A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults With Systemic Lupus Erythematosus
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Sponsor: MedImmune LLC

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A Phase 2, Open-label Extension Study to Evaluate 
Long-term Safety of MEDI-546 in Adults with Systemic 
Lupus Erythematosus
Sponsor Protocol Number: CD-IA-MEDI-546-1145
Application Number:
IND 101849
EudraCT number: 2012-004619-30
Investigational Product:
MEDI-546
Sponsor:
MedImmune, LLC, a wholly owned subsidiary of AstraZeneca, 
One MedImmune Way, 
Gaithersburg, Maryland, 20878, USA
Medical Monitor:
Warren Greth, MD, MSc
Senior Director, Clinical Development, MedImmune
Phone: 301-398-2312; Fax: 301-398-7443
Contract Research Organization: INC Research
Protocol History, Date:
Original Protocol, 04Dec2012
Amendment 1, 12Feb2013
Amendment 2, 01Apr2013
Amendment 3, 26Mar2014
Amendment 4, 12Feb2015

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TABLE OF CONTENTS
LIST OF ABBREVIATIONS....................................................................................................8
STUDY ABSTRACT ..............................................................................................................11
1
INTRODUCTION.........................................................................................................13
1.1
Disease Background ...........................................................................................13
1.2
MEDI-546 Background ......................................................................................14
1.2.3Summary of Clinical Experience................................................................17
1.3
Research Hypothesis...........................................................................................18
1.4
Rationale for Study Conduct...............................................................................18
2
STUDY OBJECTIVES.................................................................................................19
2.1
Primary Objective...............................................................................................19
2.2
Secondary Objective...........................................................................................20
3
STUDY DESIGN..........................................................................................................20
3.1
Overview of Study Design..................................................................................20
3.2
Estimated Duration of Subject Participation ......................................................21
3.3
Study-stopping Criteria.......................................................................................21
3.4
Rationale for Study Design, Doses, and Control Groups ...................................22
3.4.1Rationale for Study Design.........................................................................22
4
SUBJECT SELECTION, TREATMENT, AND WITHDRAWAL .............................22
4.1
Subject Participation and Identification..............................................................22
4.2
Subject Selection and Withdrawal......................................................................23
4.2.1Inclusion Criteria ........................................................................................23
4.2.2Exclusion Criteria .......................................................................................24
4.2.3Withdrawal Criteria ....................................................................................25
4.2.4Replacement of Subjects.............................................................................27
4.3
Treatment Assignment........................................................................................27
4.4
Blinding ..............................................................................................................27
4.5
Study Medications ..............................................................................................27
4.5.1.1
Investigational Product Accountability.....................................28
4.5.1.2
Reporting Product Complaints..................................................29
4.5.2Other Study Medications ............................................................................30
4.5.2.1
Corticosteroids..........................................................................30

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4.5.2.2
Slow-acting Immunosuppressants ............................................31
4.5.2.3
Background SOC SLE Medications (OCS, Antimalarials, 
and Immunosuppressants)..........................................31
4.5.2.4
Use of Other Medications for Increased Disease Activity .......31
4.5.3Treatment Regimen.....................................................................................31
4.5.4Investigational Product Dose Preparation...................................................32
4.5.4.1
Dose Calculation.......................................................................33
4.5.4.2
Investigational Product Inspection............................................33
4.5.5Treatment Administration...........................................................................34
4.5.6Monitoring of Dose Administration ...........................................................36
4.5.6.1
Anaphylaxis, Hypersensitivity, and Infusion Reactions...........36
4.5.7Treatment Compliance................................................................................42
4.6
Concomitant Medications...................................................................................42
4.6.1Permitted Non-SLE Concomitant Medications..........................................42
4.6.2Excluded Concomitant Medications...........................................................42
4.7
Subject Completion.............................................................................................43
4.8
Site Completion ..................................................................................................43
4.9
End of the Study .................................................................................................43
5
STUDY PROCEDURES...............................................................................................43
5.1
Schedule of Study Procedures ............................................................................43
5.1.1Pretreatment Period.....................................................................................53
5.1.2Treatment Period.........................................................................................53
5.1.2.1
Week 0; Day 1: First Infusion (Visit 1) ....................................53
5.1.2.2
Every 4 Weeks; Weeks 4 to 152: Second through Thirty-
ninth Infusion (Visits 2 to 39) ....................................55
5.1.2.3
Every 12 Weeks; Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 
120, 132, and 144 (Visits 4, 7, 10, 13, 16, 19, 22, 
25, 28, 31, 34, and 37)................................................56
5.1.2.4
Every 24 Weeks; Weeks 24, 48, 72, 96, 120 and 144 (Visits 
7, 13, 19, 25, 31, and 37)............................................56
5.1.2.5
Every 48 Weeks; Weeks 48, 96, and 144 (Visits 13, 25, and 
37)...............................................................................57
5.1.2.6
Week 156; Last Treatment Visit (Visit 40)...............................57
5.1.3Follow-up Period ........................................................................................58
5.1.3.1
28 Days after the Last Dose (+/- 7 Days): First Safety 
Follow-up Visit or Early Discontinuation Visit 
(Visit 41) ....................................................................58
5.1.3.2
59 Days after the Last Dose (+/- 7 Days): Second Safety 
Follow-up Visit (Visit 42)..........................................59

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5.1.3.3
85 Days after the Last Dose (+/- 7 Days): Third Safety 
Follow-up Visit (Visit 43)..........................................60
5.1.4Unscheduled Visit.......................................................................................61
5.2
Description of Study Procedures ........................................................................61
5.2.1Medical History ..........................................................................................62
5.2.2Physical Examination, ECG, Weight, Cushingoid Features, and Pap 
Smear ........................................................................................62
5.2.3Vital Signs……….......................................................................................62
5.2.4Tuberculosis Testing...................................................................................63
5.2.4.1
Indeterminate Results ...............................................................63
5.2.4.2
Positive Results.........................................................................64
5.2.5Clinical Laboratory Tests............................................................................65
5.2.6Optional Urine Biomarker Testing .............................................................66
5.2.7Pharmacokinetic Evaluation and Methods .................................................67
5.2.8Immunogenicity Evaluation and Methods..................................................67
5.2.9Optional Proteomics/Biomarkers................................................................67
5.2.12Disease Evaluation and Methods..............................................................68
5.2.12.1
Systemic Lupus Erythematosus Disease Activity 
Index-2000 .................................................................68
5.2.12.2
Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology 
Damage Index ............................................................69
5.2.13Adverse Events of Special Interest ...........................................................69
5.2.14SLE Flares and Increase in SLE Disease Activity....................................69
5.2.15Patient-reported Outcomes .......................................................................70
5.2.15.1
Short Form-36 Version 2............................................70
5.2.16Estimate of Volume of Blood to Be Collected .........................................70
6
ASSESSMENT OF SAFETY .......................................................................................71
6.1
Safety Parameters ...............................................................................................71
6.1.1Adverse Events ...........................................................................................71
6.1.2Serious Adverse Events ..............................................................................72
6.1.3Adverse Events of Special Interest .............................................................73
6.1.3.1
Hepatic Function Abnormality .................................................73
6.1.3.2
New or Reactivated and Latent TB Infection ...........................73
6.1.3.3
Herpes Zoster Infection ............................................................73
6.1.3.4
Malignancy ...............................................................................74
6.1.3.5
Infusion, Hypersensitivity, and Anaphylactic Reactions..........74

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6.1.3.6
Vasculitis ..................................................................................75
6.2
Assessment of Safety Parameters .......................................................................76
6.2.1Assessment of Severity...............................................................................76
6.2.2Assessment of Relationship........................................................................76
6.2.2.1
Relationship to Investigational Product....................................76
6.2.2.2
Relationship to Protocol Procedures.........................................77
6.3
Recording of Safety Parameters .........................................................................77
6.3.1Recording of Adverse Events and Serious Adverse Events .......................77
6.3.2Recording of Adverse Events of Special Interest.......................................78
6.3.2.1
Hepatic Function Abnormality .................................................78
6.3.2.2
Other Adverse Events of Special Interest.................................78
6.4
Reporting Requirements for Safety Parameters..................................................78
6.4.1Study Reporting Period and Follow-up for Adverse Events ......................78
6.4.2Reporting of Serious Adverse Events.........................................................79
6.4.2.1
Study Reporting Period and Follow-up for Serious Adverse 
Events.........................................................................79
6.4.2.2
Notifying the Sponsor of Serious Adverse Events ...................79
6.4.2.3
Safety Reporting to Investigators, Institutional Review 
Boards or Independent Ethics Committees, and 
Regulatory Authorities...............................................80
6.4.3Other Events Requiring Immediate Reporting ...........................................80
6.4.3.1
Overdose ...................................................................................80
6.4.3.2
Hepatic Function Abnormality .................................................81
6.4.3.3
Pregnancy..................................................................................81
6.5
Safety Management During the Study................................................................82
7
STATISTICAL CONSIDERATIONS..........................................................................82
7.1
General Considerations.......................................................................................82
7.2
Analysis Populations...........................................................................................83
7.3
Endpoints ............................................................................................................83
7.3.1Primary Endpoint........................................................................................83
7.3.2Secondary Endpoint....................................................................................83
7.4
Interim Analysis..................................................................................................84
7.6
Data Safety Monitoring Board............................................................................84
8
DIRECT ACCESS TO SOURCE DOCUMENTS .......................................................85
9
QUALITY CONTROL AND QUALITY ASSURANCE............................................85
9.1
Data Collection ...................................................................................................85
9.2
Study Monitoring................................................................................................85

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9.3
Audit and Inspection of the Study ......................................................................86
10
ETHICS.........................................................................................................................86
10.1
Regulatory Considerations..................................................................................86
10.2
Institutional Review Board or Independent Ethics Committee ..........................87
10.3
Informed Consent ...............................................................................................88
10.4
Withdrawal of Consent for Continued Study Participation................................88
11
DATA HANDLING AND RECORD KEEPING.........................................................89
12
FINANCING AND INSURANCE ...............................................................................90
13
PUBLICATION POLICY.............................................................................................90
14
REFERENCES..............................................................................................................90
15
SUMMARY OF PROTOCOL AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL .......................................................................94
LIST OF IN-TEXT TABLES
Table 4.2.1-1
Effective Methods of Contraception (Two Methods Must be Used)...24
Table 4.5.1-1
Identification of Investigational Products............................................28
Table 4.5.4-1
Compatible Materials of Construction for IV Bags.............................32
Table 4.5.4-2
Compatible Materials of Construction for Ancillaries.........................32
Table 4.5.6.1-1
An Approach to Management of Anaphylactic, Hypersensitivity, and 
Infusion Reactions ...............................................................................38
Table 5.1-1
Schedule of Study Procedures for the Treatment Period.....................45
Table 5.1-2
Schedule of Study Procedures for the 85-day Follow-up Period.........51
Table 5.2.16-1
Estimated Volume of Blood to be Collected per Visit ........................70
Examples of Equivalent Doses of Oral Prednisone...............................................................116
Example of OCS Tapering Schedule.....................................................................................117
LIST OF IN-TEXT FIGURES
Figure 3.1-1
Study Flow Diagram............................................................................21
LIST OF APPENDICES
Appendix 1
Signatures...........................................................................................107
Appendix 2
General Guidance for Determination of Major Surgery....................111
Appendix 3
Restricted Medications.......................................................................112
Appendix 4
Vasculitic Syndromes Excluded from the Study...............................113
Appendix 5
Data and Safety Monitoring Board Membership...............................114
Appendix 6
Oral Corticosteroid Guidance ............................................................116
Appendix 7
Short Form-36 Version 2 ...................................................................118

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Appendix 8
Guidance for Abnormal Liver Function Tests Management.............124

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LIST OF ABBREVIATIONS
Abbreviation or 
Specialized Term
Definition
ACR
American College of Rheumatology
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine transaminase
ANA
antinuclear antibody
AST
aspartate transaminase
AUC
area under the concentration-time curve
β-HCG
beta-human chorionic gonadotropin
BCG
Bacillus of Calmette and Guerin
BP
blood pressure
C1q
multivalent for attachment to the complement fixation sites of immunoglobulin
Cmax
Maximum observed serum concentration
CML
chronic myelogenous leukemia
CRF
case report form
CRO
contract research organization
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ds
double-stranded
DSMB
Data and Safety Monitoring Board
ECG
Electrocardiogram
ECL
electrochemiluminescent
ELISA
enzyme-linked immunosorbent assay
EMA
European Medicines Agency
ePPND
enhanced pre-and post-natal development
EU
European Union
Fc
fragment, crystallizable 
Fc!RIA/IIA/IIIB/III
Fc gamma receptor I/IIA/IIB/IIIA
FcRn
Fc gamma neonatal receptor
GCP
Good Clinical Practice
GD20
Gestation Day 20
GMP
Good Manufacturing Practice
HbA1c
glycosylated hemoglobin
HBc
hepatitis B core (antibody)
HBV
hepatitis B virus
HBV DNA
hepatitis B virus deoxyribonucleic acid
HDL
high-density lipoprotein

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Abbreviation or 
Specialized Term
Definition
HED
human equivalence dose
HIPAA
Health Insurance Portability and Accountability Act
HRQL
health-related quality of life
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IFN
Interferon
IFN-α/β
interferon-alpha/beta
IFNAR1
subunit 1 of the type I interferon receptor
Ig
Immunoglobulin
IgG1κ
immunoglobulin G1 kappa
IM
Immunogenicity
IRB
Institutional Review Board
IV
Intravenous
IVRS/IWRS
interactive voice/web response system
LD28
Lactation Day 28
LDL
low-density lipoprotein
MAb
Monoclonal antibody 
MCS
Mental Component Summary
mDC
myeloid dendritic cell
MedDRA
Medical Dictionary for Regulatory Activities
mRNA
messenger ribonucleic acid
NOAEL
no-observable-adverse-effect-level
NSAID
non-steroidal anti-inflammatory drug
NZB/W
New Zealand black/white
OCS
oral corticosteroids
OLE
open-label extension
PAD
pharmacologically active dose
Pap
Papanicolaou smear
PBMC
Peripheral blood mononuclear cell
PCR
Polymerase chain reaction
PCS
Physical Component Summary
PD
pharmacodynamics
pDC
Plasmacytoid dendritic cell
PK
pharmacokinetics
PP
per protocol
Q4W
every 4 weeks
Q12W
every 12 weeks
Q24W
every 24 weeks

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Abbreviation or 
Specialized Term
Definition
Q48W
every 48 weeks
QFT-GIT
QuantiFERON-TB Gold In-tube
RBC
red blood cell
RNA
ribonucleic acid
RNP
ribonucleoprotein
SAE
serious adverse event
SC
subcutaneous
SF-36v2
Short Form-36 Version 2
SID
subject identification
SLE
systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index - 2000
SLICC/ACR
Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index
Sm
Smith
SOC
standard of care
SSc
systemic sclerosis
SUSAR
Suspected unexpected serious adverse reactions
t1/2
half-life
TB
Tuberculosis
TBD
to be determined
TEAE
treatment-emergent adverse event
TESAE
treatment-emergent serious adverse event
TLR
Toll-like receptor
ULN
upper limit of normal
USA
United States of America
USP
United States Pharmacopeia
WBC
white blood cell
w/v
weight/volume

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STUDY ABSTRACT
TITLE
A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults with Systemic 
Lupus Erythematosus
OBJECTIVES
Primary Objective: To evaluate the long-term safety and tolerability of intravenous (IV) MEDI-546 in adult 
subjects with chronic, moderately-to-severely active systemic lupus erythematosus (SLE).
Secondary Objective: To evaluate the immunogenicity (IM) of MEDI-546.
Exploratory Objectives: 
STUDY DESIGN
This is an open-label, multinational, multicenter study to evaluate the long-term safety and tolerability of 
MEDI-546 in adult subjects with chronic, moderately-to-severely active SLE who were previously treated 
with investigational product (MEDI-546 or placebo) and completed Study CD-IA-MEDI-546-1013 through 
treatment and follow-up. The study will be conducted in approximately 240 subjects at approximately up to 
100 study sites.
Once subjects have completed treatment and follow-up in Study CD-IA-MEDI-546-1013 (through Day 422), 
signed the informed consent form (ICF), and met all study eligibility criteria, they may be enrolled in this 
open-label extension (OLE) study. The start of this OLE study (defined as the day [Day 1] the subject receives 
their first dose of open-label MEDI-546) should occur within 28 days of the Day 422 visit of 
Study CD-IA-MEDI-546-1013 (with the exception of those subjects in the regions of Donetsk and Lugansk in 
the Ukraine, where the political situation necessitated a suspension of study activities) or at the discretion of 
the medical monitor if the start of this OLE study occurs outside the 28-day window. All subjects will receive 
IV MEDI-546 as a 300 mg fixed dose administered as an IV infusion over at least 30 minutes every 4 weeks 
(Q4W) starting at Day 1 (Week 0) for up to 3 years or until the sponsor discontinues development of 
MEDI-546 for SLE, whichever comes first. All subjects will be followed for 85 days after receiving their last 
dose of MEDI-546.
At every visit, the investigator will evaluate the subject’s clinical status and perform a risk/benefit analysis 
based on clinical judgment to determine if the subject should continue to receive MEDI-546 in the study.
SUBJECT POPULATION
The subjects in this study will be adult male or female subjects with chronic, moderately-to-severely active 
SLE who were previously treated with investigational product (MEDI-546 or placebo) and completed 
Study CD-IA-MEDI-546-1013 through treatment and follow-up.
TREATMENT REGIMEN
Subjects will receive MEDI-546 300 mg administered as an IV infusion Q4W starting at Day 1 (Week 0) for 
up to 3 years or until the sponsor discontinues development of MEDI-546 for SLE, whichever comes first.
ASSESSMENT OF ENDPOINTS
Primary endpoint: The safety and tolerability of MEDI-546 will be assessed primarily by summarizing 
treatment-emergent adverse events and treatment-emergent serious adverse events. Other variables used for 
the safety assessments will include serum chemistry, hematology, urinalysis, vital signs, physical examination, 
electrocardiogram, and concomitant medications.
Secondary endpoint: Immunogenicity results will be analyzed by summarizing the number and percentage of 
subjects who develop detectable anti-drug antibodies (ADA). The titer of ADAs will also be summarized. The 
association of ADA titers with adverse events, PK, Systemic Lupus Erythematosus Disease Activity Index-
2000 (SLEDAI-2K), and PD markers will also be evaluated.
Exploratory endpoints
 
 
 

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INTERIM ANALYSIS 
Although no formal interim analyses of the extension period data are planned, analyses of the accumulating 
data during the extension period may be performed to assess the ongoing safety and risk/benefit of the study 
treatment and to assist with Phase 3 planning. The final analysis of extension period data will take place after 
the last on-study subject completes the extension period follow-up visit or discontinues from the study.
SAMPLE SIZE AND POWER CALCULATIONS
 
 

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1
INTRODUCTION
1.1
Disease Background
Systemic Lupus Erythematosus
The disease pathogenesis of systemic lupus erythematosus (SLE) includes activation of 
innate immunity, with increased production of type I interferons (IFNs), including 
interferon-alpha (IFN-α), and increased numbers of plasmacytoid dendritic cells (pDCs) and 
myeloid dendritic cells (mDCs) in involved tissue (Bengtsson et al, 2000;
Baechler et al, 2003; Crow and Wohlgemuth, 2003; Ronnblom and Alm, 2003; 
Baechler et al, 2004; Banchereau et al, 2004; Dall’era et al, 2005; Crow, 2010). Specific parts 
of the humoral and cellular immune systems are activated. Autoantibodies are present 
universally and may precede development of clinically apparent disease 
(Arbuckle et al, 2003). Systemic lupus erythematosus-associated autoantibodies include 
anti-double-stranded (ds) deoxyribonucleic acid (DNA), anti-nucleosomes, 
anti-ribonucleoprotein (RNP) complex, and anti-Smith (Sm) antibodies 
(Rahman and Isenberg, 2008). Immune complexes containing anti-dsDNA or anti-RNP 
antibodies can activate type I IFN production (Bengtsson et al, 2000;
Ronnblom and Alm, 2003).
Multiple lines of evidence indicate a role of type I IFNs in the pathogenesis of SLE:
•
Genetic polymorphisms associated with type I IFNs are associated with susceptibility to
SLE (Criswell, 2008; Sigurdsson et al, March 2008; Sigurdsson et al, September 2008).
•
High IFN-α levels and type I IFN activity have been reported in SLE 
(Bengtsson et al, 2000; Dall’era et al, 2005). 
•
Increased levels of messenger ribonucleic acid (mRNAs) whose transcriptions are 
induced by type I IFNs (type I IFN signature) are prominent in peripheral blood 
mononuclear cells (PBMCs) and whole blood in approximately 60% of SLE patients and
are associated with greater disease activity (Baechler et al, 2003; Bennet et al, 2003;
Crow and Wohlgemuth, 2003; Kirou et al, 2004; Kirou et al, 2005; Feng et al, 2006). 
Transcripts induced by type I IFN are the most overexpressed transcripts in SLE 
(Yao et al, 2010).
•
Proteins induced by IFN are increased in SLE patients (Hylton et al, 1986; 
Okamoto et al, 2004; Huang et al, 2008).
•
Overexpression of type I IFN, type I IFN signature, and proteins induced by type I IFNs 
have been associated with greater disease activity and organ system involvement in SLE. 
High IFN-α levels, type I IFN activity, and increased type I IFN signature have been 
associated with greater disease activity (Bengtsson et al, 2000; Dall’era et al, 2005). 
Patients with high anti-dsDNA antibody titers, lupus nephritis, and progressive skin 

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rashes have high serum levels of type I IFN (Bengtsson et al, 2000). In addition, patients 
with acute skin involvement tend to have elevated IFN in blood and skin 
(Dall’era et al, 2005). Skin biopsies from patients with SLE also show increased type I 
IFN signature (Blomberg et al, 2001; Farkas et al, 2001; Yao et al, 2009). Proteins 
induced by IFN are increased in patients with active central nervous system symptoms 
(Okamoto et al, 2004).
•
Immune complexes containing SLE autoantibodies, such as anti-dsDNA or anti-RNP
antibodies, can activate type I IFN production (Bengtsson et al, 2000;
Ronnblom and Alm, 2003). After internalization through Fc receptors, autoantibody-
containing immune complexes bind endosomal Toll-like receptor 7 (TLR7) and TLR9, 
stimulating production of type I IFN. Type I IFN stimulates mDC maturation, which 
promotes loss of tolerance and generation of autoreactive T and B cells, autoantibody 
production, immune complex formation, and further production of type I IFN, creating a 
self-perpetuating cycle of autoimmunity (Banchereau et al, 2004;
Ronnblom and Pascual, 2008; Pascual et al, 2006).
•
Treatment with IFN-α has been associated with the development of SLE autoantibodies 
and clinical features of the disease (Ioannou and Isenberg, 2000; 
Niewold and Swedler, 2005).
These clinical observations in humans are supported by data that show a key role for 
type I IFN in animal models of SLE. Interferon-alpha can induce glomerulonephritis in 
normal mice and accelerate the onset of the spontaneous autoimmune disease of New 
Zealand black/white (NZB/W) mice (Mathian et al, 2005). Autoimmune-predisposed mice 
deficient in the interferon-alpha/beta (IFN-α/β) receptor exhibit significantly reduced 
anti-erythrocyte autoantibodies, hemolytic anemia, anti-DNA autoantibodies, kidney disease, 
and mortality (Santiago-Raber et al, 2003). Together, these human and animal data support 
the hypothesis that inhibiting type I IFN may reduce disease activity in patients with SLE.
1.2
MEDI-546 Background
MEDI-546 is briefly described below. Refer to the current Investigator’s Brochure (IB) for 
details. 
1.2.1
Product Derivation
 
 
 
 
 
 
 

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1.2.2
Summary of Nonclinical Experience
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.2.3
Summary of Clinical Experience
MEDI-546 has been or is being investigated in 4 MedImmune/AstraZeneca-sponsored 
clinical studies in adult subjects with systemic sclerosis (SSc) or SLE. One study in SSc is 
complete (Study MI-CP180) and 3 studies in SLE, including the current study, are ongoing 
(Studies CD-IA-MEDI-546-1013, CD-IA-MEDI-546-1145, and D3461C00002).
 
 
 
 
 
 
 
 
 
 
 
Study CD-IA-MEDI-546-1013, a Phase 2b, randomized, double-blind, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of MEDI-546 in adult subjects with 
chronic, moderately-to-severely active SLE with an inadequate response to standard of care 
treatment for SLE, is currently ongoing and remains blinded. Enrollment in this study is
complete. An interim analysis was conducted after the 210th randomized subject completed 
the Day 169 visit or discontinued from study treatment early. A total of 307 subjects have 
been randomized in a 1:1:1 ratio to receive a fixed IV dose of MEDI-546 (300 or 1000 mg) 
or placebo every 4 weeks (Q4W) for 48 weeks on Days 1, 29, 57, 85, 113, 141, 169, 197, 
225, 253, 281, 309 and 337 for a total of 13 doses. There is an 85-day follow-up period in 
Study CD-IA-MEDI-546-1013, which the subjects must complete to be considered for 
enrollment into Study CD-IA-MEDI-546-1145.
Study D3461C00002, a Phase 2, multicenter, open-label, dose-escalation study to evaluate 
the safety and tolerability of MEDI-546 in adult Japanese subjects with active SLE, is 

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currently ongoing. Enrollment in this study is complete. A total of 17 subjects are receiving a 
fixed IV dose of MEDI-546 (100, 300, or 1000 mg) Q4W for 48 weeks for a total of 13 doses 
followed by a fixed IV dose of MEDI-546 (300 or 1000 mg) Q4W for 104 weeks for a total 
of 27 doses.
1.3
Research Hypothesis
The research hypothesis is that neutralization of IFN signaling through the human 
type I IFN receptor with MEDI-546 in subjects with chronic, moderately-to-severely active 
SLE is safe and well tolerated when administered at a fixed dose of 300 mg Q4W. 
1.4
Rationale for Study Conduct
Systemic lupus erythematosus is a serious and potentially life-threatening condition with 
significant unmet medical need. There is an increasing body of data from multiple 
investigators indicating a pivotal role for type I IFN in the genesis and maintenance of active 
SLE (Baechler et al, 2003; Baechler et al, 2004; Crow and Wohlgemuth, 2003; 
Dall’era et al, 2005; Kirou et al, 2005).
The purpose of this open-label extension (OLE) study is to evaluate the long-term safety and 
tolerability of MEDI-546 when administered IV to adult subjects with chronic, 
moderately-to-severely active SLE.
1.5
Benefit-risk and Ethical Assessment
 
 
 
 
 
 
 
 
 
 
 
 
 

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2
STUDY OBJECTIVES
2.1
Primary Objective
The primary objective of this study is to evaluate the long-term safety and tolerability of IV 
MEDI-546 in adult subjects with moderately-to-severely active SLE.

