
• Immunosuppressive agents (e.g. methotrexate, azathioprine, mycophenolate mofetil, 
mycophenolic 
acid, 
leflunomide, 
cyclosporine, 
cyclophosphamide, 
tacrolimus, 
6-mercaptopurine) will be stopped or tapered off during screening.   
• Patients entering the study on oral corticosteroids (not to exceed the equivalent of 15 mg 
of prednisone per day – see Table 1) will taper their oral steroids to 10 mg per day or less  
by randomization (Day 1) and then may continue on a ≤10 mg daily dose through the 
remainder  of the study. 
Table 1: Prednisone Equivalence 
 
 
 
 
 
 
 
 
 
Details of all prior and concomitant medications will be 
recorded at study entry (i.e., at the first visit) including prior treatment for SLE, prior SLE 
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 will 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 whether or not prescribed by the study 
site.  If the change might influence the patient’s eligibility to continue in the study, the Sponsor 
Prednisone 
10 
mg 
Hydrocortisone 
40 
mg 
Prednisolone 
10 
mg 
Triamcinolone 
8 
mg 
Methylprednisolone 
8 
mg 
Dexamethasone 
1.5 
mg 
Betamethasone 
1.2 
mg 
Cortisone acetate 
50 
mg 

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must be informed.  Concomitant medication use may be warranted for the treatment of AEs.  In 
the interests of patient safety and acceptable standards of medical care it is expected that the 
Investigator will 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 are considered to be of childbearing potential unless there is a documented reason (i.e., 
postmenopausal by history with no menses for one year and confirmed by FSH [using local 
reference ranges], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history 
of bilateral oophorectomy). 
Women of childbearing potential must have a negative pregnancy test during screening and at 
Day 1 prior to study drug infusion and must use 1 highly effective method of birth control during 
the study and 3 months following last dose of XmAb5871.  Highly effective methods of birth 
control include hormonal birth control, 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. 
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 
Timing of assessments is shown in Table 6 Schedule of Assessments. 
6.1.1. 
Medical History, Demographic and Other Baseline Information 
The medical history comprises: 
• General medical history including SLE history 
• Medication history 
• Reproductive history 
 

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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 reporting will begin upon the signing of the informed consent document and will 
continue until the last study visit. 
6.1.2.1. 
Definitions 
An AE is any untoward medical occurrence in a study patient administered an IMP which 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 investigational products or placebo, lack of efficacy is 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 than the usual course of disease in a given patient.   
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 patient’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 

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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 that does not fulfill categories 1-3.  AE -
 Yes 
6.1.2.2. 
Recording of Adverse Events 
Adverse events should be collected and recorded for each patient from the date the informed 
consent form (ICF) was signed until the end of their participation in the study, i.e., the patient 
has discontinued or completed the study.   
Adverse events may be volunteered spontaneously by the study patient, or discovered by the 
study staff during physical examinations or by asking an open, non-leading question such as 
‘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 patient’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 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 (see Table 2): 

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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 patient 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 
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 below and all contributing factors (see Table 3). 

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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 patient in the past is readministered to that 
patient.  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; 
• 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) 

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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 that occurs at any dose if it: 
• Results in death; 
• Is life-threatening; this means that the patient 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 patient 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. 
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. 

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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): 

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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 × 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: 
 

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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, 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.

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Infusion-Associated Gastrointestinal-Related Symptoms 
In the completed XmAb5871 single-dose FIH 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, 
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 first 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 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 patient 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 patient’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 

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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 patient experiences during their participation in study 
within 24 hours of becoming aware of the event. Vigilare will provide the information to the 
Sponsor.  
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 patient’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 

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request additional information on the SAE in order to obtain the full clinical picture, which the 
PI or an authorized delegate must respond to Vigilare within 24 hours of the request.  
SERIOUS ADVERSE EVENT REPORTING INSTRUCTIONS 
SAEXmAb5871-04@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 patient, 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 
patient 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.  In the event of pregnancy in a female 
participant, no more study drug will be given.  However, the Investigator must follow-up and 
document the course and the outcome of all pregnancies if possible even if the patient was 

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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. 
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, 183, 197, 211, 225 and 253 (EOS).  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 patient 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, 127, 183, and 
253 (EOS).  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.  

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The 12-lead ECGs will be performed after the patient 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 
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 
Physical examinations will be performed at Screening and on Days 1, 8, 29, 57, 85, 113, 141, 
169, 197, 225 and 253(EOS). 
The physical examination includes an assessment of general appearance and dermatologic, head, 
eyes, ears, nose, mouth/throat/neck, thyroid, lymph nodes, respiratory, cardiovascular, 
gastrointestinal, extremities, musculoskeletal, neurologic, and psychiatric system evaluations. 
6.1.6. 
Clinical Laboratory Assessments 
Safety clinical laboratory assessments and 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 Cancer Genetics Inc., Morrisville, NC.  
Mechanistic studies will be done at Oklahoma Medical Research Foundation, Oklahoma City, 
OK. 
Blood samples should be taken using standard venipuncture techniques.  Blood sampling will be 
performed according to local 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, 183, 197, 211, 225 and 
253(EOS):  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, 8, 29, 57, 85, 113, 141, 169, 197, 225 and 253(EOS):  total 
protein, sodium, potassium, calcium, chloride, bicarbonate (HCO3), inorganic phosphate, 
albumin, glucose, blood urea nitrogen (BUN), creatinine, uric acid, bilirubin, alkaline 
phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), 

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gamma-glutamyl 
transferase 
(GGT), 
lactate 
dehydrogenase 
(LDH), 
creatine 
phosphokinase (CPK), amylase, and lipase. 
• Immunoglobulin: Serum IgG, IgE, and IgM will be assessed at Screening and on Days 
1, 15, 71, 127, 155, 183, 211 and 253(EOS). 
• Complement levels:  C3 and C4 levels will be assessed at Screening and on Days 1, 29, 
57, 85, 113, 141, 169, 197, 225 and 253(EOS). 
• Coagulation: The following coagulation parameters will be assessed on Screening, and 
Days 1, 29, 85, 141, 197 and 253(EOS):  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, 57, 85, 113, 141, 169, 197, 225 and 253(EOS):  pH, glucose, ketones, 
specific gravity, nitrite, protein, bilirubin, urobilinogen, leukocytes and blood.  
Microscopic urinalysis will be performed if urinalysis results are abnormal.  A spot urine 
protein/creatinine ratio will be performed for urine dipstick of 2+ or greater protein. 
• Serology: HBsAg, HBcAb, and HCV Ab will be performed at Screening.   
• Urine pregnancy test: Urine pregnancy testing will be performed in female patients at 
Screening, Days 1, 15, 43, 71, 99, 127, 155, 183, 211 and 253(EOS). 
• 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 
on Days 1, 15, 43, 85, 127, 183, 225 and 253(EOS). 
• Flow Cytometry B Cell and T Cell Assessment:  
o CD20+ B cells and T cells will be quantified at Screening and on Days 1, 8, 15, 29, 
57, 85, 113, 141, 169, 197, 225 and 253(EOS).   
o 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 at Screening and on Days 1, 8, 15, 29, 57, 85, 
113, 141, 169, 197, 225 and 253(EOS).  
 
 

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Mechanistic Studies:  
For randomized patients, mechanistic studies that will be performed on Days 1, 29, and at the 
LOI visit (either at the visit at which loss of response is noted or on Day 225, whichever comes 
first) may include one or more of the following studies: BioPlex 2200 Autoantibody profiling, 
plasma cytokines by multiplex analysis and BioMark HD 96 gene RNA expression panel.  Some 
or all of the following may also be measured: MMPs/TIMP levels,  osteopontin, vonWillibrand's 
factor, and hsCRP, CXCL13, exosomal assays for numbers, size, function in patients with 
increased and suppressed disease activity, serum stimulation assays to assess ability to induce 
cytokine secretion, netosis, cell death pathways, and an expanded gene expression panel.  
Additional samples will be collected at screening and on Days 8, 15, 57, 71, 99, 113, 127, 141, 
155, 169, 183, 197, 211 and 253(or EOS 6 weeks after loss of improvement, whichever comes 
first) and stored for potential mechanistic studies.  Screening samples for all patients will be 
analyzed for ANA with pattern and anticardiolipin antibodies, with a repeat anticardiolipin 
antibody panel at LOI or Day 225, whichever comes first.   
Blood requirements: 
Blood will be collected for clinical laboratory testing as outlined below:  
• Hematology: Blood (3 mL) will be collected into a lavender-top (EDTA) tube. 
• Chemistry panel and FSH (if warranted): Blood (5.0 mL) will be collected into a serum gel 
(SST) tube.  
• Hepatitis serologies (HBsAg, HBcAb, HCVAb): Blood (4.0 mL) will be collected into a 
serum gel (SST) tube. 
• Coagulation panel: Blood (3.0 mL) will be collected into a blue top (Na Cit) tube. 
• Immunoglobulins (IgG, IgM, IgE), Complement C3 and C4: Blood (5.0 mL) will be 
collected into a serum gel (STT) tube. 
• SLE autoantibodies:  Blood (4.0 mL) will be collected into a serum gel (SST) tube.   
• 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. 

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• Flow Cytometry B Cell and T Cell Assessment:  Blood (5 mL) will be collected into a 
Cyto-Chex BCT glass streck CE marked tube. 
• Mechanistic Studies: Blood (25 mL) will be collected into one 10 mL SST tube, one 10 mL 
green top (heparin) tube and 2 RNA PAX gene tubes. 
The total blood volume collected for clinical labs over the duration of the study will be 
approximately 770 mL over the course of the entire study, with approximately 50 mL collected 
per visit.   
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 
XmAb5871 or placebo dosing:  prior to the start of the infusion and at EOI on Study Days 1, 15, 
29, 57, 85, 113, 141, and 155 and at visit time on Days 8, 225 and 253(EOS).  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.  PK peak and trough values will be plotted over time. 
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, and CD19 
receptor occupancy (RO).   
6.4. 
Pharmacogenomics Variables 
Blood will be collected as outlined as in Table 6 Schedule of Assessments on Day 1 (predose) 
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 

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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.  Where patients provided informed consent, the residual FcγR 
polymorphism sample was retained by Xencor or Xencor’s designee (below), for future 
exploratory genotyping research.  Samples are to be maintained for no more than 15 years before 
destruction.  Samples are to be stored at: 
Cancer Genetics Inc. 
133 Southcenter Court, Suite 400, 
Morrisville, NC 27560, 
USA 
6.4.1. 
Efficacy Measurements 
Disease activity will be measured at Screening and on Days 1, 29, 57, 85, 113, 141, 169, 197, 
225 and 253(EOS).  The following efficacy assessments will be performed according to the time 
points defined in Table 6 Schedule of Assessments: 
SELENA SLEDAI 
The SELENA SLEDAI is a tool designed to quantitate the amount of SLE disease activity a 
patient is experiencing at the present time (and in the proceeding 28 days).  The instrument is 
intended to evaluate current SLE activity and not chronic damage, severity is accounted for in 
part by the "weightedness" of the scale.  While it assesses the organs and systems commonly 
involved in SLE, it is weighted most heavily towards CNS and kidney involvement.  The score 
will be recorded as the sum of descriptors present within the 28 days prior to the visit and visit 
day.  
A sample assessment form is included in Appendix 11.1.1 and instructions for use are in 
Appendix 11.1.4. 
BILAG 
The British Isles Lupus Activity Group (BILAG) index assesses the month prior to the visit and 
is based on intent to treat logic.  Organ systems are rated on whether the system has never been 
involved (E), has been involved in the past (D) but is not currently active, currently contains 
descriptor(s) which are mild (C), of moderate intensity (B), or severe in intensity (A).  Each of 
the 9 systems receives an overall rating which incorporates the intensity and the change (if any) 
of each feature in that system during the past month. 

