BEL114333, a Multicenter, Continuation Study of Belimumab in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed the Phase III Study BEL113750 in Northeast Asia or Completed the Open-label Extension of HGS1006-C1115 in Japan
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Sponsor: GlaxoSmithKline

YM2010/00145/03
CONFIDENTIAL
The GlaxoSmithKline group of companies
BEL114333
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
BEL114333, a multicenter, continuation study of belimumab in 
subjects with systemic lupus erythematosus (SLE) who 
completed the phase III study BEL113750 in Northeast Asia or 
completed the open-label extension of HGS1006-C1115 in Japan
Compound Number:
GSK1550188
Development Phase:
III
Effective Date:
16-MAY-2014
Protocol Amendment Number:  3
Authors:
 (Immuno-Inflammation Therapy Area); 
 
(Immuno-Inflammation Therapy Area); 
 (Global Clinical Safety and 
Pharmacovigilance); 
 (Immuno-Inflammation Therapy Area –
Statistics and Programming); 
 (Immuno-Inflammation Therapy Area); 
 (Clinical Pharmacology Modelling & Simulation)
Copyright 2014 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD
PPD
PPD
PPD

YM2010/00145/03
CONFIDENTIAL
The GlaxoSmithKline group of companies
BEL114333
2
Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
YM2010/00145/00
2011-NOV-18
Original
YM2010/00145/01
2012-MAR-27
Amendment No. 1
Addition of inadvertently omitted sentence in Protocol Summary Study Design Section 
Addition in Section 4.2 Inclusion Criteria of supplemental birth control recommendation 
for subjects taking MMF
Modification of Section 4.4 Withdrawal Criteria redundant item
Modification of Section 5 for the addition of a 3-hour clinical supervision time after 
subjects receive the first 2 infusions
Addition of footnote to Section 6 Time and Events Table (Year 1 only) for 3-hour clinical 
supervision after subjects receive the first 2 infusions 
Addition of footnote to Section 6 Time and Events Table (Additional Years) for 
Laboratory Test clarification
Modification of Section 6.3.9 for the addition of a 3-hour clinical supervision time after 
subjects receive the first 2 infusions
Deletion of 2 clinical laboratory tests in Appendix 5 inadvertently listed
Correction of minor typographical errors and consistency errors
YM2010/00145/02
2012-JUL-17
Amendment No. 2
Addition of Protocol Summary Study Design B-cell subset labs
Modification of Protocol Summary Study Design immunogenicity labs at 6 months post 
last dose
Clarification of Protocol Summary Study Endpoint/Assessments for B-cell subsets at 
selected sites
Modification of Section 3.1 immunogenicity labs at 6 months post last dose
Clarification of Section 3.1 for B-cell subsets lab collection times at selected sites
Modification of Section 4.4 immunogenicity and B-cell subsets labs at 6 months post last 
dose
Modification of Section 5 immunogenicity and B-cell subsets labs at 6 months post last 

YM2010/00145/03
CONFIDENTIAL
The GlaxoSmithKline group of companies
BEL114333
3
dose
Addition of Section 6 Time and Events Table, Year 1 and Additional Years, B-cell 
marker labs at Week 48
Modification of Section 6 Time and Events Table, Year 1 and Additional Years, 
immunogenicity labs at 6 months post last dose in footnotes
Addition of Section 6 Time and Events Table, Year 1 and Additional Years, B-cell 
subsets at selected sites in footnotes
Clarification of Section 6.1.1 for B-cell subsets collected only at selected sites
Addition and clarification of Section 6.3 B-cell markers at Week 48 and at selected sites
Modification of Section 6.3 immunogenicity labs at 6 months post last dose
Modification of Section 6.3.13.1 immunogenicity labs at 6 months post last dose
Clarification of Section 6.4 for B-cell subsets collected only at selected sites
YM2010/00145/03
2014-MAY-16
Amendment No. 3
Changes were made to the following sections to allow subjects who complete the open-
label SC extension of C1115 in Japan the option of continuing treatment with IV 
belimumab, as an add-on to their standard of care SLE therapy:
Modification of Study Title
Modification of Protocol Summary Rationale and Study Design
Addition of new heading Section 1.3.1, “Belimumab Administered Intravenously”
Addition of new section Section 1.3.2, “Belimumab Administered Subcutaneously”
Modification of Section 1.4, Rationale
Modification of Section 3.1, Study Design
Modification of Section 3.2, Discussion of Design
Modification of Section 4.1, Number of Subjects
Modification of Section 4.2, Inclusion Criteria
Modification of Section 4.3, Exclusion Criteria
Modification of Section 5, Study Treatments
Modification of Section 5.4, Treatment after the End of the Study

YM2010/00145/03
CONFIDENTIAL
The GlaxoSmithKline group of companies
BEL114333
4
Modification of Section 6 Time and Events Table, Column headings for first 2 
columns, and footnote 1
Modification of Section 6 Time and Events Table Additional Years, footnote 3
Modification of Section 6.1, Critical Baseline Assessments
Modification of Section 6.1.1, Procedures (Day 0)
Modification of Section 6.2.1.2, Secondary Endpoints
Modification of Section 7, Data Management
Modification of Section 8.1.1, Primary Efficacy Analysis
Modification of Section 8.1.2, Analysis of Additional Efficacy and Biomarkers
Modification of Section 8.1.3, Analysis of Safety Variables
Modification of Section 9.5, Study Site Closure
Updating of Section 10, References
Updating of Progressive Multifocal Leukoencephalopathy wording to reflect new 
information received by the Sponsor:
Modification of Section 6.3.10.1, Progressive multifocal leukoencephalopathy.
Modification of Section 6.2.13.2 to reflect current methods
Change to Appendix 7: 
Addition of sub-headings for each protocol amendment for clarification 

PPD

PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

YM2010/00145/03
CONFIDENTIAL
BEL114333
7
INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number BEL114333
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date

YM2010/00145/03
CONFIDENTIAL
BEL114333
8
TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS...........................................................................................11
PROTOCOL SUMMARY...............................................................................................14
1.
INTRODUCTION....................................................................................................17
1.1.
Disease Background Relevant to Clinical Study..........................................17
1.2.
Belimumab..................................................................................................18
1.2.1.
Mechanism of Action ...................................................................18
1.3.
Clinical Experience with Belimumab ...........................................................18
1.3.1.
Belimumab Administered Intravenously .......................................18
1.3.2.
Belimumab Administered Subcutaneously...................................19
1.4.
Rationale ....................................................................................................20
2.
OBJECTIVE(S) ......................................................................................................21
2.1.
Primary Objective .......................................................................................21
2.2.
Secondary Objective...................................................................................21
3.
INVESTIGATIONAL PLAN.....................................................................................21
3.1.
Study Design ..............................................................................................21
3.2.
Discussion of Design ..................................................................................22
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA.......................................23
4.1.
Number of Subjects ....................................................................................23
4.2.
Inclusion Criteria.........................................................................................23
4.3.
Exclusion Criteria........................................................................................24
4.4.
Withdrawal Criteria .....................................................................................25
5.
STUDY TREATMENTS..........................................................................................26
5.1.
Product Accountability ................................................................................28
5.2.
Treatment Compliance................................................................................28
5.3.
Concomitant Medications and Non-Drug Therapies....................................28
5.3.1.
Permitted Medications and Non-Drug Therapies..........................28
5.3.2.
Prohibited Medications and Non-Drug Therapies.........................29
5.3.3.
Live Vaccines ..............................................................................29
5.4.
Treatment after the End of the Study ..........................................................29
5.5.
Treatment of Study Treatment Overdose....................................................29
6.
STUDY ASSESSMENTS AND PROCEDURES .....................................................30
6.1.
Critical Baseline Assessments....................................................................35
6.1.1.
Procedures (Day 0)......................................................................35
6.1.1.1.
Subjects in BEL113750 ..............................................35
6.1.1.2.
Subjects in C1115 ......................................................37
6.2.
Efficacy.......................................................................................................38
6.2.1.
Efficacy Endpoints .......................................................................38
6.2.1.1.
Primary Endpoint........................................................38
6.2.1.2.
Secondary Endpoints .................................................39
6.2.1.3.
Other Endpoints .........................................................39
6.2.2.
SELENA SLEDAI.........................................................................40

YM2010/00145/03
CONFIDENTIAL
BEL114333
9
6.2.2.1.
SELENA SLEDAI Score .............................................40
6.2.2.2.
Laboratory Tests for SELENA SLEDAI and 
BILAG.........................................................................41
6.2.2.3.
Guidelines for Scoring Proteinuria for SELENA 
SLEDAI ......................................................................42
6.2.2.3.1.
Scoring for Proteinuria at Day 0 
and Subsequent Study Visits..................42
6.2.2.4.
SELENA SLEDAI Flare Index.....................................42
6.2.2.5.
Physician’s Global Assessment (PGA) .......................43
6.2.3.
BILAG..........................................................................................43
6.2.4.
SLICC/ACR Damage Index .........................................................44
6.3.
Safety .........................................................................................................44
6.3.1.
Liver Chemistry Stopping and Follow up Criteria..........................45
6.3.2.
Adverse Events............................................................................48
6.3.2.1.
Definition of an AE......................................................48
6.3.2.2.
Definition of a SAE .....................................................49
6.3.3.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs.........................................................49
6.3.4.
Investigator Evaluation of Adverse Events...................................50
6.3.5.
Pregnancy ...................................................................................50
6.3.6.
Time Period and Frequency of Detecting AEs and SAEs.............51
6.3.7.
Prompt Reporting of Serious Adverse Events and Other 
Events to GSK.............................................................................51
6.3.7.1.
Regulatory Reporting Requirements for SAEs............53
6.3.7.2.
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs ................53
6.3.8.
Laboratory Evaluations ................................................................54
6.3.9.
Infusion-related Reactions and Hypersensitivity Reactions ..........54
6.3.10.
Other Immunosuppression Related Considerations.....................54
6.3.10.1.
Progressive Multifocal Leukoencephalopathy.............55
6.3.11.
Vital Signs and Weight.................................................................55
6.3.12.
Physical Examination...................................................................55
6.3.13.
Immunogenicity............................................................................55
6.3.13.1.
Sample Collection and Handling.................................55
6.3.13.2.
Assay Methods...........................................................56
6.4.
Biomarker(s)...............................................................................................56
6.5.
Pharmacokinetic Assessments ...................................................................56
7.
DATA MANAGEMENT ...........................................................................................57
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS...................................57
8.1.
Data Analysis Considerations .....................................................................57
8.1.1.
Primary Efficacy Analysis.............................................................57
8.1.2.
Analysis of Additional Efficacy and Biomarkers............................58
8.1.3.
Analysis of Safety Variables.........................................................58
8.1.4.
Interim Analysis ...........................................................................58
9.
STUDY CONDUCT CONSIDERATIONS ...............................................................59
9.1.
Posting of Information on Clinicaltrials.gov..................................................59
9.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................59
9.3.
Quality Control (Study Monitoring) ..............................................................59

YM2010/00145/03
CONFIDENTIAL
BEL114333
10
9.4.
Quality Assurance.......................................................................................60
9.5.
Study and Site Closure ...............................................................................60
9.6.
Records Retention......................................................................................60
9.7.
Provision of Study Results to Investigators, Posting to the Clinical 
Trials Register and Publication ...................................................................61
10. REFERENCES.......................................................................................................62
11. APPENDICES........................................................................................................67
11.1.
Appendix 1:  SELENA SLEDAI Disease Assessment Scales......................67
11.2.
Appendix 2: BILAG Index Assessment .......................................................70
11.3.
Appendix 3: SLICC/ACR Damage Index.....................................................72
11.4.
Appendix 4: Liver Chemistry Stopping and Followup Criteria......................74
11.5.
Appendix 5: Clinical Laboratory Tests.........................................................75
11.6.
Appendix 6: Adverse Event and Laboratory Value Severity Grade 
Tables.........................................................................................................76
11.7.
Appendix 7:  Protocol Changes...................................................................84

YM2010/00145/03
CONFIDENTIAL
BEL114333
11
LIST OF ABBREVIATIONS
aCL
Anticardiolipin
ACE
Angiotensin-converting enzyme
ACR
American College of Rheumatology
AE
Adverse Event
ALT
alanine amininotransferase
ANA
anti-nuclear antibody
ANCOVA
Analysis of Covariance
AST
aspartate aminotransferase
BILAG
British Isles Lupus Assessment Group 
BLyS
B lymphocyte Stimulator
CBC
Complete blood count
CNS
Central Nervous System
CPK
Creatinine phosphokinase
CrCl
Creatinine clearance
CRF
Case report form
C-SSRS
Columbia Suicidality-Severity Rating Scale
CVA
Cerebrovascular accident
dL
decilitre
DMID
Division of Microbiology and Infectious Diseases
DNA
deoxyribonucleic acid
dsDNA
double stranded DNA
ECG
Electrocardiogram
ECL
electrochemiluminescence 
eCRF
electronic case report form
ELISA
enzyme linked immunosorbent assay
FACS
florescence activated cell sorting
GCP
Good clinical practice
GCSP
Global Clinical Safety and Pharmacovigilance
GFR
Glomerular filtration rate
GSK
GlaxoSmithKline
HB
Hepatitis B
HBsAg
Hepatitis B surface antigen
HBc
Hepatitis B core
HEp-2
Human Epithelial Cell Line 2
HGS
Human Genome Sciences, Inc
hpf
High power field
IB
Investigator’s Brochure
IEC
Independent ethics committee
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IL-6
Interleukin-6
IM
Intramuscular
INR
International Normalized Ratio
IRB
Institutional Review Board
IUD
Intrauterine device

YM2010/00145/03
CONFIDENTIAL
BEL114333
12
IUS
Intrauterine system
IV
Intravenous
IVIG
Intravenous immunoglobulin
IVRS
Interactive voice response system
kg
kilogram
LDH
lactate dehydrogenase
LOCF
Last observation carried forward
MedDRA
Medical Dictionary for Drug Regulatory Affairs
mg
milligram
MITT
Modified intent to treat
mL
millilitre
MMF
Mycophenolate mofetil
MSD
Meso Scale Discovery
MSDS
Materials Safety Data Sheet
NR
Nonresponder
NSAIDs
non-steroidal anti-inflammatory drugs
PCR
polymerase chain reaction
PGA
Physician’s Global Assessment
PGx
Pharmacogenetics
PK
Pharmacokinetics
PML
progressive multifocal leukoencephalopathy
PO
By mouth (per os)
PT
prothrombin time
PTT
partial thromboplastin time
RA
rheumatoid arthritis
RAP
Reporting and Analysis Plan
RBC
red blood cell
RF
Rheumatoid factor
RNA
Ribonucleic acid
SAE
Serious Adverse Event
SC
Subcutaneous
SELENA
Safety of Estrogen in Lupus National Assessment 
SFI
SLE Flare Index
SLE
Systemic Lupus Erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease Activity Index
SLICC
SOC
Systemic Lupus International Collaborating Clinics
Standard of Care
SOCs
System Organ Classes
SPM
Study Procedures Manual
SRI
SLE Responder Index
SWFI
Sterile water for injection
TACI Fc
transmembrane activator attached to the Fc portion of an 
immunoglobulin
TF
Treatment Failure
TNF
Tumour Necrosis Factor
ULN
Upper limit of normal
VAS
Visual analogue scale

YM2010/00145/03
CONFIDENTIAL
BEL114333
13
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
Benlysta
BLyS
Lymphostat-B
PASS 2005
RIBA

YM2010/00145/03
CONFIDENTIAL
BEL114333
14
PROTOCOL SUMMARY
Rationale
This study provides subjects who complete the BEL113750 Study in Northeast Asia and 
subjects who complete the open-label extension of HGS1006-C1115 (referred to as 
C1115) Study in Japan the option of receiving belimumab, as an add-on to their standard 
of care (SOC) SLE therapy.  All eligible subjects will receive belimumab 10 mg/kg 
irrespective of their randomized treatment in BEL113750 or C1115.  This is an optional 
study in which eligible subjects will be enrolled at the discretion of the investigator and 
consent of the subject. The study will also provide data on long-term safety and efficacy 
of belimumab in Northeast Asia.
Objective(s)
Primary Objective
The primary objective is to evaluate long-term safety and tolerability of belimumab in 
subjects with SLE in Northeast Asia.
Secondary Objective
The secondary objective is to evaluate the long-term efficacy of belimumab in subjects 
with SLE in Northeast Asia.
Study Design
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia or who completed the 
open-label extension of the C1115 protocol in Japan. Subjects participating in this 
protocol will continue to be monitored for safety and efficacy. 
Subjects will give written informed consent before any study procedures are performed. 
Subjects will be reconsented whenever new information becomes available that may 
affect their willingness to participate in the study.
Subjects who complete 48 weeks of treatment on the BEL113750 or complete the open-
label extension of C1115 and who meet inclusion/exclusion criteria, will be given the 
option to enter the continuation study.  All subjects will receive belimumab 10 mg/kg IV 
infused over 1 hour every 28 days. The first dose on the continuation study must be given 
4 weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750. 
For subjects enrolling from C1115, the target for the first dose of IV belimumab is 
1 week after the last dose of SC belimumab (scheduled for Week 23 in the open-label 
extension). The EXIT visit of the C1115 study (Week 24) serves as the Day 0 visit for the 
Protocol BEL114333, and will have a +1 week visit window. All subjects will continue 
therapies as prescribed by the investigator.  However, subjects who start prohibited 
medications or therapies at any time during the study must be withdrawn from treatment 
with belimumab and will enter study follow-up.  (See Section 5.3.2 and Section 5.3.3).

YM2010/00145/03
CONFIDENTIAL
BEL114333
15
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication in this protocol, then every 
24 weeks thereafter, and at the Exit visit and the Week 16 follow-up visit.  Serum IgG 
will be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) 
after the first dose of study medication and then every 48 weeks thereafter and at the Exit 
visit and the Week 16 follow-up visit.  Serum IgA and IgM will be evaluated in this 
protocol at Week 0 and Week 48, and then every 48 weeks thereafter and at the Exit visit.  
Adverse events will be assessed at every visit except at the 6 month follow-up visit.  
Subjects should be clinically evaluated by their investigating physician at each visit. It is 
the investigator’s responsibility to manage their patient’s SLE as necessary. Complete 
efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare Index along with PGA) and 
evaluation of biomarkers will occur every 24 weeks (168 days).  B-cell subsets will be 
collected at Week 48, the EXIT visit, and at approximately 6 months after the last dose of 
study agent, from subjects at selected sites only.
During the course of the study, the investigator may adjust concurrent medications (add, 
eliminate, change dose level/frequency) as clinically appropriate in response to 
improving or worsening conditions. Prohibited medications in this study are similar to 
BEL113750 and C1115.  Subjects who start prohibited medications or therapies (see 
Section 5.3.2 and Section 5.3.3) at any time during the study must be withdrawn from 
treatment with belimumab and enter study follow-up. After discontinuation of study 
medication, subjects will return for an Exit visit 4 weeks after the last study medication 
administration and for a follow up visit at 16 weeks after the last dose of study 
medication.  For any subject who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available), an attempt will be made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.  Withdrawal of subjects from treatment and the procedures to be followed 
are described in Section 4.4.
Subjects recruited into this study will continue to receive treatment with intravenous
belimumab until such time as intravenous belimumab becomes commercially available in 
a subject’s country of participation, or the subject elects to participate in another 
belimumab continuation study for SLE, or until either the subject's physician withdraws 
the subject from the study or upon the decision by the sponsor to discontinue further 
development of belimumab for SLE.
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750 plus the number of 
subjects from Japan from the open-label extension of the C1115 study. 
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time intravenous belimumab becomes commercially 
available in a subject’s country of participation, or upon the decision by the sponsor to
discontinue the study.  

YM2010/00145/03
CONFIDENTIAL
BEL114333
16
Study Endpoints/Assessments
The primary efficacy endpoint is a composite response rate at each scheduled visit when 
complete efficacy evaluations occur (e.g., Weeks 24 and 48 of Year 1 and Year 2, etc), 
consisting of

4 point reduction from baseline in SELENA SLEDAI score, AND

No worsening (increase of < 0.30 points from baseline) in Physician’s Global 
Assessment (PGA), AND

No new BILAG A organ domain score or 2 new BILAG B organ domain scores 
compared with baseline at the time of assessment (i.e., at Week 52).
All other endpoints will be derived from the following assessments: SELENA SLEDAI, 
PGA, BILAG, SLE Flare Index, prednisone dose, renal flare assessment, proteinuria,  
biomarkers (immunoglobulins, complement, anti-dsDNA autoantibodies, and B cell 
subsets (at selected sites)), immunogenicity, adverse events, clinical laboratory 
assessments (clinical chemistry and haematology) and plasma levels of belimumab.