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2.2
Secondary Objective
The secondary objective of this study is to evaluate the IM of MEDI-546. 
2.3
Exploratory Objectives
 
 
3
STUDY DESIGN
3.1
Overview of Study Design
This is an open-label, multinational, multicenter study to evaluate the long-term safety and 
tolerability of MEDI-546 in adult subjects with chronic, moderately-to-severely active SLE 
who were previously treated with investigational product (MEDI-546 or placebo) and 
completed Study CD-IA-MEDI-546-1013 through treatment and follow-up. The study will 
be conducted in approximately 240 subjects at up to 100 study sites. 
Once subjects have completed treatment and follow-up in Study CD-IA-MEDI-546-1013 
(through Day 422), signed the informed consent form (ICF), and met all study eligibility 
criteria, they may be enrolled in this OLE study. The start of this OLE study (defined as the 
day [Day 1] the subject receives their first dose of open-label MEDI-546) should occur 
within 28 days of the Day 422 visit of Study CD-IA-MEDI-546-1013 (with the exception of 
those subjects in the regions of Donetsk and Lugansk in the Ukraine, where the political 
situation necessitated a suspension of study activities) or at the discretion of the medical 
monitor if the start of this OLE study occurs outside the 28-day window. All subjects will 
receive IV MEDI-546 as a 300 mg fixed dose administered as an IV infusion over at least 
30 minutes Q4W starting at Day 1 (Week 0) for up to 3 years or until the sponsor 
discontinues development of MEDI-546 for SLE, whichever comes first. All subjects will be 
followed for 85 days after receiving their last dose of MEDI-546.
At every visit, the investigator will evaluate the subject’s clinical status and perform a 
risk/benefit analysis based on clinical judgment to determine if the subject should continue to 
receive MEDI-546 in the study.

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Figure 3.1-1
Study Flow Diagram
IV = intravenous
The endpoints to be measured in this study are described in Section 7.3.
3.2
Estimated Duration of Subject Participation
Subjects will be in this study for approximately 168 weeks (156 weeks for treatment and 
12 weeks for follow-up).
3.3
Study-stopping Criteria
If any event(s) occur that, in the opinion of the DSMB or sponsor, contraindicates further 
dosing of additional subjects, the sponsor will conduct a prompt cumulative review of safety 
data and the circumstances of the event in question will be conducted to determine whether 
dosing and study enrollment should be stopped, whether the protocol will be modified, or 
whether the study will be discontinued permanently. Review by the DSMB and sponsor 
decision to resume (with or without modifications) is required for resumption of the study in 
the event the study is interrupted. Where applicable, the regulatory authorities and 
Institutional Review Boards/Independent Ethics Committees (IRBs/IECs) will be notified of 
any actions taken with the study.
Any subjects who have already received investigational product and are currently in the 
study at the time study-stopping criteria are met will continue to be followed by the 
investigator for safety. In the unanticipated event that dosing is suspended, until a decision is 
reached by the sponsor, subjects will continue with regularly scheduled visits.
Withdrawal criteria for individual subjects are provided in Section 4.2.3.

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3.4
Rationale for Study Design, Doses, and Control Groups
3.4.1
Rationale for Study Design
This is an open-label, long-term safety and tolerability study of MEDI-546. The subjects in 
this study will be male or female with moderately-to-severely active SLE despite standard of 
care (SOC) who have been previously treated with investigational product (MEDI-546 or 
placebo) and completed Study CD-IA-MEDI-546-1013 through the treatment and follow-up 
periods. All subjects in this OLE study will receive a fixed IV dose of 300 mg MEDI-546.
3.4.2
Rationale for MEDI-546 Dose
 
 
 
 
 
 
 
 
 
4
SUBJECT SELECTION, TREATMENT, AND WITHDRAWAL
4.1
Subject Participation and Identification
Study participation begins once written informed consent is obtained (see Section 10.3 for 
details) for this OLE study. Once informed consent is obtained, a subject identification (SID) 
number will be assigned to each subject by a central system interactive voice/web response 
system (IVRS/IWRS). The SID number will be used to identify the subject during the 
screening process and throughout study participation, if applicable. 
A master log of all consented subjects will be maintained at the site and will document all 
pretreatment period failures (ie, subjects who are consented but do not meet study eligibility 
criteria), including the reason(s) for pretreatment period failure (see Section 9.1 for details).

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4.2
Subject Selection and Withdrawal
The subjects in this study will be adult male or female subjects with chronic, moderately-to-
severely active SLE who were previously treated with investigational product (MEDI-546 or 
placebo) and completed Study CD-IA-MEDI-546-1013 through treatment and follow-up.
The investigator (physician) or qualified designee will discuss the study with a subject who is 
considered a potential candidate for the study and provide the subject with the study-specific 
ICFs approved by the IRB/IEC. The investigator or designee will address any questions 
and/or concerns that the subject may have and, if there is continued interest, will secure 
written informed consent for participation in the study. Written informed consent and any 
locally required authorization (eg, Health Insurance Portability and Accountability Act 
[HIPAA] authorization in the United States of America [USA], European Union [EU] Data 
Privacy Directive authorization in the EU) will be obtained prior to conducting any protocol-
specific procedures, including Day 1 evaluations or medication washouts. See Section 10.3
for additional details concerning informed consent. 
4.2.1
Inclusion Criteria
Subjects must meet all of the following criteria:
1. Written informed consent and any locally required authorization (eg, HIPAA in the USA, 
EU Data Privacy Directive in the EU) obtained from the subject prior to performing any 
protocol-related procedures, including Day 1 evaluations. 
2. Must have qualified for and received investigational product (MEDI-546 or placebo) and 
completed the treatment period plus the follow-up period (through Day 422) in Study 
CD-IA-MEDI-546-1013. Subjects who discontinued from Study CD-IA-MEDI-546-1013 
are not eligible for this study, with the exception of those subjects in the regions of 
Donetsk and Lugansk in the Ukraine, where the political situation necessitated a 
suspension of study activities, and all other inclusion and exclusion criteria were met.
3. Females of childbearing potential who are sexually active with a nonsterilized male 
partner must use 2 methods of effective contraception for 28 days prior to Day 1, and 
must agree to continue using such precautions for 85 days after the final dose of 
investigational product; cessation of contraception after this point should be discussed 
with a responsible physician. Subjects must continue the use of their effective 
contraception as used in Study CD-IA-MEDI-546-1013. Periodic abstinence, the rhythm 
method, and the withdrawal method are not acceptable methods of contraception. 
•
Females of childbearing potential are defined as those who are not surgically sterile 
(ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy).
•
Postmenopausal is defined as 12 months with no menses without an alternative 
medical cause. 

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•
Subjects must use 2 acceptable methods of effective contraception as described in 
Table 4.2.1-1.
4. Nonsterilized males who are sexually active with a female partner of childbearing 
potential must use 2 acceptable methods of effective contraception (see Table 4.2.1-1) 
from Day 1 for 85 days after receipt of the final dose of investigational product.
Table 4.2.1-1
Effective Methods of Contraception (Two Methods Must be 
Used)
Barrier Methods
Intrauterine Device Methods
Hormonal Methods
•
Male condom plus 
spermicide
•
Cap plus spermicide
•
Diaphragm plus spermicide
•
Copper T
•
Progesterone T a
•
Levonorgestrel-releasing 
intrauterine system (eg, Mirena®) a
•
Implants
•
Hormone shot or injection
•
Combined pill
•
Minipill
•
Patch
a This is also considered a hormonal method. 
5. Willing to forgo other forms of experimental treatment during the study.
6. Has adequate peripheral venous access.
7. Able to complete the study period.
8. Has adequate reading and writing abilities (in their native language), in the opinion of the 
investigator, such that the subject can comprehend and complete the informed consent, 
and all protocol-related subject assessments.
4.2.2
Exclusion Criteria
Any of the following would exclude the subject from participation in the study:
General Exclusion Criteria
1. Any condition that, in the opinion of the investigator, would interfere with evaluation of 
the investigational product or interpretation of subject safety or study results. 
2. Major surgery within 8 weeks before signing the ICF or elective major surgery planned 
during the study period (see Appendix 2 for guidance on major surgery).
Exclusion Criteria Related to Concomitant Medications:
3. Receipt of any of the following within the last 12 weeks:
•
Azathioprine > 200 mg/day. 
•
Mycophenolate mofetil/mycophenolic acid > 2.0 g/day. 
•
Oral, SC, or intramuscular methotrexate > 25 mg/week.

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4. Receipt of any of the following:
•
Any live or attenuated vaccine within 4 weeks prior to signing the ICF 
(administration of killed vaccines is acceptable, the sponsor recommends 
investigators ensure all subjects are up to date on required vaccinations prior to study 
entry). 
•
Bacillus of Calmette and Guerin (BCG) vaccine within 1 year of signing the ICF. 
4.2.3
Withdrawal Criteria
Permanent discontinuation of investigational product: An individual subject will not 
receive any further investigational product if any of the following occur in the subject in 
question:
1. Withdrawal of consent or lost to follow-up. 
2. Adverse event (AE) that, in the opinion of the investigator or the sponsor, contraindicates 
further dosing with investigational product. 
3. The investigator or the MedImmune medical monitor determines that withdrawal is in the 
subject’s best interest. 
4. Pregnancy, positive pregnancy test, or subject expresses an interest in becoming pregnant 
at any time from Day 1 through the active treatment period of the study (see Section 
6.4.3.3). 
5. Malignancy, except squamous or basal cell carcinoma of the skin with documented 
success of curative therapy. 
6. An opportunistic or systemic fungal infection or any infection (viral, bacterial) of a 
serious nature (ie, requiring hospitalization or treatment with IV anti-infectives), that in 
the opinion of the investigator or medical monitor, contraindicates further dosing of 
investigational product after resolution. 
7. Isolated hepatitis B core (HBc) positivity with hepatitis B virus (HBV) DNA detected by 
the central laboratory. 
8. Receipt of any of the following medications (other than MEDI-546 administered as per 
protocol) any time from the last MEDI-546 dose in Study CD-IA-MEDI-546-1013 to 
85 days post last MEDI-546 dose in Study CD-IA-MEDI-546-1145:
•
Cyclophosphamide
•
IV corticosteroids > 1g Solu-Medrol or equivalent
•
IFN therapy (alpha 2a & 2b, beta 1a & 1b, and pegylated IFNs alpha 2a & 2b)
•
Investigational agents
•
Biologics (including belimumab)
•
Plasmapheresis
•
Any immunoglobulin (Ig) therapy
•
BCG vaccine

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9. A diagnosis of active tuberculosis (TB), premature discontinuation of treatment for latent 
TB, or noncompliance with TB therapy
Subjects who are permanently discontinued from further receipt of investigational product, 
regardless of the reason (withdrawal of consent, due to an AE, other), will be identified as 
having permanently discontinued treatment. Subjects who permanently discontinue treatment 
may either be considered to have completed the study or not to have completed the study (see 
Section 4.7).
Subjects who are permanently discontinued from receiving investigational product will be 
followed for safety per Section 6.4, including the collection of any protocol-specified blood 
or urine specimens, unless consent is withdrawn or the subject is lost to follow-up or enrolled 
in another clinical study. Twenty-eight days (± 7 days) after the last dose of investigational 
product, subjects will begin the follow-up period by completing the Visit 41/Early 
Discontinuation Visit assessments. Two subsequent follow-up visits will also be completed 
59 and 85 days (± 7 days) after the last dose of investigational product as per the schedule of 
study procedures. A subject who receives any SLE medication or SLE treatment listed in 
Appendix 3 (other than those prohibited medications or treatments listed above) may be 
allowed to continue receiving investigational product only if permission from the sponsor is 
obtained. 
Concomitant medications that require the sponsor to be notified immediately and the medical 
monitor to be consulted to determine if a subject may continue to receive investigational 
product include, but are not limited to:
•
Corticosteroids with a long biologic half-life (eg, dexamethasone, betamethasone)
•
Increase in oral corticosteroids (OCS) treatment above a total dose > 40 mg/day for a 
dosing period > 14 days, dosing with MEDI-546 may be continued, unless there is a 
safety concern. However, it should be noted that frequent steroid use above Study CD-
IA-MEDI-546-1013 baseline for SLE disease control (> 2 times every 6 months, higher 
doses [> 40 mg/day], and/or longer duration than permitted by the protocol) after 
12 months of open-label MEDI-546 should result in discontinuation of MEDI-546
administration for failure to achieve a favorable benefit:risk profile. 
Withdrawal of consent: If consent is withdrawn, the subject will not receive any further 
investigational product or further study observation. Note that the subject may need to 
undergo additional tests or tapering of treatment to withdraw safely.

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Lost to follow-up: Subjects will be considered lost to follow-up only if no contact has been 
established by the time the study is completed (as defined in Section 4.9) such that there is 
insufficient information to determine the subjects’ status as of their last visit. 
•
Note: Subjects refusing to return to the site or to continue participation in the study 
should be documented as “withdrawal of consent” rather than “lost to follow-up.” 
Investigators should document attempts to re-establish contact with missing subjects 
throughout the study period. If contact with a missing subject is re-established, the 
subject should not be considered lost to follow-up and any evaluations should resume 
according to the protocol.
4.2.4
Replacement of Subjects
Subjects in this OLE study will not be replaced. 
4.3
Treatment Assignment
Each subject who meets the eligibility criteria will be assigned open-label investigational 
product using an IVRS/IWRS. A subject is considered enrolled into the study when the 
investigator or delegated site personnel notifies the IVRS/IWRS that the subject meets the 
eligibility criteria and the IVRS/IWRS provides the assignment of the investigational product 
kit numbers to the subject. Confirmation of this information is sent to the 
investigator/designee who dispenses the investigational product to the subject per the 
communication and records the appropriate information in the subject’s medical records and 
investigational product accountability log.
Investigational product (MEDI-546) must be administered on the same day that the visit is 
logged into the IVRS/IWRS. If there is a delay in the administration of investigational 
product such that it will not be administered within the specified timeframe, the study 
monitor must be notified immediately.
4.4
Blinding
This study is not blinded. 
4.5
Study Medications
4.5.1
 
 

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4.5.1.1
Investigational Product Accountability
The investigator’s or site’s designated investigational product manager is required to 
maintain accurate investigational product accountability records. Upon completion of the 
study, copies of investigational product accountability records will be returned to 
MedImmune. All unused investigational product will be returned to a 
MedImmune-authorized depot or disposed of upon authorization by MedImmune.

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4.5.1.2
Reporting Product Complaints
Any defects with the investigational product must be reported immediately to the 
MedImmune Product Complaint Department by the site with further notification to the site 
monitor. All defects will be communicated to MedImmune and investigated further with the 
Product Complaint Department. During the investigation of the product complaint, all 
investigational product must be stored at labeled conditions unless otherwise instructed.
Product defects may be related to component, product, or packaging and labeling issues. The 
list below includes, but is not limited to, descriptions of product complaints that should be 
reported.
•
Component Issue: Defect in container or dosing mechanism of the investigational 
product. The component defect may be damaged, missing, or broken. Component 
examples include vials, stoppers, caps, spray barrels, spray nozzles, or plungers.
•
Product Issue: Defect in the product itself. The product appearance has visual 
imperfections such as foreign particles, crystallization, discoloration, turbidity, 
insufficient volume, or anything that does not apply to the product description.
•
Packaging/Labeling Issue: Defect in the packaging or labeling of the product. The 
packaging or labeling defects may be damaged or unreadable, or the label may be 
missing.
When reporting a product complaint, site staff must be prepared to provide the following 
information:
1. Customer information: reporter name, address, contact number, and date of complaint 
2. Product information: product name, packaging kit number or lot number, expiry date, and 
clinical protocol number
3. Complaint information: complaint issue category and description
MedImmune contact information for reporting product complaints:

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4.5.2
Other Study Medications
Permitted SOC SLE medications include OCS (up to 40 mg/day of prednisone or equivalent), 
intramuscular corticosteroids, intra-articular/tendon sheath/bursa corticosteroid injections, 
antimalarials, slow-acting immunosuppressants (methotrexate, mycophenolate 
mofetil/mycophenolic acid, and azathioprine), prescription NSAIDs, 
analgesics/nonprescription NSAIDs, and topical therapy. However, when OCS medications 
are > 40 mg/day of prednisone (or equivalent) for greater than 14 days, dosing with 
MEDI-546 may be continued, unless there is a safety concern. 
However, it should be noted that frequent steroid use above Study CD-IA-MEDI-546-1013 
baseline for SLE disease control (> 2 times every 6 months, higher doses [> 40 mg/day],
and/or longer duration than permitted by the protocol) after 12 months of open-label 
MEDI-546 should result in discontinuation of MEDI-546 administration for failure to 
achieve a favorable benefit:risk profile.
All permitted SOC SLE medications received from initiation from Day 1 through the end of 
the study will be recorded on the source document and include the specific indication for use 
(eg, general SLE activity, skin involvement, nephritis, pleurisy) as well as the dose, start and 
stop dates, frequency, and route of administration. In addition, any change in permitted SOC 
SLE medications and reason for change must be documented. All OCS’s taken during the 
study for a burst or a taper must be identified if the OCS is being taken for an SLE condition 
or a non-SLE condition.
4.5.2.1
Corticosteroids
When OCS treatment is above a total dose > 40 mg/day for a dosing period > 14 days, dosing 
with MEDI546 may be continued, unless there is a safety concern. 
However, it should be noted that frequent steroid use above Study CD-IA-MEDI-546-1013 
baseline for SLE disease control (> 2 times every 6 months, higher doses [> 40 mg/day],
and/or longer duration than permitted by the protocol) after 12 months of open-label 
MEDI-546 should result in discontinuation of MEDI-546 administration for failure to 
achieve a favorable benefit:risk profile. 

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4.5.2.2
Slow-acting Immunosuppressants
If subjects are on slow-acting immunosuppressants, dosing must not exceed the following:
•
Azathioprine > 200 mg/day
•
Mycophenolate mofetil/mycophenolic acid > 2.0 g/day
•
Oral, SC, or intramuscular methotrexate > 25 mg/week
4.5.2.3
Background SOC SLE Medications (OCS, Antimalarials, and 
Immunosuppressants)
Subjects may undergo changes in their background SOC SLE medication (OCS, 
antimalarials or immunosuppressants) doses, based on the opinion of the investigator. On 
treatment days, changes in doses will commence after all assessments have been completed 
and investigational product has been administered.
Investigators should change background SOC SLE medications based on disease activity in 
all subjects throughout the study. There is no minimum dose requirement for background 
SOC SLE medications, and subjects are encouraged to taper off as permitted by disease 
activity. Due to variability in subject responses to background SOC SLE medications and 
tolerability of taper, investigators are asked to use their clinical judgment with respect to the 
taper schedule. An example of a tapering schedule is provided in Appendix 6 as guidance. If 
the subject experiences an increase in SLE disease activity secondary to background SOC 
SLE medications, the dose may be adjusted according to the investigator’s clinical judgment 
but may not exceed maximally permitted doses as defined by exclusionary criteria.
4.5.2.4
Use of Other Medications for Increased Disease Activity
If during the course of the study permitted SOC SLE medications are not adequate for the 
treatment of increased SLE disease activity, a subject may receive other medications as 
deemed necessary by the investigator or the subject’s treating physician after notifying the 
medical monitor. However, if the subject receives (or is intended to receive) any 
medications/treatments listed in Appendix 3, the sponsor must be notified immediately and 
procedures outlined in Section 4.2.3 must be followed. The subject may only continue to 
receive investigational product with sponsor approval.
4.5.3
Treatment Regimen
Subjects will receive MEDI-546 300 mg administered as an IV infusion Q4W starting at 
Day 1 (Week 0) or the visit following approval of this amendment (for those subjects who 

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have already been dosed in this study) for up to 3 years or until the sponsor discontinues 
development of MEDI-546 for SLE, whichever comes first.
4.5.4
Investigational Product Dose Preparation
No incompatibilities between MEDI-546 and 100 mL 0.9% w/v saline polyolefin bags have 
been observed. Additional studies also demonstrated that MEDI-546 is compatible with 
IV bags and ancillaries comprised of materials including: polyolefin, glass, polyethylene, 
polyvinylchloride, polypropylene, polybutadiene, and ethylene polyvinyl acetate. Because 
compatibility of MEDI-546 with IV medications and solutions other than normal saline 
(0.9% sodium chloride for injection), is not known, the investigational product solution 
should not be infused through an IV line in which other solutions or medications are being 
administered. 
Additional studies demonstrate that MEDI-546 is compatible with IV bags and ancillaries 
comprised of materials are presented in Table 4.5.4-1 and Table 4.5.4-2.
Table 4.5.4-1
Compatible Materials of Construction for IV Bags
IV Bag Diluent
Materials of Construction
0.9% saline
Glass
0.9% saline
Polyolefin copolymer, ethylene and propylene
0.9% saline
PVC and DEHP
0.9% saline
Polyethylene
0.9% saline
Ethylene polyvinyl acetate
0.9% saline
Polypropylene
DEHP = diocytl-phthalate; IV = intravenous; PVC = polyvinylchloride
Table 4.5.4-2
Compatible Materials of Construction for Ancillaries
Materials of Construction
Polyethylene
PVC with DEHP
PVC with 2-ethylhexyltrimellitate
Polybutadiene
DEHP = diocytl-phthalate; PVC = polyvinylchloride

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4.5.4.1
Dose Calculation
All subjects will receive MEDI-546 300 mg administered as an IV infusion. Dose 
calculations for MEDI-546 Drug Product using the 100 and 150 mg/mL formulations are
presented in Table 4.5.4.1-1.
4.5.4.2
Investigational Product Inspection
Each vial selected for dose preparation should be inspected. MEDI-546 is supplied in cartons 
of either 10 vials (100 mg/mL formulation) or 3 vials (150 mg/mL formulation) per kit. Each 
kit has a unique number that is printed on all labels within the kit (ie, the outer carton label 
and the label of each vial within the carton). Each vial contains either 1.0 mL (100 mg/mL 
formulation) or 2.3 mL (150 mg/mL formulation) of a clear, colorless to slightly yellow 
liquid that is free from visible particles. Ensure that all vials within a kit are of the same 
dosage strength. The 100 and 150 mg/mL formulations may not be mixed to prepare a dose. 
If there are any defects noted with the investigational product, the investigator and site 
monitor should be notified immediately. Refer to the Product Complaint section for further 
instructions.
4.5.4.3
Dose Preparation Steps
 
 
 

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.
4.5.5
Treatment Administration
The first day of dosing is considered Day 1.
Every dose of investigational product should be administered using the following guidelines:
•
Females of childbearing potential must have a negative urine pregnancy test prior to 
receiving investigational product.
•
MEDI-546 must be administered at room temperature by controlled infusion via an 
infusion pump into a peripheral vein. A physician must be present at the site or 
immediately available to respond to emergencies during all administrations of 
investigational product.
•
MEDI-546 does not contain preservatives and any unused portion must be discarded. The 
dose of MEDI-546 must be prepared using aseptic technique. Total in-use storage time 
from needle puncture of the first vial of MEDI-546 for investigational product 
preparation to start of administration should not exceed 4 hours at room temperature or 

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24 hours at 2°C-8°C (36°F to 46°F). If storage time exceeds these limits, a new dose must 
be prepared from new vials. 
•
Administration should be performed using an extension line with a low protein-binding 
0.2-μm in-line filter. The entire contents of the IV bag should be administered using an 
infusion pump over at least 30 minutes. 
•
MEDI-546 should be administered over at least 30 minutes. If a subject has a history of 
infusion reactions, MEDI-546 administration may be lengthened per the investigator’s 
discretion. The subject’s vital signs (temperature, blood pressure [BP], pulse rate, and 
respiratory rate) should be taken after the first 15 (± 5) minutes of infusion of 
investigational product into the subject and the subject should be assessed for signs of an 
infusion reaction. 
•
Immediately following the initial dosing, up to an additional 25 mL of saline will be 
given via infusion pump at the same pump speed utilized at the completion of the initial 
dosing. 
•
The duration of the MEDI-546 infusion and duration of MEDI-546 administration will be 
calculated as follows:
•
Duration of Infusion: The amount of time elapsed from the infusion start time to the 
infusion stop time. Infusion start time is defined as the time point where MEDI-546 is 
first infused into the subject. Infusion stop time is defined as the time point where the 
infusion pump completes infusion of MEDI-546, not including the saline flush.
•
For example: An infusion with a start time of 12:00 PM would have a duration of 
infusion recorded as at least 30 minutes (a time of at least 12:30 PM).
•
Duration of Administration: The amount of time elapsed from the infusion pump 
start time to the infusion pump stop time PLUS the time required to complete the 
additional flush of saline. The duration of administration will always be greater than 
the duration of infusion and will always include the additional flush of saline.
•
Both the duration of the investigational product infusion and the duration of 
investigational product administration will be recorded.
•
Subjects should not be premedicated unless they have had a prior infusion reaction to 
MEDI-546. However, if a prior infusion reaction has been documented, the investigator 
may elect to administer an antihistamine or acetaminophen/paracetamol prophylactically 
for the comfort and safety of the subject prior to subsequent infusions. Prophylactic use 
of glucocorticosteroids prior to subsequent infusions is not permitted.
•
Because compatibility of MEDI-546 with IV medications and solutions other than 0.9% 
sodium chloride for injection, United States Pharmacopeia (USP), is not known, 
MEDI-546 solution should not be infused through an IV line in which other solutions or 
medications are being administered.