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A sample assessment form is included in Appendix 11.1.2 and instructions for use are in 
Appendix 11.1.4. 
SELENA SLEDAI Physician Global Assessment Anchored VAS and SELENA SLEDAI 
Flare Index 
The physician’s overall assessment of the patient’s current disease activity will be recorded on a 
3 point (normalized to 100 mm) linear horizontal VAS, where the left hand extreme of the line is 
considered “none” (symptom free and no SLE symptoms) and the right hand extreme is 
considered “maximum” (maximum possible SLE activity).  Anchors at “1” and “2” indicate 
increments for mild and moderate disease activity. The SELENA SLEDAI Flare Index combines 
changes (if any) in the Physician’s Global Disease Activity with a variety of descriptors that 
define mild/moderate or severe flare.  
A sample PGA form and SELENA SLEDAI Flare Index are included in Appendix 11.1.3. 
7. 
STUDY CONDUCT 
7.1. 
Schedule of Assessments 
The study consists of a Screening visit (Day -28 to Day -1) followed by sixteen infusions of 
XmAb5871 given every two weeks (Days 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 
183, 197 and 211) with collection of disease activity assessments, safety data, 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 225 and 253[EOS]).  Patients who experience loss of disease 
activity improvement will have their study drug infusions discontinued and will receive 
appropriate SLE rescue therapy at the discretion of the principal investigator.  The patient should 
be followed for an additional 6 weeks from the time of the last study drug infusion.  Assessments 
listed for the Day 225 visit should be performed at the time of loss of disease activity 
improvement (LOI).  Assessments listed for the Day 253(EOS) visit should be performed at the 
follow-up visit 6 weeks from the time of the last study drug infusion.  The maximal study 
duration for an individual patient will be 253 days after the first infusion.   
Please see Table 6 for the Schedule of Assessments.  
7.1.1. 
Assessments by Visit 
Please refer to Table 6 for a description of the assessments to be performed at each study visit.  

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7.1.2. 
Early Termination Visit 
If a patient withdraws prematurely after dosing, assessments listed for the Day 225 visit should 
be performed at the time of loss of disease activity improvement or time of discontinuation for 
other reasons.  Assessments listed for the Day 253(EOS) visit should be performed at the follow-
up visit 6 weeks from the time of the last study drug infusion as a final safety check.  Please see 
7.1 above for those patients who experience a loss of improvement. 
7.1.3. 
End-of-Study 
End-of-Study is defined as completion of the End-of Study Visit on Day 253.  For those patients 
who withdraw prematurely, EOS is defined as the time of the patient’s last data collection. 

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Table 6: Schedule of Assessments [a]   
Study Phase 
SCR 
Treatment 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Study Week 
-4  
1 
2 
3 
5 
7 
9 
11 
13 
15 
17 
19 
21 
23 
Study Day 
-28 to 
-1 
1 
8 
+/-1 
15 +/-
1 
29 +/-
1   
43 +/-
1  
57 +/-
1 
71 +/-
1  
85 +/-
1 
99 +/-
2 
113 
+/-2 
127 
+/-2 
141 
+/-2 
155 +/-
2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Withdraw immuno-
suppressant  
X [c] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Depomedrol IM 
X[d] 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Improvement assessment 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration  
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Vital signs[e] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
X 
X[f] 
 
 
X 
 
 
 
 
 
 
X 
 
 
CBC, differential, platelets 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry panel 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
PT/INR and APTT 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Urinalysis 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
HBsAg, HCV Ab, HBc Ab 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test[g] 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
FSH[h] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
FcγR polymorphisms[i]  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
T and B cell enumeration, 
CD19RO and B cell subsets  
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
SELENA SLEDAI 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
BILAG 2004 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
SLE Autoantibody Panel 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
C3 and C4 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
PGA 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Serum IgM, IgG, IgE 
X 
X 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
PK blood[j] 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
Immunogenicity (ADA) [k] 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
Mechanistic studies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 

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Study Phase 
 
EOS 
Visit Number 
15 
16 
17 
18 
19[b] 
20[b] 
Study Week 
25 
27 
29 
31 
33[b] 
37[b] 
Study Day 
169 
+/-2 
183 
+/-2 
197 
+/-2 
211 
+/-2 
225[b]   
+/-3 
253[b] 
+/-3 
Informed consent 
 
 
 
 
 
 
Withdraw immuno-
suppressant  
 
 
 
 
 
 
Depomedrol IM 
 
 
 
 
 
 
Improvement assessment 
 
 
 
 
 
 
Study drug administration  
X 
X 
X 
X 
 
 
AE Assessment 
X 
X 
X 
X 
X 
X 
Medical history 
 
 
 
 
 
 
Physical exam 
X 
 
X 
 
X 
X 
Vital signs[e] 
X 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
 
X 
 
 
 
X 
CBC, differential, platelets 
X 
X 
X 
X 
X 
X 
Chemistry panel 
X 
 
X 
 
X 
X 
PT/INR and APTT 
 
 
X 
 
 
X 
Urinalysis 
X 
 
X 
 
X 
X 
HBsAg, HCV Ab, HBc Ab 
 
 
 
 
 
 
Pregnancy test[g] 
 
X 
 
X 
 
X 
FSH[h] 
 
 
 
 
 
 
FcγR polymorphisms[i]  
 
 
 
 
 
 
T and B cell enumeration, 
CD19RO and B cell subsets  
X 
 
X 
 
X 
X 
SELENA SLEDAI 
X 
 
X 
 
X 
X 
BILAG 2004 
X 
 
X 
 
X 
X 
SLE Autoantibody Panel 
X 
 
X 
 
X 
X 
C3 and C4 
X 
 
X 
 
X 
X 
PGA 
X 
 
X 
 
X 
X 
Serum IgM, IgG, IgE 
 
X 
 
X 
 
X 
PK blood[j] 
X 
 
X 
X 
X 
X 
Immunogenicity (ADA) [k] 
 
X 
 
 
X 
X 
Mechanistic studies 
X 
X 
X 
X 
X 
X 
 
 
 

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[a] 
Unless otherwise stated, assessments should be performed pre-dose. 
[b] 
If a patient experiences a loss of disease activity improvement (LOI), they will receive no more infusions of study drug.  Assessments listed above under 
Day 225 should be performed at the time of loss of disease activity improvement and assessments for Day 253 (EOS) should be performed at a visit 6 weeks 
from the time of the last study drug infusion. 
[c] 
Immunosuppressants may be discontinued anytime from screening start but before Day 1.  During screening, investigators may give additional steroids IM 
up to 320 mg total at their discretion to achieve the targeted disease improvement.   
[d] 
Patients receive 160 mg depomedrol IM at the beginning of screening and may receive up to additional 320 mg during screening to suppress disease activity 
at the principal investigator’s discretion. All patients will receive 80 mg of IM depomedrol on Days 1 and 15.  
[e] 
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.  
[f] 
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. 
[g] Pregnancy test only for women of child-bearing potential 
[h] 
FSH only in women of non-childbearing potential 
[i] 
Sample to be taken pre-dose. 
[j] 
PK blood at trough levels prior to infusion and at end of infusion 
[k]    ADA sample should be drawn at the time of any suspected immunological related AE and at the time of each subsequent visit  X 4.  

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8. 
STATISTICAL METHODS 
Before database lock, a statistical analysis plan (SAP) will be issued as a separate document, 
providing detailed methods for the analyses and may supersede 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 screened, enrolled, randomized and 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: 
• Enrolled Population:  All patients who were enrolled in the study (signed informed consent, 
met inclusion and exclusion criteria and were randomized), 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 or placebo.   
• Efficacy Evaluable Population:  All patients who: 
o Complete study through Day 225 assessments 
o Discontinue due to reaching the protocol specified LOI endpoint (and have not missed 
2 or more consecutive doses prior to the LOI visit) 
o Discontinue due to drug-related adverse event (nonresponder) 
• Safety Population:  All patients who received at least a partial dose of XmAb5871 or 
placebo.  In this study, this will be 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. 

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• 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 
This is a randomized, double-blind, placebo-controlled study where descriptive and inferential 
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 methods (median, number censored, etc.) and 
Kaplan-Meier plots.  Inferential statistical methodologies will be described below and 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 analysis will be performed on the Efficacy 
Evaluable and ITT Populations, and safety analysis on the Safety Population. 
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.  
8.3. 
Determination of Sample Size 
It is anticipated that approximately 90 patients will be enrolled in the study.  Sample size is based 
on a previously completed study of SLE patients treated with IM depomedrol for 2 weeks 
following cessation of background immunosuppressant therapy.  In that study, by month 6, 
40/41 patients lost the disease activity improvement achieved following IM steroid therapy; a 
2.4% placebo response.   
Assuming a 10% placebo response (defined as no loss of disease activity improvement from 
Day 1 to Day 169) and a 38% response in the XmAb5871 treatment arm (i.e., a 28% delta 
between treatment arms), 40 patients per treatment arm will provide 80% power to detect this 
difference at alpha=0.05 (two-sided) by use of the Fishers exact test.  Adding 10% for 
unevaluable patients, the total number per arm is calculated as 45.  
8.4. 
Treatment Assignment and Drop-Outs 
Approximately 90 patients will be randomized in a 1:1 treatment allocation scheme; therefore, 
45 patients will be assigned to the XmAb5871 arm and 45 patients assigned to the placebo arm. 