YM2010/00145/03
CONFIDENTIAL
BEL114333
17
1.
INTRODUCTION
1.1.
Disease Background Relevant to Clinical Study
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterised by 
autoantibody production and abnormal B lymphocyte function [Pisetsky, 2001].  This 
disease is more common in women (~90% of patients) than men [NWHIC, 2003] and 
prevalence varies with race [OMHRC, 2001; NWHIC, 2003].  SLE can lead to arthritis, 
kidney failure, heart and lung inflammation, and central nervous system (CNS) changes. 
A clinical diagnosis of SLE includes features that are thought to involve dysregulation of 
B lymphocytes [Liossis, 1996; Lipsky, 2001].  The B lymphocyte stimulator (BLyS) 
protein is a potent co-stimulator of B lymphocytes and elevated levels of BLyS are 
observed in autoimmune diseases in humans and animal models [Cheema, 2001; Gross, 
2001; Khare, 1999; Mackay, 1999; Moore, 1999; Zhang, 2001; Carter, 2003].  In SLE,
the elevation of BLyS may contribute to the persistence of B cell subsets that produce 
pathogenic autoantibodies or promote inflammation that would otherwise be subject to 
down regulation.  Thus a therapeutic strategy which involves an antagonist to BLyS, to 
reduce B lymphocyte stimulation, reducing autoantibody production, may have 
therapeutic benefit in SLE.
Patients with SLE have about a 3-fold greater risk of mortality than the general 
population.  Approximately 70% of SLE patients survive 20 years from time of diagnosis 
[Houssiau, 2004].  Standard therapies for SLE include corticosteroids (the mainstay of 
therapy), anti-malarial agents (e.g., hydroxychloroquine), non-steroidal anti-
inflammatory drugs (NSAIDs), cytotoxic agents like cyclophosphamide, and  
immunosuppressive/immunomodulatory agents (e.g., azathioprine, cyclosporine, 
mycophenolate mofetil (MMF), methotrexate, leflunomide, thalidomide, 6-
mercaptopurine) [Petri, 2001; Reveille, 2001; Ginzler, 2005; Houssiau, 2004; Ruiz-
Irastorza, 2001; Wallace, 2002; Brocard, 2005; Chatham, 2001].  Although active lupus 
nephritis and CNS vasculitis can usually be controlled with several courses of high dose 
steroids and cyclophosphamide over a 1 to 2 year period, there tends to be progressive 
relapsing of disease over time [Petri, 2001; Houssiau, 2002; Illei, 2001; Ruiz-Irastorza, 
2001].  These therapies can be associated with significant toxicity. Long-term use of 
high-dose corticosteroids can cause significant morbidity including osteoporosis, 
osteonecrosis, metabolic disorders (including exacerbation of diabetes), increased 
infection risk, edema, weight gain and hyperlipidemia [Chatham, 2001].  Cytotoxic 
agents like cyclophosphamide are immunosuppressive, resulting in increased risk of 
serious infections and certain cancers.
The prevalence of SLE in Hong Kong & mainland China was found to range from 
58.8/100,000 to 73.3/100,000 in two studies [Mok, 2003; Xiang, 2009]. When compared 
with US SLE prevalence estimates of 100.0/100,000 [Naleway, 2005; Chakravarty, 
2007], SLE disease burden does not appear to be higher in China.  Conversely, SLE 
prevalence in the EU 5 regions (UK, Germany, France, Spain, and Italy) was estimated at 
43.0/100,000 [Govoni, 2006; Lopez, 2003; Nightingale, 2006] which is lower than in 
China.  Regarding disease activity, Boers [Boers, 2006] reported more severe SLE among 
Asian patients admitted to a medical centre in Australia, with Southeastern Asian/Chinese 

YM2010/00145/03
CONFIDENTIAL
BEL114333
18
patients having a median Systemic Lupus Erythematosus Disease Activity Index 
(SLEDAI) of 13 at first admission compared to a median SLEDAI of 8 among 
Caucasians.
1.2.
Belimumab
The trade name of the investigational product is BENLYSTA (also known as 
Lymphostat-B).  The generic (USAN/INN) name is belimumab.
1.2.1.
Mechanism of Action
Belimumab, (also known as LymphoStat-B; BENLYSTA), developed by Human 
Genome Sciences (HGS), is a B lymphocyte stimulator (BLyS)-specific inhibitor that 
blocks the binding of soluble BLyS, a B-cell survival factor, to its receptor on B cells.  
Belimumab does not bind B-cells directly, but by binding BLyS, belimumab inhibits the 
survival of B cells, including autoreactive B cells, and reduces the differentiation of B 
cells into immunoglobulin-producing plasma cells.  Further information on the risk 
benefit of belimumab is provided in the Investigator Brochure (IB). 
1.3.
Clinical Experience with Belimumab
1.3.1.
Belimumab Administered Intravenously
Belimumab administered as an IV infusion has been studied in SLE patients in 1 Phase 1 
trial (LBSL01), 1 Phase 2 randomized, double-blind, placebo-controlled trial (LBSL02) 
and 2 Phase 3 randomized, double-blind, placebo-controlled trials [BLISS 52 (HGS1006-
C1057) and BLISS 76 (HGS1006-C1056)], and in RA patients in a Phase 2 double-blind, 
placebo-controlled trial (LBRA01). 
Phase 3 studies of belimumab in SLE were completed in 2009 and 2010 and formed the 
basis of the approval of IV belimumab in the US, Canada and the EU. The Phase 3 trials 
included 1,684 subjects where belimumab 10 mg/kg plus standard therapy demonstrated 
superiority over placebo plus standard therapy in reduction in disease activity as 
measured by the SLE responder index (SRI) with an acceptable safety profile. The 
primary safety population supporting approval also included data from a Phase 2 study in 
449 subjects with SLE. Evidence of benefit in other clinical measures such as reductions 
in disease activity as measured by SELENA SLEDAI, severe flare, and reduced steroid 
use was also observed. Treatment with belimumab plus standard of care was generally 
well tolerated, with rates of adverse events (AEs), severe AEs, serious AEs, AEs leading 
to discontinuation, and serious/severe infections generally comparable to the rates 
observed in the placebo plus standard of care group. Mortality rates in the controlled 
clinical trials were low, although numerically higher in the belimumab groups: 0.4% and 
0.8% in the placebo and belimumab groups, respectively. Causes of death were as 
expected in an SLE population with active disease receiving a wide range of standard 
therapies, such as steroids and immunosuppressants, and included infection, 
cardiovascular disease, and suicide. Serious infections were observed in 5.2% and 6.0% 
of subjects receiving placebo and belimumab, respectively. The rate of malignancy 
(excluding non-melanoma skin cancer) was the same between the placebo and 
belimumab groups at 0.4%; however as with other immunomodulating agents, the 

YM2010/00145/03
CONFIDENTIAL
BEL114333
19
mechanism of action of belimumab could increase the risk for the development of 
malignancies. Hypersensitivity and infusion reactions were observed. Anaphylaxis was 
also observed, though rare (<1%). Depression-related events, common in patients with 
SLE, were observed more frequently with belimumab than with placebo; it is unknown if 
belimumab treatment is associated with an increased risk for these events. The most 
commonly-reported adverse reactions, occurring in ≥ 5% of patients in clinical trials were 
nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, 
depression, migraine, and pharyngitis.
Experience from open-label, long-term continuation trials of belimumab in SLE subjects 
suggests that prolonged treatment with belimumab remains generally well tolerated, with 
no apparent increase in the incidence rate of AEs or serious adverse events (SAEs) over 
time, including important events such as infections and malignancies. The prevalence rate 
of AEs and SAEs has also remained relatively stable over time. Long term belimumab 
treatment through 6 years appears to provide sustained improvement in SLE disease 
activity.
Results of the clinical trials of belimumab administered IV are described in further detail 
in the Investigator’s Brochure (IB). 
1.3.2.
Belimumab Administered Subcutaneously
A subcutaneous (SC) liquid formulation of belimumab has been developed and is 
currently in a Phase 3 trial (Protocol HGS1006-C1115, referred to as C1115).  
Based on PK data from the Phase 1 SC study (Protocol HGS1006-C1105, referred to as
C1105), subjects given belimumab (200 mg/mL) 200 mg SC every week are expected to 
achieve on average similar steady-state AUC levels compared to those observed in the IV 
Phase 3 trials with 10 mg/kg IV every 4 weeks.
In the Phase 3 study, patients self-administer a fixed dose of 200 mg belimumab as an SC 
injection. Due to the relatively slow absorption from the subcutaneous to the central 
compartment, maximal serum belimumab concentrations following SC administration are 
not expected to exceed those observed following IV administration in the Phase 3 trials 
even for lower weight subjects (Figure 1). 
Safety data for SC administration have been generated in a 24-week Phase 2 study using 
the original 100 mg/mL SC formulation in SLE patients (Protocol HGS1006-C1070, 
referred to as C1070). Although the number of subjects is small (N = 28), a dose of 
300 mg weekly (100 mg SC 3x/wk) was generally well-tolerated (Study C1070, see 
Investigator’s Brochure). In healthy Japanese male subjects, a single 200 mg SC dose vs 
a single IV dose of belimumab were evaluated in terms of safety and PK (BEL116119, 
see Investigator’s Brochure). The bioavailability of the single SC dose of 200 mg 
belimumab in the subjects was estimated to be 77.5%. Geometric mean terminal half-life 
after single SC administration was 15.9 days which was comparable to the 17.7 days 
observed after single IV administration. All 7 AEs were mild or moderate in intensity. 
One event (cellulitis) reported in the IV group was judged to be related to the belimumab. 
No SAEs or AEs related to injection site reactions were reported during the study. [Shida, 
2014]. Four weekly SC doses of belimumab at 2x120 or 200 mg were evaluated in 

YM2010/00145/03
CONFIDENTIAL
BEL114333
20
healthy subjects in terms of safety and PK in Study C1105 and have been generally well 
tolerated.
Figure 1
Comparison of simulated mean belimumab serum concentration 
time profile with 10 mg/kg IV on days 0, 14, and 28 and Q4 weeks 
thereafter with simulated profile of 200 mg weekly SC
10 mg/kg IV data simulated using PK parameters from population PK analysis in SLE patients (HGS1006-POPPK); SC 
profile simulated using PK parameters from Study C1105 in healthy subjects.
The ongoing Phase 3 trial of SC belimumab in SLE patients (C1115) has completed 
enrollment with 839 patients as of 10 February 2014.  The independent Data and 
Monitoring Committee reviews data from this study every 6 months; the most recent 
review was 29 October 2013 and no changes were recommended.
1.4.
Rationale
This study provides subjects who complete the BEL113750 Study in Northeast Asia or 
subjects from Japan who complete the open-label extension of C1115 the option of 
receiving belimumab, as an add-on to their standard of care (SOC) SLE therapy.  All 
eligible subjects will receive belimumab 10 mg/kg irrespective of their randomized 
treatment in BEL113750 or C1115.   This is an optional study in which eligible subjects 
will be enrolled at the discretion of the investigator and consent of the subject. The study 
will also provide data on long-term safety and efficacy of belimumab.  
Belimumab (also known as LymphoStat-B; BENLYSTA ) 10 mg/kg administered IV 
was approved on 09 March 2011 in the United States (US), on 06 July 2011 in Canada, 

YM2010/00145/03
CONFIDENTIAL
BEL114333
21
and on 13 July 2011 in the European Union (EU) for the treatment of adult patients with 
active autoantibody-positive SLE who are receiving standard therapy.
2.
OBJECTIVE(S)
2.1.
Primary Objective
The primary objective is to evaluate long-term safety and tolerability of belimumab in 
subjects with SLE in Northeast Asia. 
2.2.
Secondary Objective
The secondary objective is to evaluate the long-term efficacy of belimumab in subjects 
with SLE in Northeast Asia.
3.
INVESTIGATIONAL PLAN
3.1.
Study Design
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia and subjects who 
completed the open-label extension of C1115 in Japan. Subjects participating in this 
protocol will continue to be monitored for safety and efficacy. The frequency of safety
laboratory evaluations has been reduced in this protocol compared with BEL113750 and 
C1115 based on the safety profile of belimumab studies to date and is not anticipated to 
compromise the well being and safety of subjects.
Subjects must give written informed consent before any study procedures are performed. 
Subjects will be reconsented whenever new information becomes available that may 
affect their willingness to participate in the study.
Subjects who complete 48 weeks of treatment on the BEL113750 study or complete the 
open-label extension of C1115 and who meet inclusion/exclusion criteria, and provide 
informed consent, will be given the option to enter the continuation study.  All subjects 
will receive belimumab 10 mg/kg IV infused over 1 hour every 28 days. The first dose on 
the continuation study must be given 4 weeks (minimum of 2 weeks, maximum of 8 
weeks) after the last dose in BEL113750. For subjects enrolling from C1115, the target 
for the first dose of IV belimumab is 1 week after the last dose of SC belimumab 
(scheduled for Week 23 in the open-label extension). The EXIT visit of the C1115 study 
(Week 24) serves as the Day 0 visit for the Protocol BEL114333, and will have a 
+1 week visit window. All subjects will continue therapies as prescribed by the 
investigator.  During the course of the study, the investigator may adjust concurrent 
medications (add, eliminate, change dose level/frequency) as clinically appropriate in 
response to improving or worsening conditions.    However, subjects who start prohibited 
medications or therapies (see Section 5.3.2 and Section 5.3.3) at any time during the 
study must be withdrawn from treatment with belimumab and enter study follow-up.  
After discontinuation of belimumab, subjects will return for an Exit visit 4 weeks after 
the last study medication administration and for follow up visit at 16 weeks after the last 

YM2010/00145/03
CONFIDENTIAL
BEL114333
22
dose of belimumab.  For any subject who had an anti-belimumab antibody response at the 
16-week follow-up visit (or last study visit at which immunogenicity was assessed if the 
16-week follow-up immunogenicity sample is not available), an attempt will be made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.  Withdrawal of subjects from treatment and the procedures to be followed 
are described in Section 4.4. 
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication on this protocol, then every 
24 weeks thereafter and at the Exit visit and the Week 16 follow-up visit.  Serum IgG will 
be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) after 
the first dose of study medication and then every 48 weeks thereafter and at the Exit visit 
and the Week 16 follow-up visit.  Adverse events will be assessed at every visit except at 
the 6 month follow-up visit.  Subjects should be clinically evaluated by their investigating 
physician at each visit. It is the investigator’s responsibility to manage their patient’s SLE 
as necessary. Complete efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare 
Index along with PGA) and evaluation of biomarkers will occur every 24 weeks (168 
days).  B-cell subsets will be collected at Week 48, the EXIT visit, and at approximately 
6 months after the last dose of study agent, from subjects at selected sites only.
Subjects recruited into this study will continue to receive treatment with intravenous 
belimumab until such time as intravenous belimumab becomes commercially available in 
a subject’s country of participation, or the subject elects to participate in another 
belimumab continuation study for SLE, or until either the subject's physician withdraws 
the subject from the study, or upon the decision by the sponsor to discontinue further 
development of belimumab for SLE.  
Protocol waivers or exemptions are not allowed. Therefore, adherence to the study design 
requirements, including those specified in the Time and Events Table, are essential. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM). The SPM will provide 
the site personnel with administrative and detailed technical information that does not 
impact subject safety.
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time intravenous belimumab becomes commercially 
available in a subject’s country of participation, or upon the decision by the sponsor to 
discontinue the study.
3.2.
Discussion of Design
The BEL113750 study design was based on 2 global, Phase III clinical trials (HGS1006-
C1057 and HGS1006-C1056) which demonstrated that subjects treated with belimumab 
had a statistically significantly better response rate at the primary endpoint at week 52, 
than those treated with placebo.  BEL114333 provides subjects who complete the 
BEL113750 study the option of continuing treatment with belimumab for those 
randomized to belimumab, or the option to begin treatment with belimumab for those 

YM2010/00145/03
CONFIDENTIAL
BEL114333
23
randomized to placebo, as an add-on to their standard of care SLE therapy. Subjects who 
completed 48 weeks of treatment and return for the final 52-week evaluation on 
BEL113750 may be recruited into this continuation protocol of open-label belimumab. 
BEL114333 provides subjects who complete the open-label SC extension of C1115 in 
Japan the option of continuing treatment with IV belimumab, as an add-on to their 
standard of care SLE therapy.
This study will continue until the subject withdraws from the trial, or intravenous
belimumab becomes commercially available in the relevant participating country, or the 
subject elects to participate in another belimumab continuation study for SLE, or upon 
the decision by the sponsor to discontinue development/marketing of belimumab for 
SLE. 
In the Phase II and Phase III continuation trials, the incidence rates of adverse events 
(AEs) in general and by SOCs (including infections), serious AEs, and malignancies were 
comparable to placebo per 100 subject years of exposure. The overall incidence rate of 
adverse events remained stable or decreased over 6 years of exposure to belimumab. 
GlaxoSmithKline (GSK) will remain blinded to subjects’ treatment until all data from the 
Phase III study, BEL113750, are locked and unblinded. Clinical sites will remain blinded 
to previous treatment on BEL113750 until after the results of BEL113750 are publicly 
disclosed. 
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA
4.1.
Number of Subjects
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750 in Northeast Asia
plus the number of subjects from Japan in the open label extension of the C1115 study. 
4.2.
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on belimumab that may impact subject eligibility is 
provided in the Investigator Brochure (IB).
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.   
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.
Have completed the BEL113750 Protocol in Northeast Asia through Week 48 OR
have completed the open-label extension of C1115 in Japan.
2.
Be able to receive the first dose of belimumab for BEL114333 four weeks (minimum 
of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750 OR be able to 
receive the first dose of IV belimumab 1 week (plus a 1 week visit window) after the 
last dose of open-label SC belimumab in C1115.

YM2010/00145/03
CONFIDENTIAL
BEL114333
24
3.
A female subject not pregnant or nursing is eligible to enter the study if at least one 
of the following conditions apply:  

Of non-childbearing potential (i.e., women who had a hysterectomy, are 
postmenopausal which is defined as 1 year without menses, have both ovaries 
surgically removed or have current documented female sterilization procedure); 
or 

Of childbearing potential (i.e., women with functional ovaries and no 
documented impairment of oviductal or uterine function that would cause 
sterility).  This category includes women with oligomenorrhoea (even severe), 
women who are perimenopausal or have just begun to menstruate.  These 
women must have a negative urine pregnancy test at screening, and agree to one 
of the following:
- Complete abstinence from penile-vaginal intercourse, when this is the female’s 
preferred and usual lifestyle, from 2 weeks prior to administration of the first 
dose of belimumab until 16 weeks after the last dose of belimumab; or
- Consistent and correct use of one of the following acceptable methods of birth 
control for 1 month prior to the start of belimumab and for 16 weeks after the 
last dose of belimumab:

Implants of etonogestrel or levonorgestrel;

Estrogenic vaginal ring 

Injectable progesterone; 

Any intrauterine device (IUD) or intrauterine system (IUS) with a 
documented failure rate of less than 1% per year;

Oral contraceptives (either combined or progesterone only); 

Double barrier method with vaginal spermicidal agent: Condom and an 
occlusive cap (cervical cap/vault or diaphragm) with a vaginal spermicidal 
agent (foam/gel/film/cream/suppository); 

Percutaneous contraceptive patch; 

Male partner who is sterile prior to the female subject’s entry into the study 
and is the sole sexual partner for the female subject.
Note: MMF and other forms of mycophenolate affect the metabolism of oral 
contraceptives and may reduce their effectiveness. As such, women receiving 
mycophenolate who are using oral contraceptives for birth control should 
employ an additional method (e.g., barrier method).
4.3.
Exclusion Criteria
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
Subjects meeting any of the following criteria must not be enrolled in the study:

YM2010/00145/03
CONFIDENTIAL
BEL114333
25
1.
Have developed clinical evidence of significant, unstable or uncontrolled, acute or 
chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, 
gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or 
experienced an adverse event (AE) in the respective Phase 3 studies that could, in the 
opinion of the principal investigator, put the subject at undue risk.
2.
Have developed any other medical diseases (e.g., cardiopulmonary), laboratory 
abnormalities, or conditions (e.g., poor venous access) that, in the opinion of the 
principal investigator, makes the subject unsuitable for the study.
4.4.
Withdrawal Criteria
A subject may voluntarily discontinue participation in this study at any time.  The 
investigator may also, at his or her discretion, discontinue a subject from this study.  
Every effort should be made by the investigator to keep subjects in the study and to 
ensure return for the Exit visit 4 weeks after the last dose of belimumab, and the follow-
up visits 16 weeks after the last dose.  For any subject who had an anti-belimumab 
antibody response at the 16-week follow-up visit (or last study visit at which 
immunogenicity was assessed if the 16-week follow-up immunogenicity sample is not 
available), an attempt will be made to obtain a serum sample for anti-belimumab 
antibodies at least 6 months after the last dose of study agent.  From subjects at selected 
sites only, B-cell subsets will be collected at the EXIT visit and at approximately 6 
months after the last dose of study agent.  
Notwithstanding this requirement, the investigator should adjust concurrent medications 
as clinically required.
Reasons for subject withdrawal include “adverse event”, “lack of efficacy”, “protocol 
deviation”, “study closed/terminated”, “lost to follow-up”, “investigator discretion”, and 
“withdrew consent”.  The investigator will record the primary reason in the electronic 
case report form (eCRF) and any data collected up until the point of withdrawal, and the 
follow-up visits will be used in the analyses.
If a subject is permanently discontinued from belimumab during the course of the study, 
the subject must be withdrawn from the study.  In addition, subjects will be withdrawn 
from the study if any of the following criteria are met:

Unacceptable toxicity including:

Laboratory parameters: Demonstrate clinically important changes in 
laboratory parameters.

Liver Chemistry: Detailed in Section 6.3.1.

Pregnancy: Positive urine pregnancy test.

Concurrent Medication: Prohibited concurrent medication or therapy 
(See Section 5.3.2 and Section 5.3.3).

Consent: Withdrawal of consent.

Compliance: Missed 3 or more consecutive study infusions.