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4.5.6
Monitoring of Dose Administration 
Vital signs (temperature, BP, pulse rate, and respiratory rate) will be obtained with the 
subject in a sitting position and monitored at the following times:
•
Shortly before the IV infusion (within 15 minutes of the beginning of the investigational 
product infusion)
•
Every 15 [± 5] minutes during infusion
•
Immediately after completion of administration of investigational product, including 
postdose saline flush (within 15 [± 5] minutes after completion of investigational product 
administration)
•
At 30 [± 5] and 60 [± 5] minutes after completion of investigational product 
administration, and every 30 [± 5] minutes thereafter or until stable and ready for 
discharge (as judged by the investigator).
If an anaphylactoid-like infusion reaction or anaphylactic reaction occurs, vital signs will be 
taken more frequently, as warranted by the severity of the reaction. 
As with any antibody, allergic reactions to dose administration are possible. Therefore, 
appropriate drugs and medical equipment to treat acute anaphylactic reactions must be 
immediately available, and study personnel must be trained to recognize and treat 
anaphylaxis.
4.5.6.1
Anaphylaxis, Hypersensitivity, and Infusion Reactions
Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly 
after contact with an allergy-causing substance, such as investigational product.
For the purposes of this study, MedImmune is providing the following definition as a simple 
and rapid means to make the diagnosis of anaphylaxis during infusion with investigational 
product. This definition was a product of a symposium convened by the National Institute of 
Allergy and Infectious Diseases and Food Allergy and Anaphylaxis Network 
(Sampson et al, 2006).
In adults, anaphylaxis is highly likely when any one of the following 3 criteria is fulfilled:

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1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips, tongue 
and/or uvula) AND AT LEAST ONE OF THE FOLLOWING:
•
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia).
•
Reduced BP (see #3 below for definition) or associated symptoms of end-organ 
dysfunction (eg, hypotonia [collapse], syncope, incontinence).
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that subject (minutes to several hours):
•
Involvement of the skin-mucosal tissue (eg, generalized hives, itch, flush, swollen 
lips, tongue and/or uvula).
•
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia).
•
Reduced BP (see #3 below for definition) or associated symptoms (eg, hypotonia 
[collapse], syncope, incontinence).
•
Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting).
3. Reduced BP after exposure to known allergen for that subject (minutes to several hours); 
for adults a systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
subject’s baseline BP (taken at or immediately prior to start of the infusion), whichever 
BP is lower.
For the purposes of this study, a hypersensitivity reaction is defined as an acute onset of an 
illness with involvement of the skin, mucosal tissue, or both during infusion of 
investigational product (but does not meet the definition of anaphylaxis described above).
For the purposes of this study, an infusion reaction is defined as any other reaction occurring 
during infusion of investigational product or felt to be temporally related to the infusion 
within 24 hours of investigational product administration. 
Subjects should not be premedicated unless they have had a prior infusion reaction to 
MEDI-546. However, if a prior infusion reaction has been documented, the investigator may 
elect to administer prophylactically an antihistamine and/or acetaminophen/paracetamol for 
the comfort and safety of the subject prior to subsequent infusions. Prophylactic use of 
glucocorticosteroids prior to subsequent infusions is not permitted.
An approach to these reactions based on severity of symptoms is given in Table 4.5.6.1-1, 
with suggested treatment options. Final treatment is at the discretion of the investigator and 
should reflect local standard of care.

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Table 4.5.6.1-1
An Approach to Management of Anaphylactic, Hypersensitivity, and Infusion Reactions
Severity of Symptoms
Treatment
MEDI-546
Mild reactions (infusion and 
hypersensitivity)
Mild infusion reactions such as 
headache, nausea, non-pruritic 
rash, or mild hypersensitivity 
reactions including localized 
cutaneous reactions such as 
mild pruritus, flushing, rash, 
dizziness, headache, 
≤20 mmHg change in systolic 
BP from pre-infusion 
measurement
•
Evaluate subject, including close monitoring of 
vital signs 
•
At the discretion of the investigator, treat subject,
(for example) with:
•
Normal saline (~500-1000 mL/hour IV) and/or
•
Diphenhydramine 50 mg IV or equivalent and/or
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol and/or
•
Topical antihistamines and/or low-potency topical 
corticosteroid preparations and/or
•
Anti-nausea medication, as needed
•
Stop MEDI-546 infusion immediately
•
Option 1: Do not resume MEDI-546 infusion; OR at the 
discretion of the investigator, resume current MEDI-546 
infusion under observation and complete infusion at no 
more than half the planned infusion rate
•
Option 2: Discontinue any further administration of 
MEDI-546; OR at the discretion of the investigator, 
continue future administrations and consider slowing 
infusion rate and pretreating subject 0.5-1.5 hours prior 
to MEDI-546 administration (for example) with:
•
Diphenhydramine 50 mg IV or equivalent
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol

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Table 4.5.6.1-1
An Approach to Management of Anaphylactic, Hypersensitivity, and Infusion Reactions
Severity of Symptoms
Treatment
MEDI-546
Moderate reactions (infusion)
Infusion reaction such as those 
listed above under mild 
reactions but excluding 
moderate hypersensitivity 
reactions (see below)
•
Evaluate subject, including close monitoring of 
vital signs 
•
Treat subject (for example) with:
•
Normal saline (~500-1000 mL/hour IV) and/or
•
Diphenhydramine 50 mg IV or equivalent and/or
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol and/or
•
Anti-nausea and/or antiemetic intramuscular, as 
needed
•
Stop MEDI-546 infusion immediately
•
Option 1: Do not resume MEDI-546 infusion; OR based 
on risk/benefit evaluation, at the discretion of the 
investigator, resume current infusion under observation 
and at no more than half the planned infusion rate after 
treatment of current signs and symptoms as suggested 
(eg, normal saline and/or acetaminophen and/or topical 
antihistamines)
Additional options for future administration of MEDI-
546
•
Discontinue any further administrations of MEDI-546; 
OR
•
Further MEDI-546 infusions, at the discretion of the 
investigator, continue administration and consider 
slowing infusion rate and pretreating subject 0.5-1.5 
hours prior to MEDI-546 administration (for example) 
with:
•
Diphenhydramine 50 mg IV or equivalent
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol 
•
Anti-nausea and/or antiemetic PO
•
Prior to next administration of MEDI-546, consider 
initiating at a slower infusion rate and pretreating subject 
0.5-1.5 hours prior to next administration of MEDI-546 
(for example) with:
•
Diphenhydramine 50 mg IV or equivalent
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol
•
If moderate event recurs in the same subject, discontinue 
further MEDI-546 administration

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Table 4.5.6.1-1
An Approach to Management of Anaphylactic, Hypersensitivity, and Infusion Reactions
Severity of Symptoms
Treatment
MEDI-546
Moderate hypersensitivity 
reactions
Infusion reactions which may 
include generalized rash or 
urticaria, palpitations, chest 
discomfort, shortness of breath, 
hypo- or hypertension with 
> 20 mmHg change in systolic 
BP from pre-infusion 
measurement
•
Evaluate subject, including close monitoring of 
vital signs 
•
Treat subject (for example) with:
•
Normal saline (~500-1000 mL/hour IV) and/or
•
Diphenhydramine 50 mg IV or equivalent and/or
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol and/or
•
IV corticosteroids, such as hydrocortisone 100 mg 
or methylprednisolone 20-40 mg
•
Stop MEDI-546 infusion immediately
•
DO NOT resume current infusion
•
Discontinue any further administrations of MEDI-546
•
Consider need for additional oral antihistamine 
administration or OCS administration to prevent 
reoccurrence of symptoms over subsequent 2-3 days

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Table 4.5.6.1-1
An Approach to Management of Anaphylactic, Hypersensitivity, and Infusion Reactions
Severity of Symptoms
Treatment
MEDI-546
Severe
Above plus fever with rigors, 
hypo- or hypertension with 
≥40 mmHg change in systolic 
BP, signs of end organ 
dysfunction (eg, symptomatic 
hypotension such as hypotonia, 
syncope, incontinence, seizure) 
from pre-infusion 
measurement, or wheezing, 
angioedema, or stridor
OR
Life threatening
Defined as a reaction that is life 
threatening and requires 
pressor and/or ventilator 
support or shock associated 
with acidemia and impairing 
vital organ function due to 
tissue hypoperfusion
•
Evaluate subject, including close monitoring of 
vital signs
•
Maintain airway, oxygen if available
•
Treat subject immediately, for example with:
•
Normal saline (~500-1000 mL/hour IV)
•
Epinephrine for bronchospasm, hypotension 
unresponsive to IV fluids, or angioedema. Dose 
and route as per local standard of care, example, 
epinephrine 1:1000, 0.5-1.0 mL administered SC 
for mild cases and intramuscular for more severe 
cases
•
IV corticosteroids, such as hydrocortisone 100 mg 
or methylprednisolone 20-40 mg
•
Diphenhydramine 50 mg IV or equivalent
•
Acetaminophen 500-650 mg or equivalent dose of 
paracetamol
•
Call emergency medical transport for transport to 
emergency hospital based on judgment of the 
investigator
•
Grade 3 wheezing, hypotension or angioedema is 
unresponsive to single dose of epinephrine
•
Grade 4 event
At the discretion of the investigator
•
Stop MEDI-546 infusion immediately
•
Do not resume current infusion 
•
Permanently discontinue MEDI-546 administration
•
Consider need for additional oral antihistamine 
administration or OCS administration to prevent 
reoccurrence of symptoms over subsequent 2-3 days
BP = blood pressure; IV = intravenous; OCS = oral corticosteroid; PO = orally; SC = subcutaneous

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4.5.7
Treatment Compliance
Investigational product is administered by study site personnel, who will monitor 
compliance.
4.6
Concomitant Medications
4.6.1
Permitted Non-SLE Concomitant Medications
Investigators may prescribe non-SLE concomitant medications or treatments deemed 
necessary to provide adequate supportive care except for those medications identified as 
“excluded” as listed in Section 4.6.2.
The following concomitant medications are permitted from Day 1 through the end of the 
study for the treatment of AEs or for supportive care (eg, menstrual discomfort):
1. Prescription and over-the-counter medications (including analgesics and NSAIDs, etc.)
2. Herbal supplements/teas and vitamins
3. Increase in OCS treatment above a total dose > 40 mg/day for a dosing period > 14 days. 
Dosing with MEDI-546 may be continued, unless there is a safety concern. However, it 
should be noted that frequent steroid use above Study CD-IA-MEDI-546-1013 baseline 
for SLE disease control (> 2 times every 6 months, higher doses [> 40 mg/day], and/or
longer duration than permitted by the protocol) after 12 months of open-label MEDI-546 
should result in permanent discontinuation of MEDI-546 for failure to achieve a 
favorable benefit:risk profile.
All concomitant medications (SLE and non-SLE) taken during the study period should be 
recorded. All OCS’s taken during the study for a burst or a taper must be identified if the 
OCS is being taken for an SLE condition or a non-SLE condition.
4.6.2
Excluded Concomitant Medications
Subjects must be instructed not to take any medications, including over-the-counter products, 
without first consulting with the investigator.
The following medications are considered exclusionary if given from Day 1 to the end of the 
study.
1. Etanercept
2. Adalimumab, infliximab, or golimumab
3. Rituximab or certolizumab pegol
4. Azathioprine > 200 mg/day 
5. Mycophenolate mofetil/mycophenolic acid > 2.0 g/day

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6. Oral, SC, or intramuscular methotrexate > 25 mg/week 
7. Any change in route of administration of oral, SC, or intramuscular methotrexate
8. Cyclophosphamide and leflunomide 
9. IV corticosteroids
10. IFN therapy (alpha 2a & 2b, beta 1a & 1b, and pegylated IFNs alpha 2a & 2b)
11. Live or attenuated vaccines (the sponsor recommends that investigators ensure all 
subjects are up to date with required vaccinations prior to entry into the study)
12. Investigational agents
13. Biologics (including belimumab)
14. Plasmapheresis
15. Any Ig therapy
16. BCG vaccine
4.7
Subject Completion
An individual subject will be considered to have completed the study if the subject was 
followed up through 85 days post the subject’s last dose (Section 4.9). 
Subjects will be considered to have not completed the study if consent was withdrawn or the 
subject was lost to follow-up (see Section 4.2.3).
4.8
Site Completion
Site completion is defined as the date of the last protocol-specified visit/assessment 
(including telephone contact) for the last subject in the study at the given site. All materials 
or supplies provided by the sponsor will be returned to the sponsor or designee upon site 
completion of the study, as directed by the site monitor. The investigator will notify the 
IRB/IEC when the study has been completed at his/her site.
4.9
End of the Study
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last subject in the study. 
5
STUDY PROCEDURES
5.1
Schedule of Study Procedures
All subjects will be assigned a SID number and receive 300 mg MEDI-546 unless consent is 
withdrawn. The investigator must notify the sponsor or designee of deviations from protocol 
visits or evaluations and these evaluations, if applicable, must be rescheduled or performed at 

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the nearest possible time to the original schedule. Protocol deviations will be recorded on the 
source document with an explanation for the deviation and any study-specific case report 
forms (CRFs) or logs designated for capturing protocol deviations, if applicable for the study. 
The investigator must comply with the applicable requirements related to the reporting of 
protocol deviations to the IRB/IEC.
Subjects will be instructed to call study personnel to report any abnormalities during the 
intervals between study visits and to come to the study site if medical evaluation is needed 
and the urgency of the situation permits. For emergency and other unscheduled visits to a 
medical facility other than the study site, medical records will be obtained by the investigator 
and made available to the sponsor or designee during monitoring visits.
A Schedule of Study Procedures is presented in Table 5.1-1 for the treatment period and in 
Table 5.1-2 for the 85-day follow-up period, followed by a description of each visit. 
A description of the study procedures is included in Section 5.2.
If Day 1 of this study occurs on the same day as Day 422 (+ 28 days) of 
Study CD-IA-MEDI-546-1013, then many of the procedures and samples only need to be 
collected one time and will be utilized for both studies (see Table 5.1-1 for more detailed 
information). However, the informed consent for this study must be signed prior to using any 
of the Study CD-IA-MEDI-546-1013 data.
If Day 1 of this study occurs 28 days after Day 422 of Study CD-IA-MEDI-546-1013, then 
Day 1 procedures and samples of this study will need to be collected (see Table 5.1-1 for 
more detailed information).

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Table 5.1-1
Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
Written informed consent/HIPAA information/ 
assignment of SID number
X a
Verify eligibility criteria
X b
SF-36v2 (should be completed prior to any clinical 
assessments)
X b
X
X
Concomitant medications
X b
X
X
X
X
X
Review medical history and add any 
AEs/SAEs/AESIs from 
Study CD-IA-MEDI-546-1013 (if appropriate)
X b
Physical examination (For Day 1 assessment only: 
if Day 422 [+ 28 days] of Study CD-IA-MEDI-
546-1013 occurs on the same day as Day 1 of this 
study, then the data only need to be collected one 
time and will be used for both studies)
X
X
Weight (For Day 1 assessment only: if Day 422 
[+ 28 days] of Study CD-IA-MEDI-546-1013 
occurs on the same day as Day 1 of this study, 
then the data only need to be collected one time 
and will be used for both studies)
X
X
Vital signs
X b
X
X
X
X
X

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Table 5.1-1
Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
ECG (from Day 396 of 
Study CD-IA-MEDI-546-1013; required at Day 1 
if not done at Day 396 of 
Study CD-IA-MEDI-546-1013)
X
X
X
Assessment of Cushingoid features (For Day 1 
assessment only: if assessment of Cushingoid 
features was performed on Day 365 of 
Study CD-IA-MEDI-546-1013, then the data can 
also be used for Day 1 of this study)
X
X
Blood sample collection for: (For the Day 1 samples only [excluding lipid profile]: if Day 422 [+ 28 days] of Study CD-IA-MEDI-546-1013 occurs on the 
same day as Day 1 of this study, then the samples only need to be collected one time and will be used for both studies.)
Serum chemistry
X b
X
(Weeks 4 and 8 only)
X
X
Hematology
X b
X
(Weeks 4 and 8 only)
X
X
Lipid profile (Subjects will be required to fast for 
at least 8 hours prior to this assessment. If a 
subject has not fasted, the assessment should be 
performed under fasted conditions at the next 
visit.)
X
(Week 4 only)
X

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Table 5.1-1
Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
HBV DNA PCR TaqMan (Subjects with isolated 
hepatitis B core antibody positivity during Study 
CD-IA-MEDI-546-1013 or at any time during this 
study will be tested monthly for HBV DNA. To 
remain eligible for this study, the subject’s HBV 
DNA levels must remain undetectable as per the 
central lab [ie, < 29 IU/mL HBV DNA detected]).
X b
X
(if appropriate)
X
QFT-GIT test (TB testing, only if negative or if 
indeterminate at any visit during Study CD-IA-
MEDI-546-1013)
X b
X c
X
X
SLEDAI-2K-associated lab tests (C3, C4, CH50, 
anti-dsDNA)
X b
X
X
Immunology profile (ANA, extractable nuclear 
antigens [RNP, Sm, SSA, SSB], quantitative 
immunoglobulins)
X b
X
X
X
Pap smear in females only
X d
Predose sample Q12W-First Year: (For the Day 1 samples only: if Day 422 [+ 28 days] of Study CD-IA-MEDI-546-1013 occurs on the same day as Day 1 of 
this study, then the samples only need to be collected one time and will be used for both studies.)
PK (MEDI-546 serum concentration)
X b
X
(Weeks 12, 24, 
36, 48 only)

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Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
PD (type I IFN signature 21-gene assay)
X b
X
(Weeks 12, 24,
36, 48 only)
IM (ADA to MEDI-546)
X b
X
(Weeks 12, 24, 
36, 48 only)
Predose type I IFN signature 4-gene assay 
(diagnostic test)
X b
Predose sample Q24W (starting at Week 72) After First Year:
PK MEDI-546 serum concentration
X
X
PD (type I IFN signature 21-gene assay)
X
X
IM (ADA to MEDI-546)
X
X
Proteomics/biomarkers, 1st year Q12W (optional) 
X
X
(Weeks 12, 24 
and 48 only)
Proteomics/biomarkers, after 1st year Q24W 
(optional)
X
X
Urine sample collection: (For the Day 1 samples only: if Day 422 [+ 28 days] of Study CD-IA-MEDI-546-1013 occurs on the same day as Day 1 of this study, 
then the samples only need to be collected one time and will be used for both studies.)
Urinalysis
X b
X
X

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Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
Urine β-HCG (dipstick)
X b
X
X
X
X
X
SLEDAI-2K-associated tests: urine protein/ 
creatinine ratio
X b
X
X
Urine biomarker (optional)
X b
X
Disease Evaluations
SLEDAI-2K (For Day 1 SLEDAI-2K only: if 
Day 422 [+ 28 days] of Study CD-IA-MEDI-546-
1013 occurs on the same day as Day 1 of this 
study, then the data only need to be collected one 
time and will be used for both studies.)
X b
X
X
SLICC/ACR Damage Index
X b
X
Assess worsening and/or flare of SLE disease 
activity
X b
X
X
Assessment of AEs/SAEs/AESIs (nonserious AEs 
will only be captured during the first year of the 
subject’s participation in the study; however, 
nonserious AEs that result in interruption of 
investigational product and/or discontinuation 
from the study will be captured at any time during 
the subject’s participation in the study)
X b
X
X
X
X
X
Evaluate subject for signs and symptoms of TB 
using a TB surveillance form
X
X
X
X
X
X

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Schedule of Study Procedures for the Treatment Period
Interval
Treatment Period
Day 1
Q4W
Q12W
Q24W
Q48W
LTV
Week
0
4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 
48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 
92, 96, 100, 104, 108, 112, 116, 120, 
124, 128, 132, 136, 140, 144, 148, 152
12, 24, 36, 48, 
60, 72, 84, 96, 
108, 120, 132, 
144
24, 48, 72, 
96, 120, 
144
48, 96, 
144
156
Procedure / Visit Number
V1
V2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 
26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 
37, 38, 39
V4, 7, 10, 13, 16, 
19, 22, 25, 28, 
31, 34, 37
V7, 13, 19, 
25, 31, 37
V13, 
25, 37
V40
Investigational product administration (Q4W)
X
X
X
X
X
X
AE = adverse event; AESI = adverse event of special interest; ADA = anti-drug antibodies; ANA = antinuclear antibody; β-HCG = beta human chorionic 
gonadotropin; CH50 = 50% hemolytic complement; DNA = deoxyribonucleic acid; ds = double-stranded; ECG = electrocardiogram; HBV = hepatitis B virus; 
HIPAA = Health Insurance Portability and Accountability Act; IFN = interferon; IM = immunogenicity; LTV = Last Treatment Visit; Pap = Papanicolaou; PCR 
= polymerase chain reaction; PD = pharmacodynamic; PK = pharmacokinetic; Q4W = every 4 weeks; Q12W = every 12 weeks; Q24W = every 24 weeks; Q48W 
= every 48 weeks; QFT-GIT = QuantiFERON-TB Gold In-tube; RNP = ribonucleoprotein; SAE = serious adverse event; SF-36v2 = Short Form-36 Version 2; 
SID = subject identification; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index-2000; SLICC/ACR = 
Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; Sm = Smith; SSA = ; SSB = ; TB = tuberculosis; TBD = 
to be determined; V = visit.
a
Informed consent needs to be signed prior to using any of the Study CD-IA-MEDI-546-1013 data for this study.
b
These procedures need to be performed on the same day as investigational product administration on Day 1 or unless otherwise noted.
c
Subjects whose QFT-GIT test result is indeterminate at Day 1 or at any time during this study must be retested Q12W for the duration of the trial; subjects 
whose test result is negative at Day 1 are to be tested annually.
d
Only at Visit 37, Week 144.   

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Table 5.1-2
Schedule of Study Procedures for the 85-day Follow-up Period
Days After Last Dose
28 Days (± 7 Days)
59 Days (± 7 Days)
85 Days (± 7 Days)
Procedure / Visit Number
V41/EDV
(Safety Follow-up 
V1)
V42
(Safety Follow-up 
V2)
V43
(Safety Follow-up 
V3)
SF-36v2
X
Concomitant medications
X
X
X
Vital signs
X
X
X
ECG
X
Evaluate subject for signs and symptoms of TB using a TB surveillance form
X
X
X
Blood sample collection for:
Serum chemistry
X
X
Hematology
X
X
Lipid profile (Subjects will be required to fast for at least 8 hours prior to this assessment.)
X
SLEDAI-2K-associated lab tests (C3, C4, CH50, anti-dsDNA)
X
X
Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], quantitative 
immunoglobulins)
X
X
PK MEDI-546 serum concentration
X
X
PD (type I IFN signature 21-gene assay)
X
X
IM (ADA to MEDI-546)
X
X
Proteomics/biomarkers, after 1st year Q24W (optional)
X
X
Urine sample collection
Urinalysis
X
X
Urine β-HCG (dipstick)
X
X
X
SLEDAI-2K-associated tests: urine protein/creatinine ratio
X
X
Urine biomarker (optional)
X
X
Disease Evaluations
SLEDAI-2K
X
X
SLICC/ACR Damage Index
X

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Table 5.1-2
Schedule of Study Procedures for the 85-day Follow-up Period
Days After Last Dose
28 Days (± 7 Days)
59 Days (± 7 Days)
85 Days (± 7 Days)
Procedure / Visit Number
V41/EDV
(Safety Follow-up 
V1)
V42
(Safety Follow-up 
V2)
V43
(Safety Follow-up 
V3)
Assess worsening and/or flare of SLE disease activity
X
X
X
Assessment of AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of the subject’s participation in the study; however, nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study will be captured 
at any time during the subject’s participation in the study)
X
X
X
ADA = anti-drug antibodies; AE = adverse event; AESI = adverse event of special interest; ANA = antinuclear antibody; β-HCG = beta human chorionic 
gonadotropin; CH50 = 50% hemolytic complement; DNA = deoxyribonucleic acid; ds = double-stranded; ECG = electrocardiogram; EDV = Early 
Discontinuation Visit; IFN = interferon; IM = immunogenicity; PD = pharmacodynamic; PK = pharmacokinetic; Q24W = every 24 weeks; RNP = ribonuclear 
protein; SAE = serious adverse event; SF-36v2 = Short Form-36 Version 2; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus 
Disease Activity Index-2000; SLICC/ACR = Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; Sm = 
Smith; TB = tuberculosis; V = visit. 