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There are no stratification factors planned for this randomization.  A clinical research 
organization independent of the clinical trial team will develop the randomization schedule and 
the actual randomization assignment will be made through a secure Interactive Web-Based 
System (IWRS). 
After obtaining oral and written informed consent, patients will be screened according to the 
inclusion and exclusion criteria.  The screening number will be used throughout the screening 
period.  Patients who meet all selection criteria will then be randomized and receive a patient 
number on Day 1.  The patient number will ensure identification throughout the study.   
Patients dropping-out or withdrawing, for any reason, without completing all screening 
evaluations successfully, will be considered as “screening failures“.  Such patients will not 
receive a patient number, however, screening data will be collected in the electronic Case Report 
Forms (eCRFs).  The Investigator will keep a screening log of all patients screened in order to 
assess the numbers and characteristics of the excluded patients, and the reasons for their 
exclusion. 
8.5. 
Blinding 
The study will be conducted in a double-blind manner.  All patients, investigators, and study 
staff/clinicians will be blinded to the study treatment assignment (XmAb5871 or Placebo) until 
the study is formally unblinded for data analysis purposes.  The Sponsor’s team members 
responsible for study conduct and safety monitoring will also be blinded to study treatment.  The 
randomization schedule will be held at an independent clinical research organization not 
affiliated with the study conduct and will only release the full randomization schedule after the 
database is formally locked for data analysis purposes.  
However, individual patient treatment assignment may be revealed due to the occurrence of a 
medical emergency requiring medical intervention or if the Medical Monitor for the study 
determines that patient safety requires knowledge of the study drug assignment.  Documentation 
of the breaking of the randomization code, including the date and reason for such unblinding, 
must be documented in the EDC system.   
8.6. 
Study Endpoints and Statistical Analyses 
Efficacy analyses will be performed on the Efficacy Evaluable and ITT Populations.  The 
Efficacy Evaluable will serve as the primary population for all efficacy analyses and the ITT will 
be conducted for sensitivity analysis purposes. 

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8.6.1. 
Primary Efficacy Endpoint (Loss of Improvement at Day 225) 
The primary endpoint will be evaluated as the percentage of SLE patients without loss of disease 
activity improvement from Day 1 to Day 225 (i.e., responders).  Loss of improvement will be 
defined as worsening of disease activity that in the opinion of the principal investigator requires 
a change in treatment (exclusive of a decrease in oral steroids) AND one of: 
1) SELENA- SLEDAI increase of ≥4 points from maximal improvement OR  
2) Worsening of at least 1 BILAG A or B score OR  
3) New BILAG A or B score. 
The number of “responders” will be presented as frequency counts and percentages by treatment 
arm.  The primary efficacy analysis will employ the Fisher’s Exact Test testing for differences in 
treatment response rate (patients without loss of disease activity improvement from Day 1 to 
Day 225) between the two treatment groups.  Exact confidence intervals will be computed for 
each treatment’s binomial proportion of response. 
8.6.2. 
Secondary Efficacy Endpoints  
The percentage of SLE patients without loss of disease activity improvement from Day 1 to Day 
169 (i.e., responders) will be evaluated as above. 
The time to loss of SLE disease activity improvement achieved by a short period of IM steroid 
therapy in SLE patients will be summarized by treatment arm using Kaplan-Meier methods 
(median, 95% CI, number of events, number censored, etc.) and Kaplan-Meier plots.  The 
log-rank test will be used to test for treatment group differences. 
8.6.3. 
Exploratory Efficacy Endpoints 
The following disease assessment indices will be used for exploratory analyses of disease 
activity over time: 
• SELENA SLEDAI hybrid version with SELENA SLEDAI Flare index 
• BILAG 2004 
• Physician’s Global Disease activity VAS 
The SLEDAI, BILAG and PGA will be summarized by treatment arm 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.  Categorical 
variables will be presented as frequency counts and percentages. 

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Additional analyses on exploratory parameters will be described in the SAP. 
8.6.4. 
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 by treatment 
arm.  Treatment-emergent adverse events will also be tabulated according to intensity and 
causality by treatment arm. 
• 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 by treatment arm.  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) by treatment arm 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 for 
each treatment arm. 
• Physical Examinations will be presented in patient listings.  
8.7. 
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).    

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8.8. 
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. 
8.9. 
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 and anti-dsDNA 
antibody levels 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. 
8.10. 
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. 
8.11. 
Immunogenicity Analysis 
Frequency and titer of anti-XmAb5871 antibodies (ADA) will be listed.  
8.12. 
Interim Analyses 
No formal interim analysis is planned, however aggregate blinded interim safety reviews may be 
performed for submission to regulatory authorities.    
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 

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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 will 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 PPD.  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. 
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 patient receiving IMP. 

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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 contact 
information 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 
aware of the potential risks, inconveniences, or AEs that may occur.  The study 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 

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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 patient 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 must receive IRB approval prior to implementation.  Where a protocol deviation occurs for 
the well-being of the patient, the Sponsor must be informed of the action. Any deviations and 
protocol violations that occur must be reported to the Sponsor and to the IRB as per local IRB 
requirements. 
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 
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 patient number, initial or birth date, not by name.  Documents that identify 

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the patient (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. 
Bruce IN, Gordon C, Merrill JT, Isenberg D. 2010. Clinical trials in lupus: what have we learned 
so far? Rheumatology 49:1025–1027. 
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. 
Dharajiya N, Vaidya SV, Murai H, Cardenas V, Kurosky A, Boldogh I, et al. 2010. FcgRIIb 
inhibits allergic lung inflammation in a murine model of allergic asthma. PloS one 5:e9337. 
Floto RA, Clatworthy MR, Heilbronn KR, Rosner DR, MacAry PA, Rankin A, et al. 2005. Loss 
of function of a lupus-associated FcgRIIb polymorphism through exclusion from lipid rafts. Nat 
Med 11:1056-8. 
Guthridge JM, Lou R, Kamp S, Munroe ME, Bean K, Macwana SR, Sridharan S, Merrill JT, 
James JA.  2014.  Predictive modeling of immunologic and inflammatory markers of impending 
disease flare in patients with systemic lupus erythematosus not taking immunosuppressive 
medications.  Ann Rheum Dis 73(Suppl2): 192. 
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. 
Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S, et al. 2006. Selective 
dysregulation of the FcgIIB receptor on memory B cells in SLE. J Exp Med 203:2157-64. 
McGaha TL, Sorrentino B, Ravetch JV. 2005. Restoration of tolerance in lupus by targeted 
inhibitory receptor expression. Science 307:590-3. 

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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. 
Merrill JT, Zhou T, James JA, Guthridge JM, Lehmann M, Masferrer J, Immermann F, 
Sridharan S. 2011.  Biologic impact of immunosuppressants in patients with active lupus: interim 
report from the biomarkers of lupus disease (BOLD) study.  Ann Rheum Dis 70(Suppl3):319. 
Merrill J.  2013. Clinical trials in SLE: what have we learned? Rheum Dis 72(Suppl3):14. 
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. 2006. 
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 117:391-7. 
Smith KG, Clatworthy MR. 2010. FcgammaRIIB in autoimmunity and infection: evolutionary 
and therapeutic implications. Nature Rev Immunol 10:328-343. 
Su K, Yang H, Li X, et al. 2007.  Expression profile of FcγRIIb and leukocytes and its 
dysregulation in systemic lupus erythematosus.  J Immunol 178:3272-3280. 
Tan EM, Cohen AS, Fries JF, et al. 1982. The 1982 revised criteria for the classification of 
systemic lupus erythematosus. Arthritis Rheum 25:1271-1277. 
Tarasenko T, Dean JA, Bolland S. 2007. FcgRIIB as a modulator of autoimmune disease 
susceptibility. Autoimmunity 40:409-17. 
Thanou A, Merrill JT. 2014. Treatment of systemic lupus erythematosus: new therapeutic 
avenues and blind alleys. Nature Rev Rheum 10:23-34. 
Tsuchiya N, Honda Z, Tokunaga K. 2006. Role of B cell inhibitory receptor polymorphisms in 
systemic lupus erythematosus: a negative times a negative makes a positive. J Hum Genet 
51:741-50. 
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Medical Association General Assembly Seoul, October 2008. 
 
 

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11. 
APPENDICES 
11.1. 
Efficacy Assessments 
11.1.1. 
Hybrid SELENA SLEDAI and SELENA SLEDAI Flare Index 
The Hybrid SELENA SLEDAI is a tool designed to detect amount of disease activity and 
identify improvements and worsening of disease.     
Hybrid SELENA SLEDAI with SELENA SLEDAI FLARE INDEX and PGA  
(Hybrid SLEDAI is the SELENA SLEDAI except using proteinuria definition from SLEDAI 2K) 
(Circle in SLEDAI Score column if descriptor is present at the time of the visit or in the preceding 4 weeks)  
(The same instrument can also be used going back only ten days) 
 
Item 
no. 
SLEDAI 
SCORE 
Descriptor 
Definition 
1 
8 
Seizure 
Recent onset, exclude metabolic, infectious or drug 
causes 
2 
8 
Psychosis 
Altered ability to function in normal activity due to severe 
disturbance in the perception of reality. Include 
hallucinations, incoherence, marked loose associations, 
impoverished thought content, marked illogical thinking, 
bizarre, disorganised, or catatonic behaviour. Exclude 
uraemia and drug causes 
3 
8 
Organic brain 
syndrome 
Altered mental function with impaired orientation, memory, 
or other intellectual function, with rapid onset and 
fluctuating clinical features, inability to sustain attention to 
environment, plus at least 2 of the following: perceptual 
disturbance, incoherent speech, insomnia or daytime 
drowsiness, or increased or decreased psychomotor 
activity. Exclude metabolic, infectious or drug causes 
4 
8 
Visual disturbance 
Retinal changes of SLE. Include cytoid bodies, retinal 
hemorrhages, serous exudates or hemorrhages in the 
choroid, or optic neuritis, scleritis or episcleritis. Exclude 
hypertension, infection, or drug causes 
5 
8 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy involving 
cranial nerves 
6 
8 
Lupus headache 
Severe, persistent headache; may be migrainous, but 
must be non-responsive to narcotic analgesia THIS 
WOULD RARELY BE ATTRIBUTED TO SLE...ALMOST 
NEVER SCORED 
7 
8 
CVA 
New onset Cerebrovascular accident(s). Exclude 
arteriosclerosis 
8 
8 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual 
infarction, splinter hemorrhages or biopsy or angiogram 
proof of vasculitis 
9 
4 
Arthritis 
> 2 joints with pain and signs of inflammation (i.e. 
tenderness with swelling or effusion) 
10 
4 
Myositis 
Proximal muscle aching/weakness, associated with 
elevated creatinine phosphokinase (CK)/aldolase, or EMG 
changes or a biopsy showing myositis 
11 
4 
Urinary casts 
Heme-granular or RBC casts 
12 
4 
Hematuria 
> 5 RBC/high power field. Exclude stone, infection or 
other cause 

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13 
4 
Proteinuria 
> 0.5 gram/24 hours 
14 
4 
Pyuria 
> 5 WBC/high power field. Exclude infection 
15 
2 
Rash 
Inflammatory type rash 
16 
2 
Alopecia 
Abnormal, patchy or diffuse loss of hair 
17 
2 
Mucosal ulcers 
Oral or nasal ulcerations 
18 
2 
Pleurisy 
Pleuritic chest pain or pleural rub or effusion, or pleural 
thickening (does not require an objective component if 
medically convincing) 
19 
2 
Pericarditis 
Classic pericardial pain and/or rub, effusion or ECG or 
echocardiogram confirmation (does not require an 
objective component if medically convincing) 
20 
2 
Low complement 
Decrease in CH50, C3 or C4 < lower limit of nl for testing 
laboratory  
21 
2 
Increased DNA 
binding 
Increased DNA binding above normal range for testing 
laboratory 
22 
1 
Fever 
> 38ºC. Exclude infectious cause 
23 
1 
Thrombocytopenia 
< 100 × 109 platelets/L, exclude drug causes 
24 
1 
Leukopenia 
< 3 × 109 WBC/L, exclude drug causes 
      ______________ Total SCORE   
 