YM2010/00145/03
CONFIDENTIAL
BEL114333
26
5.
STUDY TREATMENTS
A summary of the characteristics of belimumab is presented in Table 1.
Table 1
Belimumab Characteristics
Property
Belimumab
Formulation
Belimumab 400 mg per vial plus excipients (citric acid/sodium 
citrate/sucrose/polysorbate)
Dosage Form
Reconstituted solution
Unit dose strength
400mg per vial (to contain 80mg/mL when reconstituted with 4.8mL 
sterile water for injection [SWFI])
Physical description
White uniform lyophilised cake in a 20mL vial
Manufacturer
Human Genome Sciences, Inc.
Route of administration
Intravenous
The contents of the label will be in accordance with all applicable regulatory 
requirements.
Under normal conditions of handling and administration, belimumab is not expected to 
pose significant safety risks to site staff.  Take adequate precautions to avoid direct eye or 
skin contact and the generation of aerosols or mists. Notify the monitor of any 
unintentional occupational exposure.  A Material Safety Data Sheet (MSDS) describing 
the occupational hazards and recommended handling precautions will be provided to site 
staff if required by local laws or will otherwise be available from GSK upon request.  
Belimumab should be diluted to 250 mL normal saline after reconstitution, using a 
typical approved plastic intravenous administration set for the infusion.
Belimumab must be stored in a secure area under the appropriate physical conditions for 
the product, which includes storage in a refrigerator at a temperature of 2-8C.  Access to 
and administration of belimumab will be limited to the investigator and authorised site 
staff.  Maintenance of a temperature log (manual or automated) is required.  Belimumab 
must be dispensed or administered only to subjects enrolled in the study and in 
accordance with the protocol.
All used belimumab vials should be destroyed according to site guidelines for the 
destruction of investigational products, after the monitor has conducted a check of the 
product accountability log during the study.  At the end of the study, unused belimumab 
vials will be destroyed on site at the study closeout visit, after the monitor has conducted 
final belimumab accountability and given the site approval to destroy all remaining 
supplies.
Belimumab for injection will be supplied in glass and labelled in accordance with all 
applicable regulatory requirements.  The belimumab IV solution should be made up by a 
pharmacist.
The 400 mg single use vial of belimumab will be reconstituted with 4.8 mL sterile water 
for injection, to yield a final concentration of 80 mg/mL of belimumab.  After 

YM2010/00145/03
CONFIDENTIAL
BEL114333
27
reconstitution and dilution in normal saline, the material is stable for up to 8 hours at 2-
8°C, or at room temperature.
The reconstituted belimumab will be diluted in 250 mL normal saline for IV infusion.  
An amount of normal saline, equal to the calculated amount of belimumab to be added, 
should be removed from the infusion bag prior to adding the belimumab.  After adding 
the reconstituted belimumab, gently invert the bag to mix the solution.  The prepared 
belimumab should be infused over 1 hour. 
Refer to the Pharmacy Manual for detailed instructions on the preparation, 
administration, and storage of belimumab.
The first dose on the continuation trial must be given 4 weeks (minimum 2 weeks, 
maximum 8 weeks) after the last dose in BEL113750.  For subjects enrolling from 
C1115, the target for the first dose of IV belimumab is 1 week after the last dose of SC 
belimumab (scheduled for Week 23 in the open-label extension). The EXIT visit of the 
C1115 study (Week 24) serves as the Day 0 visit for the Protocol BEL114333, and will 
have a +1 week visit window. All subjects will receive belimumab 10 mg/kg IV infused 
over 1 hour every 28 days. 
The dose of belimumab administered may not be altered.  The rate of infusion may be 
slowed or interrupted if the subject appears to develop signs of adverse reaction or 
infusion-associated symptoms.  Rate of infusion should not be increased above 
recommended rate.
In the post-marketing setting, delayed onset of symptoms of acute hypersensitivity 
reactions has been observed. Subjects should remain under clinical supervision for 3 
hours after completion of the first 2 infusions. Should symptoms of acute 
hypersensitivity occur, an extended period of monitoring may be appropriate, based on 
clinical judgment.  Otherwise, subjects will be monitored during and after each infusion 
according to study sites’ guidelines or standard operating procedure for IV infusions.  
This may include, but is not limited to, monitoring vital signs and observing for any 
untoward reactions.
Subjects should be made aware of the potential risk, the signs and symptoms of such 
reactions, and the importance of immediately seeking medical attention.  Trained rescue 
personnel and rescue medications/equipment should be available for a minimum of the 
first 2 doses.  For subjects who have previously received intravenous immunoglobulins 
(IVIG) or subjects with a history of allergies (allergic responses to food, drugs, insects, or 
a history of urticaria), administering premedication for prophylaxis against infusion 
reactions and hypersensitivity reactions should be considered. If a subject experiences a 
clinically significant AE that, in the clinical judgement of the investigator, is possibly, 
probably or definitely related to belimumab, and this AE continues at the next scheduled 
dose, or could potentially be exacerbated by the next dose, the investigator may delay the 
dose by up to 2 weeks or withhold 1 dose.  If a similar concern is present at the time of 
the next scheduled dose, the investigator should contact the Medical Monitor to 
determine whether treatment with belimumab should be discontinued.  
If a subject experiences a clinically significant, potentially life-threatening (Grade 4) AE
that in the clinical judgement of the investigator is possibly, probably or definitely related 

YM2010/00145/03
CONFIDENTIAL
BEL114333
28
to belimumab then treatment with belimumab will be discontinued.  The subject should 
be withdrawn from the study and followed at regularly scheduled monthly study visits as 
required until resolution of the AE(s) and must also return for follow-up at the EXIT visit 
4 weeks after the last dose of belimumab, and the follow-up visit 16 weeks after the last 
dose.  For any subject who had an anti-belimumab antibody response at the 16-week 
follow-up visit (or last study visit at which immunogenicity was assessed if the 16-week 
follow-up immunogenicity sample is not available), an attempt will be made to obtain a 
serum sample for anti-belimumab antibodies at least 6 months after the last dose of study 
agent.  From subjects at selected sites only, B-cell subsets will be collected at the EXIT 
visit and at approximately 6 months after the last dose of study agent. 
5.1.
Product Accountability
In accordance with local regulatory requirements, the investigator, designated site staff, 
or head of the medical institution (where applicable) must document the amount of 
belimumab dispensed and/or administered to study subjects, the amount returned by
study subjects, and the amount received from and returned to GSK, when applicable.  
Product accountability records must be maintained throughout the course of the study.
5.2.
Treatment Compliance
All doses administered within the study unit will be administered under the supervision 
of the investigator, designee or study nurses and the data entered into the electronic case 
report form (eCRF).
If a subject misses 3 or more consecutive study infusions, they will be withdrawn from 
the study (See Section 4.4).
Drug dispensing /accountability logs will be maintained by the separate pharmacist or 
pharmacy designee.
5.3.
Concomitant Medications and Non-Drug Therapies
This section reviews the medications allowed and prohibited during the course of the 
study.  Subjects who start prohibited medications or therapies (see Section 5.3.2 and 
Section 5.3.3) will be withdrawn from treatment with belimumab and enter protocol 
required follow-up.
5.3.1.
Permitted Medications and Non-Drug Therapies
All concomitant medications taken during the study will be recorded in the eCRF.  
Complete information must be recorded on the concomitant medication page. 
Once the subject receives the first dose of belimumab on Day 0, the investigator may 
adjust concurrent medications (add, eliminate, change dose level/frequency) as clinically 
required in response to improving or worsening conditions. More latitude will be 
permitted for background medication changes in this extension study as compared to the 
parent study. Prohibited medications as outlined in Section 5.3.2 and Section 5.3.3 will 
still apply.  

YM2010/00145/03
CONFIDENTIAL
BEL114333
29
5.3.2.
Prohibited Medications and Non-Drug Therapies
Subjects who start prohibited medications or therapies at any time during the study must 
be withdrawn from treatment with belimumab and enter study follow-up. The following 
medications and therapies are prohibited at any time during the study:

Other investigational agents (biologic or non-biologic). Investigational applies to any 
drug not approved for sale in the country in which it is being used.

Co-enrolment into another study of an investigational agent or non-drug therapy that 
may interfere with the conduct of this protocol.

Anti-TNF or anti-IL-6 therapy (e.g., adalimumab, etanercept, infliximab).

Other biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist 
[anakinra]).

Intravenous immunoglobulin (IVIG).

IV cyclophosphamide.

Plasmapheresis, leukapheresis.
5.3.3.
Live Vaccines
Live vaccines are not permitted in the study. Subjects who require a live vaccine during 
the study should have belimumab discontinued prior to receiving the live vaccine and 
will be withdrawn from the study.
5.4.
Treatment after the End of the Study
The continuation protocol of open-label belimumab will continue until the subject 
withdraws from the trial, or the subject elects to participate in another belimumab 
continuation study for SLE, or intravenous belimumab becomes commercially available 
in a subject’s country of participation, or upon the decision by the sponsor to discontinue 
development/marketing of belimumab for SLE. 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the patient’s medical condition whether or not GSK is providing specific 
post study treatment.
5.5.
Treatment of Study Treatment Overdose
The dose of belimumab considered to be an overdose has not been defined.  There are no 
known antidotes and GSK does not recommend a specific treatment in the event of a 
suspected overdose.  The investigators will use clinical judgement in treating the 
symptoms of a suspected overdose.

YM2010/00145/03
CONFIDENTIAL
BEL114333
30
6.
STUDY ASSESSMENTS AND PROCEDURES
Table 2
Time and Events Table (Year 1)
Study Visit
Wk 48 
of BEL
113750/
On/before 
Day 168
of C11151
Wk 0 
(Wk 52 of 
BEL11375
0/Day 168
of C1115)
+1 week1
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
EXIT2
16 wk 
FU 
7d post 
infusion
6 month 
FU 7d 
post 
infusion
Study Day
Day 0
28 
7d
56 
7d
84 
7d
112 
7d
140 
7d
168 
7d
196 
7d
224 
7d
252 
7d
280 
7d
308 
7d
336 
7d
Written Informed 
Consent
X
Inclusion/Exclusion 
Criteria
X*
Efficacy 
Assessments
Disease Activity 
Scales: SELENA 
SLEDAI, SLE Flare 
Index, BILAG and PGA 
3
X
X
X
X
SLICC/ACR Damage 
Index
X
X
X
Safety Assessments
Symptom-driven 
Physical Exam
X
X
X
X
X
Record Concurrent 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess/Record 
Adverse Events4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs 5, 11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

YM2010/00145/03
CONFIDENTIAL
BEL114333
31
Study Visit
Wk 48 
of BEL
113750/
On/before 
Day 168
of C11151
Wk 0 
(Wk 52 of 
BEL11375
0/Day 168
of C1115)
+1 week1
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
EXIT2
16 wk 
FU 
7d post 
infusion
6 month 
FU 7d 
post 
infusion
Study Day
Day 0
28 
7d
56 
7d
84 
7d
112 
7d
140 
7d
168 
7d
196 
7d
224 
7d
252 
7d
280 
7d
308 
7d
336 
7d
Laboratory 
Assessments
Labs: Haematology & 
Modified Chem 20 
(non fasting) 5
X
X
X
X
X
X
X
X
Urinalysis5
X
X
X
X
X
X
X
X
Spot urine (protein to 
creatinine ratio)5, 6
X
X
X
X
Urine Pregnancy Test
5,7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C3, C4, Anti-ds DNA 
Autoantibodies5
X
X
X
X
IgG 5, 8
X
X
X
X
X
X
IgA & IgM 5, 8 
X
X
X
PT/ PTT
X*
Exploratory Lab 
Assessments
Immunogenicity 9
X
X
X
X
X
X9A
B cell Markers10
X
X
X
X
Investigational 
Product
Belimumab 
Administration11, 12
X*
X
X
X
X
X
X
X
X
X
X
X
X

YM2010/00145/03
CONFIDENTIAL
BEL114333
32
Table 2
Time and Events Table (Continued)
Calendar represents a yearly (48-week) ongoing visit schedule until the subject is terminated from the study. During the first 48 weeks, the 1st visit is Baseline/Day 0. For all 
subsequent 48 week calendar years, the 1st visit will be Week 4.
*See footnote 1.
1.
For subjects from BEL113750: The Week 52 visit in the parent study Protocol BEL113750 serves as the Day 0 visit for the Protocol BEL114333. Performance of all the Week 52 
procedures in BEL113750 will cover nearly all the procedures that are required for Day 0 of this protocol. Procedures necessary for both this protocol and the prior Phase III 
protocol need only be performed once and shall be recorded to CRFs as described in Section 6.1.  At Week 48 of BEL113750, a subject should sign the informed consent for the 
BEL114333 study.  In addition to the Week 52 procedures for BEL113750, a subject should be reassessed for inclusion/exclusion criteria of the BEL114333 study and receive 
belimumab (those procedures marked with an asterisk).  Subjects must be able to receive the 1st dose of belimumab (Day 0) for BEL114333 four weeks (minimum of 2 weeks, 
maximum of 8 weeks) after the last dose in BEL113750. 
For subjects from C1115: The Day 168 (Week 24) visit in the open-label extension phase of C1115 serves as the Day 0 visit for the Protocol BEL114333. Performance of all the 
Day 168 procedures in C1115 will cover nearly all the procedures that are required for Day 0 of this protocol. Procedures necessary for both this protocol and the prior Phase III 
protocol need only be performed once and shall be recorded to CRFs as described in Section 6.1.  On or before the Day 168 visit, a subject should sign the informed consent for 
the BEL114333 study. In addition to the Day 168 procedures for C1115, a subject should be reassessed for inclusion/exclusion criteria of the BEL114333 study and receive IV 
belimumab. The target for starting IV belimumab (Day 0) for BEL114333 is 1 week after the last dose of SC belimumab (scheduled for Week 23 in the open-label extension). The 
EXIT visit of the C1115 study (Week 24) serves as the Day 0 visit for the Protocol BEL114333, and will have a +1 week visit window.
2.
The Exit visit will occur approximately 4 weeks after the last dose of belimumab. Belimumab should not be administered, and all Exit visit assessments must be completed.
3.
Refer to Section 6.2.2.3 for guidelines for scoring proteinuria for SELENA SLEDAI and BILAG evaluation.
4.
AE reports should be updated or completed prior to dosing. Ongoing Adverse events of BEL113750 have to be transferred and followed up in BEL114333.
5.
Samples should be obtained prior to dosing.
6.
A 24-hour urine may be done as an additional assessment if clinically indicated (e.g., renal flare). 
7.
Results of urine pregnancy test at subsequent visits, if required, must be available prior to dose. See ‘Critical Baseline Assessments’, Section 6.1 for definition of those exempted 
from subsequent pregnancy testing.
8.
Serum immunoglobulin isotypes: IgG, IgM, IgA.
9.
Immunogenicity testing includes quantifying the amount of belimumab present in the samples using the belimumab PK assay.  
9AFor any subject who had an anti-belimumab antibody response at the 16-week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-week follow-
up immunogenicity sample is not available), an attempt will be made to obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose of study 
agent.
10. Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells).  Note:  B-cell subsets to be drawn at selected sites only.
11. It is recommended the patient be weighed at each visit prior to dosing. If weight changes by more than 5% from the Day 0 weight, the weight at the current visit should be used for 
calculating the dose.  Systolic and diastolic blood pressure (sitting), heart rate, and oral temperature will be measured (see Section 6.3.11).
12. Subjects will remain under clinical supervision for 3 hours after completion of the first 2 infusions.  See Section 5 and Section 6.3.9. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
33
Table 3
Time and Events Table (Additional Years)
Study Visit
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
EXIT1
16 wk FU 
7d post 
infusion
6 month FU 7d 
post infusion
Study Day
28   
7d
56   
7d
84   
7d
112 
7d
140 
7d
168 
7d
196 
7d
224 
7d
252 
7d
280 
7d
308 
7d
336 
7d
Efficacy Assessments
Disease Activity Scales: 
SELENA SLEDAI, SLE 
Flare Index, BILAG and 
PGA 2
X
X
X
SLICC/ACR Damage 
Index
X
X
Safety Assessments
Symptom-driven Physical 
Exam
X
X
X
X
Record Concurrent 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess/Record Adverse 
Events 3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs 4, 10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory 
Assessments
Labs: Haematology & 
Modified Chem 20 (non 
fasting) 4, 11
X
X
X
X
Urinalysis 5, 11
X
X
X
X
Spot urine (protein to 
creatinine ratio) 4, 5, 11
X
X
X
Urine Pregnancy Test 6, 11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C3, C4, Anti-dsDNA 
Autoantibodies4, 11
X
X
X
IgG 4, 7, 11
X
X
X
IgA & IgM 4, 7, 11
X
X

YM2010/00145/03
CONFIDENTIAL
BEL114333
34
Study Visit
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
EXIT1
16 wk FU 
7d post 
infusion
6 month FU 7d 
post infusion
Study Day
28   
7d
56   
7d
84   
7d
112 
7d
140 
7d
168 
7d
196 
7d
224 
7d
252 
7d
280 
7d
308 
7d
336 
7d
Exploratory Lab 
Assessments
Immunogenicity 8
X
X
X
X
X8A
B cell Markers 9
X
X
X
Investigational Product
Belimumab  
Administration10
X
X
X
X
X
X
X
X
X
X
X
X
Calendar represents a yearly (48-week) ongoing visit schedule until the subject is terminated from the study. 
1.
The Exit visit will occur approximately 4 weeks after the last dose of belimumab. Study agent should not be administered, and all Exit visit assessments must be 
completed.
2.
Refer to Section 6.2.2.3 for guidelines for scoring proteinuria for SELENA SLEDAI and BILAG evaluation.
3.
AE reports should be updated or completed prior to dosing. Ongoing Adverse events of BEL113750 or C1115 have to be transferred and followed up in BEL114333.
4.
Samples should be obtained prior to dosing.
5.
A 24-hour urine may be done as an additional assessment if clinically indicated (e.g., renal flare). 
6.
Results of urine pregnancy test at subsequent visits, if required, must be available prior to dose. See ‘Critical Baseline Assessments’, Section 6.1 for definition of those 
exempted from subsequent pregnancy testing.
7.
Serum immunoglobulin isotypes: IgG, IgM, IgA.
8.
Immunogenicity testing includes quantifying the amount of belimumab present in the samples using the belimumab PK assay.  
8AFor any subject who had an anti-belimumab antibody response at the 16-week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available), an attempt will be made to obtain a serum sample for anti-belimumab antibodies at least 6 months after the 
last dose of study agent.
9.
Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ 
plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells).  Note:  B-cell subsets to be drawn at selected sites only.
10. It is recommended the patient be weighed at each visit prior to dosing. If weight changes by more than 5% from the Day 0 weight, the weight at the current visit should 
be used for calculating the dose.  Systolic and diastolic blood pressure (sitting), heart rate, and oral temperature will be measured (see Section 6.3.11).
11. During “Additional years”, investigators can obtain any of the same laboratory assessments that are mentioned for Year 1 (hematology, modified Chem 20, urinalysis, 
spot urine to creatinine ratio, urine pregnancy, C3, C4, anti-ds DNA autoantibodies, IgG, IgA, and IgM), as unscheduled laboratory tests at any time during Year 2 and 
beyond, if clinically indicated.  Any additional laboratory tests beyond this, if not related to the protocol, will be the responsibility of the investigator and subject.

YM2010/00145/03
CONFIDENTIAL
BEL114333
35
6.1.
Critical Baseline Assessments
For subjects in BEL113750: Subjects will be assessed for eligibility at the Week 48 visit 
of BEL113750. Only subjects who complete BEL113750 through the Week 48 visit and 
have a final BEL113750 disease assessment at Week 52 are eligible for this study. 
Written informed consent (including consent for the use and disclosure of research-
related health information) must be obtained. Subjects must be able to receive the first 
dose of belimumab for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 
weeks) after the last dose in BEL113750.
For subjects in C1115: Subjects will be assessed for eligibility at the Day 168 visit of 
C1115. Only subjects who complete C1115 through the open-label extension phase and 
have a final disease assessment at Day 168 are eligible for this study. Written informed 
consent (including consent for the use and disclosure of research-related health 
information) must be obtained on or before the Day 168 visit. Subjects must be able to 
receive the first dose of IV belimumab (Day 0) for BEL114333 one week after the last 
SC dose in C1115. The EXIT visit of the C1115 study (Week 24) serves as the Day 0 
visit for the Protocol BEL114333, and will have a +1 week visit window. 
6.1.1.
Procedures (Day 0)
6.1.1.1.
Subjects in BEL113750
The Week 52 visit in BEL113750 will serve as the Day 0 visit for Protocol BEL114333. 
The subject must sign the informed consent for this protocol between the Week 48 and 
Week 52 visits of the BEL113750 study prior to any procedure in this protocol (that is 
not present in the BEL113750 protocol) being performed. On Day 0 of this study, a 
subject will be reassessed for Inclusion/Exclusion criteria of the BEL114333 study and 
receive belimumab, after completing the Week 52 procedures from the BEL113750 
study. Site personnel will access the IVRS to enrol the subject in the study. 
Procedures necessary for this protocol and for the prior Phase III protocol (BEL113750) 
need only be performed once. The results of any Day 0 procedure in this protocol which 
are also part of the BEL113750 protocol should be recorded on the BEL113750 eCRF. 
Only the additional procedures required for this protocol will be recorded in the 
BEL114333 protocol eCRF. The relevant Week 52 eCRF data will be transferred to the 
Day 0 BEL114333 eCRF.
The following assessments will be performed as part of the Week 52 assessment on 
BEL113750 and need only be performed once as described above.

Urine for pregnancy testing- for all women with an intact uterus, unless exempted 
from pregnancy testing (i.e., of non-childbearing potential - women who had a 
hysterectomy, are post-menopausal which is defined as 1 year without menses, have 
both ovaries surgically removed or have current documented female sterilization 
procedure).

Record of Concurrent Medications.

YM2010/00145/03
CONFIDENTIAL
BEL114333
36

Adverse Events.

Physical exam

Vital signs (Systolic and diastolic blood pressure (sitting), heart rate, and oral 
temperature will be measured.  See Section 6.3.11).

Blood samples for: (see Appendix 5– Laboratory Tests):

Haematology.

Modified Chem 20 (non-fasting). (CPK MUST be done for subjects with 
myositis in order to score SELENA SLEDAI/BILAG).

Serum Immunoglobulin isotypes (IgG, IgM, IgA).

Immunogenicity testing.

Biological markers (Complement C3 and C4)

Anti-dsDNA autoantibodies.
B-cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+
activated,  CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and 
CD20-/138+ plasma cells) at selected sites.

Urine sample for:

Routine urinalysis.

Spot urine for macroscopic/microscopic/proteinuria assessments.

Disease activity scales:

Physician’s Global Assessment (PGA). (See Appendix 1).

SELENA SLEDAI (See Appendix 1; refer to Section 6.2.2.3 Guidelines for 
Scoring Proteinuria).

SLE Flare Index. (See Appendix 1).

BILAG. (See Appendix 2).

SLICC/ACR Damage Index (See Appendix 3).
The following additional procedures beyond those described above are required at Day 0 
for Protocol BEL114333:

Ensure Informed Consent Form has been signed.

Confirm Eligibility.

PT/PTT

Administer belimumab.

YM2010/00145/03
CONFIDENTIAL
BEL114333
37
6.1.1.2.
Subjects in C1115
The Day 168 visit of the open-label extension of C1115 will serve as the Day 0 visit for 
Protocol BEL114333. The subject must sign the informed consent for this protocol on or 
before the Day 168 visit of the open-label extension of C1115 prior to any procedure in 
this protocol (that is not present in the C1115 protocol) being performed. On Day 0 of 
this study, a subject will be reassessed for Inclusion/Exclusion criteria of the BEL114333 
study and receive IV belimumab, after completing the Day 168 procedures from the 
C1115 study. Site personnel will access the IVRS to enrol the subject in the study. 
Procedures necessary for this protocol and for the prior Phase III protocol (C1115) need 
only be performed once. The results of any Day 0 procedure in this protocol which are 
also part of the C1115 protocol should be recorded on the C1115 eCRF. Only the 
additional procedures required for this protocol will be recorded in the BEL114333 
protocol eCRF. 
The following assessments will be performed as part of the Day 168 assessment on 
C1115 and need only be performed once as described above and entered into the C1115 
eCRF only.

Urine for pregnancy testing- for all women with an intact uterus, unless exempted 
from pregnancy testing (i.e., of non-childbearing potential - women who had a 
hysterectomy, are post-menopausal which is defined as 1 year without menses, have 
both ovaries surgically removed or have current documented female sterilization 
procedure).

Record of Concurrent Medications.

Adverse Events.

Blood samples for: (see Appendix 5– Laboratory Tests):

Haematology.

Modified Chem 20 (non-fasting). (CPK MUST be done for subjects with 
myositis in order to score SELENA SLEDAI/BILAG).

PT/PTT

Serum Immunoglobulin isotypes (IgG, IgM, IgA).

Immunogenicity testing.

Biological markers (Complement C3 and C4)

Anti-dsDNA autoantibodies.
B-cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+
activated,  CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and 
CD20-/138+ plasma cells) at selected sites.

Urine sample for:

Routine urinalysis.

YM2010/00145/03
CONFIDENTIAL
BEL114333
38

Spot urine for macroscopic/microscopic/proteinuria assessments.

Disease activity scales:

Physician’s Global Assessment (PGA). (See Appendix 1).

SELENA SLEDAI (See Appendix 1; refer to Section 6.2.2.3 Guidelines for 
Scoring Proteinuria).

SLE Flare Index. (See Appendix 1).

BILAG. (See Appendix 2).
The above Day 168 eCRF data will be transferred programmatically from the C1115 
eCRF and merged with the datasets for BEL114333.  This data will not be visible in the 
BEL114333 eCRF.
The following additional procedures beyond those described above are required at Day 0 
for Protocol BEL114333:

Ensure Informed Consent Form has been signed.

Confirm Eligibility.