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5.1.1
Pretreatment Period
Written informed consent and any locally required privacy act document authorization must 
be obtained prior to performing any protocol-specific procedures, including Day 1 eligibility 
criteria. In this OLE study, the written informed consent will explain that certain specified 
clinical data results collected in Study CD-IA-MEDI-546-1013 may be used for pretreatment 
period purposes and to determine eligibility for Study CD-IA-MEDI-546-1145.
5.1.2
Treatment Period
The visit windows during the treatment period are ± 7 days; however, in this long-term study, 
this may not always be possible; therefore, the IVRS/IWRS will be programmed to ensure 
that consecutive doses are administered more than 14 days apart, which will not be 
considered a protocol deviation.
5.1.2.1
Week 0; Day 1: First Infusion (Visit 1)
These procedures should be performed before using any of the 
Study CD-IA-MEDI-546-1013 data for this study:
1. Obtain written informed consent and appropriate privacy act document authorization (eg, 
HIPAA)
2. Assign an SID number
These procedures should be performed on the same day as investigational product 
administration on Day 1:
3. Verify eligibility criteria
4. Administer Short Form-36 Version 2 (SF-36v2; should be completed prior to any clinical 
assessments)
5. Review medical history and add any AEs/serious adverse events (SAEs)/AESIs (if 
appropriate)
6. Record concomitant medications (if appropriate)
7. Electrocardiogram (ECG; data to be used from Day 396 of Study CD-IA-MEDI-546-
1013; required at Day 1 if not done at Day 396 of Study CD-IA-MEDI-546-1013)
8. Assess for Cushingoid features (if this assessment was performed on Day 365 of Study 
CD-IA-MEDI-546-1013, then data can also be used for Day 1 of this study)
If Day 1 of this study occurs on the same day as Day 422 (+ 28 days) of 
Study CD-IA-MEDI-546-1013, then the following procedures and samples can be collected 
one time and can be utilized for both studies; if Day 1 of this study does not occur on the 

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same day as Day 422 (+ 28 days) of Study CD-IA-MEDI-546-1013, then the following 
procedures and samples should be collected at Day 1:
9. Perform physical examination (if applicable, record new findings as AEs or SAEs)
10. Measure weight
11. Collect predose blood samples
•
Serum chemistry
•
Hematology
•
Hepatitis B virus DNA polymerase chain reaction (PCR) TaqMan (subjects with 
isolated hepatitis B core antibody positivity during Study CD-IA-MEDI-546-1013 or 
at any time for the duration of this study will be tested monthly for HBV DNA. To 
remain eligible for this study, the subject’s HBV DNA levels must remain 
undetectable as per the central lab [ie, < 29 IU/mL HBV DNA detected])
•
QuantiFERON-TB Gold (QFT-GIT; TB testing, only if negative or if indeterminate at 
any visit during Study CD-IA-MEDI-546-1013)
•
Immunology profile (antinuclear antibodies [ANA], extractable nuclear antigens 
[RNP, Sm, SSA, SSB], quantitative immunoglobulins)
•
Proteomics/biomarkers (optional)
•
Systemic Lupus Erythematosus Disease Activity Index-2000 
(SLEDAI-2K)-associated lab tests (C3, C4, 50% hemolytic complement [CH50], 
anti-dsDNA)
•
Pharmacokinetics (MEDI-546 serum concentration)
•
Type I IFN signature with 4-gene assay (one-time collection only)
•
Pharmacodynamics (type I IFN signature with 21-gene assay)
•
Immunogenicity (ADA to MEDI-546)
12. Collect urine samples:
•
Urinalysis
•
Urine beta-human chorionic gonadotropin (β-HCG); dipstick (females of childbearing 
potential only, ensure result is negative)
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
•
Urine biomarker (optional)
13. Perform SLEDAI-2K
14. Perform Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index (SLICC/ACR)
15. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable 
16. Evaluate subject for signs and symptoms of TB using a TB surveillance form

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17. Take vital signs before administration of investigational product (within 15 minutes of 
the beginning of the investigational product infusion)
18. Administer investigational product
•
Take vital signs (BP, pulse, respiration, and temperature) approximately every 15 
(± 5) minutes during the infusion, immediately after completion of the infusion, 
approximately 30 (± 5) and 60 (± 5) minutes after completion of administration of 
investigational product, and every 30 (± 5) minutes thereafter or until stable and ready 
for discharge (as judged by the investigator)
19. Assess for AEs/SAEs/AESIs
5.1.2.2
Every 4 Weeks; Weeks 4 to 152: Second through Thirty-ninth Infusion 
(Visits 2 to 39)
The following procedures and assessments are to be performed Q4W starting at Week 4 
through Week 152:
1. Record concomitant medications
2. Collect predose blood samples for:
•
Serum chemistry (Weeks 4 and 8 only)
•
Hematology (Weeks 4 and 8 only)
•
Lipid profile (Week 4 only; subjects will be required to fast for at least 8 hours prior 
to this assessment. If a subject has not fasted, the assessment should be performed 
under fasted conditions at the next visit)
•
Hepatitis B virus DNA PCR TaqMan (if appropriate; Subjects with isolated hepatitis 
B core antibody positivity during Study CD-IA-MEDI-546-1013 or at any time for 
the duration of this study will be tested monthly for HBV DNA. To remain eligible 
for this study, the subject’s HBV DNA levels must remain undetectable as per the 
central lab [ie, < 29 IU/mL HBV DNA detected])
3. Collect predose urine sample for:
•
Urine β-HCG (dipstick; females of childbearing potential only, ensure result is 
negative)
4. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable
5. Evaluate subject for signs and symptoms of TB using a TB surveillance form
6. Take vital signs before administration of investigational product (within 15 minutes of 
the beginning of the investigational product infusion)
7. Administer investigational product
•
Take vital signs (BP, pulse, respiration, and temperature) approximately every 15 
(± 5) minutes during the infusion, immediately after completion of the infusion, 
approximately 30 (± 5) and 60 (± 5) minutes after completion of administration of 

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investigational product, and every 30 (± 5) minutes thereafter or until stable and ready 
for discharge (as judged by the investigator)
8. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of the subject’s participation in the study; however, nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study will be 
captured at any time during the subject’s participation in the study)
5.1.2.3
Every 12 Weeks; Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144 
(Visits 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, and 37)
In addition to procedures and assessments performed Q4W, the following are to be 
performed every 12 weeks (Q12W):
1. Collect predose blood samples for:
•
Serum chemistry
•
Hematology
•
QuantiFERON-TB Gold (QFT-GIT; TB testing, only if indeterminate at any visit 
during Study CD-IA-MEDI-546-1013)
•
SLEDAI-2K-associated lab tests (C3, C4, CH50, anti-dsDNA)
•
Pharmacokinetics (MEDI-546 serum concentration; Weeks 12, 24, 36 and 48 only)
•
Pharmacodynamics (type I IFN signature with 21-gene assay; Weeks 12, 24, 36 and 
48 only)
•
Immunogenicity (ADA to MEDI-546; Weeks 12, 24, 36 and 48 only)
•
Proteomics/biomarkers (Weeks 12, 24 and 48 only; optional)
2. Collect urine sample for:
•
Urinalysis
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
•
Urine biomarker (optional)
3. Perform SLEDAI-2K
5.1.2.4
Every 24 Weeks; Weeks 24, 48, 72, 96, 120 and 144 (Visits 7, 13, 19, 25, 31, 
and 37)
1. Administer SF-36v2 (should be completed prior to any clinical assessments)
2. Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], 
quantitative immunoglobulins)
3. Perform SLICC/ACR Damage Index

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In addition to procedures and assessments performed Q4W, the following are to be 
performed every 24 Weeks (Q24W) starting at Week 72:
4. Collect predose blood samples for:
•
Pharmacokinetics (MEDI-546 serum concentration) 
•
Pharmacodynamics (type I IFN signature with 21-gene assay)
•
Immunogenicity (ADA to MEDI-546)
•
Proteomics/biomarkers (optional)
5.1.2.5
Every 48 Weeks; Weeks 48, 96, and 144 (Visits 13, 25, and 37)
In addition to procedures and assessments performed Q4W, the following are to be 
performed every 48 weeks (Q48W) starting at Week 48:
1. Record weight
2. Assess for Cushingoid features
3. Perform Papanicolaou (Pap) smear examination in females only (only at Visit 37, 
Week 144)
4. Perform ECG
5. Collect blood samples for:
•
Lipid profile (Subjects will be required to fast for at least 8 hours prior to this 
assessment. If a subject has not fasted, the assessment should be performed under 
fasted conditions at the next visit)
•
Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], 
quantitative immunoglobulins)
5.1.2.6
Week 156; Last Treatment Visit (Visit 40)
1. Administer SF-36v2 (should be completed prior to any clinical assessments)
2. Perform physical examination
3. Perform ECG
4. Take vital signs (within 15 minutes of the beginning of the investigational product 
infusion)
5. Record concomitant medications
6. Collect predose blood samples for:
•
Serum chemistry
•
Hematology
•
Hepatitis B virus DNA PCR TaqMan (Subjects with isolated hepatitis B core 
antibody positivity during Study CD-IA-MEDI-546-1013 or at any time for the 

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duration of this study will be tested monthly for HBV DNA. To remain eligible for 
this study, the subject’s HBV DNA levels must remain undetectable as per the central 
lab [ie < 29 IU/mL HBV DNA detected])
•
QFT-GIT test (only if negative or if indeterminate at any visit during Study CD-IA-
MEDI-546-1013)
•
SLEDAI-2K-associated lab tests (C3, C4, CH50, anti-dsDNA)
•
Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], 
quantitative immunoglobulins)
•
Pharmacokinetics (MEDI-546 serum concentration)
•
Pharmacodynamics (type I IFN signature with 21-gene assay)
•
Immunogenicity (ADA to MEDI-546)
•
Proteomics/biomarkers (optional)
7. Collect urine sample for:
•
Urinalysis
•
Urine β-HCG; dipstick (females of childbearing potential only, ensure result is 
negative)
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
8. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable
9. Perform SLEDAI-2K
10. Evaluate subject for signs and symptoms of TB using a TB surveillance form
11. Administer investigational product
•
Take vital signs (BP, pulse, respiration, and temperature) approximately every 
15 (± 5) minutes during the infusion, immediately after completion of the infusion, 
approximately 30 (± 5) and 60 (± 5) minutes after completion of administration of 
investigational product, and every 30 (± 5) minutes thereafter or until stable and ready 
for discharge (as judged by the investigator).
12. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of the subject’s participation in the study; however, nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study will be 
captured at any time during the subject’s participation in the study)
5.1.3
Follow-up Period
5.1.3.1
28 Days after the Last Dose (+/- 7 Days): First Safety Follow-up Visit or 
Early Discontinuation Visit (Visit 41)
1. Record concomitant medications
2. Take vital signs
3. Collect blood samples for:

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•
Serum chemistry
•
Hematology
•
SLEDAI-2K-associated lab tests (C3, C4, CH50 complement, anti-dsDNA)
•
Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], 
quantitative immunoglobulins)
•
Pharmacokinetics (MEDI-546 serum concentration)
•
Pharmacodynamics (type I IFN signature with 21-gene assay)
•
Immunogenicity (ADA to MEDI-546)
•
Proteomics/biomarkers (optional)
4. Collect urine sample for:
•
Urinalysis
•
Urine β-HCG (dipstick; females of childbearing potential only, ensure result is 
negative)
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
•
Urine biomarker (optional)
5. Perform SLEDAI-2K
6. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable.
7. Evaluate subject for signs and symptoms of TB using a TB surveillance form
8. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of subject’s participation in the study; however, nonserious AEs that result in interruption 
of investigational product and/or discontinuation from the study will be captured at any 
time during the subject’s participation in the study)
5.1.3.2
59 Days after the Last Dose (+/- 7 Days): Second Safety Follow-up Visit 
(Visit 42)
1. Record concomitant medications
2. Take vital signs
3. Collect urine sample for:
•
Urine β-HCG (dipstick, females of childbearing potential only, ensure result is 
negative)
4. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable
5. Evaluate subject for signs and symptoms of TB using a TB surveillance form
6. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of subject’s participation in the study; however, nonserious AEs that result in interruption 

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of investigational product and/or discontinuation from the study will be captured at any 
time during the subject’s participation in the study)
5.1.3.3
85 Days after the Last Dose (+/- 7 Days): Third Safety Follow-up Visit (Visit 
43)
1. Administer SF-36v2 (should be completed prior to any clinical assessments) 
2. Record concomitant medications
3. Take vital signs
4. Perform ECG
5. Collect blood samples for:
•
Serum chemistry
•
Hematology
•
Lipid profile
•
SLEDAI-2K-associated lab tests (C3, C4, CH50, anti-dsDNA)
•
Immunology profile (ANA, extractable nuclear antigens [RNP, Sm, SSA, SSB], 
quantitative immunoglobulins) 
•
Pharmacokinetics (MEDI-546 serum concentration)
•
Pharmacodynamics (type I IFN signature with 21-gene assay)
•
Immunogenicity (ADA to MEDI-546)
•
Proteomics/biomarkers (optional)
6. Collect urine sample for:
•
Urinalysis
•
Urine β-HCG (dipstick; females of childbearing potential only, ensure result is 
negative)
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
•
Urine biomarker (optional)
7. Perform SLEDAI-2K
8. Perform SLICC/ACR Damage Index
9. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable
10. Evaluate subject for signs and symptoms of TB using a TB surveillance form
11. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of the subject’s participation in the study; however, nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study will be 
captured at any time during the subject’s participation in the study)

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5.1.4
Unscheduled Visit
1. Perform physical examination (if applicable, record new findings as AEs or SAEs)
2. Record concomitant medications
3. Take vital signs
4. Collect blood samples for:
•
Serum chemistry
•
Hematology
•
Lipid profile (Subjects will be required to fast for at least 8 hours prior to this 
assessment. If a subject has not fasted, the assessment should be performed under 
fasted conditions at the next visit)
•
SLEDAI-2K-associated lab tests (C3, C4, CH50, anti-dsDNA)
•
Pharmacokinetics (MEDI-546 serum concentration)
•
Immunogenicity (ADA to MEDI-546)
5. Collect urine sample for:
•
Urinalysis
•
Urine β-HCG (if appropriate; dipstick; females of childbearing potential only, ensure 
result is negative)
•
SLEDAI-2K-associated lab tests: urine protein/creatinine ratio
•
Urine biomarker (optional)
6. Perform SLEDAI-2K
7. Perform SLICC/ACR Damage Index
8. Assess worsening and/or flare of SLE disease activity using SLE Increase in Disease 
Activity CRF and complete for SLE related AEs that are not serious, if applicable
9. Evaluate subject for signs and symptoms of TB using a TB surveillance form
10. Assess for AEs/SAEs/AESIs (nonserious AEs will only be captured during the first year 
of the subject’s participation in the study; however, nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study will be 
captured at any time during the subject’s participation in the study)
5.2
Description of Study Procedures
A Laboratory Manual will be provided to the sites that specifies the procedures for 
collection, processing, storage, and shipment of samples, as well as laboratory contact 
information, specific to this clinical research study. 

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5.2.1
Medical History 
A complete medical history by body system will be documented for each subject and will 
include any viral reactivation events as well as the subject’s full SLE and non-SLE history. 
The SLE history includes all previous manifestations of SLE including SLE medication 
history. Only new events or worsening of previous events that occur between Day 422 of 
Study CD-IA-MEDI-546-1013 and prior to signing of informed consent of 
Study CD-IA-MEDI-546-1145 should be recorded in the Medical History CRF. On Day 1, 
the medical history will be reviewed and any changes will be documented, if applicable.  
5.2.2
Physical Examination, ECG, Weight, Cushingoid Features, and Pap 
Smear
A complete physical examination will be performed at intervals designated in the schedule of 
study procedures and include the following examinations: head, eyes, ears, nose and throat, 
lungs, heart, abdomen, joints, muscles and soft tissues, neurologic system, skin, and lymph 
nodes; body weight will be captured according to the Schedule of Study Procedures
(Table 5.1-1). Medically significant changes from Day 1 physical examination will be 
recorded as AEs.
A computerized 12-lead ECG will be performed according to the Schedule of Study 
Procedures (Table 5.1-1 and Table 5.1-2). The investigator or qualified designee will review 
and indicate if the ECG is normal or abnormal. Any medically significant changes from the 
Study CD-IA-MEDI-546-1013 Day 396 ECG will be recorded as an AE.
Subjects will be assessed for Cushingoid features at Day 1 (if appropriate) and at Q48W. 
Features, such as moon face, buffalo hump, purple or violaceous striae, central obesity, 
hirsutism, acne, easy bruising, and fragile skin, will be captured separately to evaluate 
whether resolution of same can occur over time with OCS reduction.
A Pap smear will be performed in females only at Week 144 (Visit 37). Subjects with an 
abnormal Pap smear result of high-grade squamous intraepithelial lesion (CIN-3/CIN III 
carcinoma in situ) or endocervical adenocarcinoma in situ will discontinue investigational 
product. In the event a female subject discontinues prematurely, a repeat Pap smear must be 
performed as part of the Early Discontinuation Visit.
5.2.3
Vital Signs……….
Vital signs (temperature, BP, pulse rate, and respiratory rate) will be obtained at each study 
visit. On infusion days, subjects will be monitored for vital signs taken in a sitting position at 
the following times:

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•
Shortly before the IV infusion (within 15 minutes of the beginning of the infusion)
•
Every 15 (± 5) minutes during the infusion
•
Immediately after completion of MEDI-546 infusion, including post-dose saline flush 
(within 15 minutes [± 5] after completion of MEDI-546 infusion)
•
At 30 (± 5) and 60 (± 5) minutes after completion of MEDI-546 infusion, and every 
30 (± 5) minutes thereafter or until stable and ready for discharge (as judged by the 
investigator).
If anaphylaxis, a hypersensitivity reaction, or an infusion-related reaction occurs during the 
IV infusion, vital signs will be taken more frequently, based on investigator judgment and as 
warranted by the severity of the reaction (see Section 4.5.6.1). 
5.2.4
Tuberculosis Testing
A QFT-GIT will be performed at Day 1 for all subjects who tested negative or indeterminate 
at Day 337 in Study CD-IA-MEDI-546-1013. If a subject missed being tested at Day 1, a 
QFT-GIT should be performed at the next scheduled visit and then per protocol. An annual 
TB screen is not required for subjects who have tested positive and have been treated for 
latent TB in Study CD-IA-MEDI-546-1013.
Upon approval of Study CD-IA-MEDI-546-1145 Protocol Amendment 4, any subject whose 
last QFT-GIT result was negative or indeterminate (whether in this study or in 
Study CD-IA-MEDI-546-1013) and has not had a QFT-GIT performed in the previous year 
(from local approval date) should have it performed at the next scheduled visit and then per 
protocol.
All subjects must be evaluated by the physician for clinical signs/symptoms of active TB 
prior to each scheduled infusion visit using a TB surveillance form. If the evaluation raises 
suspicion that a subject may have a new or reactivated TB, an immediate and thorough 
investigation should be undertaken, including where possible, consultation with experts 
specializing in TB. Please note that TB in immunocompromised subjects may present as 
disseminated disease or with extrapulmonary features and should be referred for appropriate 
treatment.
5.2.4.1
Indeterminate Results
A newly indeterminate QFT-GIT test at Day 1 for subjects who had a negative result in 
Study CD-IA-MEDI-546-1013 must be repeated as soon as possible at least one time by the 
central laboratory. If the result remains indeterminate, a chest radiograph shows no evidence 
of active TB, there are no signs or symptoms of active TB, no recent contact with anyone 

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with active TB, and there is no history of latent (unless diagnosed with documentation of 
completion of appropriate treatment) or active TB, the subject may be enrolled in 
Study CD-IA-MEDI-546-1145. The subject will have additional QFT-GIT testing performed 
Q12W if the result remains indeterminate. If the subject has been in contact with anyone with 
active TB, or if the subject shows signs or symptoms of active TB, the subject should be 
referred to a physician specializing in TB to undergo additional evaluation prior to 
randomization and, if warranted, receive appropriate treatment for latent TB at or before the 
first administration of investigational product.
A QFT-GIT test will be performed at Day 1 for subjects whose results in 
Study CD-IA-MEDI-546-1013 were indeterminate and remain indeterminate in this study. If 
the result remains indeterminate, the chest radiograph from Study CD-IA-MEDI-546-1013 
shows no evidence of active TB, there are no signs or symptoms of active TB, there has been 
no recent contact with anyone with active TB, and there is no history of latent (unless 
diagnosed with documentation of completion of appropriate treatment) or active TB, the 
subject may be enrolled in Study CD-IA-MEDI-546-1145. The subject will have additional 
QFT-GIT testing performed Q12W if the result remains indeterminate. If the subject has 
been in contact with anyone with active TB, or if the subject shows signs or symptoms of 
active TB, the subject should be referred to a physician specializing in TB to undergo 
additional evaluation prior to randomization and, if warranted, receive appropriate treatment 
for latent TB at or before the first administration of investigational product.
5.2.4.2
Positive Results
If, during the study, a subject is determined to have a positive QFT-GIT test result, the local 
country guidelines should be consulted for acceptable anti-TB treatment regimens. If no local 
guidelines exist for immunocompromised individuals, then USA guidelines must be 
followed:
To aid in the early detection of new or reactivated TB, subjects will be evaluated for signs 
and symptoms of TB at every visit (prior to drug infusion) using a TB surveillance form. If 
the evaluation raises suspicion that a subject may have a new or reactivated TB infection, an 
immediate and thorough investigation should be undertaken, including where possible, 
consultation with experts specializing in TB. Please note that TB in immunocompromised 
subjects may present as disseminated disease or with extrapulmonary features and should be 
referred for appropriate treatment.

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A subject must be withdrawn from study treatment if they are diagnosed with active TB, if 
they prematurely discontinue treatment for latent TB, or if they are noncompliant with latent 
TB treatment.
5.2.5
Clinical Laboratory Tests
Clinical laboratory safety tests will be performed in a central clinical laboratory. Urine 
pregnancy tests may be performed at the site using a licensed test (dipstick). Abnormal 
laboratory results should be repeated as soon as possible (preferably within 24 to 48 hours). 
Subjects will be required to fast for at least 8 hours prior to the assessment of lipid profile 
(high-density lipoprotein [HDL], low-density lipoprotein [LDL], cholesterol, and 
triglycerides) according to the Schedule of Study Procedures (Table 5.1-1 and Table 5.1-2).
The following clinical laboratory tests will be performed (see Table 5.1-1 and Table 5.1-2 for 
the schedule of tests): 
Serum Chemistry
•
Calcium
•
Gamma glutamyl transferase (GGT)
•
Chloride
•
Blood urea nitrogen (BUN)
•
Potassium
•
Creatinine
•
Sodium
•
Total bilirubin (reflexively fractionated if elevated)
•
Aspartate transaminase (AST)
•
Glucose
•
Alanine transaminase (ALT)
•
Albumin
•
Alkaline phosphatase (ALP)
•
Creatine kinase (CK)
Note for serum chemistries: Tests for AST, ALT, ALP, and total bilirubin must be conducted concurrently 
and assessed concurrently. 
Hematology
•
White blood cell (WBC) count with differential
•
Platelet count
•
Red blood cell (RBC) count
•
Mean corpuscular volume (MCV)
•
Hematocrit
•
Mean corpuscular hemoglobin concentration 
(MCHC)
•
Hemoglobin

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Urinalysis
•
Color
•
Glucose
•
Appearance
•
Ketones
•
Specific gravity
•
Blood
•
pH
•
Bilirubin
•
Protein
•
Microscopy including WBC/high power field (HPF), RBC/HPF
Pregnancy Test (females of childbearing potential only)
•
Urine human chorionic gonadotropin (HCG)
Note: Any female subject who is postmenopausal based on documented results from the serum 
follicle-stimulating hormone test will not require urine HCG tests in this study. Any female subject who feels 
that they have had a change in status to postmenopausal at any point during this study can request a serum 
follicle-stimulating hormone test. If the results show that the subject is postmenopausal, then the subject will not 
require any further urine HCG tests.
Additional Tests
•
Lipid profile (HDL, LDL, cholesterol, triglycerides, direct LDL when triglycerides are > 400 mg/dL) 
requiring a fasting blood sample of at least 8 hours
•
Immunology profile: ANA, extractable nuclear antigen (RNP, Sm, SSA, SSB), quantitative 
immunoglobulins
•
Isolated HBc with HBV DNA detected by reflex testing at any time during Study CD-IA-MEDI-546-1013 
or at any time for the duration of this study. To remain eligible for this study, the subject’s HBV DNA 
levels should remain undetectable as per the central lab (ie, < 29 IU/mL HBV DNA detected).
SLEDAI-2K-related Laboratory Tests
•
C3
•
Anti-dsDNA
•
C4
•
Urine protein/creatinine ratio
•
CH50 complement
5.2.6
Optional Urine Biomarker Testing
Urine will be collected for exploratory studies during visits specified in the Schedule of 
Study Procedures (see Table 5.1-1 and Table 5.1-2). These studies will include but are not 
limited to SLE biomarker testing and may serve as an ideal source for biomarkers of renal 
diseases. Urine for exploratory studies will only be collected from subjects who provide 
written consent for this procedure. A subject may withdraw their consent to have their urine 
samples used for exploratory studies at any time. Urine for exploratory studies will be 
analyzed at a central laboratory using established methods.