 
CLASSIC SELENA SLEDAI FLARE INDEX (Can be used with any version of the 
SLEDAI) 
 
Physician’s Global Assessment (PGA) 
Visual Analog Scale with anchors 
 
 
0             1             2               3               (this was developed as a three inch scale but has been 
None    Mild    Moderate   Severe            used in trials as a 100mm scale) 
 
 
Mild or Moderate Flare   
 
 Change in SELENA SLEDAI instrument score of 3 points or more (but not to more than 12) 
 New/worse: Discoid, photosensitive, profundus, bullous lupus, 
 Nasopharyngeal ulcers  
 Pleuritis  
 Pericarditis  
 Arthritis  
 Cutaneous Vasculitis 
 Fever (SLE)  
 Increase in prednisone, but not to >0.5 mg/kg/day  
 Added NSAID or hydroxychloroquine for SLE activity  
 ≥1.0 increase in PGA score, but not to more than 2.5  
 
Severe Flare  

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 Change in SELENA SLEDAI instrument score to greater than 12 
 New/worse: CNS-SLE 
                       cutaneous vasculitis,  
 Vasculitis 
 Nephritis 
 Myositis 
 Plt <60,000 
 Hemolytic anemia: Hb <70 g/L or decrease in Hb >30 g/L 
Requiring: double prednisone, or prednisone increase to 
>0.5 mg/kg/day, or hospitalization 
 Increase in prednisone to >0.5 mg/kg/day 
 New cyclophosphamide, azathioprine, methotrexate for SLE activity 
 Hospitalization for SLE activity 
 Increase in Physician’s Global Assessment score to >2.5 
 
 
 

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11.1.2. 
BILAG2004 
 

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11.1.3. 
Physician Global Assessment of Disease Activity (VAS) 
Physician’s Global Assessment of Disease Activity (100 mm-VAS) 
Place a mark on the line below to indicate disease activity:  
Physician’s Global Assessment (PGA) 
Visual Analog Scale with anchors 
 
 
0             1             2               3               (this was developed as a three inch scale but has been 
None    Mild    Moderate   Severe            used in trials as a 100mm scale) 
 
VASPhysician Global Assessment of Disease Activity = _______ mm 
 
 
11.1.4. 
BILAG2004 and SELENA SLEDAI Instructions 
GUIDELINES FOR USE OF THE SELENA SLEDAI MODIFIED FOR ASSESSMENT 
OVER 28 DAYS: TO ASSESS DISEASE ACTIVITY  
General guidelines for the SELENA SLEDAI  
(Hybrid Version using SLEDAI 2K Proteinuria Definition) 
• 
The main principle to keep in mind is that this instrument is intended to evaluate current 
lupus activity and not chronic damage, severity is accounted for in part by the 
"weightedness" of the scale. 
• 
Points are given exactly as defined. 
• 
A descriptor is either scored the exact points allotted or not scored, i.e. given a zero. 
Descriptors are scored only if they are present at the time of the physician encounter or in 
the preceding 28 days. (The SLEDAI 2K instrument is validated both for the original use 
with a 10 day window and for the use of a 28 day window, and any of the SLEDAI 
versions can be used with a 28 day window). Small deviations in this window which are 
allowed in a clinical trial protocol for monthly visits are acceptable in scoring the 
SLEDAI. However, it is never acceptable to fill in gaps which cover activity over 2-3 
months or more. The reason for this is that disease activity at the visit might have 
changed several times in such intervals and the recording of distant activity becomes 
meaningless.  
 
Please note that in the original SLEDAI the disease activity being scored was meant to 
cover only a ten day period, the modification to 28 days is a more useful assessment for 
use in clinical trials, in order to capture disease activity between monthly visits. However 
the SLEDAI does require documented confirmation of events that may have occurred and 
resolved between visits. 
It is critical to record all new events that have developed during this time, for which there 
are very convincing lupus symptoms and/or signs consistent with glossary definitions for 

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the items, even if the item has since disappeared. However, if a feature that was present 
at the last visit disappears soon after the last visit (within one week) then the item is not 
recorded on the SELENA SLEDAI form.  
•
The descriptors which are scored must be documented by the notes written in the
physician encounter form. This rule generally applies to the clinical data and not to the
laboratory data. The laboratory data is strictly defined as per cutoffs and documentation is
provided by the reports from the commercial laboratory.
•
Descriptors do not have to be new but can be. They can be ongoing, recurrent, or initial
events. Each would be scored the same way. An example would be a malar rash or
mucosal ulcer. In these situations a malar rash observed at the initial visit but which
remains unchanged for the next six months, irrespective of any treatment, is scored 2
points each time the SLEDAI is completed. Since the nature of lupus is that clinically
significant manifestations are not usually fleeting it would be rare for descriptors to be
present during the month and not seen at the time of the encounter. This is discussed in
more detail for each descriptor but is especially relevant for some neurologic, pulmonary,
and cutaneous manifestations. A major exception would be seizure, due to lupus, which
requires solid documentation but obviously would not need to be continuing at the time
of the visit.
•
In some descriptors the exclusions written may not be exhaustive. The intent of the
SLEDAI is that the descriptor be attributed to SLE. If the physician does not attribute the
descriptor to SLE it should not be scored, but documentation in support of this decision
must be provided.
Written in italics is the definition for each descriptor precisely provided in the SLEDAI SCORE 
SEIZURE 
Definition: Recent onset (last 28 days). Exclude metabolic, infectious or drug cause, or seizure 
due to past irreversible CNS damage. 
This descriptor is scored if the patient has had a witnessed seizure or convincing description 
(such as tongue biting or incontinence) within 30 days of the current encounter. The patient need 
not have a positive EEG, CT scan, PET scan, QEEG, or MRI. The CSF may be totally normal. 
A seizure is also not counted: 
1. If a metabolic cause is determined.
2. In the presence of a proven infectious meningitis, brain abscess, or fungal foci.
3. If there is a history of recent head trauma.
4. In the presence of an offending drug.
5. In the presence of severe hyperthermia or hypothermia.
6. If the patient has stopped taking anticonvulsant medication.
7. If the patient has a documented sub-therapeutic anticonvulsant drug level.

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PSYCHOSIS 
Definition: Altered ability to function in normal activity due to severe disturbance in the 
perception of reality. Include hallucinations, incoherence, marked loose associations, 
impoverished thought content, marked illogical thinking, bizarre, disorganized, or catatonic 
behavior. Exclude uremia and drug causes. 
This descriptor is scored if any of the criteria above are met. 
With regard to drug causes the most problematic situation is glucocorticoids. If the treating 
physician attributes the psychosis to glucocorticoids this descriptor should not be counted. 
ORGANIC BRAIN SYNDROME  
Definition: Altered mental function with impaired orientation, memory or other intellectual 
function, with rapid onset and fluctuating clinical features. Include clouding of consciousness 
with reduced capacity to focus, and inability to sustain attention to environment, plus at least 
two of the following: perceptual disturbance, incoherent speech, insomnia or daytime 
drowsiness, or increased or decreased psychomotor activity. Exclude metabolic, infectious or 
drug causes. 
a. reduced capacity to focus as exemplified by new inability to perform everyday 
mathematical computations or disorientation to person, place, time, or purpose 
 
OR 
b. inability to carry on a conversation 
 
OR 
c. reduction in short term memory 
PLUS: Documented abnormality on neuropsychiatric testing  
Neuropsychiatric testing may take the form of a "mini-mental-status exam" or a formal 
neuropsychiatric examination. The important aspect for scoring OBS is that it be reversible. 
Consideration should be given to the improvement of OBS after institution of glucocorticoids. 
This descriptor is not scored in the presence of a metabolic, infectious, or drug cause. If the 
problem is chronic this descriptor is not scored in SLEDAI but is scored on the damage index.  
VISUAL DISTURBANCE 
Definition: Retinal and eye changes of SLE. Include cytoid bodies, retinal hemorrhages, serous 
exudate or hemorrhages in the choroid, optic neuritis, scleritis or episcleritis. Exclude 
hypertension, infection or drug causes. 
This is scored exactly as defined with the understanding that it must be supported by objective 
evidence. 

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CRANIAL NERVE DISORDER 
Definition: New onset of sensory or motor neuropathy involving cranial nerves. Include vertigo 
due to lupus. 
This is scored exactly as defined with the understanding that it must be supported by objective 
evidence. However, it should be noted that hydroxychloroquine can affect the eighth cranial 
nerve. 
LUPUS HEADACHE 
Definition: Severe persistent headache: may be migrainous, but must be non-responsive to 
narcotic analgesia. 
For this descriptor to be counted, the headache must be present for greater than 24 hours and 
must not be responsive to narcotic analgesia. Objective documentation need not be present 
although it is expected that such a complaint, given the severity, would prompt formal testing 
such as MRI, CT, LP, etc. Furthermore, the headache should be of sufficient severity to warrant 
the initiation of glucocorticoids or additional immunosuppressive agents. Scoring of this 
descriptor means attribution of the headache to CNS lupus. 
Most headaches, including most severe and/or migrainous headaches are not attributable to lupus 
and this descriptor should only be scored very rarely. 
CVA 
Definition: New onset of cerebrovascular accident (s). Exclude arteriosclerosis or hypertensive 
causes. 
This descriptor is scored if the patient has had a CVA within 28 days of the current encounter. A 
patient recovering from a CVA that was documented more than 28 days prior to the current 
encounter is not given points for this descriptor. A patient may have had a previous CVA but to 
be scored the current CVA must be new. 
This descriptor is scored in the presence or absence of anti-phospholipid antibodies, i.e., the 
precise pathophysiologic mechanism need not be known. 
The CVA is scored even in the presence of a normal CT or MRI. A TIA is also scored if the 
patient gives a convincing history. To exclude atherosclerosis the patient has to have a normal 
carotid and/or vertebral Doppler and cannot have uncontrolled hypertension. 
VASCULITIS 
Definition: Ulceration, gangrene, tender finger nodules, periungual infarction, splinter 
hemorrhages, or biopsy or angiogram proof of vasculitis. 
To score this descriptor the above definitions must be present. For example, erythematous 
lesions on the hands or feet which may be characteristically considered "leukocytoclastic 
vasculitis" but do not fulfill at least one of the above definitions and if not biopsied, are not 