Physical exam

Vital signs (Systolic and diastolic blood pressure (sitting), heart rate, and oral 
temperature will be measured.  See Section 6.3.11).

SLICC/ACR Damage Index (See Appendix 3).

Administer belimumab.
6.2.
Efficacy
6.2.1.
Efficacy Endpoints
6.2.1.1.
Primary Endpoint
The primary efficacy endpoint is response rate at each scheduled visit when complete 
efficacy evaluations occur (e.g., Weeks 24 and 48 of Year 1 and Year 2, etc).

A response is defined as:

4 point reduction from baseline in SELENA SLEDAI score, 
AND

No worsening (increase of <0.30 points from baseline) in Physician’s Global 
Assessment (PGA), 
AND

YM2010/00145/03
CONFIDENTIAL
BEL114333
39

No new BILAG A organ domain score or 2 new BILAG B organ domain scores 
compared with baseline at the time of assessment (i.e., Weeks 24 and 48 of Year 
1 and Year 2, etc).
6.2.1.2.
Secondary Endpoints

Percent of subjects with 4 point reduction from baseline in SELENA SLEDAI 
score assessed every 24 weeks.

Number of days of daily prednisone dose 7.5 mg/day and/or reduced by 25% from 
baseline over time.

Time to first severe SLE Flare Index (SFI) flares assessed over time.
NOTE:  Baseline will be defined as study Day 0 of BEL113750 study or C1115 
study as appropriate. Additionally, for the group of subjects who received placebo in 
BEL113750, a secondary analysis will be performed by defining the baseline as Day 
0 of the current study the day placebo subjects in BEL113750 will have begun to 
receive belimumab treatment.  (See Section 8.1)
6.2.1.3.
Other Endpoints
Disease Activity:

Duration of primary response assessed every 24 weeks. 

Change in Systemic Lupus International Collaborating Clinics (SLICC)/ACR 
Damage Index assessed every 24 weeks. 

Percent change in PGA assessed every 24 weeks.
Flares:

For analysis, SLE Flares will be defined in 3 ways:
- BILAG 1A/2B Flare: A new BILAG A organ domain score or 2 new BILAG B 
organ domain scores compared with baseline.
- BILAG A Flare: A new BILAG A organ domain score compared with baseline.
- SFI Flare: A mild/moderate or severe flare according to the modified SELENA 
SLEDAI SLE Flare Index (modified excludes severe flares from the SELENA 
SLEDAI flare assessment that were triggered only by an increase in SELENA 
SLEDAI score to >12).

Time to first SFI flare assessed over time. 

Time to first 1A/2B BILAG flare assessed over time. 

Time to first BILAG A flare assessed over time. 
Organ-specific Measures:

Renal flare rate and time to first renal flare assessed over time.

A SLE renal flare is defined as the occurrence of 1 or more of the following in 2 
or more consecutive visits during the study:

YM2010/00145/03
CONFIDENTIAL
BEL114333
40
1.
A reproducible increase in 24-hour urine protein equivalent levels to 
a. 1 g if the baseline value was 0.2 g, 
b. 2 g if the baseline value was 0.2 to 1 g, or 
c. More than twice the value at baseline if the baseline value is 1 g.
2.
A reproducible increase in serum creatinine of >20% or at least 0.3 mg/dL, 
accompanied by proteinuria (1 g/24 hour equivalent), haematuria (4 red 
blood cells [RBCs]/high-power field [hpf]), and/or RBC casts.
3.
Treatment emergent, reproducible hematuria (11 to 20 RBCs/ hpf) or a 
reproducible increase in hematuria by 2 grades compared with baseline, 
associated with 25% dysmorphic RBCs, glomerular in origin, exclusive of 
menses, accompanied by either an 0.8 g increase in 24-hour urinary protein 
levels (equivalent) or new RBC casts [Alarcón-Segovia, 2003] .

Percent change in proteinuria by visit.
Prednisone:

Percent change from baseline of prednisone dose at each scheduled visit.

Percent of subjects whose average prednisone dose has been reduced to 7.5 mg/day 
from > 7.5 mg/day at baseline over time.
Details of the analysis of other supporting endpoints will be given in the Reporting and 
Analysis Plan (RAP).
6.2.2.
SELENA SLEDAI
All site staff scoring SELENA SLEDAI are required to pass proficiency tests before 
carrying out assessments to ensure consistency across centres.
6.2.2.1.
SELENA SLEDAI Score
The SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) is a validated 
index for assessing SLE disease activity [Bombardier, 1992].  It is a weighted index in 
which signs and symptoms, laboratory tests, and physician’s assessment for each of 9 
organ systems are given a weighted score and summed, if present at the time of the visit 
or in the preceding 10 days:

Score of 8 each for CNS and vascular items.

Score of 4 each for renal and musculoskeletal items.

Score of 2 each for serosal, dermal, and immunologic items.

Score of 1 each for constitutional and hematologic items.
The SELENA SLEDAI used in this study is a slightly modified version of the SLEDAI 
developed for a National Institutes of Health sponsored multicentre study of 
estrogen/progesterone hormone use in women with SLE [Buyon, 2005; Petri, 2005]. The 
descriptions for some of the items are slightly modified, but the organ systems and 
weighted scores are the same as the SLEDAI.  The maximum theoretical score for the 

YM2010/00145/03
CONFIDENTIAL
BEL114333
41
SELENA SLEDAI is 105 (all 24 descriptors present simultaneously) with 0 indicating 
inactive disease.  Completion of the index requires collection of a 24-hour urine sample 
for assessment of proteinuria (although spot urine protein:creatinine ratio is commonly 
substituted in practice, see Section 6.2.2.2), measurement of anti-dsDNA, C3, C4, 
haematology, and urinalysis, and for subjects with myositis, CPK.  Guidelines for scoring 
proteinuria are provided in Section 6.2.2.3. 
SELENA SLEDAI will be assessed at Day 0 and then every 24 weeks thereafter. 
A copy of the index is provided in Appendix 1.
6.2.2.2.
Laboratory Tests for SELENA SLEDAI and BILAG
It has been demonstrated that there is a strong correlation between the protein content of 
a 24-hour urine collection and the protein:creatinine ratio in a single urine sample 
[Ginsberg, 1983; Ruggenenti, 1998; K/DOQI Clinical Practice Guidelines for Chronic 
Kidney Disease, 2002; Price, 2005].  Given this information, spot urine protein:creatinine 
ratio will be used for determining proteinuria in this study for both the SELENA SLEDAI 
and BILAG disease activity indices.
Measurement of creatinine clearance (CrCl)/glomerular filtration rate (GFR) using timed 
(for example, 24-hour) urine collections is time consuming and error prone and has 
consistently been shown to be no more, and often less, reliable than serum creatinine 
based equations for the estimation of GFR [K/DOQI Clinical Practice Guidelines for 
Chronic Kidney Disease, 2002].  Therefore, GFR estimated by the Cockroft-Gault 
formula will be used in the BILAG disease activity index, as was done in the Phase II 
trial of belimumab (LBSL02) and Phase III.
Cockroft-Gault Equation [Cockcroft, 1976]
female
if
x
dL
mg
tinine
xserumcrea
kg
xweight
yrs
age
mL
Clcr
85
.0
)
/
(
72
)
(
))
(
140
(
min)
/
(


Values outside the reference laboratory normal range that require the investigator’s 
assessment of relationship to SLE:
BILAG item # 75 for Creatinine (plasma/serum)
Sex
US (units)
UK (units)
Male and Female
0.5 – 1.4 mg/dL
44 – 124 µmol/l
BILAG item # 76 for Creatinine Clearance/GFR 
Sex
US (units)
Male
85 – 125 ml/min
Female
75 – 115 ml/min

YM2010/00145/03
CONFIDENTIAL
BEL114333
42
6.2.2.3.
Guidelines for Scoring Proteinuria for SELENA SLEDAI
The following guidelines should be followed for scoring for proteinuria in the SELENA 
SLEDAI disease activity index.
6.2.2.3.1.
Scoring for Proteinuria at Day 0 and Subsequent Study Visits
According to the SELENA SLEDAI scoring rules, unless the proteinuria continues to rise 
such that it has increased by > 0.5 g/24 hour equivalent at Day 0 (i.e., baseline), the 
subject, by default, will have an improving SELENA SLEDAI score prior to treatment.  
Two assessments of 24-hour proteinuria (by spot urine protein to creatinine ratio) 
obtained in a 2 to 3 week period are unlikely to show a > 0.5 g/24 hour equivalent 
increase except in acute renal flare.  This is problematic for data analysis since the 
percent change in the disease activity scales are calculated from the baseline (not 
screening) SELENA SLEDAI score.  As such, the following scoring rules will be 
applied:
Scoring for a Subject with Proteinuria and 4 Points Assigned in SELENA SLEDAI
If there is an increase from the last visit of >0.5 g/24 hour equivalent, only 4 points for 
proteinuria will continue to be applied (so no subject can get more than 4 points for 
proteinuria at any 1 time point).
If the proteinuria has not improved (i.e., there has not been a decrease in proteinuria of 
>0.5 g/24 hour equivalent) since the previous assessment, then 4 points will continue to 
be assigned on the SELENA SLEDAI index at the current visit.
If proteinuria has improved (decrease of >0.5 g/24 hour equivalent or a decrease to 
≤0.5 g/24 hour equivalent) from the previous visit to the current visit, then 0 points will 
be assigned on the SELENA SLEDAI index at the current visit.
Scoring for a Subject with 0 Points for Proteinuria in SELENA SLEDAI
If the proteinuria score for SELENA SLEDAI is 0 and at the subsequent visit the 
assessment of 24-hour proteinuria (by spot urine protein to creatinine ratio) shows 
>0.5 g/24 hour equivalent increase above the previous value or the subject develops new 
onset of proteinuria >0.5 g/24 hour equivalent, 4 points will be assigned at this current 
visit.
6.2.2.4.
SELENA SLEDAI Flare Index
The SLE Flare Index categorizes SLE flare as “mild or moderate” or “severe” based on a 
positive assessment for at least one of 5 variables [Buyon, 2005; Petri, 2001; Petri, 2005].

Change in SELENA SLEDAI score from the most recent assessment to current. (not 
used for severe flare)

Change in signs or symptoms of disease activity.

Change in prednisone dosage.

YM2010/00145/03
CONFIDENTIAL
BEL114333
43

Use of new medications for disease activity or hospitalization.

Change in PGA score.
Hospitalization for SLE activity is an additional category included only for a severe flare.
A copy of the SLE Flare Index is provided in Appendix 1.  
6.2.2.5.
Physician’s Global Assessment (PGA)
The PGA is a 0-10 cm visual analogue scale (VAS), anchored at 0 (none) and 3 (severe), 
with intermediate lines at 1 (mild), and 2 (moderate) designed for the physician to 
indicate the subject’s overall disease activity at a particular visit [Petri, 1999].  It is part 
of the validated SELENA SLEDAI index.  Either the primary investigator or a 
subinvestigator will score the PGA for the subject, and the same person will evaluate the 
subject each time, unless agreed with the GSK medical monitor.  Each PGA 
measurement will be transformed linearly (x 3/10) to obtain a value between 0.00 and 
3.00.
PGA will be assessed at Day 0 and then every 24 weeks thereafter.
A copy of the PGA VAS is provided in Appendix 1.
6.2.3.
BILAG
The BILAG index is a clinical measure of lupus disease activity.  The scoring system for 
the BILAG index was developed based upon the principle of the physician’s intention to 
treat.  The main distinguishing feature of the BILAG index from other disease activity 
indices is that disease activity in different organs/systems is reported separately.  There 
are 8 organ systems: general, mucocutaneous, neurological, musculoskeletal, 
cardiorespiratory, vasculitis, renal, and hematological [Hay, 1993; Isenberg, 2000; 
Gordon, 2003].  A score is calculated for each system depending on the SLE clinical 
manifestations (or signs and symptoms) present and whether they are new, worse, the 
same, improving, or not present in the last 4 weeks compared with the previous 4 weeks.  
The SLE disease manifestations considered severe in each system are those that would 
normally require high dose steroids (prednisolone > 20 mg/day or equivalent) and/or 
cytotoxic agents; these define a BILAG A score.  More moderate SLE disease 
manifestations that would be considered appropriate to treat with lower dose steroids, 
antimalarial drugs or NSAIDs contribute to a BILAG B score.  Mild symptomatic SLE 
features that require only symptomatic therapy (e.g., analgesics and NSAIDs) contribute 
to a C score.  If there are no current symptoms, but the system has previously been 
involved, then a D is recorded, while if the system has never been involved an E score is 
assigned.  
The BILAG will be assessed at Day 0 and then every 24 weeks thereafter.
A copy of the BILAG index is provided in Appendix 2.  All site staff scoring BILAG 
assessments are required to pass proficiency tests before carrying out assessments to 
ensure consistency across centres.

YM2010/00145/03
CONFIDENTIAL
BEL114333
44
6.2.4.
SLICC/ACR Damage Index
The Systemic Lupus International Collaborative Clinics/American College of 
Rheumatology (SLICC/ACR) Damage Index is a validated instrument developed to 
assess the accumulated damage in patients with SLE, resulting from either the disease 
process or its sequelae.  It can identify changes in damage seen in patients with both 
active and inactive disease and records damage occurring in patients with SLE regardless 
of its cause [Gladman, 1996].  The index is a predictor of severe outcome and an 
indicator of morbidity in different ethnic groups [Stoll, 1996]. SLICC/ACR Damage 
Index was designed to be useful both as a descriptor for patient populations included in 
studies, and as an outcome measure for therapeutic trials and studies of prognosis 
[Gladman, 1996].
The SLICC/ACR Damage index consists of 39 items in 12 different organ systems.  In 
order for a feature to represent damage, it had to be present for at least 6 months, to 
enable discrimination between active inflammation and tissue damage [Gladman, 1996] 
Scoring is usually 0 or 1, although in 6 items, a score of 2 can be given if there is a repeat 
episode more than 6 months apart.  The exception is end-stage renal disease, which 
scores 3. 
SLICC/ACR Damage Index will be assessed at Day 0 and the 48/Exit visit. 
A copy of the SLICC/ACR Damage Index is provided in Appendix 3.
6.3.
Safety
The safety assessments will be as follows:

Adverse Event (including infusion-related and hypersensitivity reactions, infections 
and malignancies) reported throughout each 48 week period.

Haematological and clinical chemistry parameters (including urinalysis) throughout 
each 48 week period and follow-up.

B Cell Markers assessed at the Week 48 visit, EXIT visit, and at approximately 6 
months after the last dose of study agent.  Samples will be collected pre-dose where 
taken at dosing visits.  Blood samples for measurement of B-cell subsets will be 
collected from subjects at selected sites only.

Immunogenicity over each 24 week period, at the Exit visit and the 16 week follow-
up visit for subjects who withdraw prior to completion of the 52-week treatment 
period.  An attempt will be made to obtain a serum sample for anti-belimumab 
antibodies at least 6 months after the last dose of study agent for any subject who had 
an anti-belimumab antibody response at the 16-week follow-up visit (or last study 
visit at which immunogenicity was assessed if the 16-week follow-up 
immunogenicity sample is not available).   Any anti-belimumab antibody positive 
sample will be tested for neutralization. 

Additional safety tests (such as vital signs, physical examinations and laboratory 
safety tests) or change in timing or addition of assessments may be performed during 

YM2010/00145/03
CONFIDENTIAL
BEL114333
45
the course of the study based on newly available data if recommended by the GSK 
internal Safety Review Team, to ensure appropriate safety monitoring.  IRB/IEC will 
be informed of any safety issues that require alteration of the safety monitoring 
scheme.

Note:  The Columbia Suicide Severity Rating Scale (C-SSRS) will not be collected; 
however, investigators will continue to observe and clinically assess subjects for 
potential suicidality at all visits.
6.3.1.
Liver Chemistry Stopping and Follow up Criteria
Refer to the diagram in Appendix 4 for a visual presentation of the procedures listed 
below.
NOTE: if serum bilirubin fractionation is not immediately available, belimumab should 
be discontinued if ALT 3xULN and bilirubin 2xULN. Serum bilirubin fractionation 
should be performed if testing is available. If testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.
Phase III-IV liver chemistry stopping and follow up criteria have been designed to 
assure subject safety and evaluate liver event aetiology (in alignment with the FDA 
premarketing clinical liver safety guidance).  
Phase III-IV liver chemistry stopping criteria 1-5 are defined below:
1. ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) (or ALT 3xULN and
INR>1.5, if INR measured)
NOTE: if serum bilirubin fractionation is not immediately available, belimumab should 
be discontinued if ALT 3xULN and bilirubin 2xULN. Serum bilirubin fractionation 
should be performed if testing is available. If testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.
2. ALT 8xULN.
3. ALT 5xULN but <8 x ULN persists for 2 weeks
4. ALT 3xULN if associated with the appearance or worsening of symptoms of 
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash or eosinophilia.
5. ALT 5xULN but <8 x ULN and cannot be monitored weekly for 2 weeks
When any of the liver chemistry stopping criteria 1-5 is met, do the following:

Immediately withdraw belimumab

Report the event to GSK within 24 hours of learning its occurrence

Complete the liver event CRF and SAE data collection tool if the event also meets 
the criteria for an SAE. All events of ALT 3xULN and bilirubin 2xULN (>35% 

YM2010/00145/03
CONFIDENTIAL
BEL114333
46
direct) (or ALT 3xULN and INR>1.5, if INR measured); INR measurement is not 
required and the threshold value stated will not apply to patients receiving 
anticoagulants), termed ‘Hy’s Law’, must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
NOTE: if serum bilirubin fractionation is not immediately available, belimumab 
should be discontinued if ALT 3xULN and bilirubin 2xULN. Serum bilirubin 
fractionation should be performed if testing is available. If testing is unavailable, 
record presence of detectable urinary bilirubin on dipstick, indicating direct 
bilirubin elevations and suggesting liver injury.

Complete the liver imaging and/or liver biopsy CRFs if these tests are performed

Perform liver event follow up assessments, and monitor the subject until liver 
chemistries resolve, stabilize, or return to baseline values as described below. 

Withdraw the subject from the study (unless further safety follow up is required) 
after completion of the liver chemistry monitoring as described below.

Do not re-challenge with belimumab.
In addition, for criterion 1: 

Make every reasonable attempt to have subjects return to clinic within 24 hours for 
repeat liver chemistries, liver event follow up assessments (see below), and close 
monitoring

A specialist or hepatology consultation is recommended

Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within baseline values
For criteria 2, 3, 4 and 5:

Make every reasonable attempt to have subjects return to clinic within 24-72 hrs for 
repeat liver chemistries and liver event follow up assessments (see below)

Monitor subjects weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within baseline values; criterion 5 subjects 
should be monitored as frequently as possible.
Subjects with ALT 5xULN and <8xULN which exhibit a decrease to ALT x3xULN, 
but <5xULN and bilirubin <2xULN without hepatitis symptoms or rash, and who can be 
monitored weekly for 4 weeks:

Notify the GSK medical monitor within 24 hours of learning of the abnormality to 
discuss subject safety

Can continue belimumab

Must return weekly for repeat liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to within baseline 

If at any time these subjects meet the liver chemistry stopping criteria, proceed as 
described above

YM2010/00145/03
CONFIDENTIAL
BEL114333
47

If, after 4 weeks of monitoring, ALT <3xULN and bilirubin <2xULN, monitor 
subjects twice monthly until liver chemistries normalize or return to within baseline 
values. 
For criteria 1-5, make every attempt to carry out the liver event follow up assessments
described below:

Viral hepatitis serology including:

Hepatitis A IgM antibody

Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM)

Hepatitis C RNA

Cytomegalovirus IgM antibody  

Epstein-Barr viral capsid antigen IgM antibody

Hepatitis E IgM antibody 

Blood sample for PK analysis, obtained within approximately one to two weeks after 
the liver event.  Record the date/time of the PK blood sample draw and the date/time 
of the last dose of belimumab prior to blood sample draw on the CRF. If the date or 
time of the last dose is unclear, provide the subject’s best approximation. If the 
date/time of the last dose cannot be approximated OR a PK sample cannot be 
collected in the time period indicated above, do not obtain a PK sample. Instructions 
for sample handling and shipping are in the SPM. 

Serum creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH)

Fractionate bilirubin, if total bilirubin 2xULN

Obtain complete blood count with differential to assess eosinophilia

Record the appearance or worsening of clinical symptoms of hepatitis or 
hypersensitivity, such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever rash or eosinophilia as relevant on the AE report form

Record use of concomitant medications, acetaminophen, herbal remedies, other over 
the counter medications, or putative hepatotoxins, on the concomitant medications 
report form

Record alcohol use on the liver event alcohol intake case report form
The following are required for subjects with ALT 3xULN and bilirubin 2xULN (>35% 
direct) but are optional for other abnormal liver chemistries:

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies

Liver imaging (ultrasound, magnetic resonance, or computerized tomography) to 
evaluate liver disease

YM2010/00145/03
CONFIDENTIAL
BEL114333
48
6.3.2.
Adverse Events
The investigator or site staff will be responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.  Subjects will also be issued a paper 
diary to record adverse events and concomitant medications during the study. This will be 
used to assist subject recall in discussions with the investigator, for site staff to then enter 
as appropriate in the eCRF.
6.3.2.1.
Definition of an AE
Any untoward medical occurrence in a patient or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product.
Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product.  For marketed medicinal products, this 
also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Events meeting the definition of an AE include:

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition

New conditions detected or diagnosed after belimumab administration even though it 
may have been present prior to the start of the study

Signs, symptoms, or the clinical sequelae of a suspected interaction

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
belimumab or a concomitant medication (overdose per se will not be reported as an 
AE/SAE).
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. However, the signs and symptoms and/or clinical sequelae 
resulting from lack of efficacy will be reported if they fulfill the definition of an AE or 
SAE.  
Events that do not meet the definition of an AE include:

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital)

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen

The disease/disorder being studied, or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 
condition

YM2010/00145/03
CONFIDENTIAL
BEL114333
49
6.3.2.2.
Definition of a SAE
A serious adverse event is any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
NOTE:  The term 'life-threatening' in the definition of 'serious' 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, which hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:  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 the physician’s 
office or out-patient setting.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in disability/incapacity, or
NOTE:  The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained ankle) which 
may interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect
f.
Is medically important
NOTE: medical or scientific judgement should be exercised in deciding whether 
reporting is appropriate in other situations, such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition.  These should also be considered 
serious.  Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
6.3.3.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 

YM2010/00145/03
CONFIDENTIAL
BEL114333
50
including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgement of the investigator are to be recorded as AEs or SAEs.
All events of possible drug-induced liver injury with hyperbilirubinaemia defined as ALT 
3xULN and bilirubin 2xULN (>35% direct) (or ALT 3xULN and INR>1.5, if INR
measured) termed ‘Hy’s Law’ events (INR measurement is not required and the threshold 
value stated will not apply to patients receiving anticoagulants), will be recorded as an 
SAE as this is judged to be clinically significant.
NOTE: bilirubin fractionation is performed if testing is available. If testing is unavailable, 
record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury. If testing is unavailable and a subject meets the 
criterion of total bilirubin 2xULN, then the event is still reported as an SAE. If INR is 
obtained, include values on the SAE form. INR elevations >1.5 suggest severe liver 
injury.   
However, any clinically significant safety assessments that are associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for 
the subject’s condition, are not to be reported as AEs or SAEs.
6.3.4.
Investigator Evaluation of Adverse Events
The investigator will evaluate all adverse events with respect to seriousness (criteria for 
serious are listed in Section 6.3.2.2), severity (intensity) and causality (relationship to 
belimumab).  The investigator will make an assessment of intensity for each AE and SAE 
based on the Division of Microbiology and Infectious Diseases (DMID), 2001 Adverse 
Event Severity Grade Tables (see Appendix 6), where possible:
SEVERITY:
Mild
- An event that is easily tolerated by the subject, causing minimal discomfort and 
not interfering with everyday activities (Grade 1 DMID)
Moderate - An event that is sufficiently discomforting to interfere with normal everyday 
activities (Grade 2 DMID)
Severe - An event that prevents normal everyday activities (Grade 3 or 4 DMID)
An AE that is assessed as severe will not be confused with an SAE. Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe. An event is defined as ‘serious’ when it meets at least one of the pre-
defined outcomes as described in the definition of an SAE.
6.3.5.
Pregnancy
Any pregnancy that occurs during study participation and through 16 weeks following the 
last dose must be reported using a clinical trial pregnancy form.  To ensure subject safety, 
each pregnancy must be reported to GSK within 2 weeks of learning of its occurrence.  
The pregnancy must be followed up to determine outcome (including premature 

YM2010/00145/03
CONFIDENTIAL
BEL114333
51
termination) and status of mother and child.  Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE.  Spontaneous 
abortions must be reported as an SAE.
Any SAE occurring in association with a pregnancy brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK.
In the event that a subject becomes pregnant during the study, they should discontinue the 
study medication and be withdrawn from the study.
6.3.6.
Time Period and Frequency of Detecting AEs and SAEs
The investigator or site staff is responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.
AEs will be collected from the start of study treatment (Week 0) and until the 16 week 
follow up visit.  
SAEs will be collected over the same time period as stated above for AEs. However, any 
SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant 
medication, will be recorded from the time a subject consents to participate in the study 
up to and including any follow up contact. All SAEs will be reported to GSK within 24 
hours, as indicated in Section 6.3.7. 
6.3.7.
Prompt Reporting of Serious Adverse Events and Other Events 
to GSK
SAEs, pregnancies and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to GSK as described in the following table once the 
investigator determines that the event meets the protocol definition for that event.