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5.2.7
Pharmacokinetic Evaluation and Methods
Details for collection, aliquoting, storage, and shipment of serum samples for PK evaluations 
are presented in a separate Laboratory Manual. All PK laboratory evaluations will be 
performed by MedImmune or a contract laboratory. MEDI-546 serum concentrations will be 
measured by electrochemiluminescent (ECL) immunoassay at multiple time points as 
indicated in the Schedule of Study Procedures (Table 5.1-1 and Table 5.1-2). Sera that are 
collected may be used for additional PK analyses.
A subject should not have predose PK samples redrawn after administration of MEDI-546. 
5.2.8
Immunogenicity Evaluation and Methods
Details for collection, aliquoting, storage, and shipment of serum samples for IM evaluations 
are presented in a separate Laboratory Manual. All IM laboratory evaluations will be 
performed by MedImmune or a contract laboratory. MEDI-546 antibody detection will be 
measured using an ECL bridging immunoassay at multiple time points as indicated in the 
Schedule of Study Procedures (Table 5.1-1 and Table 5.1-2). Sera that are collected may be 
used for additional MEDI-546 antibody assays.
5.2.9
Optional Proteomics/Biomarkers
Serum will be collected for exploratory correlative studies during visits specified in the 
Schedule of Study Procedures (see Table 5.1-1 and Table 5.1-2). These studies will include 
the analyses of protein analytes associated with inflammatory pathways and SLE. Serum for 
proteomics/biomarkers will only be collected from subjects who provide written consent for 
this procedure. A subject may withdraw their consent to have their serum samples used for 
exploratory correlative studies at any time.
 
 
 
 
 
 
 
 
 
 

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5.2.11
Pharmacodynamic Assay using 21-gene Assay
 
 
 
 
5.2.12
Disease Evaluation and Methods
5.2.12.1
Systemic Lupus Erythematosus Disease Activity Index-2000
The SLEDAI-2K index consists of a list of organ manifestations, each with a definition. A 
certified investigator or designated physician will complete the SLEDAI-2K assessment and 
decide whether each manifestation is “present” or “absent” in the last 4 weeks. The 
assessment also includes the collection of whole blood for analysis of CH50, C3, C4, and 
anti-dsDNA.
The SLEDAI-2K assessment consists of 24 SLE-related items. It is a weighted instrument, in 
which descriptors are multiplied by a particular organ’s “weight.” For example, renal 
descriptors are multiplied by 4 and central nervous descriptors by 8 and these weighted organ 
manifestations are totaled into the final score. The SLEDAI-2K score range is 0-105 points 
with 0 indicating inactive disease. The SLEDAI-2K scores are valid, reliable, and sensitive 
clinical assessments of SLE disease activity. The SLEDAI-2K calculated using a timeframe 
of 30 days prior to a visit for clinical and laboratory values has been shown to be similar to 
the SLEDAI-2K with a 10-day window (Touma et al, 2010). A timeframe of 28 days will be 
used in this study.
The “Clinical” SLEDAI-2K score is the SLEDAI-2K assessment score without the inclusion 
of points attributable to any urine or laboratory results including immunologic measures. Its 
use may permit earlier clinical decisions to be made without waiting for immunologic 
measures (including anti-dsDNA and C3, C4 and CH50 complement levels). However, in 
any circumstance where the “Clinical” SLEDAI-2K score is used, sites must subsequently 

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update the SLEDAI-2K assessment when laboratory data become available so that the full 
SLEDAI-2K score is made available to the sponsor.
Anyone assessing the SLEDAI-2K at the sites must have had appropriate training prior to 
conducting the SLEDAI-2K.
5.2.12.2
Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index
The Systemic Lupus International Collaborating Clinics/American College of Rheumatology 
(SLICC/ACR) Damage Index was developed to assess irreversible damage in SLE patients 
independently of its cause (ie, SLE activity, therapy, comorbidities), but occurring after 
disease onset. Damage (ie, irreversible impairment since onset of SLE) is usually defined as a 
clinical feature that must be continuously present for at least 6 months to score. In addition, 
some irreversible events such as myocardial infarction or a cerebrovascular accident score as 
damage on their occurrence. Damage is defined for 12 organ systems: peripheral vascular (0-
5); ocular (0-2); neuropsychiatric (0-6); renal (0-3); pulmonary (0-5); cardiovascular (0-6); 
gastrointestinal (0-6); musculoskeletal (0-7); skin (0-3); endocrine (diabetes; 0-1); gonadal 
(0-1); and malignancies (0-2). Damage over time can be stable or increase, theoretically to a 
maximum of 47 points (Stoll et al, 2004). 
5.2.13
Adverse Events of Special Interest
The investigator is required to assess for AESIs. The investigator should use medical or 
scientific judgment in deciding whether the identified AESI is serious or nonserious. An 
AESI that meets one of the seriousness outcomes listed in Section 6.1.2 will be treated as an 
SAE for the purposes of follow-up responsibility and safety reporting. A nonserious AESI 
will be treated as an AE.
5.2.14
SLE Flares and Increase in SLE Disease Activity
The worsening and/or flare of SLE disease activity will be captured in the disease activity 
assessments or other study-specific CRFs (ie, SLE Increase in Disease Activity CRF), and 
not recorded as an AE, unless it meets the definition for an SAE or AESI. The SLE Increase 
in Disease Activity CRF does not need to be completed for SAEs of SLE Increase in Disease 
Activity. 

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5.2.15
Patient-reported Outcomes
5.2.15.1
Short Form-36 Version 2
The SF-36v2 is a general HRQL instrument that consists of 36 items (see Appendix 7). 
These 36 items yield 8 domains of functional health and well-being. These domains include 
Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social 
Functioning, Role Emotional and Mental Health. The 8 domains can further be combined to 
provide 2 summary measures: 1) Physical Component Summary (PCS); and 2) Mental 
Component Summary (MCS). It is a validated instrument for measuring a person’s general 
health status over the past 4 weeks (Ware et al, 2008). The range of SF-36v2 score and scales 
is 0-100, with a higher score indicating better HRQL. Scale scores and the 2 summary 
measures are standardized to have a mean score of 50 and a standard deviation of 10. 
The SF-36v2 should be completed prior to any clinical assessments.
5.2.16
Estimate of Volume of Blood to Be Collected
An estimate of blood volumes for each visit during the study is provided in Table 5.2.16-1.
Table 5.2.16-1
Estimated Volume of Blood to be Collected per Visit
Visit/Week
Estimated Blood Volume (mL)
Visit 1/Week 0
72.5 mL
Visit 2/Week 4
4.5 mL
Visit 3/Week 8
4.5 mL
Visit 4/Week 12
28.5 mL
Visit 7/Week 24
29.5 mL
Visit 10/Week 36
22 mL
Visit 13/Week 48
32.5 mL
Visit 16/Week 60
7 mL
Visit 19/Week 72
32 mL
Visit 22/Week 84
9.5 mL
Visit 25/Week 96
32.5 mL
Visit 28/Week 108
7 mL
Visit 31/Week 120
32 mL
Visit 34/Week 132
9.5 mL
Visit 37/Week 144
29.5 mL
Visit 40/LTV Week 156
40 mL
Visit 41/EDV (Safety Follow-up Visit 1) 
29.5 mL
Visit 43 (Safety Follow-up Visit 3)
29.5 mL
Unscheduled/Optional Visit
44.5 mL

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Table 5.2.16-1
Estimated Volume of Blood to be Collected per Visit
Visit/Week
Estimated Blood Volume (mL)
Total Volume
496.5 mL
EDV = Early Discontinuation Visit; LTV = Last Treatment Visit.
6
ASSESSMENT OF SAFETY
6.1
Safety Parameters
6.1.1
Adverse Events
The International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice 
(GCP) E6(R1) defines an AE as:
•
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product.
An AE includes but is not limited to any clinically significant worsening of a subject’s 
pre-existing condition. An abnormal laboratory finding (including ECG finding) that requires 
an action or intervention by the investigator, or a finding judged by the investigator to 
represent a change beyond the range of normal physiologic fluctuation, should be reported as 
an AE. The worsening and/or flare of SLE disease activity will be captured in the disease 
activity assessments or other study-specific CRFs (ie, SLE Increase in Disease Activity 
CRF), and not recorded as an AE, unless it meets the definition for an SAE or AESI. If 
clinical sequelae are associated with a laboratory abnormality, the diagnosis or medical 
condition should be reported (eg, renal failure, hematuria) not the laboratory abnormality 
(eg, elevated creatinine, urine RBC increased). Abnormal laboratory values that are not, in 
the investigator’s opinion, medically significant and do not require intervention should not be 
reported as AEs.
Adverse events may be treatment emergent (ie, occurring after initial receipt of 
investigational product) or nontreatment emergent. A nontreatment-emergent AE is any new 
sign or symptom, disease, or other untoward medical event that begins after written informed 
consent has been obtained but before the subject has received investigational product. 

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Elective treatment or surgery or preplanned treatment or surgery (that was scheduled prior to 
the subject being enrolled into the study) for a documented pre-existing condition that did not 
worsen from baseline is not considered an AE (serious or nonserious). An untoward medical 
event occurring during the prescheduled elective procedure or routinely scheduled treatment 
should be recorded as an AE or SAE.
Nonserious AEs will only be captured during the first year of subject’s participation in the 
study; however, nonserious AEs that result in interruption of investigational product and/or 
discontinuation from the study will be captured at any time during the subject’s participation 
in the study. Serious adverse events and AESIs will be captured throughout the entire study 
participation.
6.1.2
Serious Adverse Events
An SAE is any AE that:
•
Results in death
•
Is immediately life-threatening
This term refers to an event in which the subject was at risk of death at the time of the event; 
it does not refer to an event that may have led to death.
•
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the subject has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in an outpatient setting. 
•
Results in persistent or significant disability/incapacity
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions.
•
Is a congenital anomaly/birth defect in offspring of the subject
•
Is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above
Medical or scientific judgment should be exercised in deciding whether expedited reporting 
is appropriate in this situation. Examples of medically important events are intensive 

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treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, or 
convulsions that do not result in hospitalizations; or development of drug dependency or drug 
abuse. 
6.1.3
Adverse Events of Special Interest
An AESI is one of scientific and medical interest specific to understanding of the 
investigational product and requires close monitoring. An AESI may be serious or 
nonserious. The rapid reporting of AESIs allows ongoing analysis of these events in order to 
characterize and understand them in association with the use of this investigational product.
Both serious and nonserious AESIs will be captured at any time during the subject’s 
participation in the study.
6.1.3.1
Hepatic Function Abnormality
Adverse events of hepatic function abnormality of special interest to the sponsor are defined 
as any increase in ALT or AST to greater than 3 × upper limit of normal (ULN) and
concurrent increase in bilirubin to greater than 2 × ULN. Concurrent findings are those that 
derive from a single blood draw or from separate blood draws taken within 8 days of each 
other. In the event of hepatic function abnormality where the etiology is unknown, timely 
follow-up investigations and inquiries should be initiated by the investigational site, based on 
medical judgment, to make an informed decision regarding the etiology of the event.
If ALT or AST is greater than 3 × ULN, please refer to Guidance for Abnormal Liver 
Function Tests Management in Appendix 8.
6.1.3.2
New or Reactivated and Latent TB Infection  
For the purposes of this study, new or reactivated TB infection is defined as any new or 
reactivated clinical pulmonary or extra-pulmonary infection with the Mycobacterium 
tuberculosis bacterium, with associated clinical signs/symptoms and/or other evidence 
(radiologic, clinical laboratory, microbiologic) of active infection. Latent TB infection in this 
study is defined as a new positive and confirmed QFT-GIT test result with no evidence of 
active TB.  
6.1.3.3
Herpes Zoster Infection
For the purposes of this study, herpes zoster infection is defined as an infection caused by 
reactivation of the varicella zoster virus from a previous chickenpox infection, with typical 
manifestations of painful herpetiform vesicles on an erythematous base. The manifestations 

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are usually preceded by radicular pain and confined to cutaneous surfaces innervated by one 
sensory nerve, but sometimes involve multiple dermatomes, or can be generalized and/or can 
involve non-cutaneous organs. 
6.1.3.4
Malignancy
For the purposes of this study, malignancy is defined as a malignant neoplasm of any type, 
including solid tumors and hematologic malignancies, typically characterized by cells with 
abnormal features, uncontrolled rapid growth with invasive and/or metastatic tendencies and 
diagnosed based on standard pathologic and clinical assessments. The nature, extent, and 
type (subtype) of tumor should be characterized, as clinically appropriate, for evaluation and 
treatment. This does not include benign neoplasms. 
6.1.3.5
Infusion, Hypersensitivity, and Anaphylactic Reactions
Infusion Reactions
For the purposes of this study, an infusion reaction is defined as any other reaction occurring 
during infusion of investigational product or felt to be temporally related to the infusion 
within 24 hours of investigational product administration (see Section 4.5.6.1).
Hypersensitivity Reactions
For the purposes of this study, a hypersensitivity reaction is defined as an acute onset of an 
illness with involvement of the skin, mucosal tissue, or both during infusion of 
investigational product (but does not meet the definition of anaphylaxis as described in 
Section 4.5.6.1).
Anaphylactic Reactions
Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly 
after contact with an allergy-causing substance, such as investigational product.
For the purposes of this study, MedImmune is providing the following definition as a simple 
and rapid means to make the diagnosis of anaphylaxis during infusion with investigational 
product. This definition was a product of a symposium convened by the National Institute of 
Allergy and Infectious Diseases and Food Allergy and Anaphylaxis Network 
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In adults, anaphylaxis is highly likely when any one of the following 3 criteria is fulfilled:
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips, tongue and/or uvula) 
AND AT LEAST ONE OF THE FOLLOWING:
•
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia).
•
Reduced BP (see #3 below for definition) or associated symptoms of end-organ 
dysfunction (eg, hypotonia [collapse], syncope, incontinence).
Two or more of the following that occur rapidly after exposure to a likely allergen for that 
subject (minutes to several hours):
•
Involvement of the skin-mucosal tissue (eg, generalized hives, itch, flush, swollen 
lips, tongue and/or uvula).
•
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia).
•
Reduced BP (see #3 below for definition) or associated symptoms (eg, hypotonia 
[collapse], syncope, incontinence).
•
Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting).
Reduced BP after exposure to known allergen for that subject (minutes to several hours); for 
adults a systolic BP of less than 90 mm Hg or greater than 30% decrease from that subject’s 
baseline BP (taken at or immediately prior to start of the infusion), whichever BP is lower.
See Section 4.5.6.1 for infusion related event categorization and accompanying table for 
suggested guidelines for treatment.
6.1.3.6
Vasculitis
For the purposes of this study, vasculitis is defined as an inflammatory disorder involving the 
vasculature and characterized by typical clinical signs/symptoms (along with clinical 
laboratory testing, or other diagnostic testing and pathology findings) consistent with the 
diagnosis. Underlying causes should be identified, such as systemic inflammatory 
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6.2
Assessment of Safety Parameters
6.2.1
Assessment of Severity
Assessment of severity is one of the responsibilities of the investigator in the evaluation of 
AEs and SAEs. The determination of severity should be made by the investigator based upon 
medical judgment and the severity categories of Grade 1 to 5 as defined below. 
Grade 1 (mild)
An event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not 
generally interfere with usual activities of daily living.
Grade 2 (moderate)
An event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual 
activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject.
Grade 3 (severe)
An event that requires intensive therapeutic intervention. The 
event interrupts usual activities of daily living, or significantly 
affects the clinical status of the subject.
Grade 4 (life threatening)
An event, and/or its immediate sequelae, that is associated with 
an imminent risk of death 
Grade 5 (fatal)
Death (loss of life) as a result of an event.
It is important to distinguish between serious criteria and severity of an AE. Severity is a 
measure of intensity whereas seriousness is defined by the criteria in Section 6.1.2. A 
Grade 3 AE need not necessarily be considered an SAE. For example, a Grade 3 headache 
that persists for several hours may not meet the regulatory definition of an SAE and would be 
considered a nonserious event, whereas a Grade 2 seizure resulting in a hospital admission 
would be considered an SAE.
6.2.2
Assessment of Relationship
6.2.2.1
Relationship to Investigational Product
The investigator is required to provide an assessment of relationship of AEs and SAEs to the 
investigational product.
An event will be considered “not related” to use of the investigational product if any of the 
following tests are met:

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•
An unreasonable temporal relationship between administration of the investigational 
product and the onset of the event (eg, the event occurred either before, or too long after, 
administration of the investigational product for it to be considered product-related)
•
A causal relationship between the investigational product and the event is biologically 
implausible (eg, death as a passenger in an automobile accident)
•
A clearly more likely alternative explanation for the event is present (eg, typical adverse 
reaction to a concomitant drug and/or typical disease-related event)
Individual AE/SAE reports will be considered “related” to use of the investigational product 
if the “not related” criteria are not met. 
“Related” implies that the event is considered to be “associated with the use of the drug” 
meaning that there is “a reasonable possibility” that the event may have been caused by the 
product under investigation (ie, there are facts, evidence, or arguments to suggest possible 
causation).
6.2.2.2
Relationship to Protocol Procedures
The investigator is also required to provide an assessment of relationship of SAEs to protocol 
procedures on the SAE Report Form. This includes nontreatment-emergent SAEs (ie, SAEs 
that occur prior to the administration of investigational product) as well as treatment-
emergent SAEs. A protocol-related SAE may occur as a result of a procedure or intervention 
required during the study (eg, blood collection, washout of an existing medication). The 
following guidelines should be used by investigators to assess the relationship of SAEs to the 
protocol:
Protocol related:
The event occurred due to a procedure/intervention that was described 
in the protocol for which there is no alternative etiology present in the 
subject’s medical record.
Not protocol related: The event is related to an etiology other than the procedure/ 
intervention that was described in the protocol (the alternative etiology 
must be documented in the study subject’s medical record).
6.3
Recording of Safety Parameters
6.3.1
Recording of Adverse Events and Serious Adverse Events
Adverse events will be recorded on the CRF using a recognized medical term or diagnosis 
that accurately reflects the event. Adverse events will be assessed by the investigator for 
severity, relationship to the investigational product, possible etiologies, and whether the 

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event meets criteria of an SAE and therefore requires immediate notification to MedImmune 
Patient Safety. See Section 6.1.2 for the definition of SAEs, and Section 6.2.1 and 
Section 6.2.2 for guidelines for assessment of severity and relationship, respectively. If an 
AE evolves into a condition that meets the regulatory definition of “serious,” it will be 
reported on the SAE Report Form.
6.3.2
Recording of Adverse Events of Special Interest
Both serious and nonserious AESIs will be captured at any time during the subject’s 
participation in the study.
6.3.2.1
Hepatic Function Abnormality
Nonserious and serious events of hepatic function abnormality (as defined in Section 6.1.3.1) 
should be recorded in the CRF according to the definitions of AE and SAE (Section 6.1.1 and 
Section 6.1.2, respectively):
•
If the underlying diagnosis for the hepatic function abnormality is known, the diagnosis 
should be recorded as an AE/SAE per Section 6.3.1.
•
If the underlying diagnosis for the hepatic function abnormality remains unknown, the 
term “hepatic function abnormal” should be used to report the AE/SAE per Section 6.3.1.
6.3.2.2
Other Adverse Events of Special Interest
Nonserious and serious events of new or reactivated TB infection, herpes zoster infection, 
malignancy, infusion, hypersensitivity or anaphylactic reactions, and vasculitis (as defined in 
Section 6.1.3.2 to Section 6.1.3.6) should be recorded in the CRF according to the definitions 
of AE and SAE (Section 6.1.1 and Section 6.1.2, respectively).
6.4
Reporting Requirements for Safety Parameters
6.4.1
Study Reporting Period and Follow-up for Adverse Events
The reporting period for AEs is the period immediately following the time that written 
informed consent is obtained until the end of subject participation in the study. 
Nonserious AEs will only be captured during the first year of the subject’s participation in 
the study, but will be followed to resolution until the end of subject participation in the study.
Nonserious AEs that result in interruption of investigational product and/or discontinuation 
from the study will be captured at any time during the subject’s participation in the study.

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6.4.2
Reporting of Serious Adverse Events 
6.4.2.1
Study Reporting Period and Follow-up for Serious Adverse Events
The reporting period for SAEs is the period immediately following the time that written 
informed consent is obtained through the end of subject participation in the study. After 
submitting an initial SAE report for a subject (to MedImmune Patient Safety), the 
investigator is required to follow the subject proactively and provide further information on 
the subject’s condition to MedImmune Patient Safety.
At any time after completion of the study, if an investigator or qualified designee becomes 
aware of an SAE that is suspected by the investigator or qualified designee to be related to 
investigational product, the event must be reported to MedImmune Patient Safety.
The investigator is responsible for following all SAEs until resolution, until the subject 
returns to baseline status, or until the condition has stabilized with the expectation that it will 
remain chronic, even if this extends beyond study participation. 
6.4.2.2
Notifying the Sponsor of Serious Adverse Events
Within 24 hours of identifying an SAE, regardless of the presumed relationship to the 
investigational product, the investigator or qualified designee must complete the SAE 
Report Form and fax it to MedImmune Patient Safety.
MedImmune contact information: 
Patient Safety 
MedImmune
One MedImmune Way
Gaithersburg, MD 20878
Fax: +1 301 398 4205
The sponsor is responsible for reporting certain SAEs as expedited safety reports to 
applicable regulatory authorities, ethics committees, and participating investigators, in 
accordance with ICH Guidelines and/or local regulatory requirements (see Section 6.4.2.3). 
The sponsor may be required to report certain SAEs to regulatory authorities within 
7 calendar days of being notified about the event; therefore, it is important that investigators 
submit additional information requested by the sponsor as soon as it becomes available.
Investigators should provide all available information at the time of SAE Report Form 
completion. Investigators should not wait to collect additional information to fully document 
the event before notifying MedImmune Patient Safety of an SAE. When additional 

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information becomes available, investigators should submit a follow-up SAE Report Form 
(separate from the initial report form) with the new information. Any follow-up information 
to an SAE also needs to be provided to MedImmune Patient Safety within 24 hours of 
learning of the new information. 
6.4.2.3
Safety Reporting to Investigators, Institutional Review Boards or 
Independent Ethics Committees, and Regulatory Authorities
The sponsor is responsible for reporting all applicable SAEs to regulatory authorities, 
investigators, and IRBs/IECs, as applicable, in accordance with national regulations in the 
countries where the study is conducted. The sponsor will also prepare an expedited report for 
other safety issues where these might materially alter the current risk/benefit assessment of 
an investigational product or that would be sufficient to consider changes in the 
administration of the investigational product or in the overall conduct of the study.
For all investigators located in the European Economic Area, the sponsor will be responsible 
for reporting suspected unexpected serious adverse reactions (SUSARs) and any other 
applicable SAEs to regulatory authorities including the European Medicines Agency (EMA), 
investigators, and IRBs/IECs, as applicable, in accordance with national regulations in the 
countries where the study is conducted. The SUSARs will be submitted within 7 days for 
fatal and life-threatening events and within 15 days for other serious events, unless otherwise 
required by national regulations. 
For all other investigators, the sponsor will prepare an expedited report for all SAEs that are 
unexpected and potentially related to the investigational product, and copies will be 
distributed to all concerned regulatory authorities, investigator(s), and IRBs/IECs according 
to applicable laws and regulations. The investigational site also will forward a copy of all 
expedited reports to the site’s applicable IRB/IEC. Investigators must also submit safety 
information provided by the sponsor to the IRB/IEC as detailed in Section 10.1 and 
Section 10.2.
6.4.3
Other Events Requiring Immediate Reporting
6.4.3.1
Overdose
An overdose is defined as a subject receiving a dose of investigational product in excess of 
that specified in the IB, unless otherwise specified in this protocol.
Any overdose of a study subject with the investigational product, with or without associated 
AEs/SAEs, is required to be reported within 24 hours of knowledge of the event to 
MedImmune Patient Safety using the Safety Fax Notification Form (see Section 6.4.2.2 for 

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contact information). If the overdose results in an AE, the AE must also be recorded on the 
AE CRF (see Section 6.3.1). Overdose does not automatically make an AE serious, but if the 
consequences of the overdose are serious, for example death or hospitalization, the event is 
serious and must be reported as an SAE (see Section 6.3.1 and Section 6.4.2).
6.4.3.2
Hepatic Function Abnormality
Hepatic function abnormality (as defined in Section 6.1.3) of unknown etiology, or which is 
considered attributable to investigational product, is required to be reported as “hepatic 
function abnormal” within 24 hours of knowledge of the event to MedImmune Patient 
Safety using the SAE Report Form, even if the event is considered to be nonserious (see 
Section 6.4.2.2 for contact information). The investigator will review the data with the 
medical monitor. The investigator should then use clinical judgment to establish the cause 
based on local SOC and follow the subject by conducting testing as clinically indicated:
•
If, after appropriate workup, in the opinion of the investigator, the underlying diagnosis 
for the abnormality remains unexplained, or is considered attributable to investigational 
product, dosing of the study subject should be discontinued.
•
If ALT or AST is greater than 3 × ULN please refer to Guidance for Abnormal Liver 
Function Tests Management in Appendix 8.
Each reported event of hepatic function abnormality will be followed by the investigator and 
evaluated by the sponsor. If the etiology of the event remains unconfirmed and/or is 
considered related to investigational product (see Section 6.2.2.1), a prompt cumulative 
review of safety data and the circumstances of the event in question will be conducted and 
assessed by a MedImmune safety review committee (see Section 6.5) to determine whether 
continued dosing of current study subjects and/or study entry should be interrupted, whether 
the protocol will be modified, or whether the study will be discontinued permanently. 
Review and approval by the committee is required for resumption of subject dosing or study 
entry in the event that the study is interrupted. Where applicable, regulatory authorities and 
IRBs/IECs will be notified of any actions taken with the study.
6.4.3.3
Pregnancy
Pregnancy in a female subject who has received investigational product is required to be 
reported within 24 hours of knowledge of the event to MedImmune Patient Safety or 
designee using the Safety Fax Notification Form (see Section 6.4.2.2 for contact 
information).