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counted. Similarly livedo reticularis is not counted. Healed ulcers with residual scar are not to be 
counted, but be sure to count these in the damage index. A lesion consistent with erythema 
nodosum should be counted regardless of whether it is biopsied or not. Purpura in the presence 
of a normal platelet count should be counted regardless of whether it has been biopsied or not. 
ARTHRITIS 
Definition: More than two joints with pain and signs of inflammation, i.e., tenderness, swelling, 
or effusion. 
Arthritis is scored if it is ongoing; it need not be new or recurrent. 
Arthritis is scored only if more than two joints manifest signs of inflammation. For example if 
only the right second and left third PIPs are involved or only both wrists, points for this 
descriptor are not given. 
Inflammation is strictly defined in this activity index as the presence of tenderness (the patient 
complains of pain on palpating the joint or upon going through range of motion) PLUS any one 
of the following: 
1. swelling  
2. effusion 
3. warmth 
4. erythema, but must exclude overlying cellulitis 
The presence of tenderness alone is not sufficient. A patient's complaints of pain in specific 
joints without objective findings is not sufficient. An exception would be arthritis of the hip in 
which case pain in the groin on range of motion accompanied by decreased range of motion in 
the absence of swelling, warmth, or erythema would be counted.  Inflammation of the tendons, 
ligaments, bursae, and other periarticular structures are not scored. For example subacromial 
bursitis and trochanteric bursitis are not scored. If further evaluation reveals osteonecrosis or 
osteoarthritis, this descriptor is not counted.  
MYOSITIS 
Definition: Proximal muscle aching/weakness, associated with elevated creatine 
phosphokinase/aldolase or electromyogram changes or a biopsy showing myositis. 
The patient complains of muscle aching and/or weakness in the proximal muscles PLUS one of 
the following must be present: 
1. elevated serum creatine phosphokinase and/or aldolase 
2. abnormalities on electromyogram consistent with myositis 
3. biopsy-proven myositis 
URINARY CASTS 
Definition: Heme-granular or red blood cell casts. 
This is scored if red blood cell casts are seen, even if it is only one. Pigmented casts are counted 
but non-pigmented granular casts, hyaline or waxy casts are not counted. 
HEMATURIA 
Definition: >5 red blood cells/high power field. Exclude stone, infection or other cause. 
With regard to this descriptor, every attempt should be made to see patients when they are not 
menstruating. If this is not possible the urinalysis should be deferred until the next visit. 
This descriptor is not scored if there is documented renal calculi or infection. The latter must be 
confirmed by a positive urinary culture. However it is acknowledged that associated conditions 
such as chlamydia or urethral irritation may result in mild hematuria and the physician's best 
judgment is warranted. The important point is attribution: there must be other evidence of 
nephritis and other causes of hematuria must be excluded.  

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In the complete absence of proteinuria, attribution of hematuria to active nephritis would be very 
unlikely unless pathology is limited to the mesangium. 
PROTEINURIA 
Definition: more than 0.5 g/24 hours attributed to lupus nephritis. 
PYURIA 
Definition: >5 white blood cells/high power field. Exclude infection. 
This descriptor is not scored if there is evidence of vaginal contamination (presence of any 
squamous epithelial cells) or a documented infection. The latter must be confirmed by a positive 
urinary culture. However, it is acknowledged that associated conditions such as chlamydia, 
trichomonas or urethral irritation may result in mild pyuria and the physician's best judgment is 
warranted. The important point is attribution; there must be other evidence of nephritis, 
and other causes of pyuria should be excluded. In the complete absence of proteinuria, 
attribution of hematuria to active nephritis would be very unlikely unless pathology is limited to 
the interstitium. 
RASH 
Definition: Ongoing inflammatory lupus rash. 
A rash is scored if it is ongoing, new or recurrent. Even if it is identical in terms of distribution 
and character to that observed on the last visit and the intensity is improved, it is counted. 
Therefore, despite improvement in a rash, if it is still ongoing it represents disease activity. The 
rash must be attributable to SLE. A description of the rash must appear in the physical exam and 
should include distribution, characteristics such as macular or papular, and size.  
The following should not be scored: 
1. Chronic scarred discoid plaques in any location. 
2. Transient malar flush, i.e., it is not raised and is evanescent 
A common problem one may encounter is the differentiation between scoring a lesion as "rash" 
and/or "vasculitis". If a lesion meets the descriptive criteria of the latter it should not also be 
counted as rash, i.e., the score would be 8 points not 10 points. If a separate rash characteristic of 
SLE is present only then would "rash" also be scored. 
ALOPECIA: 
Definition: Ongoing abnormal, patchy or diffuse loss of hair due to active lupus. 
This should be scored if any of the following conditions are present: 
1. There is temporal thinning which is newly present for less than six months (if temporal 
alopecia is present for more than six months with no change it should not be counted)  
2. Areas of scalp with total bald spots if present for less than six months (does not need to 
have accompanying discoid lesion or follicular plugging) 
3. The presence of "lupus frizz" i.e., short of strands of unruly hair in the frontal or temporal 
area 
If a patient complains of hair loss and there is nothing apparent on exam this descriptor is not 
scored. 
MUCOSAL ULCERS: 
Definition: Ongoing oral or nasal ulcerations due to active lupus. 
An ulcer is scored if it is ongoing, it need not be new or recurrent. Ulcers can be present in either 
the nose or oral cavity. Erythema alone without frank ulceration is not sufficient to be scored, 
even if the erythema is present on the upper palate. Ulcers on the buccal mucosa and tongue are 
counted. 
Mucosal ulcers are not counted as vasculitis. 

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PLEURISY 
Definition: Classic and severe pleuritic chest pain or pleural rub or effusion or new pleural 
thickening due to lupus. 
This descriptor is scored if the patient complains of pleuritic chest pain lasting greater than 12 
hours. The pain should be classic, i.e., exacerbated by inspiration, to help distinguish it from 
musculoskeletal conditions such as costochondritis, which could be confused with pleurisy. The 
symptom does not have to be accompanied by any objective findings. The presence of objective 
findings such as pleural rub or pleural effusions (in the absence of infection, congestive heart 
failure, malignancy, or nephrosis) is counted, even if not accompanied by symptoms. New 
pleural thickening should be counted only if other causes as described above are absent. 
PERICARDITIS: 
Definition: Classic and severe pericardial pain or rub or effusion, or electrocardiogram, or echo 
confirmation. 
The symptom does not have to be accompanied by objective findings.  
LOW COMPLEMENT: 
Definition: Decrease in CH50, C3 or C4 below the lower limit of normal for testing laboratory. 
Exclude a low C4 or CH50 in patients with known inherited deficiency of C4. 
INCREASED DNA BINDING 
Definition: >25% binding by Farr assay or above normal range for testing laboratory. 
FEVER: 
Definition: >38°C. Exclude infectious cause. 
This would be scored if one of the following conditions are present: 
1. A documented temperature elevation >100.4°F or >38°C at the time of the visit. 
2. A convincing history from the patient that she/he has been febrile within the preceding 10 
days prior to the visit without any signs or symptoms suggestive of infection. Febrile is 
defined as above and not simply that the patient felt feverish. In this case the patient need 
not be febrile at the time of the visit for a score of 2 to be given. 
As stated in the SLEDAI, fever secondary to infection is not to be scored although it is 
acknowledged that concomitant lupus activity and infection can occur. Fever in the presence of 
infection should only be scored on the SLEDAI if other evidence of lupus activity is present.  
THROMBOCYTOPENIA: 
Definition: <100,000 platelets/mm3. 
LEUKOPENIA: 
Definition: <3,000 white blood cells/mm3. Exclude drug causes. 
This is exactly as described, WBC <3,000/mm3. The presence of an absolute lymphopenia does 
not count in the SLEDAI. A note of caution, do not confuse this WBC with that used to satisfy 
the ACR criteria for SLE which is WBC <3,500/mm3. 
With regard to current use of possible offending drugs, the following guidelines are to be 
considered: 
1. The nadir after cyclophosphamide, i.e., low WBC at 10 days after receiving 
cyclophosphamide in a patient known to have a WBC ≥ 3,000 at the time of receiving 
cyclophosphamide should not be counted. 
2. Do not score leukopenia appearing after initiation of a new medication known to be 
associated with leukopenia, such as azathioprine or sulfa drugs. If the patient develops a 
WBC <3000 while taking drugs which may cause leukopenia, score this only if the 
dosage of medication is unchanged since the last WBC determination. 

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CLASSIC SELENA SLEDAI FLARE INDEX (SFI) instructions  
THE SELENA SLEDAI FLARE INDEX RULES ARE FOLLOWED EXPLICITLY AS 
WRITTEN. HOWEVER THERE ARE SOME CLARIFICATIONS TO KEEP IN MIND 
WHEN USING THE SELENA SLEDAI COMPOSITE INDEX.  
 
Instructions for using the SELENA SLEDAI Physicians Global Assessment Scale 
This PGA is a modification of the classic analogue scale in that it is anchored with numbers from 
0-3 demarcating mild, moderate and severe disease. Please note several things about this scale. 
The number 3 indicates severe disease and is at the very end of the scale. This refers to the most 
severe possible disease, and does not reflect the most severe ever seen in a particular patient but 
the most severe disease ever seen in all SLE patients. Therefore, the line made by the physician 
along this scale should virtually never get to this edge. Any disease rated greater than 2.5 is very 
severe. The range of moderate disease covers about 1.5-2.4. Mild disease falls below 1.5. 
Clearly, this is a bit like a logarithmic scale with greater distances or demarcations possible 
among more mild-moderate symptoms. This needs to be kept in mind when scoring the 
instrument. 
When scoring the PGA always look back at the score from the previous visit and move the mark 
relative to that previous visit. This is a global assessment, factoring in all aspects of the patients 
lupus disease activity. It should not reflect non-lupus medical conditions.  
These instructions are quite discrete from those given for other analogue (Lichert) scales and are 
specific for the scoring of the SELENA SLEDAI PGA.  
 
When is a flare not a flare? 
It is important to keep in mind that on the SELENA SLEDAI flare index flare can be defined 
simply by a decision to institute new therapy for lupus disease activity, whether or not the patient 
meets the other criteria for flare listed. It is important for the physician not to override the intent 
of the instrument which is to actually define flare in this manner. However there are logical 
exceptions, for which a common sense rule may prevail. Switching treatments for safety reasons, 
or increasing treatment in patients who are improving might often warrant withdrawal from a 
protocol. However if the protocol allows these medication changes, the flare index will need to 
be scored, but it does not make sense to call these situations flares.  
 