YM2010/00145/03
CONFIDENTIAL
BEL114333
52
Initial Reports
Follow-up Information on a 
Previous Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
“SAE” data 
collection tool
24 hours
Updated “SAE” 
data collection tool 
Pregnancy
2 Weeks
Pregnancy 
Notification Form
2 Weeks
Pregnancy Follow 
up Form
Liver chemistry 
abnormalities Phase 
III-IV:
ALT3xULN and
Bilirubin2xULN 
(>35% direct) (or 
ALT3xULN and
INR>1.5, if INR 
measured)***
24 hours*
SAE data 
collection tool.
**Liver Event CRF 
and liver imaging 
and/or biopsy 
CRFs if applicable
24 hours
Updated SAE data 
collection tool. 
**Updated Liver 
Event CRF
ALT8xULN; 
ALT5xULN with 
hepatitis or rash or 
3xULN and <5xULN 
that persists 4 
weeks
24 hours*
**Liver event CRF
24 hours 
**Updated Liver 
Event CRF
ALT5xULN plus 
bilirubin <2xULN
24 hours*
**Liver event CRF 
does not need 
completing unless 
elevations persist 
for 2 weeks or 
subject cannot be 
monitored weekly 
for 2 weeks
24 hours
ALT5xULN and 
bilirubin <2xULN that 
persists 2 weeks
24 hours*
**Liver event CRF 
24 hours
Updated liver 
event CRF
ALT3xULN and <5x 
ULN and bilirubin 
<2xULN
24 hours*
**Liver event CRF 
does not need 
completing unless 
elevations persist 
for 4 weeks or 
subject cannot be 
monitored weekly 
for 4 weeks
*GSK to be notified at onset of liver chemistry elevations to discuss subject safety.
** Liver event documents should be completed as soon as possible.
*** INR measurement is not required; if measured, the threshold value stated will not apply to patients receiving 
anticoagulants

YM2010/00145/03
CONFIDENTIAL
BEL114333
53
Criteria for liver chemistry stopping and follow up criteria can be found in Section 6.3.1.
The method of detecting, recording, evaluating and follow-up of AEs and SAEs plus 
procedures for completing and transmitting SAE reports to GSK are provided in the 
SPM.  Procedures for post-study AEs/SAEs are provided in the SPM.
6.3.7.1.
Regulatory Reporting Requirements for SAEs
Prompt notification of SAEs by the investigator to GSK is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
6.3.7.2.
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs
The following conditions (preferred terms; MedDRA v. 14.0) are disease-related events 
(DRE) that can occur in the study population regardless of belimumab exposure. 
When these conditions are considered SAEs, they must be reported to the sponsor within 
24 hours of site personnel becoming aware as described in Section 6.3.6 .However, 
because these events are typically associated with the disease under study, the sponsor 
will not submit these events as expedited reports to regulatory authorities, investigators, 
or IRBs/IECs (unless considered by the sponsor to be related to study agent). 
Butterfly rash
Cutaneous lupus erythematosus
Glomerulonephritis membranoproliferative 
Glomerulonephritis membranous 
Glomerulonephritis proliferative 
Lupus encephalitis
Lupus endocarditis
Lupus enteritis
Lupus hepatitis
Lupus myocarditis
Lupus nephritis  
Lupus pancreatitis
Lupus pneumonitis
Lupus vasculitis
Nephritic syndrome
Nephritis
Neuropsychiatric lupus
Pericarditis lupus
Peritonitis lupus
SLE arthritis
Systemic lupus erythematosus rash
Systemic lupus erythematosus

YM2010/00145/03
CONFIDENTIAL
BEL114333
54
6.3.8.
Laboratory Evaluations
Clinical laboratory tests will consist of a complete blood count (CBC) with differential, 
Chem-20, magnesium, and urinalysis (see list in Appendix 5).  At the discretion of the 
Investigator, additional samples may be taken for safety reasons.  Immunoglobulins, 
autoantibodies and serum complement (C3 and C4), will also be assessed (see 
Section 6.4). Samples (blood and urine) for clinical laboratory tests will be collected as 
described in the Time and Events schedule (Table 2 and Table 3).
All clinical laboratory blood samples will be sent to a central laboratory for analysis 
(details provided in the SPM).  Standard reference ranges will be used.  Full details of the 
collection and shipping requirements for the central laboratory are provided in the Central 
Laboratory Investigator Manual.  The central laboratory will fax laboratory results to the 
Investigator and will transmit the results electronically to GlaxoSmithKline.  
6.3.9.
Infusion-related Reactions and Hypersensitivity Reactions
Infusion-related reactions on the day of an infusion occurred in approximately 17% of 
patients treated with belimumab 1mg/kg or 10mg/kg during the double-blind portion of 
the Phase 2 and 3 SLE studies, but at rates similar to placebo (15%). Most infusion-
related/hypersensitivity events have been mild-moderate in nature; however, severe and 
or serious events have been reported infrequently (<2% of patients). These events have 
included reports of rash, urticaria, angioedema, hypotension and anaphylaxis. As has 
been done in recent protocols, this protocol recommends that administering 
premedication for prophylaxis against infusion reactions and hypersensitivity reactions 
should be considered for subjects with a history of allergies or urticaria.  
In the post-marketing setting, delayed onset of symptoms of acute hypersensitivity 
reactions has been observed. Subjects should remain under clinical supervision for 3 
hours after completion of the first 2 infusions. Should symptoms of acute 
hypersensitivity occur, an extended period of monitoring may be appropriate, based on 
clinical judgment.  Subjects should be made aware of the potential risk, the signs and 
symptoms of such reactions, and the importance of immediately seeking medical 
attention.  
6.3.10.
Other Immunosuppression Related Considerations
Although there is no evidence to date for an increased risk with belimumab treatment, the 
possibility of immunosuppression resulting in an increase in the frequency and/or 
severity of infection and/or an increased risk of malignancy cannot be excluded.  During 
the trial, subjects will be questioned at all study visits about adverse events and results 
recorded in the eCRF.  Examinations and laboratory evaluations will be performed 
routinely and the results, including markers of potential immunosuppression, will be 
reported to the investigators. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
55
6.3.10.1.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) resulting in neurological deficits, 
including fatal cases, has been reported in SLE patients receiving immunosuppressant 
pharmacotherapy, including belimumab.  A diagnosis of PML should be considered in 
any subject presenting with new-onset or deteriorating neurological signs and symptoms.  
The subject should be referred to a neurologist or other appropriate specialist for 
evaluation.  If PML is confirmed, study agent should be discontinued and consideration 
should be given to stopping immunosuppressant therapy. 
If PML is suspected, this should be immediately reported to the Medical Monitor.  
The appropriateness of continuing study agent, while the case is being assessed, should 
be discussed.
6.3.11.
Vital Signs and Weight
Systolic and diastolic blood pressure (sitting), heart rate, and oral temperature will be 
measured.  Measurements of vital signs and weight will be taken prior to dosing on Day 0 
and every 4 weeks up to week 48/Exit; and at the 16-week follow-up visit (vital signs 
only) for subjects who withdraw prior to study completion.  At the discretion of the 
Investigator, vital signs may be assessed at unscheduled visits.
6.3.12.
Physical Examination
Abbreviated, symptom-driven examinations will be performed at Day 0, every 24 weeks, 
at the study Exit, and at the 16-week follow-up visit for subjects who withdraw.  At the 
discretion of the Investigator, physical examinations may be performed at unscheduled 
visits.
As a minimum, brief physical examination will include assessment of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen). 
6.3.13.
Immunogenicity
6.3.13.1.
Sample Collection and Handling
Serum samples will be collected for belimumab immunogenicity assays prior to dosing at 
Day 0, and Weeks 24 and 48 of Year 1 and Year 2, etc., and at the Exit visit, and 16 week 
follow-up visit.  An attempt will be made to obtain a serum sample for anti-belimumab 
antibodies at least 6 months after the last dose of study agent for any subject who had an 
anti-belimumab antibody response at the 16-week follow-up visit (or last study visit at 
which immunogenicity was assessed if the 16-week follow-up immunogenicity sample is 
not available).
At each collection time, blood will be collected in a 6 mL plain tube.  Each specimen will 
be allowed to clot, and the tube then centrifuged at approximately 1,600 g for 15 minutes 
at room temperature to separate the clot from the serum.  The serum (approximately 1 mL 
per sample) will be harvested and placed in duplicate 2-mL Sarstedt vials for storage.  
Serum samples will be stored at -20°C at the sites before weekly batch shipment to Quest 

YM2010/00145/03
CONFIDENTIAL
BEL114333
56
Diagnostics.  Samples will be stored at -70°C at Quest Diagnostics until shipment to HGS 
and stored at -80°C after they arrive at HGS. Samples will be shipped on dry ice in both 
shipments.
6.3.13.2.
Assay Methods
Immunogenicity testing will be carried out at GSK (Clinical Immunology department) or 
Frontage Laboratories in Shanghai, China.  The assay is performed in a 4-tiered 
belimumab immunogenicity assay paradigm (screening, confirmation/specificity and 
neutralisation and titer).
In the screening assay, the presence of anti-belimumab antibodies will be assessed using 
an electrochemiluminescence (ECL)-based (Meso Scale Discovery [MSD]) bridging 
assay after dissociation of belimumab from the anti-drug antibodies (ADA).  Any 
samples testing positive will then be tested using a confirmatory ECL based assay which 
is able to distinguish between ADA (true positive) and BLyS-belimumab complexes in 
serum (false positive).  The confirmed positive samples will be analyzed for the presence 
of neutralizing antibodies by a neutralisation assay and also assayed for titer.  The results 
of the anti-belimumab antibody tests for all subjects will be reported at the end of the 
study. 
6.4.
Biomarker(s)
As yet, no clear surrogate endpoints have been widely accepted that clearly define 
clinical outcomes for the multi-organ system manifestations of SLE.  However 
autoantibodies have been shown to be important early markers of specific disease 
processes or severity in SLE [Hahn, 1998; Leslie, 2001; Ravirajan, 2001] and are 
associated with disease activity [Villarreal, 1997]. Therefore autoantibody levels will be 
included as endpoints.
Blood samples will be collected pre-dose at the visits specified in the Time and Events 
schedule (Table 2 and Table 3), to enable to following endpoints to be assessed:

Percent change from baseline:
- Total serum immunoglobulin (IgG and other isotypes: IgM and IgA)
- Autoantibodies (anti-dsDNA) and complement (C3, C4)

Percent change in absolute B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–
naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells) at the 
Exit visit and 6 month  Follow-up at selected sites.
All biomarker samples will be analysed centrally.
6.5.
Pharmacokinetic Assessments
No PK sampling independent of immunogenicity testing, or liver chemistry stopping and 
follow-up criteria will be done. Immunogenicity samples will be tested for drug 

YM2010/00145/03
CONFIDENTIAL
BEL114333
57
levels using the belimumab PK assay to assist in the interpretation of the immunogenicity 
results.
7.
DATA MANAGEMENT
For this study subject data will be entered into electronic case report forms (eCRFs), 
transmitted electronically to GSK or its partner company, HGS, and combined with data 
provided from other sources in a validated data system.  
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
errors and inconsistencies in the data.  Adverse events and concomitant medications 
terms will be coded using MedDRA and an internal validated medication dictionary.  
eCRFs (including queries and audit trails) will be retained by GSK, and copies will be 
sent to the investigator to maintain as the investigator copy.  In all cases, subject initials 
will not be collected or transmitted to GSK according to GSK policy.
Data from C1115 Day 168 will be entered into the eCRF for C1115 and 
programmatically merged with the BEL114333 datasets.  Any data cleaning procedures 
performed on this C1115 data will be completed in the C1115 eCRF before the final data 
transfer into BEL114333.  
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
There is no statistical sample size calculation. All analyses will be performed using 
descriptive statistics and will be exploratory in nature.  The data base will be locked once 
all subjects have completed the Week 16 follow-up visit.  Immunogenicity and B cell 
marker data collected at the 6-month post-treatment visit will be reported separately as an 
addendum to the clinical study report.  Details of the analysis will be given in the 
Reporting and Analysis Plan (RAP).
8.1.
Data Analysis Considerations
8.1.1.
Primary Efficacy Analysis
The number and percent of subjects who respond at each scheduled visit when complete 
efficacy evaluations occur will be tabulated by treatment groups according to the 
treatment group that the subjects were assigned to during randomisation in BEL113750 
study and the actual treatment they receive in the current study. The baseline will be 
defined as study Day 0 of BEL113750 study. Additionally, for the group of subjects who 
received placebo in BEL113750, a secondary analysis will be performed by defining the 
baseline as Day 0 of the current study the day placebo subjects in BEL113750 will have 
begun to receive belimumab treatment.
Subjects who previously received SC belimumab will be evaluated separately and this 
analysis will be described in the Reporting and Analysis Plan.

YM2010/00145/03
CONFIDENTIAL
BEL114333
58
8.1.2.
Analysis of Additional Efficacy and Biomarkers
For the primary analysis of the additional efficacy and biomarkers, the baseline will be 
defined as study Day 0 of BEL113750 Study. Additionally, for the group of subjects who 
received placebo in BEL113750 study, a secondary analysis will be performed by 
defining the baseline as the day placebo subjects in BEL113750 will have begun to 
receive belimumab treatment.
The major analysis of the additional efficacy and biomarkers will include the descriptive 
tabulation of secondary endpoints by treatment groups according to the treatment group 
that the subjects were assigned to during randomisation in BEL113750 study and the 
actual treatment they are assigned to in the current study.
Subjects who previously received SC belimumab will be evaluated separately and this 
analysis will be described in the Reporting and Analysis Plan.
8.1.3.
Analysis of Safety Variables
AEs will be graded for severity by the investigator using Adverse Event Severity Grading 
Tables (Appendix 6) or the grades in Section 6.3.4, as appropriate. The frequency of AEs 
will be tabulated by MedDRA system organ class and preferred term and by treatment 
groups, according to the treatment group that the subjects were assigned to during 
randomisation in the BEL113750 or C1115 study. Additional analysis may be performed 
based on event rates adjusting for subject-years on study agent. The number of subjects 
with AEs and the incidence rate of AEs will be summarised in each 6-month time 
interval. AEs will also be summarised by MedDRA SOCs and preferred terms for those 
that are considered to be at least possibly related to study agent and those that are 
considered to be severe (Grade 3 and Grade 4). Discontinuations due to AEs will be 
summarised.
The frequency of laboratory abnormalities will be tabulated by treatment group. 
Laboratory values will be assessed for significant changes from baseline. Laboratory 
toxicity will be graded using Adverse Event Severity Grading Tables when possible. 
Shift tables will be used to determine if subjects move from normal to abnormal during 
the course of the study. Shifts of ≥2 grades and Grade 3 or Grade 4 laboratory 
abnormalities will be summarised.
Immunogenicity (anti-belimumab antibodies) will be summarized at baseline and during 
treatment and follow-up.
8.1.4.
Interim Analysis
An unblinded interim analysis of the data in this continuation trial may be performed to 
support a submission to regulatory authorities relating to marketing authorization (e.g., to 
summarize and submit this long term safety data to regulatory authorities in the initial 
BLA and other marketing authorization submissions).  Additional interim analyses may 
be required to support subsequent safety updates to regulatory authorities.

YM2010/00145/03
CONFIDENTIAL
BEL114333
59
9.
STUDY CONDUCT CONSIDERATIONS
9.1.
Posting of Information on Clinicaltrials.gov
Study information from this protocol will be posted on clinicaltrials.gov before enrolment 
of subjects begins.
9.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a study site, GSK will obtain approval from the appropriate 
regulatory agency to conduct the study in accordance with ICH Good Clinical Practice 
(GCP) and applicable country-specific regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with ICH GCP, all applicable subject privacy 
requirements, and the ethical principles that are outlined in the Declaration of Helsinki 
2008, including, but not limited to:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
approval of study protocol and any subsequent amendments.

Subject informed consent.

Investigator reporting requirements.
GSK will provide full details of the above procedures, either verbally, in writing, or both.
Written informed consent must be obtained from each subject prior to participation in the 
study.
9.3.
Quality Control (Study Monitoring)
In accordance with applicable regulations, GCP, and GSK procedures, GSK monitors 
will contact the site prior to the start of the study to review with the site staff the protocol, 
study requirements, and their responsibilities to satisfy regulatory, ethical, and GSK 
requirements.  When reviewing data collection procedures, the discussion will include 
identification, agreement and documentation of data items for which the CRF will serve 
as the source document.
GSK will monitor the study to ensure that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements.
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.

YM2010/00145/03
CONFIDENTIAL
BEL114333
60
9.4.
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance audit of the site records, and the regulatory agencies may 
conduct a regulatory inspection at any time during or after completion of the study. In the 
event of an audit or inspection, the investigator (and institution) must agree to grant the 
auditor(s) and inspector(s) direct access to all relevant documents and to allocate their 
time and the time of their staff to discuss any findings/relevant issues.
9.5.
Study and Site Closure
Subjects recruited into this study will continue to receive treatment with intravenous 
belimumab until such time as intravenous belimumab becomes commercially available in 
Northeast Asia, or the subject elects to participate in another belimumab continuation 
study for SLE, or until either the subject's physician withdraws the subject from the study 
or upon the decision by the sponsor to discontinue further development of belimumab for 
SLE.  Upon completion of treatment, every effort should be made to evaluate subjects for 
Week 16 post-treatment follow-up visit and the 6-month post-treatment visit.  Once all 
reasonable efforts have been made, the study will be considered complete/terminated.
Upon completion or termination of the study, the GSK monitor will conduct site closure 
activities with the investigator or site staff (as appropriate), in accordance with applicable 
regulations, GCP, and GSK Standard Operating Procedures.
GSK reserves the right to temporarily suspend or terminate the study at any time for 
reasons including (but not limited to) safety issues, ethical issues, or severe non-
compliance.  If GSK determines that such action is required, GSK will discuss the 
reasons for taking such action with the investigator or head of the medical institution 
(where applicable).  When feasible, GSK will provide advance notice to the investigator 
or head of the medical institution of the impending action.
If a study is suspended or terminated for safety reasons, GSK will promptly inform all 
investigators, heads of the medical institutions (where applicable),and/or institutions 
conducting the study.  GSK will also promptly inform the relevant regulatory authorities 
of the suspension/termination along with the reasons for such action.  Where required by 
applicable regulations, the investigator or head of the medical institution must inform the 
IRB/IEC promptly and provide the reason(s) for the suspension/termination.
9.6.
Records Retention
Following closure of the study, the investigator or head of the medical institution (where 
applicable) must maintain all site study records (except for those required by local 
regulations to be maintained elsewhere) in a safe and secure location.  The records must 
be easily accessible when needed (e.g., for a GSK audit or regulatory inspection) and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of the 
records may be maintained in a format other than hard copy (e.g., microfiche, scanned, 