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Subjects who become pregnant during the study period must not receive additional doses of 
investigational product and will be withdrawn from the study. After obtaining the subject’s 
consent, the pregnancy will be followed for outcome of the mother and child (including any 
premature terminations) and should be reported to MedImmune Patient Safety after outcome.
Should the investigator become aware of a pregnancy in the partner of a male study subject 
who has received investigational product this should be reported within 24 hours of 
knowledge of the event to MedImmune Patient Safety using the Safety Fax Notification 
Form (see Section 6.4.2.2 for contact information). The sponsor will endeavor to collect 
follow-up information on such pregnancies provided the partner of the study subject provides 
consent.
6.5
Safety Management During the Study
The MedImmune medical monitor has primary responsibility for the ongoing medical review 
of safety data throughout the study. This includes review of SAEs and timely review of AEs 
and “other events” reported during the study. MedImmune Patient Safety is responsible for 
the receipt, immediate review, investigation, and follow-up of SAEs and other immediately 
reportable events (eg, overdose and pregnancies) reported from the clinical study sites.
A MedImmune safety review committee provides safety surveillance, guidance, and 
oversight for all clinical development studies in which MedImmune has sponsor 
accountabilities. The Committee is chaired by the Clinical Medical Director and includes 
appropriate representatives from Patient Safety, Pre-Clinical Development, and Regulatory 
Affairs. The committee reviews protocol and program-specific safety data and assessed 
changes to the benefit/risk profile of the molecule during early phases of development. Based 
on review of safety data, the committee may suspend enrollment or subject dosing in clinical 
studies, request modification of study documents, or take other actions as deemed necessary.
An independent DSMB is an advisory to the sponsor and will perform evaluations of safety 
data at specified time points throughout the study in accordance with the DSMB Charter and 
make recommendations to the sponsor regarding the conduct of the study (see Section 7.6).
7
STATISTICAL CONSIDERATIONS
7.1
General Considerations
Data will be provided in data listings sorted by SID number. Categorical data will be 
summarized by the number and percentage of subjects in each category. Continuous 
variables will be summarized by descriptive statistics, including mean, standard deviation, 

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median, minimum, and maximum. Baseline will be defined as the Day 1 value of this OLE 
study prior to investigational product administration. Details of endpoint analyses will be 
described in the Statistical Analysis Plan.
7.2
Analysis Populations
The Safety Population includes all subjects who receive any amount of investigational 
product. Demographics, safety endpoints, IM, PD, and disease activity will be summarized 
based on the Safety Population. Additional analysis populations may be defined as needed. 
7.3
Endpoints
7.3.1
Primary Endpoint
The primary objective of this study is to evaluate the long-term safety and tolerability of IV 
MEDI-546 in adult subjects with moderately-to-severely active SLE. The safety and 
tolerability of MEDI-546 will be assessed primarily by summarizing treatment-emergent AEs 
(TEAEs) and treatment-emergent SAEs (TESAEs). Other variables used for the safety 
assessments will include serum chemistry, hematology, urinalysis, vital signs, physical 
examination, ECG, and concomitant medications. 
All TEAEs and TESAEs will be summarized by system organ class and preferred terms, by 
severity and relationship to investigational product. No formal statistical testing will be 
performed. Other safety variables as well as their changes from baseline (if applicable) will 
be summarized descriptively.
7.3.2
Secondary Endpoint
The secondary objective of this study is to evaluate the IM of MEDI-546. Immunogenicity 
results will be analyzed by summarizing the number and percentage of subjects who develop 
detectable ADAs. The titer of ADAs will also be summarized. The association of ADA titers 
with AEs, PK, SLEDAI-2K, and PD markers will also be evaluated. 
7.3.3
Exploratory Endpoints
 
 
 
 
 

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7.4
Interim Analysis
Although no formal interim analyses of the extension period data are planned, analyses of the 
accumulating data during the extension period may be performed to assess the ongoing safety 
and risk/benefit of the study treatment and to assist with Phase 3 planning. The final analysis 
of extension period data will take place after the last on-study subject completes the 
extension period follow-up visit or discontinues from the study.
7.5
Sample Size and Power Calculations
 
 
 
 
 
7.6
Data Safety Monitoring Board
An independent DSMB is an advisory to the sponsor and will perform evaluations of safety 
data at specified time points throughout the study in accordance with the DSMB Charter (see
Appendix 5) and make recommendations to the sponsor regarding the conduct of the study. 
At any time during the study, as well as on an ad hoc basis, the DSMB will also review any 
safety data assessed by the medical monitor to be medically relevant. 

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8
DIRECT ACCESS TO SOURCE DOCUMENTS
The study will be monitored by the sponsor or designee on a regular basis throughout the 
study period. During monitoring visits, the investigator will provide direct access to all 
source documentation relevant to the subject’s participation in the study. Source 
documentation includes, but is not limited to, the subject’s clinic and/or office chart, hospital 
chart, ICFs, treatment notes, laboratory reports, pharmacy records, radiographs, recorded data 
from automated instruments, and any other records maintained to conduct and evaluate the 
clinical study. The investigator must also ensure that direct access to study documents be 
made available for study-related audits, IRB/IEC review, or regulatory inspection.
9
QUALITY CONTROL AND QUALITY ASSURANCE
9.1
Data Collection
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate and accurate case histories for the subjects treated under this protocol. 
Case histories include CRFs and supporting data including, but not limited to, signed and 
dated ICFs, progress notes, hospital charts, nurse’s notes, diary cards or other worksheets 
provided to subjects, laboratory reports, ECG strips, etc.
Subject demographics and key/essential disease baseline characteristics thought to affect 
outcome, ie, stratification variables and other prognostic factors may be collected, as 
available, for all subjects who provide written informed consent. For subjects who provided 
informed consent and were not entered into the study, the reason the subject was not entered, 
ie, did not meet one or more inclusion criteria, met one or more exclusion criteria, or other 
(eg, lost to follow-up, consent withdrawn), may also be collected.
9.2
Study Monitoring
The primary source document for this study will be the subject’s medical record. If separate 
research records are maintained by the investigator(s), both the medical record and the 
research records will be monitored/audited for the purposes of the study.
The investigator and institutions involved in the study will permit study-related monitoring 
and provide direct access to all study records and facilities. Adequate time and space for 
monitoring visits should be made by the investigator or other investigator site staff.
The monitor will visit study facilities at periodic intervals, in addition to maintaining 
necessary contact through telephone, e-mail, and letter, to ensure that the study is conducted 

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and documented in accordance with the protocol, GCP, and applicable regulations. The 
monitor will assess subject enrollment and informed consent procedures; investigational 
product storage, dispensing, administration and accountability; compliance with protocol 
procedures; completeness and accuracy of data entered onto validated data collection 
instruments (paper CRF or electronic data screen) against original source documents; the 
continued acceptability of the facilities and qualifications of the site staff; and the occurrence 
of AEs/SAEs. All aspects of the study will be carefully monitored for compliance with the 
protocol, applicable regulatory requirements, GCP, and the site’s standard operating 
procedures.
The monitor will discuss the conduct and progress of the study with the investigator and 
other site staff. The investigator must cooperate with the monitor to ensure that corrective 
action is taken to resolve any problems noted in the course of the monitoring, and that the 
preventative measures are put into place to prevent recurrence of issues. In cases where 
compliance is not achieved, shipment(s) of investigational product to the investigator will be 
discontinued and study participation by that investigator will be terminated.
9.3
Audit and Inspection of the Study
During and after the study, the sponsor or its representative may conduct audits of any data 
and any facility participating in the study. The investigator and institutions involved in the 
study will permit such study-related audits and provide direct access to all study records and 
facilities. The investigator must maintain a comprehensive and centralized filing system of 
all study-related documentation that is suitable for inspection by the sponsor or its designated 
monitors, auditors, or regulatory agency representatives. The investigator agrees to 
participate in audits conducted at a convenient time in a reasonable manner.
Government regulatory authorities may also perform inspections either during or after the 
study. In the event of an inspection by any regulatory authority, the investigator should 
promptly notify the sponsor. The investigator agrees to cooperate fully with inspections 
conducted by regulatory authorities and to allow representatives of the regulatory authority 
access to all study records. The investigator will forward to the sponsor a copy of any 
inspection records received.
10 ETHICS
10.1
Regulatory Considerations
The study will be conducted in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with the ICH guidelines on GCP, any applicable 

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laws and requirements, and any conditions required by a regulatory authority and/or IRB/IEC 
that approves this study to be conducted in its territory. Good Clinical Practice is defined as a 
standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and 
reporting of clinical studies in a way that provides assurance that the data and reported results 
are credible and accurate, and that the rights, safety, and well-being of study subjects are 
protected.
Per GCP, the protocol will be reviewed and approved by the IRB or IEC of each participating 
center prior to study initiation. Serious adverse events regardless of causality will be reported 
to MedImmune Patient Safety or designee, and the investigator will keep the IRB/IEC 
informed as to the progress of the study.
The investigator will explain the nature of the study and will inform the subject that 
participation is voluntary and that the subject can withdraw or be withdrawn from the study 
at any time. Written informed consent will be obtained from each subject prior to the Day 1 
procedures to determine if study eligibility criteria are met. A copy of the signed consent 
form(s) will be given to every subject, and the original(s) will be maintained with the 
subject’s records.
10.2
Institutional Review Board or Independent Ethics Committee
A list of IRB/IEC members or a Statement of GCP Compliance should be obtained by the 
investigator and provided to the sponsor.
Any documents that the IRB/IEC may need to fulfill its responsibilities, such as protocol 
amendments, and information concerning subject recruitment, payment, or compensation 
procedures, or information from the sponsor will be submitted to the IRB/IEC. The 
IRB/IEC’s written unconditional approval of the study protocol, the ICF(s), and any other 
written materials to be provided to subjects will be in the possession of the investigator and 
the sponsor before the study is initiated. The IRB/IEC’s unconditional approval statement 
will be transmitted by the investigator to the sponsor prior to shipment of investigational 
product supplies to the site. This approval must refer to the study by exact protocol title and 
number, and should identify the documents reviewed and the date of review.
Protocol modifications or changes may not be initiated without prior written IRB/IEC 
approval except when necessary to eliminate immediate hazards to the subjects or when the 
change(s) involves only logistical or administrative aspects of the study. Such modifications 
will be submitted to the IRB/IEC and written verification that the modification was submitted 
should be obtained.

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The IRB/IEC must be informed by the investigator of ICF changes or revisions of other 
documents originally submitted for review; serious and/or unexpected adverse experiences 
occurring during the study (as applicable according to local regulations); new information 
that may affect adversely the safety of the subjects or the conduct of the study; an annual 
update and/or request for re-approval; and when the study has been completed.
10.3
Informed Consent
Freely given informed consent will be obtained and documented for all subjects under this 
protocol (or a subject’s legal representative, if the subject is unable to provide informed 
consent) in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and are consistent with the ICH guidelines on GCP, any applicable laws and 
requirements, and any conditions required by a regulatory authority and/or IRB/IEC.
Information should be given in both oral and written form, and subjects or their legal 
representatives must be given ample opportunity to inquire about details of the study.
The consent form(s) generated by the investigator must be approved by the IRB/IEC and be 
acceptable to the sponsor. Consent forms must be written so as to be understood by the 
prospective subject/legal representative. Informed consent will be documented by the use of 
a written consent form(s) approved by the IRB/IEC and signed and dated by the subject or 
the subject’s legal representative, and by the person who conducted the informed consent 
discussion. The signature confirms the consent is based on information that has been 
understood. Each subject’s signed ICF(s) must be kept on file by the investigator for possible 
inspection by the sponsor or its designated monitors, auditors, or regulatory agency 
representatives. The subject or the subject’s legal representative should receive a copy of the 
signed and dated written ICF(s) and any other written information provided to the subject, 
and should receive copies of any signed and dated consent form updates and any 
amendments to the written information provided to subjects. 
10.4
Withdrawal of Consent for Continued Study Participation
Data and Samples Obtained for the Main Study
Study data are protected by the use of an SID number, which is a number specific to the 
subject. The investigator is in control of the information that is needed to connect a study 
sample to a subject. A subject’s consent to the use of data does not have a specific expiration 
date, but the subject may withdraw consent at any time by notifying the investigator. If 
consent is withdrawn, any data collected prior to that time may still be given to and used by 

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the sponsor but no new data or samples will be collected unless specifically required to 
monitor safety of the subject.
Samples Obtained for Future Research
Samples obtained for future research will be labeled with a sample identification number but 
will not be labeled with personal identifiers such as the subject’s name. A file linking this 
sample identification number with the SID number will be kept in a secure place at the 
sponsor with restricted access. If the subject withdraws consent for participating in the future 
research, this link will allow the sponsor to locate the subject’s sample and destroy it. The 
coding of samples and results is to ensure that these research results are kept confidential by 
keeping the subject’s identity and these results separate. 
If the subject consents to have his/her urine or sera samples used for future research, this 
additional research may not start immediately and may start at any time during the storage 
period. The subject’s sample(s) will be stored by the sponsor with similar samples from other 
subjects at a secure central laboratory. The subject’s samples will not be kept for more than 
25 years after the end of the study in which they were collected. If the subject chooses not to 
allow his/her study samples to be used for future research, the samples will be destroyed by 
the sponsor once they are no longer required for the main study.
If consent is withdrawn after a sample has been taken but before the subject’s sample is sent 
to the sponsor for future research, the investigator will arrange to have it destroyed. If 
consent is withdrawn after the subject’s sample(s) have been sent to the sponsor for future 
research, the sponsor and the investigator will ensure that these sample(s) are destroyed 
unless the sample identification number has been removed and the subject can no longer be 
linked to any sample(s). However, if the subject’s samples have already been used for 
research, the sponsor is not required to destroy results of this research. In this case only the 
remaining sample(s) will be destroyed.
11 DATA HANDLING AND RECORD KEEPING
To maintain confidentiality, all laboratory specimens, evaluation forms, reports, and other 
records transmitted outside the clinical site will be identified by a subject’s identification 
number or coded number. All study records, source medical records, and code sheets or logs 
linking a subject’s name to an SID number will be kept in a secure location. Study records 
such as CRFs may be maintained electronically and require the same security and 
confidentiality as paper. Clinical information will not be released without written permission 
of the subject/legal representative, except as specified in the ICF(s) (eg, necessary for 

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monitoring by regulatory authorities or the sponsor of the clinical study). The investigator 
must also comply with all applicable privacy regulations (eg, HIPAA 1996, EU Data 
Protection Directive 95/46/EC).
The study site (and the Principal Investigator) will retain the essential documents specified in 
the ICH GCP (eg, source document such as medical records, contract, signed consent form). 
Essential documents should be retained at the study site for at least 15 years following 
completion of the study, or per regulatory obligations if longer, and thereafter destroyed only 
after agreement with MedImmune/AstraZeneca. However this is not always applied to those 
that are not preservable such as blood samples. In the event of any inconsistency between the 
above-mentioned contents and the contract with the study site, the contract shall prevail. 
These documents should be retained for a longer period however if needed by 
MedImmune/AstraZeneca, and the specific period and method of retention will be separately 
discussed between the study site and MedImmune/AstraZeneca. MedImmune/AstraZeneca 
should notify the head of the study site in writing when the study-related records are no 
longer needed. The records should be managed by a responsible person appointed by the 
head of the study site.
12 FINANCING AND INSURANCE
Financing and insurance are addressed in the individual site contracts.
13 PUBLICATION POLICY
Publication by the site of any data from this study must be carried out in accordance with the 
clinical study site agreement.
14 REFERENCES
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Development of autoantibodies before the clinical onset of systemic lupus erythematosus. 
N Engl J Med. 2003;349(16):1526-33.
Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, 
Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW. Interferon-inducible gene 
expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad 
Sci USA. 2003; 100(5):2610-5. 
Baechler EC, Gregersen PK, Behrens TW. The emerging role of interferon in human 
systemic lupus erythematosus. Curr Opin Immunol. 2004;16(6):801-7.

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Banchereau J, Pascual V, Palucka AC. Autoimmunity through cytokine-induced dendritic 
cell activation. Immunity. 2004; 20:539–50.
Bengtsson AA, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H, Ronnblom L. 
Activation of type I interferon system in systemic lupus erythematosus correlates with 
disease activity but not with antiretroviral antibodies. Lupus. 2000;9:664-71.
Bennet L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V. Interferon 
and granulopoiesis signatures in systemic lupus erythematosus blood. Journal of 
Experimental Medicine. 2003; 197(6): 711-23.
Blomberg S, Eloranta ML, Cederblad B, Nordlin K, Alm GV, Ronnblom L. Presence of 
cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. 
Lupus. 2001;10(7):484-90.
Criswell LA. The genetic contribution to systemic lupus erythematosus. Bull NYU Hosp Jt 
Dis. 2008;66(3):176-83.
Crow MK. Interferon-alpha: a therapeutic target in systemic lupus erythematosus. Rheum 
Dis Clin North Am. 2010 Feb;36(1):173-86.
Crow MK, Wohlgemuth J. Microarray analysis of gene expression in lupus. Arthritis Res 
Ther. 2003;5:279-87.
Dall’era MC, Cardarelli PM, Preston BT, Witte A, Davis Jr, JC. Type I Interferon correlates 
with clinical and serologic manifestations of systemic lupus erythematosus. Ann Rheum Dis.
2005; 64:1692-7.
Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic 
cells (natural interferon-alpha/beta-producing cells) accumulate in cutaneous lupus 
erythematosus lesions. Am J Pathol. 2001;159(1):237-43.
Feng X, Wu H, Grossman JM, Hanvivadhanakul P, FitzGerald JD, Park GS et al. Association 
of increased interferon-inducible gene expression with disease activity and lupus nephritis in 
patients with systemic lupus erythematosus. Arthritis Rheum. 2006;54(9):2951-62.
Huang X, Yang N, Ou X, Li D, Wang Z, Xie Q et al. Sequential activation of protein kinase 
C delta and JNK is required for interferon-alpha-induced expression of IFIT4. Cell Signal. 
2008 Jan;20(1):112-9.

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Hylton W, Cayley J, Dore C, Denman AM. 2',5'-oligoadenylate synthetase induction in 
lymphocytes of patients with connective tissue diseases. Ann Rheum Dis. 1986 
Mar;45(3):220-4.
Ioannou Y, Isenberg DA. Current evidence for the induction of autoimmune rheumatic 
manifestations by cytokine therapy. Arthritis Rheum. 2000;43(7):1431-42.
Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG et al. Coordinate 
overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis 
Rheum. 2004;50(12):3958-67.
Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Activation of the interferon-
alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct 
serologic features and active disease. Arthritis Rheum. 2005;52(5):1491-503.
Mathian A, Weinberg A, Gallegos M, Banchereau J, Koutouzov S. IFN-α induces early 
lethal lupus in preautoimmune (New Zealand Black X New Zealand White) F1 but not in 
BALB/c mice. J Immunol. 2005;174:2499-506.
Niewold TB, Swedler WI. Systemic lupus erythematosus arising during interferon-alpha 
therapy for cryoglobulinemic vasculitis associated with hepatitis C. Clin Rheumatol. 
2005;24(2):178-81.
Okamoto H, Katsumata Y, Nishimura K, Kamatani N. Interferon-inducible protein 
10/CXCL10 is increased in cerebrospinal fluid of patients with central nervous system lupus. 
Arthritis Rheum. 2004;50:3729-32.
Pascual V, Farkas L, Banchereau J. Systemic lupus erythematosus: all roads lead to type I 
interferons. Curr Opin Immunol. 2006;18(6):676-82.
Rahman A, Isenberg DA. Systemic lupus erythematosus. New Engl J Med. 2008;358:929-39.
Ronnblom L, Alm GV. Systemic lupus erythematosus and the type I interferon system. 
Arthritis Res Ther. 2003;5:68-75.
Ronnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic 
cells. Lupus. 2008;17(5):394-9.
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report-

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second National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis 
Network symposium. J Allergy Clin Immunol. 2006;117(2):391-7.
Santiago-Raber M-L, Baccala R, Haraldsson KM, Choubey D, Stewart TA, Kono DH, 
Theofilopoulis AN. Type I interferon receptor deficiency reduces lupus-like disease in NZB 
mice. J Exp Med. 2003;197:777-88.
Sigurdsson S, Göring HH, Kristjansdottir G, Milani L, Nordmark G, Sandling JK, et al. 
Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) 
reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus 
erythematosus. Hum Mol Genet. 2008 Mar 15;17(6):872-81.
Sigurdsson S, Nordmark G, Garnier S, Grundberg E, Kwan T, Nilsson O, et al. A risk 
haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with 
anti-dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet. 2008 
Sep 15;17(18):2868-76.
Stewart, J. Developmental toxicity testing of monoclonal antibodies: An enhanced pre- and
postnatal study design option. Reprod Toxicol. 2009;28(s): 220-5.
Stoll T, Sutcliffe N, Mach J, Klaghofer R, Isenberg DA. Analysis of the relationship between 
disease activity and damage in patients with systemic lupus erythematosus - a 5-yr 
prospective study. Rheumatology. 2004;43:1039-44. 
Touma Z, Urowitz MB, Gladmann DD. SLEDAI-2K for a 30-day window. Lupus. 
2010;19:49-50.
Yao Y, Higgs BW, Richman L, White B, Jallal B. Use of type I interferon-inducible mRNAs 
as pharmacodynamic markers and potential diagnostic markers in trials with sifalimumab, an 
anti-IFNalpha antibody, in systemic lupus erythematosus. Arthritis Res Ther. 
2010;Suppl1:S6.
Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P, et al. 
Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I 
trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. 
Arthritis Rheum. 2009 Jun;60(6):1785-96.
Ware JE, Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME. SF-36v2 
health survey: administration guide for clinical trial investigators. Lincoln, RI: Quality 
Metric Incorporated; 2008.

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15 SUMMARY OF PROTOCOL AMENDMENTS AND 
ADMINISTRATIVE CHANGES TO THE PROTOCOL
Protocol Amendment 1, 12Feb2013
Text revisions resulting from this amendment are incorporated in the body of Protocol 
Amendment 1. Major changes to the protocol are summarized below.
1. Section 1.2.3 (Summary of Clinical Experience) was revised to remove the explanation 
regarding the last day of Study CD-IA-MEDI-546-1013 and the first day of Study CD-
IA-MEDI-546-1145. This explanation has been moved to Section 3.1 (Overview of Study 
Design) and clarified.
2. Section 3.1 (Overview of Study Design) was revised to include the explanation that once 
subjects complete treatment and follow-up in Study CD-IA-MEDI-546-1013 (through 
Day 422), signed the ICF, and met all study eligibility criteria, they may be enrolled in 
this OLE study. The start of this OLE study (defined as the day [Day 1] the subject 
receives their first dose of open-label MEDI-546) should occur within 28 days of the Day 
422 visit of Study CD-IA-MEDI-546-1013 or at the discretion of the medical monitor if 
the start of this OLE study occurs outside the 28-day window.
3. Section 3.1 (Overview of Study Design), Section 3.2 (Estimated Duration of Subject 
Participation) and Section 4.5.3 (Treatment Regimen) were revised to reduce the duration 
of the study to 2 years.
4. Figure 3.1-1 (Study Flow Diagram) and Table 5.1-1 (Schedule of Study Procedures for 
the Treatment Period) was revised to reduce the duration of the study to 2 years.
5. Section 3.4.1 (Rationale for Study Design) was updated to remove the reference to 
subjects at least 18 years of age. It is assumed that subjects in this study will be at least 18 
years of age, as subjects had participated in Study CD-IA-MEDI-546-1013, which had an 
inclusion criterion of “age 18-65 years at the time of screening”.
6. Section 4.2.1 (Inclusion Criteria) inclusion criterion #3 was clarified to state that females 
of childbearing potential who are sexually active with a nonsterilized male partner must 
use 2 methods of effective contraception for 28 days prior to Day 1, and must agree to 
continue using such precautions for 85 days after the final dose of investigational 
product.
7. Section 4.2.1 (Inclusion Criteria) inclusion criterion #4 was clarified to state that 
nonsterilized males who are sexually active with a female partner of childbearing 
potential must use 2 acceptable methods of effective contraception from Day 1 for 85 
days after receipt of the final dose of investigational product.
8. Section 4.2.1 (Inclusion Criteria) inclusion criterion #5 was clarified to state that subjects 
must be willing to forgo other forms of experimental treatment (and not just experimental 
treatments for SLE) during the study.
9. Section 4.2.3 (Withdrawal Criteria) was clarified so that subjects who are permanently 
discontinued from receiving investigational product (and who have not withdrawn 
consent, are not lost to follow-up or have not enrolled in another clinical study) will 
complete the follow-up period (beginning with Visit 28/Early Discontinuation Visit) 28 