 
 

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BILAG-2004 INDEX GLOSSARY 
INSTRUCTIONS 
 
     • only record features that are attributable to SLE disease activity and not due to  
        damage, infection, thrombosis (in absence of inflammatory process) or other  
        conditions 
     • assessment refers to manifestations occurring in the last 4 weeks compared with the  
        previous 4 weeks 
     • activity refers to disease process which is reversible while damage refers to permanent  
        process/scarring (irreversible) 
     • damage due to SLE should be considered as a cause of features that are fixed/persistent  
        (SLICC/ACR damage index uses persistence ≥ 6 months to define damage) 
     • in some manifestations, it may be difficult to differentiate SLE from other conditions as  
        there may not be any specific test and the decision would then lies with the physician’s  
        judgment on the balance of probabilities 
     • ophthalmic manifestations usually need to be assessed by an ophthalmologist and these  
        items would need to be recorded after receiving the response from the ophthalmologist 
     • guidance for scoring: 
 
          (4) NEW  
                 • manifestations are recorded as new when it is a new episode occurring in the last   
                    4 weeks (compared to the previous 4 weeks) that has not improved and this  
                    includes new episodes (recurrence) of old manifestations  
                 • new episode occurring in the last 4 weeks but also satisfying the criteria for     
                    improvement (below) would be classified as improving instead of new 
 
          (3) WORSE 
                 • this refers to manifestations that have deteriorated in the last 4 weeks compared  
                    to the previous 4 weeks 
 
          (2) SAME 
                 • this refers to manifestations that have been present for the last 4 weeks and the  
                    previous 4 weeks without significant improvement or deterioration (from the  
                    previous 4 weeks) 
                 • this also applies to manifestations that have improved over the last 4 weeks  
                    compared to the previous 4 weeks but do not meet the criteria for improvement 
 
 
          (1) IMPROVING 
                 • definition of improvement: (a) the amount of improvement is sufficient for  
                  consideration of reduction in therapy and would not justify escalation in therapy 
AND             
                                                                 (b) improvement must be present currently and 
                                                                       for at least 2 weeks out of the last 4 weeks 
                                                                                        OR 
                                                                      manifestation that has completely resolved and  
                                                                      remained absent over the whole of last 1 week 
 
          (0) NOT PRESENT 
 
          (ND) NOT DONE 
                 • it is important to indicate if a test has not been performed (particularly laboratory  
                    investigations) so that this will be recorded as such in the database & not as  

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                    normal or absent (which is the default) 
 
           INDICATE (TICK) IF NOT DUE TO SLE ACTIVITY 
                 • for descriptors that are based on measurements (in renal and haematology  
                    systems), it is important to indicate if these are not due to lupus disease activity  
                    (for consideration of scoring) as they are usually recorded routinely into a  
                    database 
 
          CHANGE IN SEVERITY CATEGORY 
                 • there are several items in the index which have been divided into categories of  
                    mild and severe (depending on definition). It is essential to record mild and  
                    severe items appropriately if the manifestations fulfil both criteria during the last  
                    4 weeks 
 
                 • if a mild item deteriorated to the extent that it fulfilled the definition of severe  
                    category (ie changed into severe category) within the last 4 weeks: 
       severe item scored as new (4)  
                    AND  mild item scored as worsening (3) 
 
                 • if a severe item improved (fulfilling the improvement criteria) to the extent that it  
                    no longer fulfilled the definition of severe category (ie changed into mild  
                    category) within the last 4 weeks: 
                               severe item scored as not present (0) if criteria for severe category has not  
                                                                                              been met over last 4 weeks 
                                                         or as improving (1) if criteria for severe category has been                  
                                                                                             met at some point over last 4 weeks 
 
                   AND  
 
                               mild item scored as improving (1) if it is improving over last 4 weeks 
                                                      or as the same (2) if it has remained stable over last 4 weeks 
 
 
CONSTITUTIONAL 
 
1. Pyrexia temperature > 37.5˚C documented 
2. Unintentional weight loss > 5% 
3. Lymphadenopathylymph node more than 1 cm diameter 
                  exclude infection 
4. Anorexia 
 
 
MUCOCUTANEOUS 
5. Severe eruption > 18% body surface area 
                         
any lupus rash except panniculitis, bullous lesion  
& angio-oedema 
 
        body surface area (BSA) is estimated using the rules of nines (used to assess extent of burns) as follows: 
 
        palm(excluding fingers) = 1% BSA 
        each lower limb = 18% BSA 
        each upper limb = 9% BSA 
        torso (front) = 18% BSA 
        torso (back) = 18% BSA 

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        head = 9% BSA 
        genital (male) = 1% BSA 
 
 
 
6. Mild eruption ≤ 18% body surface area 
                             
any lupus rash except panniculitis, bullous lesion  
& angio-oedema 
 
malar rash must have been observed by a  
physician and has to be present continuously  
(persistent) for at least 1 week to be considered  
significant (to be recorded) 
 
7. Severe angio-oedema                                                potentially life-threatening eg: stridor 
 
                                                                                      angio-oedema is a variant form of urticaria which affects the  
                                                                                      subcutaneous, submucosal and deep dermal tissues 
 
8. Mild angio-oedema                                                  not life threatening 
 
9. Severe mucosal ulceration                                       disabling (significantly interfering with oral  intake), extensive 
                                                                                      & deep ulceration 
 
                                                                                      must have been observed by a physician 
 
10. Mild mucosal ulceration                                        localised &/or non-disabling ulceration 
 
11. Severe panniculitis or bullous lupus                     any one: > 9% body surface area 
                                                                                         facial panniculitis 
                                                                                 panniculitis that is beginning to ulcerate 
                                                                                 panniculitis that threatens integrity of subcutaneous tissue  
                                                                                       (beginning to cause  surface depression) on > 9% body  
                                                                                      surface area, panniculitis presents as a palpable and tender  
                                                                                      subcutaneous induration/nodule  
                                                                                       
                                                                                      note that established surface  

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                                                                                      depression and atrophy alone is likely to be damage 
        
12. Mild panniculitis or bullous lupus 
≤ 9% body surface area   
does not fulfil any criteria for severe panniculitis  
 
13. Major cutaneous vasculitis/thrombosis                   resulting in extensive gangrene or ulceration or  
skin infarction 
 
14. Digital infarct or nodular vasculitis                        localised single or multiple infarct(s) over  
digit(s) or tender erythematous nodule(s) 
 
15. Severe alopecia                                                       clinically detectable (diffuse or patchy) hair loss with scalp  
                                                                                      inflammation (redness over scalp) 
 
16. Mild alopecia                                                          diffuse or patchy hair loss without scalp inflammation 
(clinically detectable or by history) 
 
17. Peri-ungual erythema or chilblains                        chilblains are localised inflammatory lesions                                                           
                                                                                     (may ulcerate) which are precipitated by exposure to cold 
 
18. Splinter haemorrhages 
 
 
NEUROPSYCHIATRIC 
19. Aseptic meningitis criteria (all):                            acute/subacute onset headache 
              fever 
abnormal CSF (raised protein &/or lymphocyte  
predominance) but negative  cultures 
preferably photophobia, neck stiffness and  
meningeal irritation should be present as well but  
are not essential for diagnosis, exclude CNS/meningeal 
infection, intracranial  haemorrhage 
 
20. Cerebral vasculitis should be present with features of vasculitis in another system  
supportive imaging &/or biopsy findings 
 
21. Demyelinating syndrome                                     discrete white matter lesion with associated neurological deficit  
                                                                                    not recorded elsewhere 
 
                                                                                    ideally there should have been at least one previously recorded  
                                                                                    event 
 
supportive imaging required 
 
exclude multiple sclerosis 
 
22. Myelopathy  
                                                                                   acute onset of rapidly evolving paraparesis or quadriparesis  
                                                                                   and/or sensory level 
 
exclude intramedullary and extramedullary space occupying  
lesion 
 
23. Acute confusional state                                          acute disturbance of consciousness or level of arousal with 
                                                                                     reduced ability to focus, maintain or shift attention 
 

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includes hypo- and hyperaroused states and encompasses the 
spectrum from delirium to coma 
 
24. Psychosis delusion or hallucinations                      does not occur exclusively during course of a delirium 
exclude drugs, substance abuse, primary psychotic disorder 
 
25. Acute inflammatory demyelinating criteria: 
                                                                                      polyradiculoneuropathy     
                                                                                      progressive polyradiculoneuropathy 
                                                                                      loss of reflexes 
                                                                                      symmetrical involvement 
                                                                                      increased CSF protein without pleocytosis 
supportive electrophysiology study 
 
26. Mononeuropathy (single/multiplex)                       supportive electrophysiology study required 
 
27. Cranial neuropathy                                                 except optic neuropathy which is classified under ophthalmic  
                                                                                      system 
 
28. Plexopathy                                                              disorder of brachial or lumbosacral plexus  
resulting in neurological deficit not corresponding to territory  
of single root or nerve 
supportive electrophysiology study required 
 
29. Polyneuropathy                                                       acute symmetrical distal sensory and/or motor deficit 
                                                                                       supportive electrophysiology study required 
 
30. Seizure disorder 
independent description of seizure by reliable witness 
 
31. Status epilepticus                                                   a seizure or series of seizures lasting ≥ 30 minutes without full  
                                                                                     recovery to baseline 
 
32. Cerebrovascular disease                                         any one with supporting imaging:  (not due to vasculitis)    
                                                                                      stroke syndrome 
                                                                                      transient ischaemic attack 
                                                                                      intracranial haemorrhage 
 
exclude hypoglycaemia, cerebral sinus thrombosis, vascular 
malformation, tumour, abscess 
 
cerebral sinus thrombosis not included as  
definite thrombosis not considered part of lupus activity 
 
33. Cognitive dysfunction                                             significant deficits in any cognitive functions:      
                                                                                      simple attention (ability to register & maintain information) 
                                                                                      complex attention 
                                                                                      memory (ability to register, recall & recognise                                                        
                                                                                          information eg learning, recall) 
                                                                                     visual-spatial processing (ability to analyse, synthesise &  
                                                                                           manipulate visual-spatial information) 
                                                                                      language (ability to comprehend, repeat & produce   
                                                                                           oral/written material eg verbal fluency, naming) 
                                                                                      reasoning/problem solving (ability to reason &  abstract) 
                                                                                      psychomotor speed 
                                                                                      executive functions (eg planning, organising, sequencing) 
 

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                                                in absence of disturbance of consciousness or level of arousal sufficiently severe to  
                                                  interfere with daily activities 
                                               neuropsychological testing should be done or corroborating history from third party if  
                                                   possible  
                                               exclude substance abuse 
 
34. Movement disorder                                                   exclude drugs 
 
35. Autonomic disorder any one: 
    
                                                                                         fall in blood pressure to standing > 30/15 mm  
   Hg (systolic/diastolic) 
 
   increase in heart rate to standing ≥ 30 bpm 
 
   loss of heart rate variation with respiration   
   (max – min < 15 bpm, expiration:inspiration  
   ratio < 1.2, Valsalva ratio < 1.4) 
 
   loss of sweating over body and limbs  
   (anhidrosis) by sweat test 
 
                                                          exclude drugs and diabetes mellitus 
 
36. Cerebellar ataxia 
cerebellar ataxia in isolation of other CNS features 
 
 
usually subacute presentation 
 
37. Severe lupus headache (unremitting) 
disabling headache unresponsive to narcotic analgesia & 
lasting ≥ 3 days 
 
exclude intracranial space occupying lesion  
and CNS infection 
 
38. Headache from IC hypertension                           exclude cerebral sinus thrombosis 
 
 
MUSCULOSKELETAL 
 
39. Severe myositis                                                      significantly elevated serum muscle enzymes with significant  
                                                                                     muscle weakness 
 
                                                                                      exclude endocrine causes and drug-induced  myopathy 
 
electromyography and muscle biopsy are used for diagnostic 
purpose and are not required to determine level of activity 
 
40. Mild myositis                                                        significantly elevated serum muscle enzymes with myalgia but 
                                                                                     without significant muscle weakness 
 
                                                                                      asymptomatic elevated serum muscle enzymes  
not included 
 
exclude endocrine causes and drug-induced myopathy 
 

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electromyography and muscle biopsy are used for diagnostic 
purpose and are not required to determine level of activity 
 