YM2010/00145/03
CONFIDENTIAL
BEL114333
61
electronic); however, caution must be exercised before such action is taken.  The 
investigator must ensure that all reproductions are legible and are a true and accurate 
copy of the original.  In addition, they must meet accessibility and retrieval standards, 
including regeneration of a hard copy, if required.  The investigator must also ensure that 
an acceptable back-up of the reproductions exists and that there is an acceptable quality 
control procedure in place for creating the reproductions.
GSK will inform the investigator of the time period for retaining the site records in order 
to comply with all applicable regulatory requirements.  The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by local 
laws/regulations, GSK standard operating procedures, and/or institutional requirements.
The investigator must notify GSK of any changes in the archival arrangements, including, 
but not limited to archival of records at an off-site facility or transfer of ownership of the 
records in the event that the investigator is no longer associated with the site.
9.7.
Provision of Study Results to Investigators, Posting to the 
Clinical Trials Register and Publication
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The results summary will be posted to the Clinical Study Register at the time of the first 
regulatory approval or within 12 months of any decision to terminate development. In 
addition, a manuscript will be submitted to a peer-reviewed journal for publication within 
12 months of the first approval or within 12 months of any decision to terminate 
development. When manuscript publication in a peer-reviewed journal is not feasible, 
further study information will be posted to the GSK Clinical Study Register to 
supplement the results summary. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
63
Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, Petri M, Gilkeson 
GS, Wallace DJ, Weisman MH, Appel GB. Mycophenolate mofetil or intravenous 
cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353(21):2219-28. 
Gladman EM, Ginzler E, Goldsmith C, Fortin P, Liang M, Sanchez-Guerrero J, Urowitz 
M, Bacon P, Bombardieri S, Hanly J, Jones J, Hay E, Symmons D, Isenberg D, Kalunion 
K, Maddison P, Nived O, Sturfelt G, Petri M, Richter M, Snaith M, Zoma A. The 
development and initial validation of the systemic lupus international collaborating 
clinics/American college of rheumatology damage index for systemic lupus 
erythematosus. Arthritis Rheum. 1996;39(3):363-9. 
Goldfarb NS, Avery RK, Goormastic M, Mehta AC, Schilz R, Smedira N, Pien L, Haug 
MT, Gordon SM, Hague LK, Dresing JM, Evans-Walker T, Maurer JR. 
Hypogammaglobulinemia in lung transplat recipients. Transplantation. 2001;71(2):242-6. 
Gordon C, Sutcliffe N, Skan J, Stoll T, Isenberg DA. Definition and treatment of lupus 
flares measured by the BILAG index. Rheumatology (Oxford). 2003;42(11):1372-9. 
Govoni M, Castellino G, Bosi S, Napoli N, Trotta F. Incidence and prevalence of 
systemic lupus erythematosus in a district of North Italy. Lupus. 2006;15:110-113. 
Gross J, Dillon S, Mudri S, Johnston J, Littau A, Roque R, Rixon M, Schou O, Foley KP, 
Haugen H, McMillen S, Waggie K, Schreckhise RW, Shoemaker K, Vu T, Moore M, 
Grossman A, Clegg CH. TACI-Ig neutralizes molecules critical for B cell development 
and autoimmune disease. Impaired B-cell maturation in mice lacking BLyS. Immunity. 
2001;15(2):289-302. 
Hahn BH. Antibodies to DNA. N Engl J Med. 1998;338(19):1359-68. 
Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, Symmons DP, 
Viner N, Zoma A. The BILAG index: a reliable and valid instrument for measuring 
clinical disease activity in systemic lupus erythematosus. Q J Med. 1993;86(7):447-58. 
Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani, GD, de Ramon Garrido E, Danieli 
MG, Abramovicz,D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gül A, Levy 
Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, 
Cosyns J, Cervera R. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus 
Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous 
cyclophosphamide. Arthritis Rheum. 2002;46(8):2121-31. 
Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani, GD, de Ramon Garrido E, Danieli 
MG, Abramovicz,D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gül A, Levy 
Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, 
Cosyns J, Cervera R. Early Response to Immunosuppressive therapy predicts good renal 
outcome in lupus nephritis. Arthritis Rheum. 2004;50(12):3934-40. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
66
Shida, Y, Takahashi N, Sakamoto T, Ino H, Endo A, Hirama T. The pharmacokinetics 
and safety profiles of belimumab after single subcutaneous and intravenous doses in 
healthy Japanese volunteers. J Clin Pharm Ther 2014;39:97-101.
Stoll T, Seifert B, Idenberg DA. SLICC/ACR Damage Index is valid, and renal and 
pulmonary organ scores are predictors of severe outcome in patients with Systemic Lupus 
Erythematosus. Brit. J. Rheumatology. 1996;35(3):248-254. 
Villarreal GM, Drenkard C, Villa AR, Slor H, Shafrir S, Bakimer R, Shoenfeld Y, 
Alarcón-Segovia D. Prevalence of 13 autoantibodies and of the 16/6 and related 
pathogenic idiotypes in 465 patients with systemic lupus erythematosus and their 
relationship with disease activity. Lupus. 1997;6:425-35. 
Wallace DJ. Management of lupus erythematosus: recent insights. Current Opinions in 
Rheumetology. 2002;14:212-9. 
Xiang Y-J, Dai S-M. Prevalence of rheumatic diseases and disability in China. 
Rheumatology International. 2009;29:481-490. 
Yamini MH, Avery RK, Mawhorter SD, Young JB, Ratliff NB, Hobbs RE, McCarthy 
PM,  Smedira NG,  Goormastic M,  Pelegrin D, Starling RC. Hypogammaglobulinemia 
following cardiac transplantation: a link between rejection and infection. J Heart Lung 
Transplant. 2001;20(4):425-30. 
Zhang J, Roschke V, Baker KP, Wang Z, Alarcón GS, Fessler BJ, Bastian H, Kimberly 
RP, Zhou,T. Cutting edge: A role for B lymphocyte stimulator in systemic lupus 
erythematosus. J Immunol. 2001;166:6-10.

YM2010/00145/03
CONFIDENTIAL
BEL114333
67
11.
APPENDICES
11.1.
Appendix 1:  SELENA SLEDAI Disease Assessment Scales
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party
copyright laws and therefore have been excluded.

YM2010/00145/03
CONFIDENTIAL
BEL114333
68
SELENA SLEDAI Disease Assessment Scales (continued)
SLE Flare Index
SELENA SLEDAI Disease Assessment Scales (continued)
Physician’s Global Disease Assessment
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third
party copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by
third party copyright laws and therefore have been excluded.

YM2010/00145/03
CONFIDENTIAL
BEL114333
70
11.2.
Appendix 2: BILAG Index Assessment
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party
copyright laws and therefore have been excluded.

YM2010/00145/03
CONFIDENTIAL
BEL114333
72
11.3.
Appendix 3: SLICC/ACR Damage Index
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third
party copyright laws and therefore have been excluded.

YM2010/00145/03
CONFIDENTIAL
BEL114333
74
11.4.
Appendix 4: Liver Chemistry Stopping and Followup Criteria
Phase III-IV Liver Safety Algorithms
ALT>3xULN
plus 
bilirubin >2x 
ULN (>35%
direct) (or 
plus INR >1.5, 
if measured)*
No
Yes
Yes
•Instruct subject to stop investigational product (IP)
•Notify GSK + arrange clinical followup within 24-72h
•Perform liver chemistries and liver event follow up 
assessments (serology, PK sample etc as in protocol) 
•Complete liver event CRF, SAE data collection tool if 
appropriate, + liver imaging +/or biopsy CRFs if  tests 
performed.
•Obtain weekly liver chemistries [**as far as possible] 
until resolved, stabilised or returned to baseline 
•Withdraw subject from study after liver chemistry 
monitoring complete + do not re-challenge with IP
•Instruct subject to stop investigational product (IP)
•Notify GSK + arrange clinical followup within 24h
•Perform liver chemistries and liver event follow up 
assessments (serology, PK sample etc as in protocol) 
•Report as SAE (excl. hepatic impairment or cirrhosis 
studies)+ complete liver event CRF, SAE data collection 
tool, + liver imaging +/or biopsy CRFs if tests performed.
•Obtain twice weekly liver chemistries until resolved, 
stabilised or returned to baseline values
•Consultation with hepatologist/specialist recommended
•Withdraw subject from study after liver chemistry 
monitoring complete + do not re-challenge with IP
Hepatitis 
symptoms
or rash?
No
Able to 
monitor 
weekly for 
4 weeks?
Yes
No**
Yes
Continue IP
Obtain twice 
monthly liver 
chemistries until 
normalised or 
back to baseline 
values
Yes
Yes
ALT<3xULN 
+ bilirubin
<2xULN 
after ≤4 
wks?
Yes
ALT 
>5xULN 
but 
<8xULN
No
ALT  
>8xULN
Yes
ALT >5 
and 
<8xULN 
for > 2 
wks
Yes
No
ALT>3xULN 
but <5xULN 
+ bilirubin
<2xULN+no 
symptoms
No
Able to 
monitor 
weekly for 
> 2 wks?
No
No
Notify GSK within 24h 
to discuss subject 
safety
Continue IP
Check liver chemistry 
weekly for 4 weeks
Yes
No
*INR value not applicable to patients on anticoagulants

YM2010/00145/03
CONFIDENTIAL
BEL114333
75
11.5.
Appendix 5: Clinical Laboratory Tests
Hematology
Urinalysis
Modified Chem-20
Total white blood cell count 
Differential:
Absolute Neutrophils
Segmented Neutrophils
Band Neutrophils
Myelocytes
Metamylocytes
Promyelocytes
Lymphocytes
Monocytes
Eosinophils
Basophils
Hemoglobin
Hematocrit
Red blood cell (RBC) count
Platelet count
Prothrombin time (PT)
Partial thromboplastin time (PTT)
  
Protein
Glucose
Ketones
Occult blood
Microscopic examination 
including:
WBC per hpf
RBC per hpf
Dysmorphic RBC
Casts (specified by 
type e.g., RBC, WBC)
Spot Urine (protein : creatinine 
ratio)
Urine Pregnancy
Electrolytes:
Sodium
Potassium
Magnesium
Chloride
Carbon dioxide
Calcium adjusted for Albumin
Inorganic Phosphate
Enzymes:
SGOT (AST)
SGPT (ALT)
Alkaline Phosphatase
Gamma glutanyl transpeptidase (GGT)
Lactic dehydrogenase (LDH)
Other:
Creatinine
Blood urea nitrogen (BUN)
BUN/creatinine ratio
Bilirubin, total
Protein, total
Albumin
Uric acid
Glucose
Estimated Creatinine Clearance/ GFR 
(Cockroft-Gault)
Liver event follow-up assessments:
       Hepatitis A IgM antibody
       HBsAg and hep B Core antibody (IgM)
      Hepatitis C RNA
       Cytomegalovirus IgM antibody
       Epstein-Barr viral capsid antigen IgM
            antibody
       Hepatitis E IgM antibody
       CPK
       Anti-smooth muscle antibody
       Type 1 anti-liver kidney microsomal
             antibodies
       PK
Biological Markers
Serum complement (C3 and C4) 
B-cell subtypes
Immunoglobulins
Serum immunoglobulin isotypes:  IgG, IgM, IgA
Immunogenicity
Autoantibodies
Anti-dsDNA

YM2010/00145/03
CONFIDENTIAL
BEL114333
76
11.6.
Appendix 6: Adverse Event and Laboratory Value Severity 
Grade Tables
HEMATOLOGY
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-
THREATENING
Hemoglobin
> 9.5 - 11.0 
g/dL
> 8.0 – 9.5 g/dL
6.5 - 8.0 g/dL
< 6.5 g/dL
Leukocytes
3000-
3999/mm3
2000-2999/mm3 1000-1999/mm3
< 1000/mm3
Absolute Neutrophil Count
1500-
1999/mm3
1000-1499/mm3 500-999/mm3
< 500/mm3
Platelets
75,000 -
99,999/mm3
50,000 –
74,999/mm3
25,000 -
49,999/mm3
< 25,000/mm3
Prothrombin Time (PT)
> 1.0-1.25 x 
ULN*
> 1.25-1.5 x 
ULN
> 1.5-3.0 x ULN
> 3.0 x ULN
Partial Thromboplastin Time 
(PTT)
> 1.0-1.66 x 
ULN
> 1.66-2.33 x 
ULN
> 2.33-3.0 x ULN > 3.0 x ULN
Methemoglobin
5.0-10.0 %
10.1-15.0 %
15.1-20.0 %
> 20%
(continued)
*ULN = Upper Limit of Normal.                                                         Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
77
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CARDIOVASCULAR
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Cardiac Arrhythmia
-
Asymptomatic/transient; 
dysrhythmia; no treatment req
Recurrent/persistent 
dysrhythmia. Symptomatic; 
treatment req
Unstable dysrhythmia hospitalization
and treatment required
Hypotension
Transient orthostatic 
hypotension, no treatment
Symptoms correctable 
with oral fluid treatment
IV fluid req,
no hospitalization req
Hospitalization req
Hypertension
Transient, increase
> 20 mm/Hg; no treatment
Recurrent; chronic increase
> 20 mm/Hg, treatment req
Acute treatment req; out patient 
hospitalization possible
Hospitalization req
Pericarditis
Minimal effusion
Mild/moderate asymptomatic 
effusion, no treatment
Symptomatic effusion,
pain, ECG changes
Tamponade OR pericardiocentesis 
OR surgery req
Hemorrhage, Blood Loss
-
Mildly symptomatic; 
no treatment required
Gross blood loss OR
1-2 units transfused
Massive blood loss OR
> 2 units transfused
(continued)
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
78
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CHEMISTRIES
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Sodium
  Hyponatremia
130-135 meq/L
123-129 meq/L
116-122 meq/L
< 116 meq/L
  Hypernatremia
146-150 meq/L
151-157 meq/L
158-165 meq/L
> 165 meq/L
Potassium
  Hypokalemia
3.0-3.4 meq/L
2.5-2.9 meq/L
2.0-2.4 meq/L
< 2.0 meq/L
  Hyperkalemia
5.6-6.0 meq/L
6.1-6.5 meq/L
6.6-7.0 meq/L
> 7.0 meq/L
Phosphate
  Hypophosphatemia
2.0-2.4 mg/dL
1.5-1.9 mg/dL
1.0-1.4 mg/dL
< 1.0 mg/dL
Calcium- (Corrected For Albumin)
  Hypocalcemia
7.8-8.4 mg/dL
7.0-7.7 mg/dL
6.1-6.9 mg/dL
< 6.1 mg/dL
  Hypercalcemia
10.6-11.5 mg/dL
11.6-12.5 mg/dL
12.6-13.5 mg/dL
>13.5 mg/dL
Magnesium
  Hypomagnesemia
1.2-1.4 meq/L
0.9-1.1 meq/L
0.6-0.8 meq/L
< 0.6 meq/L
Albumin
  Hypoalbuminemia
3.00-3.49 g/dL
2.50-2.99 g/dL
2.00-2.49 g/dL
< 2.00 g/dL
Bilirubin (Total)
  Hyperbilirubinemia (Total)
> 1.0-1.5 x ULN
> 1.5-2.5 x ULN
> 2.5-5 x ULN
> 5 x ULN
Glucose
  Hypoglycemia
55-64 mg/dL
40-54 mg/dL
30-39 mg/dL
< 30 mg/dL
  Hyperglycemia 
116-160 mg/dL
161-250 mg/dL
251-500 mg/dL
> 500 mg/dL
  (nonfasting & no prior diabetes)
  Triglycerides
151-399 mg/dL
400-750 mg/dL
751-1200 mg/dL
> 1200 mg/dL
Creatinine
> 1.0-1.5 x ULN
> 1.5-3.0 x ULN
> 3.0-6.0 x ULN
> 6.0 x ULN
(continued)
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
79
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CHEMISTRIES (continued)
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Uric Acid
  Hyperuricemia
7.5-10.0 mg/dL
10.1-12.0 mg/dL
12.1-15.0 mg/dL
> 15.0 mg/dL
Liver Transferases  (AST, ALT, and 
GGT)
1.25-2.5 x ULN
> 2.5-5.0 x ULN
> 5.0-10.0 x ULN
> 10.0 x ULN
Alkaline Phosphatase
1.25-2.5 x ULN
> 2.5-5.0 x ULN
> 5.0-10.0 x ULN
> 10.0 x ULN
Pancreatic Enzymes
Amylase
> 1.0-1.5 x ULN
> 1.5-2.0 x ULN
> 2.0-5.0 x ULN
> 5.0 x ULN
Pancreatic amylase
> 1.0-1.5 x ULN
> 1.5-2.0 x ULN
> 2.0-5.0 x ULN
> 5.0 x ULN
Lipase
> 1.0-1.5 x ULN
> 1.5-2.0 x ULN
> 2.0-5.0 x ULN
> 5.0 x ULN
Hypoglobulinemia (IgG)*
550-700 mg/dL
400-549 mg/dL
250-399 mg/dL
< 250 mg/dL
(continued)
*[Eibl, 1995; Goldfarb, 2001; Yamini, 2001].                                                                                                                                        Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
80
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
GASTROINTESTINAL
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Nausea
Mild OR transient; 
reasonable intake 
maintained
Mod discomfort 
OR intake decreased 
for < 3 days
Severe discomfort OR 
minimal intake 
for 3 days
Hospitalization required
Vomiting
Mild OR transient; 
2-3 episodes/day OR 
mild vomiting lasting 
< 1 week
Mod OR persistent; 
4-5 episodes per day; 
OR vomiting lasting 
1 week
Severe vomiting of all 
foods/fluids in 24 hours 
OR orthostatic hypotension
OR IV treatment req
Hypotensive shock OR hospitalization 
required for IV treatment req
Diarrhea
Mild or transient; 
3-4 loose stools per day 
OR mild diarrhea lasting 
< 1 week
Mod OR persistent; 
5-7 loose stools per day 
or diarrhea lasting 
1 week
Bloody diarrhea; 
OR orthostatic hypotension 
OR > 7 loose stools/day 
OR IV treatment req
Hypotensive shock 
OR hospitalization req
Oral Discomfort/Dysphagia
Mild discomfort, no difficulty 
swallowing
Difficulty swallowing but able 
to eat and drink
Unable to swallow solids
Unable to drink fluids; 
IV fluids req
Constipation
Mild
Moderate
Severe
Distention with vomiting
(continued)
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
81
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
RESPIRATORY
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Cough 
(for aerosol studies) 
Transient; no treatment
Treatment associated 
cough; inhaled bronchodilator
Uncontrolled cough; 
systemic treatment req
Bronchospasm Acute
Transient; no treatment; 
FEV1 70% to 
< 80% 
(or peak flow)
treatment req; normalizes with 
bronchodilator; 
FEV1 50% to < 70% 
(or peak flow)
No Normalization 
with bronchodilator; 
FEV 25% to < 50% 
(or peak flow), retractions
Cyanosis; FEV1 < 25% 
(or peak flow) OR intubated
Dyspnea
Dyspnea on exertion
Dyspnea with 
normal activity
Dyspnea at rest
Dyspnea requiring O2 therapy
URINALYSIS
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Proteinuria
Dispstick
Protein
1 +
2-3 +
4 +
Nephrotic syndrome
Spot Urine:    
Protein:Creatinine 
Ratio mg/mg
0.2-1.0
> 1.0-2.0
> 2.0-3.5
> 3.5
24 Hour Urine:
Protein
200 mg - 1g loss/day
> 1-2 g loss/day
> 2-3.5 g loss/day
Nephrotic syndrome
OR > 3.5 g loss/day
Hematuria
Microscopic only
> 3 to < 10 RBC/hpf
Gross, No clots
10 RBC/hpf
Gross plus clots OR 
RBC casts
Obstructive OR transfusion required
(continued)
RBC = red blood cell; hpf = high power field.
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
82
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
MISCELLANEOUS
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Fever (oral > 12 hours)
37.7-38.5C or
100.0-101.5F
38.6-39.5C OR
101.6-102.9F
39.6-40.5C OR
103-105F
> 40.5C OR > 105F
Headache
Mild; No treatment req
Mod; or non-narcotic analgesia 
treatment
Severe; OR responds to initial 
narcotic treatment
Intractable; OR requiring 
repeated narcotic treatment
Allergic Reaction
Pruritus without rash
Localized urticaria
Generalized urticaria 
angioedema
Anaphylaxis
Cutaneous/Rash/ Dermatitis
Erythema, pruritus rash 
OR dry desquamation
Diffuse maculopapular 
OR dry desquamation
Vesiculation OR moist 
desquamation ulceration
ANY ONE: mucous membrane involvement, 
suspected 
Stevens-Johnson (TEN), erythema multiforme, 
necrosis req surgery, exfoliative dermatitis
Local Reaction (secondary 
to parenteral treatment- not 
vaccination or skin test)
Erythema
Induration < 10 mm 
OR inflammation 
OR phlebitis
Induration > 10 mm 
OR ulceration
Necrosis of skin
Fatigue
Normal activity 
Reduced < 25%
Normal activity 
Reduced 25-50%
Normal activity 
reduced > 50%; 
cannot work
Unable to care for self
(continued)
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
83
Appendix 6: Adverse Event and Laboratory Value Severity Grade Tables (continued)
NEUROLOGIC
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Neuro-cerebellar
Slight incoordination OR 
dysdiadochokinesia
Intention tremor OR 
dysmetria OR slurred speech 
OR nystagmus
Ataxia requiring assistance to walk 
or arm incoordination interfering 
with ADLs
Unable to stand
Neuro-psych/ mood
none
Severe mood changes requires 
medical intervention
Acute psychosis requiring 
hospitalization
Paresthesia 
(burning, tingling, etc)
Mild discomfort; 
no treatment needed
Mod discomfort 
non-narcotic analgesia req
Severe discomfort; OR narcotic 
analgesia req with symptomatic 
improvement
Incapacitating; OR not responsive 
to narcotic analgesia
Neuro-motor
Mild weakness in muscle 
of feet but 
able to walk and/or mild 
increase or decrease in 
reflexes
Mod weakness in feet (unable to walk on 
heels and/or toes), mild weakness in 
hands, still able to do most hand tasks 
and/or loss of previously present reflex 
or development of hyperreflexia 
and/or unable to do deep knee 
bends due to weakness
Marked distal weakness (unable to 
dorsiflex toes or foot drop), and 
mod proximal weakness ie, in 
hands interfering with ADLs and/or 
requiring assistance to walk and/or 
unable to rise from chair 
unassisted
Confined to bed or wheelchair 
because of muscle weakness
Neuro-sensory
Mild impairment 
sensations, 
(ie, vibratory, pinprick, 
hot/cold in great toes) in 
focal area or symmetrical 
distribution
Mod impairment mod de-sensation, 
(ie, of vibratory, pinprick, hot/cold to 
ankles) and/or joint position or mild 
impairment that is not symmetrical.
Severe impairment (dec or loss of 
sensation to knees or wrists) or 
loss of sensation of at least mod 
degree in multiple different body 
areas (ie, upper and lower 
extremities)
Sensory loss involves limbs 
and trunk
(concluded)
Modified from DMID Adult Toxicity Tables, 2001

YM2010/00145/03
CONFIDENTIAL
BEL114333
84
11.7.
Appendix 7:  Protocol Changes
Protocol Amendment 03
Protocol amendment 03 applies to sites in Japan.
Description of Changes
Changes are highlighted in bold.
Change 1:  Title Page
This change affects the study title.
Change from:
BEL114333, a multicenter, continuation study of belimumab in subjects with systemic 
lupus erythematosus (SLE) who completed the phase III study BEL113750 in Northeast 
Asia
To:
BEL114333, a multicenter, continuation study of belimumab in subjects with systemic 
lupus erythematosus (SLE) who completed the phase III study BEL113750 in Northeast 
Asia or completed the open-label extension of HGS1006-C1115 in Japan
Rationale:  Change made to add that the study will now include subjects who complete 
the open-label SC extension of C1115 in Japan.
Change 2:  Protocol Summary, Rationale
This change affects Protocol Summary, Rationale, sentences 1 and 2.
Change from:
This study provides subjects who complete the BEL113750 Study in Northeast Asia the 
option of receiving belimumab, as an add-on to their standard of care (SOC) SLE 
therapy.  All eligible subjects will receive belimumab 10 mg/kg irrespective of their 
randomized treatment in BEL113750.  
To:
This study provides subjects who complete the BEL113750 Study in Northeast Asia and 
subjects who complete the open-label extension of HGS1006-C1115 (referred to as 
C1115) Study in Japan the option of receiving belimumab, as an add-on to their 
standard of care (SOC) SLE therapy.  All eligible subjects will receive belimumab 10 
mg/kg irrespective of their randomized treatment in BEL113750 or C1115.  