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days (± 7 days) after the last dose of investigational product. Two subsequent follow-up 
visits will also be completed 59 and 85 days (± 7 days) after the last dose of 
investigational product as per the schedule of study procedures.
10. Section 4.5.6 (Monitoring of Dose Administration) was updated to remove the reference 
that temperature should be taken orally. 
11. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period) was revised to 
reduce the duration of the study to 2 years; to include a note that for the Day 1 assessment 
of ECG, if an assessment was performed on Day 396 of Study CD-IA-MEDI-546-1013, 
then the data can also be used for Day 1 of this study; to move the lipid profile collection 
to Week 4; to include a note that subjects will be required to fast for at least 8 hours prior 
to the lipid profile assessment and that if a subject has not fasted, the assessment should 
be performed under fasted conditions at the next visit; to state that the urine biomarker 
collection is optional; and to remove the Clinical Evaluation Questionnaire assessment.
12. Table 5.1-2 (Schedule of Study Procedures for the 85-day Follow-up Period) was updated 
to include new visit numbers (Visits 28, 29 and 30); to include the Early Discontinuation 
Visit procedures (ie, same as Visit 28); to include a note that subjects will be required to 
fast for at least 8 hours prior to the lipid profile assessment; to state that the urine 
biomarker collection is optional; and to remove the Clinical Evaluation Questionnaire 
assessment.
13. Table 5.1-2 (Schedule of Study Procedures for the 85-day Follow-up Period) and Section 
5.1.3.1 (28 Days after the Last Dose [± 7 Days]: First Safety Follow-up Visit or Early 
Discontinuation Visit [Visit 28]) were revised to remove the SLICC assessment from 
Visit 28/EDV.
14. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]) was revised to remove the lipid 
profile assessment.
15. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 (Every 4 Weeks; 
Weeks 4 to 100: Second through Twenty-sixth Infusion [Visits 2 to 26]), Section 5.1.3.1 
(28 Days after the Last Dose [± 7 Days]: First Safety Follow-up Visit or Early 
Discontinuation Visit [Visit 28]), Section 5.1.3.2 (59 Days after the Last Dose [+/- 7 
Days]: Second Safety Follow-up Visit [Visit 29]), Section 5.1.3.3 (85 Days after the Last 
Dose [± 7 Days]: Third Safety Follow-up Visit [Visit 30]) and Section 5.2.4 
(Tuberculosis Testing) were modified to remove the Clinical Evaluation Questionnaire 
assessment. Section 5.2.13 (Adverse Events of Special Interest) was also modified to 
remove the Clinical Evaluation Questionnaire, as the investigator is required to assess for 
AESIs using medical or scientific judgment.
16. Section 5.1.2.2 (Every 4 Weeks; Weeks 4 to 100: Second through Twenty-sixth Infusion 
[Visits 2 to 26]) was updated to include the lipid profile assessment (Week 4 only). 
Section 5.1.2.2 (Every 4 Weeks; Weeks 4 to 100: Second through Twenty-sixth Infusion 
[Visits 2 to 26]) and Section 5.1.2.5 (Every 48 Weeks; Weeks 48 and 96 [Visits 13 and 
25]) were updated to include a note that subjects will be required to fast for at least 8 
hours prior to this assessment. If a subject has not fasted, the assessment should be 
performed under fasted conditions at the next visit.
17. Section 5.1.2.3 (Every 12 Weeks; Weeks 12, 24, 36, 48, 60, 72, 84 and 96 [Visits 4, 7, 
10, 13, 16, 19, 22 and 25]), Section 5.1.3.1 (28 Days after the Last Dose [± 7 Days]: First 
Safety Follow-up Visit or Early Discontinuation Visit [Visit 28]) and Section 5.1.3.3 (85 

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Days after the Last Dose [± 7 Days]: Third Safety Follow-up Visit [Visit 30]) and Section 
5.2.5 (Clinical Laboratory Tests) were updated to state that the urine biomarker collection 
was optional.
18. Section 5.1.2.2 (Every 4 Weeks; Weeks 4 to 100: Second through Twenty-sixth Infusion 
[Visits 2 to 26]), Section 5.1.2.3 (Every 12 Weeks; Weeks 12, 24, 36, 48, 60, 72, 84 and 
96 [Visits 4, 7, 10, 13, 16, 19, 22 and 25]), Section 5.1.2.4 (Every 24 Weeks; Weeks 24, 
48, 72 and 96 [Visits 7, 13, 19 and 25]), Section 5.1.2.5 (Every 48 Weeks; Weeks 48 and 
96 [Visits 13 and 25]), Section 5.1.2.6 (Week 104; Last Treatment Visit [Visit 27]), 
Section 5.1.3.1 (28 Days after the Last Dose [± 7 Days]: First Safety Follow-up Visit or 
Early Discontinuation Visit [Visit 28]), Section 5.1.3.2 (59 Days after the Last Dose [+/-
7 Days]: Second Safety Follow-up Visit [Visit 29]) and Section 5.1.3.3 (85 Days after the 
Last Dose [± 7 Days]: Third Safety Follow-up Visit [Visit 30]) were revised to reduce the 
duration of the study to 2 years.
19. Section 5.1.4 (Unscheduled Visit) was added to describe procedures for an unscheduled 
study visit.
20. Section 5.2.6 (Optional Urine Biomarker Testing) was revised to include additional 
information on the collection and analysis of optional urine biomarker samples.
21. Section 5.2.12.1 (Systemic Lupus Erythematosus Disease Activity Index-2000) was 
updated to include a statement that anyone assessing the SLEDAI-2K at the sites must 
have had appropriate training prior to conducting the SLEDAI-2K.
22. Table 5.2.15-1 (Estimated Volume of Blood to be Collected per Visit) was revised to 
reduce the amount of blood that would be collected during the study, given that the 
duration of the study was reduced to 2 years.
23. Section 6.3.2 (Recording of Adverse Events of Special Interest) was clarified to state 
where nonserious and serious AESIs should be recorded. 
Protocol Amendment 2, 01Apr2013
Text revisions resulting from this amendment are incorporated in the body of Protocol 
Amendment 2. Major changes to the protocol are summarized below.
1. Section 2.3 (Exploratory Objectives)
 
.
2. Section 4.2.3 (Withdrawal Criteria) was revised to clarify how an increase in OCS 
treatment is managed in the study.
3. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period) was modified to 
include the following assessments: SF-36v2 was added to Visits 1, 7, 13, 19, 25 and 27; 
HBV DNA PCR TaqMan, QFT-GIT test, immunology profile, urinalysis, urine β-HCG, 
and Investigator Flare Question(s) were added to Visit 27.
4. Table 5.1-2 (Schedule of Study Procedures for the 85-day Follow-up Period) was 
modified to include the SF-36v2 assessment to Visit 30.
5. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.4 
(Every 24 Weeks; Weeks 24, 48, 72 and 96 [Visits 7, 13, 19 and 25]), Section 5.1.2.6 
(Week 104; Last Treatment Visit [Visit 27]) and Section 5.1.3.3 (85 Days after the Last 

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Dose [+/- 7 Days]: Third Safety Follow-up Visit [Visit 30]) were revised to include the 
SF-36v2 assessment.
6. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 (Every 4 Weeks; 
Weeks 4 to 100: Second through Twenty-sixth Infusion [Visits 2 to 26]), Section 5.1.2.6 
(Week 104; Last Treatment Visit [Visit 27]), Section 5.1.3.1 (28 Days after the Last Dose 
[+/-7 Days]: First Safety Follow-up Visit or Early Discontinuation Visit [Visit 28]), 
Section 5.1.3.2 (59 Days after the Last Dose [+/-7 Days]: Second Safety Follow-up Visit 
[Visit 29]), Section 5.1.3.3 (85 Days after the Last Dose [+/- 7 Days]: Third Safety 
Follow-up Visit [Visit 30]), Section 5.1.4 (Unscheduled Visit), Section 5.2.14 (SLE 
Flares and Increase in SLE Disease Activity), and Section 6.1.1 (Adverse Events) were 
clarified: assessment of worsening and/or flare of SLE disease activity should be 
performed using the SLE Increase in Disease Activity CRF.
7. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period), Table 5.1-2 
(Schedule of Study Procedures for the 85-day Follow-up Period), Section 5.1.2.2 (Every 
4 Weeks; Weeks 4 to 100: Second through Twenty-sixth Infusion [Visits 2 to 26]), 
Section 5.1.2.6 (Week 104; Last Treatment Visit [Visit 27]), Section 5.1.3.1 (28 Days 
after the Last Dose [+/-7 Days]: First Safety Follow-up Visit or Early Discontinuation 
Visit [Visit 28]), Section 5.1.3.2 (59 Days after the Last Dose [+/-7 Days]: Second Safety 
Follow-up Visit [Visit 29]), Section 5.1.3.3 (85 Days after the Last Dose [+/- 7 Days]: 
Third Safety Follow-up Visit [Visit 30]), Section 5.1.4 (Unscheduled Visit), Section 6.1.1 
(Adverse Events), Section 6.4.1 (Study Reporting Period and Follow-up for Adverse 
Events) were modified to include a description of how nonserious AEs that result in 
interruption of investigational product and/or discontinuation from the study would be 
collected. This addition to the protocol was made to be compliant with the United States
Food and Drug Administration draft guidance “Safety Data Collection Needed in Late 
Stage Premarket and Postapproval Clinical Investigations.”
8. Section 5.1.2.6 (Week 104; Last Treatment Visit [Visit 27]) was revised to include the 
following assessments: SF-36v2, HBV DNA PCR TaqMan, QFT-GIT test, immunology 
profile, urinalysis, urine β-HCG, and Investigator Flare Question(s).
9. Section 5.2.15 (Patient-reported Outcomes) and Section 5.2.15.1 (Short Form-36 Version 
2) were added to the protocol to describe the SF-36v2 assessment.
10. Section 6.1.3 (Adverse Events of Special Interest) was modified to remove the 
description of the AESIs, as this information is provided in the following subsections: 
Section 6.1.3.1 (Hepatic Function Abnormality), Section 6.1.3.2 (New or Reactivated TB 
Infection), Section 6.1.3.3 (Herpes Zoster Infection), Section 6.1.3.4 (Malignancy), 
Section 6.1.3.5 (Infusion, Hypersensitivity, and Anaphylactic Reactions), and Section 
6.1.3.6 (Vasculitis).
11. Section 6.1.3 (Adverse Events of Special Interest) and Section 6.3.2 (Recording of 
Adverse Events of Special Interest) were clarified to state that both serious and 
nonserious AESIs will be captured at any time during the subject’s participation in the 
study.
12. Section 6.1.3.5 (Infusion, Hypersensitivity, and Anaphylactic Reactions) was modified to 
include the following subsections: Section 6.1.3.5.1 (Infusion Reactions), Section 
6.1.3.5.2 (Hypersensitivity Reactions), and Section 6.1.3.5.3 (Anaphylactic Reactions).

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13. Section 6.1.3.6 (Vasculitis) was modified to remove the last sentence in the paragraph, as 
AESIs of vasculitis that are associated with the subject’s underlying SLE will be 
collected.
14. Section 6.3.2 (Recording of Adverse Events of Special Interest) was modified to include 
recording information for nonserious and serious events of hepatic function abnormality 
in Section 6.3.2.1 (Hepatic Function Abnormality) and serious and nonserious events of 
new or reactivated TB infection, herpes zoster infection, malignancy, infusion, 
hypersensitivity or anaphylactic reactions, and vasculitis in Section 6.3.2.2 (Other 
Adverse Events of Special Interest).
15. Section 7.3.3 (Exploratory Endpoints)
 
 
16. Section 14 (References) was modified to include Ware et al, 2008 to the reference list.
17. Appendix 7 (Short Form-36 Version 2) was added to include an example of the SF-36v2
in the protocol.
Protocol Amendment 3, 26Mar2014
Text revisions resulting from this amendment are incorporated in the body of Protocol 
Amendment 3. Major changes to the protocol are summarized below.
1. Cover page was updated to change the medical monitor from Stephen Yoo, MD, Senior 
Director, Clinical Development to Warren Greth, MD, MSc, Senior Director, Clinical 
Development.
2. Figure 3.1-1 (Study Flow Diagram) was updated to change duration of IV infusion to 
“approximately 60 minutes”. Note however that MEDI-546 should not be administered 
over a period of less than 55 minutes. If a subject has a history of infusion reactions, 
MEDI-546 administration may be lengthened per the investigator’s discretion.
3. Section 4.2.3 (Withdrawal Criteria), Section 4.5.2 (Other Study Medications), 
Section 4.5.2.1 (Corticosteroids), and Section 4.6.1 (Permitted Non-SLE Concomitant 
Medications) was modified to state that OCS medication taken > 40 mg/day of 
prednisone (or equivalent) for greater than 14 days, dosing with study medication must be 
withheld until OCS medication can be tapered to ≤40 mg/day. The change was made to 
allow OCS medication to be tapered to 40 mg/day (and not just below 40 mg/day).
4. Section 4.5.1 (Investigational Products), Section 4.5.4 (Investigational Product Dose 
Preparation), Section 4.5.4.1 (Dose Calculation), Section 4.5.4.2 (Investigational Product 
Inspection), and Section 4.5.4.3 (Dose Preparation Steps) were modified to include 
information on a new formulation of MEDI-546 Drug Product (ie, 150 mg/mL). Table 
4.5.1-1 (Identification of Investigational Products) was also modified to include 
information on a new formulation of MEDI-546 Drug Product (ie, 150 mg/mL).
5. Section 4.5.4.1 (Dose Calculation) was modified to add Table 4.5.4.1-1 (Dose 
Calculation for MEDI-546 Drug Product for IV Infusion).
6. Section 4.5.4.3 (Dose Preparation Steps) was modified to add Table 4.5.4.3-1 (Dose 
Preparation for MEDI-546). Text was also added to describe the type of syringes to be 
used and the number of needle sticks that could be made into the IV bag.

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7. Section 4.5.5 (Treatment Administration), third bullet was modified to state that the dose 
of MEDI-546 must be prepared using aseptic technique and that the total in-use storage 
time from needle puncture of the first vial of MEDI-546 for investigational product 
preparation to start of administration should not exceed 4 hours at room temperature or 
24 hours at 2°C-8°C (36°F to 46°F). The fourth and fifth bullets were modified to state 
that the entire contents of the IV bag should be administered using an infusion pump over 
approximately 60 minutes. MEDI-546 should not be administered over a period of less 
than 55 minutes. If a subject has a history of infusion reactions, MEDI-546 administration 
may be lengthened per the investigator’s discretion. The second sub-bullet of the seventh 
bullet was modified to state that an infusion with a start time of 12:00PM would have 
duration of infusion recorded as 60 minutes (a time of 1:00 PM).
8. Section 4.5.5 (Treatment Administration), Section 4.5.6 (Monitoring of Dose 
Administration), Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 
(Every 4 Weeks; Weeks 4 to 100: Second through Twenty-sixth Infusion [Visits 2 to 
26]), and Section 5.2.3 (Vital Signs) were revised to include windows (ie, [± 5]) for vital 
sign assessments.
9. Section 5.1 (Schedule of Study Procedures) was modified to state that if Day 1 of this 
study occurred on the same day as Day 422 (+ 28 days) of Study CD-IA-MEDI-546-
1013, then many of the procedures and samples only need to be collected one time and 
will be utilized for both studies. If Day 1 of this study occurs 28 days after Day 422 of 
Study CD-IA-MEDI-546-1013, then Day 1 procedures and samples of this study will 
need to be collected.
10. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period) was revised to 
denote those study procedures that should be conducted on the same day of 
investigational product administration on Day 1.
11. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period) and Table 5.1-2 
(Schedule of Study Procedures for the 85-day Follow-up Period) were clarified to state 
that serum collection for proteomics/biomarkers was optional. Section 5.1.2.1 (Week 0; 
Day 1: First Infusion [Visit 1]), Section 5.1.2.3 (Every 12 Weeks; Weeks 12, 24, 36, 48, 
60, 72, 84 and 96 [Visits 4, 7, 10, 13, 16, 19, 22 and 25]), Section 5.1.2.4 (Every 24 
Weeks; Weeks 24, 48, 72 and 96 [Visits 7, 13, 19 and 25]), Section 5.1.2.6 (Week 104; 
Last Treatment Visit [Visit 27]), Section 5.1.3.1 (28 Days after the Last Dose [+/- 7 
Days]): First Safety Follow-up Visit or Early Discontinuation Visit [Visit 28]), and 
Section 5.1.3.3 (85 Days after the Last Dose [+/- 7 Days]): Third Safety Follow-up Visit 
[Visit 30]) were also clarified to state that the serum sample collection for 
proteomics/biomarkers was optional.
12. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]) was reorganized to indicate 
assessments that need to be completed before using data from Study CD-IA-MEDI-546-
1013, assessments that need to be completed on the same day as investigational product 
dosing, and assessments where data from Day 422 [+ 28 days] of Study CD-IA-MEDI-
546-1013 can be used for this study.
13. Section 5.2.4 (Tuberculosis Testing) was modified to add information for subjects who 
may have had recent contact with anyone with active TB or who show signs or symptoms 
of active TB. Also added information for when a subject should be discontinued from the 
study due to active TB or discontinuation/noncompliance with latent TB treatment.

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14. Section 5.2.5 (Clinical Laboratory Tests) was modified to include information that any 
female subject who is postmenopausal based on documented results from the serum 
follicle-stimulating hormone test in any previous study (including 
Study CD-IA-MEDI-546-1013) will not require urine HCG tests in this study. Any 
female subject who feels that they have had a change in status to postmenopausal at any 
point during this study can request a serum follicle-stimulating hormone test. If the 
results show that the subject is postmenopausal, then the subject will not require any 
further urine HCG tests.
15. Section 5.2.9 (Optional Proteomics/Biomarkers) was modified to add that serum for 
proteomics/biomarkers will only be collected from subjects who provide written consent 
for this procedure.
16. Section 6.4.3.2 (Hepatic Function Abnormality) and Section 6.5 (Safety Management 
During the Study) were revised to remove reference to the the MedImmune Safety 
Monitoring Committee, as this committee no longer exists. A MedImmune safety review 
committee, which includes, but is not limited to, appropriate representatives from Patient 
Safety, Clinical Development, and Regulatory Affairs, will review the protocol-specific 
safety data.
17. Appendix 1 (Signatures) was modified to remove signature sheets for Stephen Yoo, MD, 
Liangwei Wang, PhD, and Theodore Phillips, as their signatures are no longer required, 
per change in the sponsor’s standard operating procedure for protocols. Added signature 
sheet for Jorn Drappa, MD, whose signature is now required, per change in the sponsor’s 
standard operating procedure for protocols.
Protocol Amendment 4, 12Feb2015
Text revisions resulting from this amendment are incorporated in the body of Protocol 
Amendment 4. Major changes to the protocol are summarized below.
1. Study Abstract (Study Design) and Section 3.1 (Overview of Study Design) - clarified 
that subjects in this study will be adult male or female subjects with chronic, moderately-
to-severely active SLE who were previously treated with investigational product (MEDI-
546 or placebo) and completed Study CD-IA-MEDI-546-1013 through treatment and 
follow-up (with the exception of those subjects in the regions of Donetsk and Lugansk in 
the Ukraine, where the political situation necessitated a suspension of study activities).
2. Study Abstract (Study Design, Treatment Regimen), Section 1.3 (Research Hypothesis), 
Section 3.1 (Overview of Study Design), Figure 3.1-1 (Study Flow Diagram), Section 
3.4.1 (Rationale for Study Design), Section 3.4.2 (Rationale for MEDI-546 Dose),
Section 4.5.3 (Treatment Regimen), Section 4.5.4.1 (Dose Calculation), Table 4.5.4.1-1 
(Dose Calculation for MEDI-546 Drug Product for IV Infusion), and Section 5.1 
(Schedule of Study Procedures) - changed dose of MEDI-546 from 1000 to 300 mg as the 
efficacy and safety data from Study CD-IA-MEDI-546-1013 indicated that the 300 mg 
dose had a more favorable benefit:risk profile than the 1000 mg dose for subjects with 
chronic, moderately-to-severely active SLE.
3. Study Abstract (Study Design), Section 3.1 (Overview of Study Design), Figure 3.1-1 
(Study Flow Diagram), and Section 4.5.5 (Treatment Administration) - changed IV 

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infusion time from approximately 60 minutes to at least 30 minutes as the efficacy and 
safety data from Study CD-IA-MEDI-546-1013 indicated that the 300 mg dose had a 
more favorable benefit:risk profile than the 1000 mg dose for subjects with chronic, 
moderately-to-severely active SLE.
4. Study Abstract (Study Design, Treatment Regimen), Section 3.1 (Overview of Study 
Design), Figure 3.1-1 (Study Flow Diagram), and Section 4.5.3 (Treatment 
Regimen) - changed the duration of investigational product administration from 2 to 
3 years. This change was made to collect more long-term safety data with MEDI-546.
5. Study Abstract (Study Design), Section 3.1 (Overview of Study Design) and Section 
3.4.2 (Rationale for MEDI-546 Dose) - removed sentence that stated that as additional 
MEDI-546 data became available, if another dose is determined to be the optimal dose, 
the protocol would be amended. This change was made based on efficacy and safety data 
from Study CD-IA-MEDI-546-1013 that indicated that the 300 mg dose had a more 
favorable benefit:risk profile than the 1000 mg dose for subjects with chronic, 
moderately-to-severely active SLE.
6. Study Abstract (Sample Size and Power Calculations), Section 1.2.3 (Summary of 
Clinical Experience), and Section 7.5 (Sample Size and Power Calculation) - updated 
sections to state that a total of 307 subjects have been randomized in Study CD-IA-
MEDI-546-1013.   
7. Section 1.2.2 (Summary of Nonclinical Experience) - updated findings from the 9-month 
repeated-dose toxicity study to state that even though the arteritis findings in male 
animals may be a consequence of species-specific immunogenicity and its relevance to 
human safety is unknown, the possibility of other factors than production of antibodies to 
MEDI-546 cannot be ruled out. Also updated findings to the ePPND study to state that 
the number of stillbirths was comparable to the control group and the testing facility’s 
historical incidence data and the growth and development of the infants were within 
normal limits for infant cynomolgus monkeys, including immune assessments keyhole 
limpet hemocyanin immunization IgM and IgG titer values, peripheral blood 
immunophenotyping, hematology analyses, and lymphoid organ histopathology (spleen, 
thymus, and lymph nodes).
8. Section 1.2.3 (Summary of Clinical Experience) - revised summary of Study MI-CP180 
for brevity; updated summary to state that an interim analysis of Study CD-IA-MEDI-
546-1013 had been conducted; and added a summary for Study D3461C00002, a Phase 2, 
multicenter, open-label, dose-escalation study to evaluate the safety and tolerability of 
MEDI-546 in adult Japanese subjects with active SLE.
9. Section 3.2 (Estimated Duration of Subject Population) - updated the duration of study 
participation based on the extension of the study from 2 to 3 years.
10. Section 3.4.2 (Rationale for MEDI-546 Dose) - updated that rationale for the MEDI-546 
dose and reduced infusion time in the OLE study. Based on the analysis of both efficacy 
and safety data from Study CD-IA-MEDI-546-1013, the Sponsor has determined that the 
300 mg dose has a more favorable benefit-risk profile than the 1000 mg dose for subjects 
with chronic, moderately-to-severely active SLE. Population modeling has demonstrated 
clinically meaningful benefit at 300 mg, with no incremental benefit at 1000 mg and also 
has predicted inadequate PK exposure and suboptimal efficacy at doses lower than 
300 mg. In addition, as the dose of 1000 mg has been administered repeatedly over

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60 minutes at a rate of 16.7 mg/min with no increased frequency of infusion related 
reactions, administering 300 mg over 30 minutes at a rate of 10 mg/min will not result in 
any increased risk to the subject for infusion related reactions. It should be noted that the 
DSMB has not made any recommendations to modify this study (including any changes 
in dose) or Study CD-IA-MEDI-546-1013, based on an ongoing review of safety data 
from both studies.
11. Section 4.2.1 (Inclusion Criteria) - modified Inclusion Criterion 2 to state that subjects 
must have qualified for and received investigational product (MEDI-546 or placebo) and 
completed the treatment period plus the follow-up period (through Day 422) in Study 
CD-IA-MEDI-546-1013. Subjects who discontinued from Study CD-IA-MEDI-546-1013 
are not eligible for this study, unless active participation was solely prevented by local 
governmental instability due to political unrest and all other inclusion and exclusion 
criteria were met. This criterion was modified because subjects in the regions of Donetsk 
and Lugansk in the Ukraine, where the political situation necessitated a suspension of 
study activities, may have been unable to complete all of the visits in 
Study CD-IA-MEDI-546-1013.
12. Section 4.2.3 (Withdrawal Criteria) - clarified Criterion 8 to state that “Receipt of any of 
the following medications (other than MEDI-546 administered as per protocol) any time 
from the last MEDI-546 dose in Study CD-IA-MEDI-546-1013 to 85 days post last 
MEDI-546 dose Study CD-IA-MEDI-546-1145...” would result in permanent 
discontinuation of investigational product.
13. Section 4.2.3 (Withdrawal Criteria), Section 4.5.2 (Other Study Medications), Section 
4.5.2.1 (Corticosteroids), and Section 4.6.1 (Permitted Non-SLE Concomitant 
Medications) - clarified that for subjects who have an increase in OCS treatment above a 
total dose > 40 mg/day for a dosing period > 14 days, dosing with MEDI-546 may be 
continued, unless there is a safety concern. Also added the statement that frequent steroid 
use above Study CD-IA-MEDI-546-1013 baseline for SLE disease control (> 2 times 
every 6 months, higher doses [> 40 mg/day], and/or longer duration than permitted by the 
protocol) after 12 months of open-label MEDI-546 should result in discontinuation of 
MEDI-546 administration for failure to achieve a favorable benefit:risk profile.
14. Section 4.5.2.2 (Slow-acting Immunosuppressants) - removed “antimalarials” as there 
were no antimalarials on the list.
15. Section 4.5.3 (Treatment Regimen) - clarified that subjects will receive MEDI-546 
300 mg administered as an IV infusion Q4W starting at Day 1 (Week 0) or the visit 
following approval of this amendment (for those subjects who have already been dosed in 
this study) for up to 3 years or until the sponsor discontinues development of MEDI 546 
for SLE, whichever comes first.
16. Table 4.5.4.1-1(Dose Calculation for MEDI-546 Drug Product for IV Infusion) - changed 
volume for IV infusion based on the new dose (300 mg) of MEDI-546.
17. Section 4.5.4.2 (Investigational Product Inspection) - changed the description of 
MEDI-546 from “clear, colorless” to “clear, colorless to slightly yellow liquid” to be 
consistent with the current formulation of the investigational product.
18. Table 4.5.4.3-1 (Dose Preparation for MEDI-546) - changed volume of saline removed 
from IV infusion bag, volume of MEDI-546 drug product added to IV infusion bag, 