41. Severe arthritis                                                       observed active synovitis ≥ 2 joints with marked loss of           
                                                                                      functional range of movements and   significant impairment of  
                                                                                      activities of daily living, that has been present on several days 
                                                                                     (cumulatively) over the last 4 weeks 
 
42. Moderate arthritis or Tendonitis or Tenosynovitis   tendonitis/tenosynovitis or active synovitis ≥ 1 joint 
(observed or through history) with some loss of functional 
range of movements, that has been present on several days 
over the last 4 weeks 
 
43. Mild arthritis or Arthralgia or Myalgia 
inflammatory type of pain (worse in the morning with 
stiffness, usually improves with activity & not brought on by 
activity) over joints/muscle  
 
inflammatory arthritis which does not fulfil the above criteria 
for moderate or severe arthritis 
 
 
CARDIORESPIRATORY 
 
44. Mild myocarditis                                                    inflammation of myocardium with raised cardiac enzymes  
                                                                                      &/or ECG changes and without resulting cardiac failure,  
                                                                                      arrhythmia or valvular dysfunction 
 
45. Cardiac failure 
cardiac failure due to myocarditis or non-infective 
inflammation of endocardium or cardiac valves (endocarditis) 
 
 
cardiac failure due to myocarditis is defined by left ventricular 
ejection fraction ≤ 40% & pulmonary oedema or peripheral 
oedema 
 
cardiac failure due to acute valvular regurgitation (from 
endocarditis) can be associated with normal left ventricular 
ejection fraction 
 
 
diastolic heart failure is not included 
 
46. Arrhythmia 
arrhythmia (except sinus tachycardia) due to myocarditis or 
non-infective inflammation of endocardium or cardiac valves 
(endocarditis) 
 
                                                                                      confirmation by electrocardiogram required  
(history of palpitations alone inadequate) 
 
47. New valvular dysfunction 
new cardiac valvular dysfunction due to myocarditis or non-
infective inflammation of endocardium or cardiac valves 
(endocarditis) 
 
                                                                                       supportive imaging required 
 
48. Pleurisy/Pericarditis 
convincing history &/or physical findings that you would 
consider treating 
 

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in absence of cardiac tamponade or pleural effusion with 
dyspnoea 
 
                                                                         
do not score if you are unsure whether or not it is 
pleurisy/pericarditis 
 
49. Cardiac tamponade                                                 supportive imaging required 
50. Pleural effusion with dyspnea                                supportive imaging required 
51. Pulmonary haemorrhage/vasculitis                         inflammation of pulmonary vasculature with  
haemoptysis &/or dyspnoea &/or pulmonary hypertension 
supportive imaging &/or histological diagnosis required 
 
52. Interstitial alveolitis/pneumonitis                            radiological features of alveolar infiltration not  
due to infection or haemorrhage required for diagnosis 
 
corrected gas transfer Kco reduced to < 70% normal or fall of 
> 20% if previously abnormal 
 
                                                                                      on-going activity would be determined by  
clinical findings and lung function tests, and  
repeated imaging may be required in those with  
deterioration (clinically or lung function tests) or failure to 
respond to therapy 
 
53. Shrinking lung syndrome                                       acute reduction (> 20% if previous measurement available) in  
                                                                                      lung volumes (to < 70% predicted) in the presence of normal  
                                                                                      corrected gas transfer (Kco) & dysfunctional diaphragmatic  
                                                                                      movements 
 
54. Aortitis                                                                    inflammation of aorta (with or without  
dissection) with supportive imaging abnormalities  
 
accompanied by > 10 mm Hg difference in BP between arms 
&/or claudication of extremities &/or vascular bruits 
 
                                                                                      repeated imaging would be required to determine  
on-going activity in those with clinical  
deterioration or failure to respond to therapy 
 
55. Coronary vasculitis                                                 inflammation of coronary vessels with  
radiographic evidence of non-atheromatous narrowing, 
obstruction or aneurysmal changes 
GASTROINTESTINAL 
 
56. Lupus peritonitis                                                     serositis presenting as acute abdomen with  
rebound/guarding 
 
57. Serositis                                                                  not presenting as acute abdomen 
 
58. Lupus enteritis or colitis 
vasculitis or inflammation of small or large bowel with 
supportive imaging &/or biopsy findings 
 
59. Malabsorption                                                         diarrhoea with abnormal D- xylose absorption  
test or increased faecal fat excretion after exclusion of 
coeliac’s disease (poor response to gluten-free diet) and gut 
vasculitis 

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60. Protein-losing enteropathy                                      diarrhoea with hypoalbuminaemia or increased  
faecal excretion of IV radiolabeled albumin after exclusion of 
gut vasculitis and malabsorption 
 
61. Intestinal pseudo-obstruction                                  subacute intestinal obstruction due to intestinal  
hypomotility 
 
62. Lupus hepatitis                                                        raised transaminases  
 
absence of autoantibodies specific to autoimmune hepatitis 
(eg: anti-smooth muscle, anti-liver cytosol 1) &/or biopsy 
appearance of chronic active hepatitis 
 
hepatitis typically lobular with no piecemeal necrosis 
 
exclude drug-induced and viral hepatitis 
 
63. Acute lupus cholecystitis                                         after exclusion of gallstones and infection 
 
64. Acute lupus pancreatitis                                          usually associated multisystem involvement 
 
 
OPHTHALMIC 
 
65. Orbital inflammation                                              orbital inflammation with myositis &/or extra- 
ocular muscle swelling &/or proptosis 
 
                                                                                      supportive imaging required 
 
66. Severe keratitis                                                       sight threatening 
includes:  corneal melt 
peripheral ulcerative keratitis 
 
67. Mild keratitis                                                           not sight threatening 
 
68. Anterior uveitis 
69. Severe posterior uveitis &/or retinal                       sight-threatening &/or retinal vasculitis 
       vasculitis                                                                not due to vaso-occlusive disease 
 
70. Mild posterior uveitis &/or retinal                           not sight-threatening 
       vasculitis 
not due to vaso-occlusive disease 
 
71. Episcleritis 
72. Severe scleritis 
                                           necrotising anterior scleritis, anterior &/or posterior scleritis  
requiring  systemic steroids/immunosuppression &/or not 
responding to NSAIDs 
 
73. Mild scleritis 
anterior &/or posterior scleritis not requiring systemic steroids 
 
                                                                                      excludes necrotising anterior scleritis 
 
74. Retinal/choroidal                                                    vaso-occlusive includes: retinal arterial & venous occlusion 
disease 
                                                         serous retinal &/or retinal pigment epithelial detachments  
                                                                             secondary to choroidal vasculopathy 

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75. Isolated cotton-wool spots                                     also known as cytoid bodies 
 
76. Optic neuritis                                                          excludes anterior ischaemic optic neuropathy 
 
77. Anterior ischaemic optic neuropathy 
visual loss with pale swollen optic disc due to occlusion of 
posterior ciliary arteries 
 
RENAL 
78. Systolic blood pressure 
79. Diastolic blood pressure 
80. Accelerated hypertension                                        blood pressure rising to > 170/110 mm Hg  
within 1 month with grade 3 or 4 Keith-Wagener-Barker 
retinal changes (flame-shaped haemorrhages or cotton-wool 
spots or papilloedema) 
 
81. Urine dipstick 
82. Urine albumin-creatinine ratio                                 on freshly voided urine sample 
 
                                                                                        conversion: 1 mg/mg = 113 mg/mmol 
                                                                                       
                                                                                       it is important to exclude other causes (especially  
infection) when proteinuria is present 
 
83. Urine protein-creatinine ratio                                   on freshly voided urine sample 
 
                                                                                        conversion: 1 mg/mg = 113 mg/mmol 
 
                                                                                       it is important to exclude other causes (especially  
infection) when proteinuria is present 
 
84. 24 hour urine protein                                               it is important to exclude other causes (especially  
infection) when proteinuria is present 
 
85. Nephrotic syndrome criteria: 
  heavy proteinuria ( ≥ 3.5 g/day or protein-  
  creatinine ratio ≥ 350 mg/mmol or albumin- 
  creatinine ratio ≥ 350 mg/mmol) 
                                                                                               hypoalbuminaemia  
                                                                                               oedema 
 
86. Plasma/Serum creatinine                                        exclude other causes for increase in creatinine  
(especially drugs) 
 
87. GFR MDRD formula: 
GFR = 170 × [serum creatinine (mg/dl)]-0.999 ×   
              [age]-0.176 × [serum urea (mg/dl]-0.17 ×   
              [serum albumin (g/dl)]0.318 × [0.762 if  
              female] × [1.180 if African ancestry] 
 
                                                                                          units = ml/min per 1.73 m2 
                                                                                          normal: male = 130 ± 40 
                                                                                          female = 120 ± 40 
 
conversion: 

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    serum creatinine  -  mg/dl = (µmol/l)/88.5 
    serum urea         - mg/dl = (mmol/l) × 2.8 
 serum albumin    -    g/dl    = (g/l)/10 
creatinine clearance not recommended as it is not reliable 
exclude other causes for decrease in GFR (especially drugs) 
88. Active urinary sediment
    pyuria (> 5 WCC/hpf or > 10 WCC/mm3 (µl)) 
   OR 
haematuria (> 5 RBC/hpf or > 10 RBC/mm3 (µl)) 
   OR 
red cell casts 
   OR 
white cell casts 
exclude other causes (especially infection, 
vaginal bleed, calculi) 
89. Histology of active nephritis
WHO Classification (1995): (any one) 
   Class III – (a) or (b) subtypes 
   Class IV – (a), (b) or (c) subtypes 
   Class V – (a), (b), (c) or (d) subtypes 
   Vasculitis 
   OR 
ISN/RPS Classification (2003): (any one) 
   Class III – (A) or (A/C) subtypes 
   Class IV – (A) or (A/C) subtypes 
   Class V 
   Vasculitis 
within last 3 months 
glomerular sclerosis without inflammation not included 
HAEMATOLOGICAL 
90. Haemoglobin
         exclude dietary deficiency & GI blood loss 
91. White cell count
  exclude drug-induced cause 
92. Neutrophil count
   exclude drug-induced cause 
93. Lymphocyte count
94. Platelet count
        exclude thrombocytopenia of antiphospholipid 
syndrome & drug-induced cause 
95. TTP
   thrombotic thrombocytopaenic purpura 
clinical syndrome of micro-angiopathic haemolytic anaemia 
and thrombocytopenia in absence of any other identifiable 
cause 

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96. Evidence of active haemolysis
positive Coomb’s test & evidence of haemolysis (raised 
bilirubin or raised reticulocyte count or reduced 
haptoglobulins) 
97. Isolated positive Coomb’s test
ADDITIONAL ITEMS 
These items are required mainly for calculation of GFR 
i. Weight
ii. African ancestry
iii. Serum urea
iv. Serum albumin

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BILAG-2004 INDEX SCORING 
   • scoring based on the principle of physician’s intention to treat   
 
 
Category 
 
 
Definition 
 
 
A 
 
Severe disease activity requiring any of the following treatment: 
 