YM2010/00145/03
CONFIDENTIAL
BEL114333
85
Rationale:  Changed made to add that subjects who complete the open-label SC 
extension of C1115 in Japan will have the option of continuing treatment with IV 
belimumab, as an add-on to their standard of care SLE therapy.
Change 3:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 1.
Change from:
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia. Subjects participating in 
this protocol will continue to be monitored for safety and efficacy.
To:
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia or who completed the 
open-label extension of the C1115 protocol in Japan. Subjects participating in this 
protocol will continue to be monitored for safety and efficacy.
Rationale:  Change made to add that subjects who complete the open-label SC extension 
of C1115 in Japan may be included in this study.
Change 4:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 3.
Change from:
Subjects who complete 48 weeks of treatment on the BEL113750 and who meet 
inclusion/exclusion criteria, will be given the option to enter the continuation study.  All 
subjects will receive belimumab 10 mg/kg IV infused over 1 hour every 28 days. The 
first dose on the continuation study must be given 4 weeks (minimum of 2 weeks, 
maximum of 8 weeks) after the last dose in BEL113750. 
To:
Subjects who complete 48 weeks of treatment on the BEL113750 or complete the open-
label extension of C1115 and who meet inclusion/exclusion criteria, will be given the 
option to enter the continuation study.  All subjects will receive belimumab 10 mg/kg IV 
infused over 1 hour every 28 days. The first dose on the continuation study must be given 
4 weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750. 
For subjects enrolling from C1115, the target for the first dose of IV belimumab is 1
week after the last dose of SC belimumab (scheduled for Week 23 in the open-label 

YM2010/00145/03
CONFIDENTIAL
BEL114333
86
extension). The EXIT visit of the C1115 study (Week 24) serves as the Day 0 visit for 
the Protocol BEL114333, and will have a +1 week visit window.
Rationale:  Change made to add that subjects who complete the open-label SC extension 
of C1115 in Japan may be included in this study and to provide timing of first dose of IV 
belimumab.
Change 5:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 5.
Change from:
Prohibited medications in this study are similar to BEL113750.  
To:
Prohibited medications in this study are similar to BEL113750 and C1115.  
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled.
Change 6:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 6.
Change from:
Subjects recruited into this study will continue to receive treatment with belimumab until 
such time as belimumab becomes commercially available in a subject’s country of 
participation, or the subject elects to participate in another belimumab continuation study 
for SLE, or until either the subject's physician withdraws the subject from the study or 
upon the decision by the sponsor to discontinue further development of belimumab for 
SLE.
To:
Subjects recruited into this study will continue to receive treatment with intravenous
belimumab until such time as intravenous belimumab becomes commercially available 
in a subject’s country of participation, or the subject elects to participate in another 
belimumab continuation study for SLE, or until either the subject's physician withdraws 
the subject from the study or upon the decision by the sponsor to discontinue further 
development of belimumab for SLE.
Rationale:  Clarification for intravenous belimumab.

YM2010/00145/03
CONFIDENTIAL
BEL114333
87
Change 7:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 7.
Change from:
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750. 
To:
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750 plus the number of 
subjects from Japan from the open-label extension of the C1115 study. 
Rationale:  Change made to add that number of subjects will include those who complete 
the open-label SC extension of C1115 in Japan. 
Change 8:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 8.
Change from:
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time belimumab becomes commercially available in a 
subject’s country of participation, or upon the decision by the sponsor to discontinue the 
study.  
To:
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time intravenous belimumab becomes commercially 
available in a subject’s country of participation, or upon the decision by the sponsor to 
discontinue the study.  
Rationale:  Clarification for intravenous belimumab.
Change 9:  Section 1.3 Clinical Experience with Belimumab
This change adds new sub-headings and a new sub-section on belimumab administered 
subcutaneously.
Added:
Section 1.3.1 Belimumab Administered Intravenously

YM2010/00145/03
CONFIDENTIAL
BEL114333
88
Section 1.3.2 Belimumab Administered Subcutaneously
A subcutaneous (SC) liquid formulation of belimumab has been developed and is 
currently in a Phase 3 trial (Protocol HGS1006-C1115, referred to as C1115).  
Based on PK data from the Phase 1 SC study (Protocol HGS1006-C1105, referred to 
as C1105), subjects given belimumab (200 mg/mL) 200 mg SC every week are 
expected to achieve on average similar steady-state AUC levels compared to those 
observed in the IV Phase 3 trials with 10 mg/kg IV every 4 weeks.
In the Phase 3 study, patients self-administer a fixed dose of 200 mg belimumab as 
an SC injection. Due to the relatively slow absorption from the subcutaneous to the 
central compartment, maximal serum belimumab concentrations following SC 
administration are not expected to exceed those observed following IV 
administration in the Phase 3 trials even for lower weight subjects (Figure 1). 
Safety data for subcutaneous administration have been generated in a 24-week 
Phase 2 study using the original 100 mg/mL SC formulation in SLE patients 
(Protocol HGS1006-C1070, referred to as C1070). Although the number of subjects 
is small (N = 28), a dose of 300 mg weekly (100 mg SC 3x/wk) was generally well-
tolerated (Study C1070, see Investigator’s Brochure). In healthy Japanese male 
subjects, a single 200 mg SC dose vs a single IV dose of belimumab were evaluated 
in terms of safety and PK (BEL116119, see Investigator’s Brochure). The 
bioavailability of the single SC dose of 200 mg belimumab in the subjects was 
estimated to be 77.5%. Geometric mean terminal half-life after single SC 
administration was 15.9 days which was comparable to the 17.7 days observed after 
single IV administration. All 7 AEs were mild or moderate in intensity. One event 
(cellulitis) reported in the IV group was judged to be related to the belimumab. No 
SAEs or AEs related to injection site reactions were reported during the study. 
[Shida, 2014]. Four weekly SC doses of belimumab at 2x120 or 200 mg were 
evaluated in healthy subjects in terms of safety and PK in Study C1105 and have 
been generally well tolerated.

Y M 2 0 1 0/ 0 0 1 4 5/ 0 3 
C O N FI D E N TI A L 
 
 
B E L 1 1 4 3 3 3 
 
8 9 
 
Fi g ure 1  
C o m p aris o n of si m ul ate d me a n beli m u m a b ser u m c o nce ntr ati o n ti me 
pr ofile wit h 1 0 m g/ k g I V o n d a ys 0, 1 4, a n d 2 8 a n d Q 4 wee ks t here after 
wit h si m ul ate d pr ofile of 2 0 0 m g wee kl y S C 
 
1 0 m g/ k g I V d at a si m ul at e d u si n g P K p ar a m et er s fr o m p o p ulati o n P K a n al y si s i n S L E p ati e nt s 
( H G S 1 0 0 6- P O P P K); S C pr ofil e si m ul at e d u si n g P K p ar a m et ers fr o m St u d y C 1 1 0 5 i n h e alt h y s u bj e ct s. 
 
T he o n g oi n g P h ase 3 tri al of S C beli m u m a b  i n S L E p atie nts ( C 1 1 1 5) h as c o m plete d 
e nr oll me nt wit h 8 3 9 p atie nts as of 1 0 Fe br u ar y 2 0 1 4.  T he i n de pe n de nt D at a a n d 
M o nit ori n g C o m mittee re vie ws d at a fr o m t his st u d y e ver y 6 m o nt hs; t he m ost 
rece nt re vie w w as 2 9 Oct o ber 2 0 1 3 a n d n o c h a n ges were rec o m me n de d. 
R ati o n ale:   Secti o n a d de d t o pr o vi de bac k gro u n d i nf or mati o n re gar di n g beli m u ma b 
a d mi nistere d s u bc uta ne o usl y. 
 
C h a n ge 1 0:  Secti o n 1. 4, R ati o n ale 
T his c ha n ge affects Rati o nale, para gra p h 1. 
C h a n ge fr o m: 
T his st u d y pr o vi des s u bjects w h o c o m plete t he B E L 1 1 3 7 5 0 St u d y i n N ort heast Asia t he 
o pti o n of recei vi n g beli m u ma b, as a n a d d- o n t o t heir sta n dar d  of care ( S O C) S L E 
t hera p y.  All eli gi ble s u bjects will recei ve beli m u ma b 1 0 m g/ k g irre s pecti ve of t heir 
ra n d o mize d treat me nt i n B E L 1 1 3 7 5 0.    

YM2010/00145/03
CONFIDENTIAL
BEL114333
90
To:
This study provides subjects who complete the BEL113750 Study in Northeast Asia or 
subjects from Japan who complete the open-label extension of C1115 the option of 
receiving belimumab, as an add-on to their standard of care (SOC) SLE therapy.  All 
eligible subjects will receive belimumab 10 mg/kg irrespective of their randomized 
treatment in BEL113750 or C1115.   
Rationale:  Changed made to add that subjects who complete the open-label SC 
extension of C1115 in Japan will have the option of continuing treatment with IV 
belimumab, as an add-on to their standard of care SLE therapy.
Change 11:  Section 3.1, Study Design
This change affects Study Design, paragraph 1.
Change from:
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia. Subjects participating in 
this protocol will continue to be monitored for safety and efficacy. The frequency of 
safety laboratory evaluations has been reduced in this protocol compared with 
BEL113750 based on the safety profile of belimumab studies to date and is not 
anticipated to compromise the well being and safety of subjects.
To:
This is a multicentre, continuation study of belimumab plus SOC in SLE subjects who 
completed the Phase III BEL113750 protocol in Northeast Asia and subjects who 
completed the open-label extension of C1115 in Japan. Subjects participating in this 
protocol will continue to be monitored for safety and efficacy. The frequency of safety 
laboratory evaluations has been reduced in this protocol compared with the respective 
parent protocol based on the safety profile of belimumab studies to date and is not 
anticipated to compromise the well being and safety of subjects.
Rationale:  Changes made to add that subjects who complete the open-label SC 
extension of C1115 in Japan may be included in this study. Change made for clarification 
as subjects from more than one parent study will be enrolled.
Change 12:  Section 3.1, Study Design
This change affects Study Design, paragraph 3.

YM2010/00145/03
CONFIDENTIAL
BEL114333
91
Change from:
Subjects who complete 48 weeks of treatment on the BEL113750 study and who meet 
inclusion/exclusion criteria, and provide informed consent, will be given the option to 
enter the continuation study.  All subjects will receive belimumab 10 mg/kg IV infused 
over 1 hour every 28 days. The first dose on the continuation study must be given 4 
weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750. 
To:
Subjects who complete 48 weeks of treatment on the BEL113750 study or complete the 
open-label extension of C1115 and who meet inclusion/exclusion criteria, and provide 
informed consent, will be given the option to enter the continuation study.  All subjects 
will receive belimumab 10 mg/kg IV infused over 1 hour every 28 days. The first dose on 
the continuation study must be given 4 weeks (minimum of 2 weeks, maximum of 8 
weeks) after the last dose in BEL113750. For subjects enrolling from C1115, the 
target for the first dose of IV belimumab is 1 week after the last dose of SC 
belimumab (scheduled for Week 23 in the open-label extension). The EXIT visit of 
the C1115 study (Week 24) serves as the Day 0 visit for the Protocol BEL114333, 
and will have a +1 week visit window.
Rationale:  Change made to add that subjects who complete the open-label SC extension 
of C1115 in Japan may be included in this study and to provide timing of first dose of IV 
belimumab.
Change 13:  Section 3.1, Study Design
This change affects Study Design, paragraph 5.
Change from:
Subjects recruited into this study will continue to receive treatment with belimumab until 
such time as belimumab becomes commercially available in a subject’s country of 
participation, or the subject elects to participate in another belimumab continuation study 
for SLE, or until either the subject's physician withdraws the subject from the study, or 
upon the decision by the sponsor to discontinue further development of belimumab for 
SLE.  
To:
Subjects recruited into this study will continue to receive treatment with intravenous 
belimumab until such time as intravenous belimumab becomes commercially available 
in a subject’s country of participation, or the subject elects to participate in another 
belimumab continuation study for SLE, or until either the subject's physician withdraws 
the subject from the study, or upon the decision by the sponsor to discontinue further 
development of belimumab for SLE.  

YM2010/00145/03
CONFIDENTIAL
BEL114333
92
Rationale:  Clarification for intravenous belimumab.
Change 14:  Section 3.1, Study Design
This change affects Study Design, last paragraph.
Change from:
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time belimumab becomes commercially available in a 
subject’s country of participation, or upon the decision by the sponsor to discontinue the 
study.
To:
A subject will be regarded as having completed the study if the subject is still 
participating in the study at the time intravenous belimumab becomes commercially 
available in a subject’s country of participation, or upon the decision by the sponsor to 
discontinue the study.
Rationale:  Clarification for intravenous belimumab.
Change 15:  Section 3.2 Discussion of Design
This change affects Discussion of Design, end of first paragraph.
Change from:
Subjects who completed 48 weeks of treatment and return for the final 52-week 
evaluation on BEL113750 may be recruited into this continuation protocol of open-label 
belimumab, which will continue until the subject withdraws from the trial, or belimumab 
becomes commercially available in the relevant participating country, or the subject 
elects to participate in another belimumab continuation study for SLE, or upon the 
decision by the sponsor to discontinue development/marketing of belimumab for SLE
To:
Subjects who completed 48 weeks of treatment and return for the final 52-week 
evaluation on BEL113750 may be recruited into this continuation protocol of open-label 
belimumab. BEL114333 provides subjects who complete the open-label SC extension 
of C1115 in Japan the option of continuing treatment with IV belimumab, as an 
add-on to their standard of care SLE therapy.
This study will continue until the subject withdraws from the trial, or intravenous 
belimumab becomes commercially available in the relevant participating country, or the 

YM2010/00145/03
CONFIDENTIAL
BEL114333
93
subject elects to participate in another belimumab continuation study for SLE, or upon 
the decision by the sponsor to discontinue development/marketing of belimumab for SLE
Rationale:  Change made to add that the study will now include subjects who complete 
the open-label SC extension of C1115 in Japan.
Change 16:  Section 4.1 Number of Subjects
This change affects the Number of Subjects.
Change from:
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750 in Northeast Asia. 
To:
The maximum number of subjects enrolled in this study will not exceed the maximum 
number of subjects enrolled and randomized in Protocol BEL113750 in Northeast Asia 
plus the number of subjects from Japan in the open label extension of the C1115 
study. 
Rationale:  Change made to add that number of subjects will include those who complete 
the open-label SC extension of C1115 in Japan. 
Change 17:  Section 4.2 Inclusion Criteria
This change affects Inclusion Criteria 1 and 2.
Change from:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Have completed the BEL113750 Protocol in Northeast Asia through Week 48.
2. Be able to receive the first dose of belimumab for BEL114333 four weeks (minimum 
of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750.
To:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Have completed the BEL113750 Protocol in Northeast Asia through Week 48 OR 
have completed the open-label extension of C1115 in Japan.
2. Be able to receive the first dose of belimumab for BEL114333 four weeks (minimum 
of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750 OR be able to 

YM2010/00145/03
CONFIDENTIAL
BEL114333
94
receive the first dose of IV belimumab 1 week (plus a 1 week visit window) after the 
last dose of open-label SC belimumab in C1115.
Rationale:  Changes made to allow subjects who complete the open-label SC extension 
of C1115 in Japan to be included in this study and to provide timing of first dose of IV 
belimumab.
Change 18:  Section 4.3 Exclusion Criteria
This change affects exclusion criteria 1.
Change from:
Have developed clinical evidence of significant, unstable or uncontrolled, acute or 
chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, 
gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or 
experienced an adverse event (AE) in the Phase 3 study that could, in the opinion of the 
principal investigator, put the subject at undue risk.
To:
Have developed clinical evidence of significant, unstable or uncontrolled, acute or 
chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, 
gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or 
experienced an adverse event (AE) in the respective Phase 3 studies that could, in the
opinion of the principal investigator, put the subject at undue risk.
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled.
Change 19:  Section 5, Study Treatments
This change affects study treatment, paragraph 10
Change from:
The first dose on the continuation trial must be given 4 weeks (minimum 2 weeks, 
maximum 8 weeks) after the last dose in BEL113750.  All subjects will receive 
belimumab 10 mg/kg IV infused over 1 hour every 28 days. 
To:
The first dose on the continuation trial must be given 4 weeks (minimum 2 weeks, 
maximum 8 weeks) after the last dose in BEL113750.  For subjects enrolling from 
C1115, the target for the first dose of IV belimumab is 1 week after the last dose of 
SC belimumab (scheduled for Week 23 in the open-label extension). The EXIT visit 

YM2010/00145/03
CONFIDENTIAL
BEL114333
95
of the C1115 study (Week 24) serves as the Day 0 visit for the Protocol BEL114333, 
and will have a +1 week visit window. All subjects will receive belimumab 10 mg/kg 
IV infused over 1 hour every 28 days. 
Rationale:  Changes made to provide timing of first dose of IV belimumab for subjects 
who enrol from the open-label SC extension of C1115 in Northeast Asia (Japan).
Change 20:  Section 5.4, Treatment after the End of the Study
This change affects Treatment after the End of the Study, paragraph 1.
Change from:
The continuation protocol of open-label belimumab will continue until the subject 
withdraws from the trial, or the subject elects to participate in another belimumab 
continuation study for SLE, or becomes commercially available in a subject’s country of 
participation, or upon the decision by the sponsor to discontinue development/marketing 
of belimumab for SLE. 
To:
The continuation protocol of open-label belimumab will continue until the subject 
withdraws from the trial, or the subject elects to participate in another belimumab 
continuation study for SLE, or intravenous belimumab becomes commercially available 
in a subject’s country of participation, or upon the decision by the sponsor to discontinue 
development/marketing of belimumab for SLE. 
Rationale:  Clarification for intravenous belimumab.
Change 21:  Section 6, Study Assessments and Procedures
This change affects Table 2, Column heading for Column 1 and 2.
Change from:
Column 1: Wk 48 of BEL 1137501
Column 2: Wk 0 (Wk 52 of BEL113750)1
To:
Column 1: Wk 48 of BEL 113750/On/before Day 168 of C11151
Column 2: Wk 0 (Wk 52 of BEL113750/Day 168 of C1115)+1 week1
Rationale:  Clarification of timing of visits for subjects enrolling from the open-label SC 
extension of C1115 in Northeast Asia (Japan)

YM2010/00145/03
CONFIDENTIAL
BEL114333
96
Change 22:  Section 6, Study Assessments and Procedures
This change affects Table 2, footnote 1.
Change from:
1. The Week 52 visit in the parent study Protocol BEL113750 serves as the Day 0 visit 
for the Protocol BEL114333. Performance of all the Week 52 procedures in BEL113750 
will cover nearly all the procedures that are required for Day 0 of this protocol. 
Procedures necessary for both this protocol and the prior Phase III protocol need only be 
performed once and shall be recorded to CRFs as described in Section 6.1.  At Week 48 
of BEL113750, a subject should sign the informed consent for the BEL114333 study.  In 
addition to the Week 52 procedures for BEL113750, a subject should be reassessed for 
inclusion/exclusion criteria of the BEL114333 study and receive belimumab (those 
procedures marked with an asterisk).  Subjects must be able to receive the 1st dose of 
belimumab (Day 0) for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 
weeks) after the last dose in BEL113750. 
To:
1. 
For subjects from BEL113750: The Week 52 visit in the parent study Protocol 
BEL113750 serves as the Day 0 visit for the Protocol BEL114333. Performance 
of all the Week 52 procedures in BEL113750 will cover nearly all the procedures 
that are required for Day 0 of this protocol. Procedures necessary for both this 
protocol and the prior Phase III protocol need only be performed once and shall 
be recorded to CRFs as described in Section 6.1.  At Week 48 of BEL113750, a 
subject should sign the informed consent for the BEL114333 study.  In addition to 
the Week 52 procedures for BEL113750, a subject should be reassessed for 
inclusion/exclusion criteria of the BEL114333 study and receive belimumab 
(those procedures marked with an asterisk).  Subjects must be able to receive the 
1st dose of belimumab (Day 0) for BEL114333 four weeks (minimum of 2 weeks, 
maximum of 8 weeks) after the last dose in BEL113750. 
For subjects from C1115: The Day 168 (Week 24) visit in the open-label 
extension phase of C1115 serves as the Day 0 visit for the Protocol 
BEL114333. Performance of all the Day 168 procedures in C1115 will cover 
nearly all the procedures that are required for Day 0 of this protocol. 
Procedures necessary for both this protocol and the prior Phase III protocol 
need only be performed once and shall be recorded to CRFs as described in 
Section 6.1.  On or before the Day 168 visit, a subject should sign the 
informed consent for the BEL114333 study. In addition to the Day 168 
procedures for C1115, a subject should be reassessed for inclusion/exclusion 
criteria of the BEL114333 study and receive IV belimumab. The target for 
starting IV belimumab (Day 0) for BEL114333 is 1 week after the last dose of 
SC belimumab (scheduled for Week 23 in the open-label extension). The 
EXIT visit of the C1115 study (Week 24) serves as the Day 0 visit for the 
Protocol BEL114333, and will have a +1 week visit window.
Rationale:  Clarification of timing of visits and procedures for subjects enrolling from 
the open-label SC extension of C1115 in Northeast Asia (Japan).