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number of vials to be used, and recommended type of syringe to be used, based on the 
new dose (300 mg) of MEDI-546.
19. Section 4.5.6 (Monitoring of Dose Administration) and Section 5.2.3 (Vital Signs) -
clarified that vital signs will be measured until stable and the subject is ready for 
discharged as judged by the investigator.
20. Table 5.1-1 (Schedule of Study Procedures for the Treatment Period) - added additional 
weeks (Weeks 108-156) and visits (Visits 27-40) to the treatment period to extend the 
treatment period by an additional year; listed out week and visit numbers for the Q4W 
column for clarity; removed duplicate line for assessment of Cushingoid features; added 
ECG assessments, which were inadvertently removed during a previous amendment, to 
Day 1, Q48W, and LTV; clarified that HBV DNA should be < 29 IU/mL to be 
considered undetectable; clarified that QFT-GIT test is to be performed only if it was 
negative or if it was indeterminate at any visit during Study CD-IA-MEDI-546-1013 and 
also added QFT-GIT assessments to Q48W and LTV; added Pap smear at Week 144 
(Visit 37); clarified that the SLICC referred to the SLICC/ACR Damage Index; clarified 
that the investigator flare question is to assess worsening and/or flare of SLE disease 
activity; added that subjects should be evaluated for signs and symptoms of TB using a
TB surveillance form at Day 1, Q4W, Q12W, Q24W, Q48W, and LTV.
21. Table 5.1-2 (Schedule of Study Procedures for the 85-day Follow-up Period) -
renumbered follow-up visits (to Visits 41-43), which follow the extended treatment 
period; added that subjects should be evaluated for signs and symptoms of TB using a TB 
surveillance form at V41, V42, and V43; clarified that the SLICC assessment included 
ACR; and clarified that the investigator flare question is to assess worsening and/or flare 
of SLE disease activity.
22. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 (Every 4 Weeks; 
Weeks 4 to 152: Second through Thirty-ninth Infusion [Visits 2 to 39]), and Section 
5.1.2.6 (Week 156; Last Treatment Visit [Visit 40]) - removed vital signs assessment 
(formerly Number [No.] 7) as vital signs will be taken before administration of 
investigational product (within 15 minutes of the beginning of the investigational product 
infusion; now No. 16); clarified that ECGs are required at Day 1 if not done at Day 396 
of Study CD-IA-MEDI-546-1013; moved assessment for Cushingoid features from 
No. 21 to No. 8 (and added that if this assessment was performed on Day 365 of Study 
CD-IA-MEDI-546-1013, then data can also be used for Day 1 of this study); clarified that 
for all remaining assessments, if Day 1 of this study occurs on the same day as Day 422 
(+ 28 days) of Study CD IA MEDI-546-1013, then the procedures and samples can be 
collected one time and can be utilized for both studies, and that if Day 1 of this study 
does not occur on the same day as Day 422 (+ 28 days) of Study CD-IA-MEDI-546-
1013, then the procedures and samples should be collected at Day 1; moved assessment 
for physical examination from No. 17 to No. 9; and combined collection of all predose 
blood samples (formerly No. 9 and No. 19) under No. 10.
23. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 (Every 4 Weeks; 
Weeks 4 to 152: Second through Thirty-ninth Infusion [Visits 2 to 39]), Section 5.1.2.6 
(Week 156; Last Treatment Visit [Visit 40]), Section 5.1.3.1 (28 Days after the Last Dose 
[± 7 Days]): First Safety Follow-up Visit or early Discontinuation Visit [Visit 41]), 
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[Visit 42]), Section 5.1.3.3 (85 Days after the Last Dose [± 7 Days]: Third Safety 
Follow-up Visit [Visit 43]), and Section 5.1.4 (Unscheduled Visit) - clarified that in 
addition to assessing worsening and/or flare of SLE disease activity using the SLE 
Increase in Disease Activity CRF, complete the CRF for SLE related AEs that are not 
serious, if applicable.
24. Section 5.1.2.1 (Week 0; Day 1: First Infusion [Visit 1]), Section 5.1.2.2 (Every 4 Weeks; 
Weeks 4 to 152: Second through Thirty-ninth Infusion [Visits 2 to 39]), Section 5.1.2.6 
(Week 156; Last Treatment Visit [Visit 40]), Section 5.1.3.1 (28 Days after the Last Dose 
[± 7 Days]): First Safety Follow-up Visit or early Discontinuation Visit [Visit 41]), 
Section 5.1.3.2 (59 Days after the Last Dose [± 7 Days]: Second Safety Follow-up Visit 
[Visit 42]), Section 5.1.3.3 (85 Days after the Last Dose [± 7 Days]: Third Safety 
Follow-up Visit [Visit 43]), and Section 5.1.4 (Unscheduled Visit) - added procedure that 
subjects should be evaluated for signs and symptoms of TB using a TB surveillance form.
25. Section 5.1.2.2 (Every 4 Weeks; Weeks 4 to 152: Second through Thirty-ninth Infusion 
[Visits 2 to 39]), Section 5.1.2.6 (Week 156; Last Treatment Visit [Visit 40]), and Section 
5.2.5 (Clinical Laboratory Tests) - clarified for hepatitis B virus DNA PCR TaqMan 
assessment, subjects with isolated hepatitis B core antibody positivity during Study CD 
IA MEDI 546-1013 or at any time for the duration of this study will be tested monthly for 
HBV DNA. To remain eligible for this study, the subject’s HBV DNA levels must 
remain undetectable as per the central lab (ie, < 29 IU/mL HBV DNA detected).
26. Section 5.1.2.2 (Every 4 Weeks; Weeks 4 to 152: Second through Thirty-ninth Infusion 
[Visits 2 to 39]) - renumbered individual weeks (Weeks 4 to 152), infusions (second 
through thirty-ninth), and visits (Visits 2-39) for clarity and consistency; changed “Week 
100” to “Week 152” due to the extension of the treatment period by an additional year; 
removed “if indicated” from “Take vital signs (BP, pulse, respiration, and temperature, if 
indicated)”, as temperature should always be taken after administration of investigational 
product, and added that vital signs should be taken “...until the subject is stable and ready 
for discharge (as judged by the investigator)”; and removed vital signs assessment (No. 2) 
since vitals are taken during administration of investigational product (No. 7).
27. Section 5.1.2.3 (Every 12 Weeks; Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 
and 144 [Visits 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, and 37]) - added weeks (Weeks 
108, 120, 132, and 144) and visits (Visits 28, 31, 34, and 37) to Q12W assessments due 
to the extension of the treatment period by an additional year; added immunogenicity 
assessment at Week 36; and removed SLICC/ACR Damage Index assessment since the 
frequency of this assessment is better suited for every 24 weeks (see Section 5.1.2.4).
28. Section 5.1.2.4 (Every 24 Weeks; Weeks 24, 48, 72, 96, 120 and 144 [Visits 7, 13, 19, 
25, 31, and 37]) - added weeks (Weeks 120 and 144) and visits (Visits 31 and 37) to 
Q24W assessments due to the extension of the treatment period by an additional year; 
clarified that only collection of predose blood samples are to be performed every 
24 Weeks (Q24W) starting at Week 72; and added SLICC/ACR Damage Index 
assessment as it is more appropriate to evaluate this tool at 6-month intervals. 
29. Section 5.1.2.5 (Every 48 Weeks; Weeks 48, 96, and 144 [Visits 13, 25, and 37]) - added 
week (Week 144) and visit (Visit 37) to Q48W assessments due to the extension of the 
treatment period by an additional year and added Pap smear assessment for females only 
at Week 144 (Visit 37) as additional safety surveillance.

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30. Section 5.1.2.6 (Week 156; Last Treatment Visit [Visit 40]) - renumbered week 
(Week 156) and visit (Visit 40) due to the extension of the treatment period by an 
additional year; added procedures for administering investigational product and assessing 
for AEs/SAEs/AESIs, which had been inadvertently omitted; added step (No. 10) for 
administration of investigational product and taking vital signs during administration of 
investigational product. Added performance of SLEDAI-2K for consistency with the 
schedule of study procedures.
31. Section 5.1.3.1 (28 Days after the Last Dose [+/- 7 Days]: First Safety Follow-up Visit or 
Early Discontinuation Visit [Visit 41]) - renumbered follow-up visit due to the extension 
of the treatment period by an additional year.
32. Section 5.1.3.2 (59 Days after the Last Dose [+/- 7 Days]: Second Safety Follow-up Visit 
[Visit 42]) - renumbered follow-up visit due to the extension of the treatment period by 
an additional year.
33. Section 5.1.3.3 (85 Days after the Last Dose [+/- 7 Days]: Third Safety Follow-up Visit 
[Visit 43]) - renumbered follow-up visit due to the extension of the treatment period by 
an additional year.
34. Section 5.2.1 (Medical History) - clarified that only new events or worsening of previous 
events that occur between Day 422 of Study CD IA-MEDI-546-1013 and prior to signing 
the informed consent of Study CD-IA-MEDI-546-1145 should be recorded in the 
Medical History CRF and removed text regarding non-SLE medical history being 
captured for the 6 months prior to study; non-SLE medical history would be captured in 
the source documents.
35. Section 5.2.2 (Physical Examination, ECG, Weight, Cushingoid Features and Pap Smear) 
- clarified that any medically significant changes from the Study CD-IA-MEDI-546-1013 
Day 396 ECG will be recorded as an AE. Details regarding the use of a Pap smear were 
added to this section.
36. Section 5.2.4 (Tuberculosis Testing) - clarified QFT-GIT testing, including what should 
be done for TB surveillance and/or treatment for indeterminate and positive results.
37. Section 5.2.13 (Adverse Events of Special Interest) - removed statement that subjects will 
be evaluated for signs and symptoms of TB at every visit, as this is now stated in Section 
5.2.4 (Tuberculosis Testing).
38. Section 5.2.14 (SLE Flares and Increase in SLE Disease Activity) - clarified that the SLE 
Increase in Disease Activity CRF does not need to be completed for SAEs of SLE 
Increase in Disease Activity.
39. Table 5.2.16-1 (Estimated Volume of Blood to be Collected per Visit) - updated blood 
volumes due to the additional TB testing at the other study visits and extension of the 
treatment period by an additional year.
40. Section 6.1.1 (Adverse Events) - Added text to clarify that only laboratory abnormalities 
resulting in clinical sequelae should be recorded as AEs.
41. Section 6.1.3.1 (Hepatic Function Abnormality) and Section 6.4.3.2 (Hepatic Function 
Abnormality) - added that if ALT or AST is greater than 3 × ULN, refer to Guidance for 
Abnormal Liver Function Tests Management in Appendix 8.
42. Section 6.1.3.2 (New or Reactivated and Latent TB Infection) - Added language defining 
latent TB infection.

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43. Section 6.2.1 (Assessment of Severity) - corrected the definition of Grade 4 (life 
threatening) AEs/SAEs to remove reference to disabilities, which was previously 
inadvertently added to this definition.
44. Section 6.5 (Safety Management During the Study) - clarified the members of the 
MedImmune safety review committee.
45. Appendix 8 (Guidance for Abnormal Liver Function Tests) - added appendix for 
guidance for abnormal liver function tests management.

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Appendix 1
Signatures

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Sponsor Signature(s) 
A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in 
Adults with Systemic Lupus Erythematosus
I agree to the terms of this protocol.
Signature and date: 
[electronic signature appended]
 

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Signature of Coordinating Investigator
A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in 
Adults with Systemic Lupus Erythematosus
I, the undersigned, have reviewed this protocol and I agree to conduct this protocol in 
accordance with ethical principles that have their origin in the Declaration of Helsinki and 
are consistent with the International Conference on Harmonisation (ICH) guidelines on Good 
Clinical Practice (GCP), any applicable laws and requirements, and any conditions required 
by a regulatory authority and/or Institutional Review Board/Independent Ethics Committee 
(IRB/IEC). 
I understand that the protocol may not be modified without written approval of the sponsor. 
All changes to the protocol must be submitted to the applicable regulatory authority and 
IRB/IEC, and must be approved by the IRB/IEC prior to implementation except when 
necessary to eliminate immediate hazards to the subjects or when the change(s), as deemed 
by the sponsor, involves only logistical or administrative changes. Documentation of 
IRB/IEC approval must be sent to the sponsor immediately upon receipt.
Signature and date: 
Name and title: 
Address including postal code: 
Telephone number: 
Site/Center Number (if available or applicable)
This document contains confidential information, which should not be copied, referred to, released, or published 
without written approval from MedImmune or AstraZeneca. Investigators are cautioned that the information in 
this protocol may be subject to change and revision.

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Signature of Principal Investigator
A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in 
Adults with Systemic Lupus Erythematosus
I, the undersigned, have reviewed this protocol, and I agree to conduct this protocol in 
accordance with ethical principles that have their origin in the Declaration of Helsinki and 
are consistent with the International Conference on Harmonisation (ICH) guidelines on Good 
Clinical Practice (GCP), any applicable laws and requirements, and any conditions required 
by a regulatory authority and/or Institutional Review Board/Independent Ethics Committee 
(IRB/IEC). 
I understand that the protocol may not be modified without written approval of the sponsor. 
All changes to the protocol must be submitted to the applicable regulatory authority and 
IRB/IEC, and must be approved by the IRB/IEC prior to implementation except when 
necessary to eliminate immediate hazards to the subjects or when the change(s), as deemed 
by the sponsor, involves only logistical or administrative changes. Documentation of 
IRB/IEC approval must be sent to the sponsor immediately upon receipt.
Signature and date: 
Name and title: 
Address including postal code: 
Telephone number: 
Site/Center Number (if available)
This document contains confidential information, which should not be copied, referred to, released, or published 
without written approval from MedImmune or AstraZeneca. Investigators are cautioned that the information in 
this protocol may be subject to change and revision.

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Appendix 2
General Guidance for Determination of Major Surgery
The goal of this guidance is to maximize the risk/benefit for each subject entering this study. 
An important aspect to this goal is taking into account all relevant history, including recent 
surgeries and/or injuries which could influence the safety of the subject potentially being 
exposed to an additional immunomodulatory medication or could bias the efficacy endpoints 
of the trial.
Given the advancement and availability of surgical techniques, major surgery is in the 
judgment of the investigator and his/her evaluation of the following criteria, regardless of the 
specific surgical procedure:
1. Has the subject completely recovered (mentally, emotionally, and physically) from the 
surgery and is not receiving additional medications related to the prior surgery (ie, 
antibiotics)?
2. Has the subject completed all follow-up visits related to the surgery, including ancillary 
services such as physical and/or occupational therapy?
3. Has the subject resumed all of their prior activities?
4. Has the subject returned to his/her baseline medications for SLE and non-SLE 
indications?

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Appendix 3
Restricted Medications
Medication
Discontinuation Prior to 
Signing of Informed 
Consent Form
Medication
Discontinuation Prior to 
Signing of Informed 
Consent Form
Abatacept (CTLA 4 Ig)
24 weeks
Immunosuppressants
Washout Time
Adalimumab
12 weeks
Infliximab
12 weeks
Alefacept
12 weeks
Intravenous Globulin
4 weeks
AMG 623
48 weeks
IPP-201101
12 weeks
Anakinra
12 weeks
Leflunomide
36 weeks
Atacicept (TACI-Ig)
12 weeks
Lenalidomide
8 weeks
Belimumab
48 weeks
Memantine
4 weeks
Biologics (eg, IFN)
Washout Time
Natalizumab
24 weeks
Certolizumab pegol
24 weeks
Ocrelizumab
48 weeks
Cyclophosphamide
24 weeks
Pimecrolimus
4 weeks
Cyclosporine
4 weeks
Plasmapheresis
24 weeks
Danazol
4 weeks
Retinoids
4 weeks
Dapsone
4 weeks
Rituximab
48 weeks
Eculizumab
12 weeks
Sulfasalazine
4 weeks
Efalizumab
12 weeks
Sirolimus
4 weeks
Epratuzumab
24 weeks
Tacrolimus
4 weeks
Etanercept
4 weeks
Thalidomide
8 weeks
Golimumab
12 weeks
Tocilizumab
12 weeks

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Appendix 4
Vasculitic Syndromes Excluded from the Study
Subjects with a history of, or current diagnosis of the following vasculitis syndromes, are 
excluded from participating in the study. Vasculitis due to SLE is allowed in the study.
•
Behçet’s Disease
•
Buerger’s Disease
•
Central Nervous System Vasculitis
•
Churg Strauss Syndrome
•
Cryoglobulinemia
•
Giant Cell Arteritis
•
Henoch-Schönlein Purpura
•
Kawasaki Disease
•
Microscopic Polyangiitis
•
Polyarteritis Nodosa
•
Polymyalgia Rheumatica
•
Takayasu’s Arteritis
•
Wegener’s Granulomatosis

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Appendix 5
Data and Safety Monitoring Board Membership
The DSMB is a multidisciplinary group, independent of MedImmune, consisting of two 
clinicians in the field of Rheumatology, one clinician in Infectious Disease, and one 
Biostatistician who, collectively, have experience with SLE and in the conduct and 
monitoring of randomized clinical trials; the Biostatistician will be a non-voting member. 
Membership Requirements
•
DSMB members will not act as investigators or sub-investigators for this study and will 
have no study involvement outside their role on the DSMB
•
Data must be treated with confidentiality
•
Members must have no financial interest in MedImmune or competitors that would be 
expected to bias their participation
•
Members cannot have a conflict of interest that materially may influence their judgment
Responsibilities and Function of the DSMB
The DSMB is established to provide an independent review and assessment of the 
accumulating safety data and to further safeguard the interests and safety of the participating 
subjects. The primary role of the DSMB is to make a recommendation to MedImmune 
regarding the safety of the study based on analysis of available data.
MedImmune is jointly responsible with the DSMB for safeguarding the interests of 
participating subjects and for the conduct of the study. The medical monitor must notify the 
DSMB regarding any new safety information related to the investigational product and 
development program (eg, toxicology information, potential safety signals, etc), other related 
products under development by the sponsor or another organization, or any other issues that 
might affect the DSMB’s review of this study. The MedImmune medical monitor may ask, if 
required, for an ad hoc DSMB meeting.
Review of Safety Summary Data
The DSMB is an advisory to the sponsor and will review summary tables of selected safety 
data (ie, laboratory values and adverse events). Adverse events of special interest will also be 
reviewed including new or reactivation of TB infections, herpes zoster infections, 
malignancy, infusion, hypersensitivity, or anaphylactic reactions, and vasculitis. 

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Periodic Review of the Data
The DSMB will meet periodically and review aggregate data on the adverse events and 
laboratory assessments in summary tables and listings.
The DSMB will use a priori defined and, when appropriate, ad hoc analyses to assess safety. 
The DSMB will utilize all available study data when forming any recommendation to 
discontinue the study. 
The DSMB will be responsible for ensuring the timely review of the accumulated safety data. 
Based on the reviews and assessments of the data, the DSMB will notify the MedImmune 
medical monitor (or designee) when safety concerns lead to a recommendation to alter the 
conduct of the study.
Reporting of DSMB
The chairman of the DSMB is responsible for providing a summary of the recommendations 
after each meeting to the designated personnel at MedImmune.
The summary will clearly communicate recommendations, which will include:
1. Study can continue as planned
2. Additional safety data are needed
3. Study must be suspended
4. Study must be permanently discontinued
5. Study must be modified such as:
•
Changes in enrollment criteria
•
Changes in safety rules 
•
Changes in stopping rules
•
Changes in dose

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Appendix 6
Oral Corticosteroid Guidance
Oral corticosteroid doses up to 40 mg/day of prednisone or equivalent are permitted at study 
entry. Examples of equivalent doses are provided in the table below. Based on the opinion of 
the investigator, OCS doses should be tapered throughout the entire study as permitted by the 
protocol. Oral corticosteroid tapering must not occur until after all assessments have been 
completed and investigational product has been administered. 
Examples of Equivalent Doses of Oral Prednisone
Oral Prednisone 
and Equivalents
Equivalent Dose
Oral Prednisone 
10 mg
20 mg
30 mg
40 mg
Cortisone
50 mg
100 mg
150 mg
200 mg
Hydrocortisone
40 mg
80 mg
120 mg
160 mg
Methylprednisolone
8 mg
16 mg
24 mg
32 mg
Prednisolone
10 mg
20 mg
30 mg
40 mg
Triamcinolone
8 mg
16 mg
24 mg
32 mg
If a subject experiences an increase in disease activity secondary to tapering of OCS, the 
daily OCS dose may be returned to the last dose that was used immediately prior to the most 
recent OCS dose taper. If the subject does not re-achieve an improvement in disease activity, 
then the daily OCS dose may be increased to the dose administered at Day 1.
If the subject re-achieves an improvement in disease activity, then further daily OCS dose 
tapering can resume with a smaller reduction of the daily OCS dose, at the discretion of the 
investigator. However, if the subject does not re-achieve an improvement in disease activity, 
then the investigator may continue to follow the subject expectantly to determine if the 
subject’s disease activity will stabilize similar to that at Day 1, will improve over time, or 
worsen significantly compared to Day 1 requiring a change in background medications.
It is up to the investigator to determine at a given visit what oral prednisone or equivalent 
dose reduction, if any, is desirable. 

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Example of OCS Tapering Schedule
Visit
Initial Dose of Oral Prednisone or Equivalent
40 mg
30 mg
20 mg
10 mg
Day 29
30 mg
25 mg
15 mg
10 mg
Day 43
25 mg
20 mg
10 mg
10 mg
Day 57
15 mg
15 mg
10 mg
7.5 mg
Day 71
10 mg
10 mg
7.5 mg
7.5 mg
Day 85
7.5 mg
7.5 mg
7.5 mg
7.5 mg

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Appendix 7
Short Form-36 Version 2

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Appendix 8
Guidance for Abnormal Liver Function Tests 
Management
This guidance is based on the July 2009 Guidance for Industry Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation.
Section IV of the US FDA document deals with the clinical evaluation of and monitoring 
of drug-induced liver injury, and this protocol-specific guidance has adopted the 
recommendations on detection of drug-induced liver disease, confirmation of abnormal 
ALT/AST with regard to retesting, follow-up observation, advice on appropriate history 
gathering and advice on the need for obtaining additional laboratory tests and 
consultations as needed. MedImmune has adopted a conservative approach to holding 
administration of investigational product based on abnormal liver function tests (LFTs) 
until a full understanding of the event has been understood by the principle investigator 
and the medical monitor. This understanding is required so that the principle investigator, 
in consultation with the medical monitor, can reach a decision as to whether dosing can 
be continued or whether it is advisable to stop investigational product permanently. The 
US FDA document acknowledges there is no published consensus on how this decision 
should be made but this protocol-specific guidance requires involvement of the medical 
monitor at any early stage of clinically significant increases in ALT/AST to provide 
additional information on accumulating clinical experience of MEDI-546 as well as input 
from the investigator regarding the nature of the subject and other factors that may be 
relevant. This approach will provide the balance necessary to permit learning about the 
investigational product while maximizing safety concerns to minimize the potential for 
functional liver impairment and damage. There are 2 separate parts to the guidance to 
detect clinically significant liver injury depending on whether the subject entered the 
study with normal or mildly elevated (up to 2 × ULN) ALT/AST or on more severe 
abnormalities in subjects with ALT/AST > 2 × ULN at baseline.
For the purpose of this document, LFTs will be AST, ALT, total bilirubin, and alkaline 
phosphatase.
The decision to include subjects in this clinical trial with baseline LFT abnormalities is 
supported by the US FDA guidance.
Copies of the document “Guidance of Industry Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation” can be located at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
s/UCM174090.pdf

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Guidance for abnormal LFTs that develop post-screening in subjects with ALT/AST 
≤2 × ULN at screening due to liver involvement by SLE in the opinion of the 
investigator:

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ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international normalization ratio; 
LFT = liver function test; MTX = methotrexate; NSAID = non-steroidal anti-inflammatory drug; PT = 
prothrombin time; RUQ = right upper quadrant; SLE = systemic lupus erythematosus; ULN = upper limit of 
normal 

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Guidance for abnormal LFTs that develop post-screening in subjects with ALT/AST 
≤2 × ULN at screening due to liver involvement by SLE in the opinion of the 
investigator:

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ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; CPK = 
creatinine phosphokinase; EBV = Epstein-Barr virus; GI = gastrointestinal; INH = isoniazid; INR = 
international normalization ratio; LFT = liver function test; MTX = methotrexate; NSAID = non-steroidal anti-
inflammatory drug; PT = prothrombin time; RUQ = right upper quadrant; SLE = systemic lupus erythematosus; 
ULN = upper limit of normal

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Guidance for abnormal LFTs that develop post-screening in subjects with ALT/AST 
> 2 × ULN at screening due to liver involvement by SLE in the opinion of the 
investigator:

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ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; CPK = 
creatinine phosphokinase; EBV = Epstein-Barr virus; GI = gastrointestinal; INH = isoniazid; INR = 
international normalization ratio; LFT = liver function test; MTX = methotrexate; NSAID = non-steroidal anti-
inflammatory drugs; PT = prothrombin time; RUQ = right upper quadrant; SLE = systemic lupus 
erythematosus; ULN = upper limit of normal

SIGNATURE PAGE
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic signature
Document Name: protocol-cd-ia-medi-546-1145-csp-5-amendment-4
Document Title:
CSP Version 5 Amendment 4
Document ID:
Doc ID-002311812
Version Label:
1.0 CURRENT LATEST APPROVED
Server Date
(dd-MMM-yyyy HH:mm ‘UTC’Z)
Signed by
Meaning of Signature
16-Feb-2015 20:21 UTC
Clinical Development
Approval
Notes: (1) Document details as stored in ANGEL, an AstraZeneca document management system.