1. systemic high dose oral glucocorticoids (equivalent to prednisolone > 20  
    mg/day) 
 
2. intravenous pulse glucocorticoids (equivalent to pulse methylprednisolone  
    ≥ 500 mg) 
 
3. systemic immunomodulators (include biologicals, immunoglobulins and  
    plasmapheresis) 
 
4. therapeutic high dose anticoagulation in the presence of high dose steroids  
    or immunomodulators 
      eg: warfarin with target INR 3 - 4 
 
 
B 
 
 
Moderate disease activity requiring any of the following treatment: 
 
1. systemic low dose oral glucocorticoids (equivalent to prednisolone ≤ 20  
    mg/day) 
2. intramuscular or intra-articular or soft tissue glucocorticoids injection  
    (equivalent to methylprednisolone < 500mg) 
3. topical glucocorticoids 
4. topical immunomodulators 
5. antimalarials or thalidomide or prasterone or acitretin 
6. symptomatic therapy 
      eg: NSAIDs for inflammatory arthritis 
 
 
C 
 
 
Mild disease 
 
 
D 
 
 
Inactive disease but previously affected 
 
 
E 
 
System never involved 
 
CONSTITUTIONAL 
CATEGORY A: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new)  AND  
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Weight loss 
Lymphadenopathy/splenomegaly 

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Anorexia 
 
CATEGORY B: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new)  OR  
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Weight loss 
Lymphadenopathy/splenomegaly 
Anorexia 
 
BUT do not fulfil criteria for Category A 
 
CATEGORY C 
Pyrexia recorded as 1 (improving)  OR 
 
One or more of the following recorded as > 0:  
 
Weight loss 
Lymphadenopathy/Splenomegaly 
Anorexia 
 
BUT does not fulfil criteria for category A or B 
 
CATEGORY D 
Previous involvement 
 
CATEGORY E 
No previous involvement 
 
MUCOCUTANEOUS 
CATEGORY A  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Skin eruption - severe  
Angio-oedema - severe 
Mucosal ulceration - severe 
Panniculitis/Bullous lupus - severe 
Major cutaneous vasculitis/thrombosis 
 
CATEGORY B 
Any Category A features recorded as 1 (improving) OR  
 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Skin eruption - mild 
Panniculitis/Bullous lupus - mild 
Digital infarcts or nodular vasculitis 
Alopecia - severe 
 
CATEGORY C  
Any Category B features recorded as 1 (improving) OR 
 
Any of the following recorded as > 0: 

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Angio-oedema - mild 
Mucosal ulceration - mild 
Alopecia - mild 
Periungual erythema/chilblains 
Splinter haemorrhages 
 
CATEGORY D 
Previous involvement 
 
CATEGORY E 
No previous involvement 
 
NEUROPSYCHIATRIC 
CATEGORY A  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Aseptic meningitis 
Cerebral vasculitis 
Demyelinating syndrome 
Myelopathy 
Acute confusional state 
Psychosis 
Acute inflammatory demyelinating polyradiculoneuropathy 
Mononeuropathy (single/multiplex) 
Cranial neuropathy 
Plexopathy 
Polyneuropathy 
Status epilepticus 
Cerebellar ataxia 
 
CATEGORY B  
Any Category A features recorded as 1 (improving) OR Any of the following recorded as 2 (same), 3 (worse) or 4 
(new): 
Seizure disorder  
Cerebrovascular disease (not due to vasculitis) 
Cognitive dysfunction 
Movement disorder 
Autonomic disorder  
Lupus headache - severe unremitting 
Headache due to raised intracranial hypertension 
 
CATEGORY C 
Any Category B features recorded as 1 (improving) 
 
CATEGORY D  
Previous involvement 
CATEGORY E  
No previous involvement 
 
MUSCULOSKELETAL 
CATEGORY A  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Severe Myositis 
Severe Arthritis 

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CATEGORY B  
Any Category A features recorded as 1 (improving)   
                                                              OR  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
                                             Mild Myositis 
                              Moderate Arthritis/Tendonitis/Tenosynovitis 
 
CATEGORY C  
Any Category B features recorded as 1 (improving) OR Any of the following recorded as > 0:   Mild 
Arthritis/Arthralgia/Myalgia 
 
CATEGORY D 
Previous involvement 
 
CATEGORY E 
No previous involvement 
 
 
CARDIORESPIRATORY 
CATEGORY A  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Myocarditis/Endocarditis + Cardiac failure 
                             Arrhythmia 
                             New valvular dysfunction 
Cardiac tamponade 
                             Pleural effusion with dyspnea 
                             Pulmonary haemorrhage/vasculitis 
                             Interstitial alveolitis/pneumonitis  
Shrinking lung syndrome 
Aortitis 
Coronary vasculitis 
 
CATEGORY B 
Any Category A features recorded as 1 (improving) OR Any of the following recorded as 2 (same), 3 (worse) or 4 
(new): 
Pleurisy/Pericarditis 
Myocarditis – mild 
 
CATEGORY C 
Any Category B features recorded as 1 (improving) 
 
CATEGORY D 
Previous involvement 
 
CATEGORY E 
No previous involvement 
 
GASTROINTESTINAL 
CATEGORY A  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Peritonitis 
Lupus enteritis/colitis 
Intestinal pseudo-obstruction  

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Acute lupus cholecystitis 
Acute lupus pancreatitis 
 
CATEGORY B  
Any Category A feature recorded as 1 (improving) OR Any of the following recorded  as 2 (same), 3 (worse) or 4 
(new): 
Abdominal serositis and/or ascites  
Malabsorption 
Protein losing enteropathy 
Lupus hepatitis 
 
CATEGORY C  
Any Category B features recorded as 1 (improving) 
  
CATEGORY D  
Previous involvement 
 
CATEGORY E   
No previous involvement 
OPHTHALMIC 
CATEGORY A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Orbital inflammation/myositis/proptosis 
Keratitis - severe 
Posterior uveitis/retinal vasculitis - severe 
Scleritis - severe 
Retinal/choroidal vaso-occlusive disease 
Optic neuritis 
Anterior ischaemic optic neuropathy 
  
CATEGORY B 
Any Category A features recorded as 1 (improving) OR  
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Keratitis - mild 
Anterior uveitis 
Posterior uveitis/retinal vasculitis - mild 
Scleritis – mild 
 
CATEGORY C 
Any Category B features recorded as 1 (improving) OR  
 
Any of the following recorded as > 0: 
 
Episcleritis 
Isolated cotton-wool spots (cytoid bodies) 
 
CATEGORY D 
Previous involvement 
 
CATEGORY E 
No previous involvement 
 
RENAL 
CATEGORY A  

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Two or more of the following providing 1, 4 or 5 is included: 
1. Deteriorating proteinuria (severe) defined as
(a) urine dipstick increased by ≥ 2 levels (used only if other methods of urine protein estimation not available); or 
 (b) 24 hour urine protein > 1 g that has not decreased (improved) by ≥ 25%; or 
 (c) urine protein-creatinine ratio > 100 mg/mmol not decreased (improved) by ≥ 25%; or 
 (d) urine albumin-creatinine ratio > 100 mg/mmol not decreased (improved) by ≥ 25% 
2. Accelerated hypertension
3. Deteriorating renal function (severe) defined as
 (a) plasma creatinine > 130 µmol/l and having risen to > 130% of previous value; or  
 (b) GFR < 80 ml/min per 1.73 m2 and having fallen to < 67% of previous value; or  
      (c) GFR < 50 ml/min per 1.73 m2, and last time was > 50 ml/min per 1.73 m2 or not done 
4. Active urinary sediment
5. Histological evidence of active nephritis within last 3 months
6. Nephrotic syndrome
CATEGORY B 
One of the following: 
1. One of the Category A features
2. Proteinuria (that has not fulfilled Category A criteria)
(a) urine dipstick which has risen by 1 level to at least 2+ (used only if other methods of urine protein 
estimation not available); or 
      (b) 24 hour urine protein ≥ 0.5 g that has not decreased (improved) by ≥ 25%; or 
      (c) urine protein-creatinine ratio ≥ 50 mg/mmol not decreased (improved) by ≥ 25%; or 
      (d) urine albumin-creatinine ratio ≥ 50 mg/mmol that has not decreased (improved) by ≥ 25% 
3. Plasma creatinine > 130 µmol/l and having risen to ≥ 115% but ≤ 130% of previous value
CATEGORY C 
One of the following: 
1. Mild/Stable proteinuria defined as
(a) urine dipstick ≥ 1+ but has not fulfilled criteria for Category A & B (used only if other methods 
 of urine protein estimation not available); or 
      (b) 24 hour urine protein > 0.25 g but has not fulfilled criteria for Category A&B ; or 
      (c) urine protein-creat ratio > 25 mg/mmol but has not fulfilled criteria for Category A&B; or 
      (d) urine albumin-creatinine ratio > 25 mg/mmol not fulfilled criteria for Category A & B 
2. Rising blood pressure (providing the recorded values are > 140/90 mm Hg) which has not fulfilled criteria for
Category A & B, defined as 
(a) systolic rise of ≥ 30 mm Hg; and 
(b) diastolic rise of ≥ 15mm Hg 
CATEGORY D 
Previous involvement 
CATEGORY E 
No previous involvement 
Note: although albumin-creatinine ratio and protein-creatinine ratio are different, we use the same cut-off values for 
this index 
HAEMATOLOGICAL 
CATEGORY A 
TTP recorded as 2 (same), 3 (worse) or 4 (new)   OR Any of the following: 
Haemoglobin  < 8 g/dl 
White cell count < 1.0 × 109/l 

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Neutrophil count < 0.5 × 109/l 
Platelet count < 25 × 109/l 
CATEGORY B   
TTP recorded as 1 (improving)   OR 
Any of the following: 
Haemoglobin  8 - 8.9 g/dl 
White cell count 1 - 1.9 × 109/l 
Neutrophil count 0.5 - 0.9 × 109/l 
Platelet count 25 - 49 × 109/l 
Evidence of active haemolysis 
CATEGORY C 
Any of the following: 
Haemoglobin  9 - 10.9 g/dl  
White cell count 2 - 3.9 × 109/l 
Neutrophil count 1 - 1.9 × 109/l 
Lymphocyte count < 1.0 × 109/L 
Platelet count 50 - 149 × 109/l 
Isolated Coombs’ test positive  
CATEGORY D OR E 
Previous involvement or no Previous involvement respectively 
Definition of Flare Using the BILAG 2004 Index 
•
Severe Flare: A score due to item(s) recorded as 4 for new or 3 for worse
•
Moderate Flare: 2 or more B scores due to items recorded as 4 for new or 3 for
worse
•
Mild Flare: 1B or ≥3 C scores due to item(s) recorded as 4 for new or 3 for worse
The increase in disease activity should be severe enough in all cases such that an increase in 
treatment, commensurate with the severity level chosen, would be appropriate. However it is not 
necessary that the treatment actually be started, given that there are too many variables in what 
the patient may have recently started that has not had time to take effect, or treatment 
withholding due to current infections, side effects, compliance etc.