YM2010/00145/03
CONFIDENTIAL
BEL114333
97
Change 23:  Section 6, Study Assessments and Procedures
This change affects Table 3, footnote 3.
Change from:
3.
AE reports should be updated or completed prior to dosing. Ongoing Adverse 
events of BEL113750 have to be transferred and followed up in BEL114333.
To:
3.
AE reports should be updated or completed prior to dosing. Ongoing Adverse 
events of BEL113750 or C1115 have to be transferred and followed up in 
BEL114333.
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled.
Change 24:  Section 6.1 Critical Baseline Assessments
This change affects Critical Baseline Assessments.
Change from:
Subjects will be assessed for eligibility at the Week 48 visit of BEL113750. Only 
subjects who complete BEL113750 through the Week 48 visit and have a final 
BEL113750 disease assessment at Week 52 are eligible for this study. Written informed 
consent (including consent for the use and disclosure of research-related health 
information) must be obtained. Subjects must be able to receive the first dose of 
belimumab for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 weeks) 
after the last dose in BEL113750.
To:
For subjects in BEL113750: Subjects will be assessed for eligibility at the Week 48 visit 
of BEL113750. Only subjects who complete BEL113750 through the Week 48 visit and 
have a final BEL113750 disease assessment at Week 52 are eligible for this study. 
Written informed consent (including consent for the use and disclosure of research-
related health information) must be obtained. Subjects must be able to receive the first 
dose of belimumab for BEL114333 four weeks (minimum of 2 weeks, maximum of 8 
weeks) after the last dose in BEL113750.
For subjects in C1115: Subjects will be assessed for eligibility at the Day 168 visit of 
C1115. Only subjects who complete C1115 through the open-label extension phase 
and have a final disease assessment at Day 168 are eligible for this study. Written 
informed consent (including consent for the use and disclosure of research-related 
health information) must be obtained on or before the Day 168 visit. Subjects must 
be able to receive the first dose of IV belimumab (Day 0) for BEL114333 one week

YM2010/00145/03
CONFIDENTIAL
BEL114333
98
after the last SC dose in C1115. The EXIT visit of the C1115 study (Week 24) serves 
as the Day 0 visit for the Protocol BEL114333, and will have a +1 week visit window.
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled. Clarification of timing of visits and procedures for subjects enrolling 
from the open-label SC extension of C1115 in Japan.
Change 25:  Section 6.1.1, Procedures (Day 0)
This change created a sub-section.
Added: 
6.1.1.1 Subjects in BEL113750
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled.
Change 26:  Section 6.1.1, Procedures (Day 0)
This change added a new sub-section.
Added:
6.1.1.2 Subjects in C1115
The Day 168 visit of the open-label extension of C1115 will serve as the Day 0 visit 
for Protocol BEL114333. The subject must sign the informed consent for this 
protocol on or before the Day 168 visit of the open-label extension of C1115 prior to 
any procedure in this protocol (that is not present in the C1115 protocol) being 
performed.  On Day 0 of this study, a subject will be reassessed for 
Inclusion/Exclusion criteria of the BEL114333 study and receive IV belimumab, 
after completing the Day 168 procedures from the C1115 study.  Site personnel will 
access the IVRS to enrol the subject in the study. 
Procedures necessary for this protocol and for the prior Phase III protocol (C1115) 
need only be performed once. The results of any Day 0 procedure in this protocol 
which are also part of the C1115 protocol should be recorded on the C1115 eCRF.  
Only the additional procedures required for this protocol will be recorded in the 
BEL114333 protocol eCRF. 
The following assessments will be performed as part of the Day 168 assessment on 
C1115 and need only be performed once as described above and entered into the 
C1115 eCRF only.

YM2010/00145/03
CONFIDENTIAL
BEL114333
99

Urine for pregnancy testing- for all women with an intact uterus, unless 
exempted from pregnancy testing (i.e., of non-childbearing potential - women 
who had a hysterectomy, are post-menopausal which is defined as 1 year 
without menses, have both ovaries surgically removed or have current 
documented female sterilization procedure).

Record of Concurrent Medications.

Adverse Events.

Blood samples for: (see Appendix 5– Laboratory Tests):

Haematology.

Modified Chem 20 (non-fasting). (CPK MUST be done for subjects with 
myositis in order to score SELENA SLEDAI/BILAG).

PT/PTT

Serum Immunoglobulin isotypes (IgG, IgM, IgA).

Immunogenicity testing.

Biological markers (Complement C3 and C4)

Anti-dsDNA autoantibodies.
B-cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+
activated,  CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset 
and CD20-/138+ plasma cells) at selected sites.

Urine sample for:

Routine urinalysis.

Spot urine for macroscopic/microscopic/proteinuria assessments.

Disease activity scales:

Physician’s Global Assessment (PGA). (See Appendix 1).

SELENA SLEDAI (See Appendix 1; refer to Section 6.2.2.3 Guidelines for 
Scoring Proteinuria).

SLE Flare Index. (See Appendix 1).

BILAG. (See Appendix 2).
The above Day 168 eCRF data will be transferred programmatically from the 
C1115 eCRF and merged with the datasets for BEL114333.  This data will not be 
visible in the BEL114333 eCRF.
The following additional procedures beyond those described above are required at 
Day 0 for Protocol BEL114333:

Ensure Informed Consent Form has been signed.

Confirm Eligibility.

YM2010/00145/03
CONFIDENTIAL
BEL114333
100

Physical exam

Vital signs (Systolic and diastolic blood pressure (sitting), heart rate, and oral 
temperature will be measured.  See Section 6.3.11).

SLICC/ACR Damage Index (See Appendix 3).

Administer belimumab.
Rationale:  Clarification of procedures on Day 0 for subjects enrolling from the open-
label SC extension of C1115 in Japan.
Change 27:  Section 6.2.1.2, Secondary Endpoints
This change affects Secondary Endpoints, Note after 3rd bullet, first sentence.
Change from:
NOTE: Baseline will be defined as study Day 0 of BEL113750 study.
To:
NOTE: Baseline will be defined as study Day 0 of BEL113750 study or C1115 study as 
appropriate.
Rationale:  Change made for clarification as subjects from more than one parent study 
will be enrolled.
Change 28:  Section 6.3.10.1 Progressive Multifocal Leukoencephalopathy
This change affects Progressive multifocal leukoencephalopathy.
Change from:
There have been no reported cases of PML in subjects with SLE or RA treated with 
belimumab.  However, patients with SLE may be at increased risk for PML secondary to 
SLE itself, as well as the concurrent use of immunosuppressive drugs.  The most 
common signs and symptoms of PML include visual disturbances, ocular movements, 
ataxia, and mental status changes such as disorientation or confusion.  Clinical signs and 
symptoms of PML and SLE can be similar.  The investigator must exercise best 
judegment in further workup and clinical intervention as appropriate.  If PML is 
suspected, this should be promptly reported to the sponsor.  
To:
Progressive multifocal leukoencephalopathy (PML) resulting in neurological 
deficits, including fatal cases, has been reported in SLE patients receiving 
immunosuppressant pharmacotherapy, including belimumab.  A diagnosis of PML 

YM2010/00145/03
CONFIDENTIAL
BEL114333
101
should be considered in any subject presenting with new-onset or deteriorating 
neurological signs and symptoms.  The subject should be referred to a neurologist or
other appropriate specialist for evaluation.  If PML is confirmed, study agent should 
be discontinued and consideration should be given to stopping immunosuppressant 
therapy.
If PML is suspected, this should be immediately reported to the Medical Monitor. 
The appropriateness of continuing study agent, while the case is being assessed, 
should be discussed.
Rationale:  Updated wording addresses new information received by the Sponsor.
Change 29:  Section 6.3.13.2 Assay Methods
This change affects Immunogenicity, Assay Methods.
Change from:
All immunogenicity testing will be carried out at HGS (Rockville, Maryland).  HGS has 
developed a 3-part (screening, confirmation/specificity and neutralisation) belimumab 
immunogenicity assay paradigm.
In the screening assay, the presence of anti-belimumab antibodies will be assessed using 
an electrochemiluminescence (ECL)-based (Meso Scale Discovery [MSD]) bridging 
assay after dissociation of belimumab from the anti-drug antibodies (ADA).  Any 
samples testing positive will then be tested using a confirmatory ECL based assay which 
is able to distinguish between ADA (true positive) and BLyS-belimumab complexes in 
serum (false positive).  The confirmed positive samples will be analyzed for the presence 
of neutralizing antibodies by a neutralisation assay.  The results of the anti-belimumab 
antibody tests for all subjects will be reported at the end of the study. 
To:
Immunogenicity testing will be carried out at GSK (Clinical Immunology department) 
or Frontage Laboratories in Shanghai, China.  The assay is performed in a 4-tiered 
belimumab immunogenicity assay paradigm (screening, confirmation/specificity and 
neutralisation and titer).
In the screening assay, the presence of anti-belimumab antibodies will be assessed using 
an electrochemiluminescence (ECL)-based (Meso Scale Discovery [MSD]) bridging 
assay after dissociation of belimumab from the anti-drug antibodies (ADA).  Any 
samples testing positive will then be tested using a confirmatory ECL based assay which 
is able to distinguish between ADA (true positive) and BLyS-belimumab complexes in 
serum (false positive).  The confirmed positive samples will be analyzed for the presence 
of neutralizing antibodies by a neutralisation assay and also assayed for titer.  The 
results of the anti-belimumab antibody tests for all subjects will be reported at the end of 
the study. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
102
Rationale: Modification to reflect current methods.
Change 30:  Section 7 Data Management
This change was added to the end of the Data Management section.
Added:
Data from C1115 Day 168 will be entered into the eCRF for C1115 and 
programmatically merged with the BEL114333 datasets.  Any data cleaning 
procedures performed on this C1115 data will be completed in the C1115 eCRF 
before the final data transfer into BEL114333.  
Rationale: Clarification for how C1115 data will be handled.
Change 31:  Section 8.1.1 Primary Efficacy Analysis
This change affects Primary Efficacy Analysis by adding a new sentence following the 
original text.
Added:
Subjects who previously received SC belimumab will be evaluated separately and 
this analysis will be described in the Reporting and Analysis Plan.
Rationale: Clarification regarding analysis of subjects enrolling from the open-label SC 
extension of C1115 in Japan.
Change 32:  Section 8.1.2 Analysis of Additional Efficacy and Biomarkers
This change affects Analysis of Additional Efficacy and Biomarkers by adding a new 
sentence following the original text.
Added:
Subjects who previously received SC belimumab will be evaluated separately and 
this analysis will be described in the Reporting and Analysis Plan.
Rationale:  Clarification regarding analysis of subjects enrolling from the open-label SC 
extension of C1115 in Japan.

YM2010/00145/03
CONFIDENTIAL
BEL114333
103
Change 33:  Section 8.1.3 Analysis of Safety Variables
This change affects Analysis of Safety Variables, paragraph 1, second sentence.
Change from:
The frequency of AEs will be tabulated by MedDRA system organ class and preferred 
term and by treatment groups, according to the treatment group that the subjects were 
assigned to during randomisation in the BEL113750 study.
To:
The frequency of AEs will be tabulated by MedDRA system organ class and preferred 
term and by treatment groups, according to the treatment group that the subjects were 
assigned to during randomisation in the BEL113750 or C1115 study.
Rationale:  Change made for clarification as subjects from more than one study will be 
in the analysis.
Change 34:  Section 9.5 Study and Site Closure
This change affects Study and Site Closure, paragraph 1, first sentence.
Change from:
Subjects recruited into this study will continue to receive treatment with belimumab until 
such time as belimumab becomes commercially available in Northeast Asia, or the 
subject elects to participate in another belimumab continuation study for SLE, or until 
either the subject's physician withdraws the subject from the study or upon the decision 
by the sponsor to discontinue further development of belimumab for SLE.  
To:
Subjects recruited into this study will continue to receive treatment with intravenous 
belimumab until such time as intravenous belimumab becomes commercially available 
in Northeast Asia, or the subject elects to participate in another belimumab continuation 
study for SLE, or until either the subject's physician withdraws the subject from the study 
or upon the decision by the sponsor to discontinue further development of belimumab for 
SLE.  
Rationale:  Clarification for intravenous belimumab.

YM2010/00145/03
CONFIDENTIAL
BEL114333
104
Change 35: Section 10 References
The following reference was added to the list of references.
Shida, Y, Takahashi N, Sakamoto T, Ino H, Endo A, Hirama T. The 
pharmacokinetics and safety profiles of belimumab after single subcutaneous and 
intravenous doses in healthy Japanese volunteers. J Clin Pharm Ther 2014;39:97-
101.

YM2010/00145/03
CONFIDENTIAL
BEL114333
105
Protocol Amendment 02
Protocol amendment 02 applies to all countries and sites.
Description of Changes
Changes are highlighted in bold.
Change 1:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, end of 4th paragraph
Change from:
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication in this protocol, then every 
24 weeks thereafter, and at the Exit visit and the Week 16 follow-up visit.  Serum IgG 
will be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) 
after the first dose of study medication and then every 48 weeks thereafter and at the Exit 
visit and the Week 16 follow-up visit.  Serum IgA and IgM will be evaluated in this 
protocol at Week 0 and Week 48, and then every 48 weeks thereafter and at the Exit visit.  
Adverse events will be assessed at every visit except at the 6 month follow-up visit.  
Subjects should be clinically evaluated by their investigating physician at each visit. It is 
the investigator’s responsibility to manage their patient’s SLE as necessary. Complete 
efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare Index along with PGA) and 
evaluation of biomarkers will occur every 24 weeks (168 days).
To:
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication in this protocol, then every 
24 weeks thereafter, and at the Exit visit and the Week 16 follow-up visit.  Serum IgG 
will be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) 
after the first dose of study medication and then every 48 weeks thereafter and at the Exit 
visit and the Week 16 follow-up visit.  Serum IgA and IgM will be evaluated in this 
protocol at Week 0 and Week 48, and then every 48 weeks thereafter and at the Exit visit.  
Adverse events will be assessed at every visit except at the 6 month follow-up visit.  
Subjects should be clinically evaluated by their investigating physician at each visit. It is 
the investigator’s responsibility to manage their patient’s SLE as necessary. Complete 
efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare Index along with PGA) and 
evaluation of biomarkers will occur every 24 weeks (168 days).  B-cell subsets will be 
collected at Week 48, the EXIT visit, and at approximately 6 months after the last dose of 
study agent, from subjects at selected sites only.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects.  Addition of B-cell subsets collected at Week 48 while subjects participate in 
the extension study will allow monitoring of B-cell subsets on a yearly basis.

YM2010/00145/03
CONFIDENTIAL
BEL114333
106
Change 2:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 5.
Change from:
During the course of the study, the investigator may adjust concurrent medications (add, 
eliminate, change dose level/frequency) as clinically appropriate in response to 
improving or worsening conditions. Prohibited medications in this study are similar to 
BEL113750.  Subjects who start prohibited medications or therapies (see Section 5.3.2 
and Section 5.3.3) at any time during the study must be withdrawn from treatment with 
belimumab and enter study follow-up. After discontinuation of study medication, 
subjects will return for an Exit visit 4 weeks after the last study medication administration 
and for follow up visits at 16 weeks and 6 months after the last dose of study medication. 
Withdrawal of subjects from treatment and the procedures to be followed are described in 
Section 4.4
To:
During the course of the study, the investigator may adjust concurrent medications (add, 
eliminate, change dose level/frequency) as clinically appropriate in response to 
improving or worsening conditions. Prohibited medications in this study are similar to 
BEL113750. Subjects who start prohibited medications or therapies (see Section 5.3.2
and Section 5.3.3) at any time during the study must be withdrawn from treatment with 
belimumab and enter study follow-up. After discontinuation of study medication, 
subjects will return for an Exit visit 4 weeks after the last study medication administration 
and for a follow up visit at 16 weeks and 6 months after the last dose of study 
medication.  For any subject who had an anti-belimumab antibody response at the 
16-week follow-up visit (or last study visit at which immunogenicity was assessed if 
the 16-week follow-up immunogenicity sample is not available), an attempt will be 
made to obtain a serum sample for anti-belimumab antibodies at least 6 months 
after the last dose of study agent. Withdrawal of subjects from treatment and the 
procedures to be followed are described in Section 4.4.
Rationale:  Subjects participating in this open-label extension study no longer need to 
remain blinded.  Only subjects who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available) will have attempts made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.
Change 3:  Protocol Summary, Study Endpoints/Assessments
This change affects Protocol Summary, Study Endpoints/Assessments, last paragraph
Change from:
All other endpoints will be derived from the following assessments: SELENA SLEDAI, 
PGA, BILAG, SLE Flare Index, prednisone dose, renal flare assessment, proteinuria,  

YM2010/00145/03
CONFIDENTIAL
BEL114333
107
biomarkers (immunoglobulins, complement, anti-dsDNA autoantibodies, and B cell 
subsets), immunogenicity, adverse events, clinical laboratory assessments (clinical 
chemistry and haematology) and plasma levels of belimumab.
To:
All other endpoints will be derived from the following assessments: SELENA SLEDAI, 
PGA, BILAG, SLE Flare Index, prednisone dose, renal flare assessment, proteinuria,  
biomarkers (immunoglobulins, complement, anti-dsDNA autoantibodies, and B cell 
subsets (at selected sites)), immunogenicity, adverse events, clinical laboratory 
assessments (clinical chemistry and haematology) and plasma levels of belimumab.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects. 
Change 4:  Investigational Plan, Study Design
This change affects Section 3.1, Investigational Plan, Study Design, end of 3rd paragraph.
Change from:
Subjects who complete 48 weeks of treatment on the BEL113750 study and who meet 
inclusion/exclusion criteria, and provide informed consent, will be given the option to 
enter the continuation study.  All subjects will receive belimumab 10 mg/kg IV infused 
over 1 hour every 28 days. The first dose on the continuation study must be given 4 
weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750. 
All subjects will continue therapies as prescribed by the investigator.  During the course 
of the study, the investigator may adjust concurrent medications (add, eliminate, change 
dose level/frequency) as clinically appropriate in response to improving or worsening 
conditions.    However, subjects who start prohibited medications or therapies (see 
Section 5.3.2 and Section 5.3.3) at any time during the study must be withdrawn from 
treatment with belimumab and enter study follow-up.  After discontinuation of 
belimumab, subjects will return for an Exit visit 4 weeks after the last study medication 
administration and for follow up visit at 16 weeks and 6 months after the last dose of 
belimumab. Withdrawal of subjects from treatment and the procedures to be followed are 
described in Section 4.4. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
108
To:
Subjects who complete 48 weeks of treatment on the BEL113750 study and who meet 
inclusion/exclusion criteria, and provide informed consent, will be given the option to 
enter the continuation study.  All subjects will receive belimumab 10 mg/kg IV infused 
over 1 hour every 28 days. The first dose on the continuation study must be given 4 
weeks (minimum of 2 weeks, maximum of 8 weeks) after the last dose in BEL113750. 
All subjects will continue therapies as prescribed by the investigator.  During the course 
of the study, the investigator may adjust concurrent medications (add, eliminate, change 
dose level/frequency) as clinically appropriate in response to improving or worsening 
conditions.    However, subjects who start prohibited medications or therapies (see 
Section 5.3.2 and Section 5.3.3) at any time during the study must be withdrawn from 
treatment with belimumab and enter study follow-up.  After discontinuation of 
belimumab, subjects will return for an Exit visit 4 weeks after the last study medication 
administration and for follow up visit at 16 weeks and 6 months after the last dose of 
belimumab.  For any subject who had an anti-belimumab antibody response at the 
16-week follow-up visit (or last study visit at which immunogenicity was assessed if 
the 16-week follow-up immunogenicity sample is not available), an attempt will be 
made to obtain a serum sample for anti-belimumab antibodies at least 6 months 
after the last dose of study agent. Withdrawal of subjects from treatment and the 
procedures to be followed are described in Section 4.4. 
Rationale:  Subjects participating in this open-label extension study no longer need to 
remain blinded.  Only subjects who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available) will have attempts made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.
Change 5:  Investigational Plan, Study Design
This change affects Section 3.1, Investigational Plan, Study Design, end of 4th paragraph
Change from:
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication on this protocol, then every 
24 weeks thereafter and at the Exit visit and the Week 16 follow-up visit.  Serum IgG will 
be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) after 
the first dose of study medication and then every 48 weeks thereafter and at the Exit visit 
and the Week 16 follow-up visit.  Adverse events will be assessed at every visit except at 
the 6 month follow-up visit.  Subjects should be clinically evaluated by their investigating 
physician at each visit. It is the investigator’s responsibility to manage their patient’s SLE 
as necessary. Complete efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare 
Index along with PGA) and evaluation of biomarkers will occur every 24 weeks (168 
days). 

YM2010/00145/03
CONFIDENTIAL
BEL114333
109
To:
Clinical laboratory evaluations (haematology, chemistry and urinalysis), will occur 
4 weeks (28 days), 12 weeks (84 days), 24 weeks (168 days), 36 weeks (252 days), and 
48 weeks (336 days) after the first dose of study medication on this protocol, then every 
24 weeks thereafter and at the Exit visit and the Week 16 follow-up visit.  Serum IgG will 
be evaluated at 12 weeks (84 days), 24 weeks (168 days) and 48 weeks (336 days) after 
the first dose of study medication and then every 48 weeks thereafter and at the Exit visit 
and the Week 16 follow-up visit.  Adverse events will be assessed at every visit except at 
the 6 month follow-up visit.  Subjects should be clinically evaluated by their investigating 
physician at each visit. It is the investigator’s responsibility to manage their patient’s SLE 
as necessary. Complete efficacy evaluations (SELENA SLEDAI, BILAG, SLE Flare 
Index along with PGA) and evaluation of biomarkers will occur every 24 weeks (168 
days). B-cell subsets will be collected at Week 48, the EXIT visit, and at 
approximately 6 months after the last dose of study agent, from subjects at selected 
sites only.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects.  Addition of B-cell subsets collected at Week 48 while subjects participate in 
the extension study will allow monitoring of B-cell subsets at selected sites on a yearly 
basis. 
Change 6:  Withdrawal Criteria
This change affects Section 4.4, Withdrawal Criteria, first paragraph
Change from:
A subject may voluntarily discontinue participation in this study at any time.  The 
investigator may also, at his or her discretion, discontinue a subject from this study.  
Every effort should be made by the investigator to keep subjects in the study and to 
ensure return for the Exit visit 4 weeks after the last dose of belimumab, and the follow-
up visits 16 weeks and 6 months after the last dose. Notwithstanding this requirement, the 
investigator should adjust concurrent medications as clinically required.
To:
A subject may voluntarily discontinue participation in this study at any time.  The 
investigator may also, at his or her discretion, discontinue a subject from this study.  
Every effort should be made by the investigator to keep subjects in the study and to 
ensure return for the Exit visit 4 weeks after the last dose of belimumab, and the follow-
up visits 16 weeks and 6 months after the last dose.   For any subject who had an anti-
belimumab antibody response at the 16-week follow-up visit (or last study visit at 
which immunogenicity was assessed if the 16-week follow-up immunogenicity 
sample is not available), an attempt will be made to obtain a serum sample for anti-
belimumab antibodies at least 6 months after the last dose of study agent.  From 
subjects at selected sites only, B-cell subsets will be collected at the EXIT visit and at 
approximately 6 months after the last dose of study agent.  Notwithstanding this 
requirement, the investigator should adjust concurrent medications as clinically required.

YM2010/00145/03
CONFIDENTIAL
BEL114333
110
Rationale:  Clarify that the 6 month visit post last dose will be for subjects who had an 
anti-belimumab antibody response at the 16-week follow-up visit (or last study visit at 
which immunogenicity was assessed if the 16-week follow-up immunogenicity sample is 
not available, and for B-cell subsets labs for subjects at selected sites).
Change 7:  Study Treatments
This change affects Section 5, last paragraph
Change from:
If a subject experiences a clinically significant, potentially life-threatening (Grade 4) AE
that in the clinical judgement of the investigator is possibly, probably or definitely related 
to belimumab then treatment with belimumab will be discontinued.  The subject should 
be withdrawn from the study and followed at regularly scheduled monthly study visits as 
required until resolution of the AE(s) and must also return for follow-up at the Exit visit, 
16 weeks, and 6 months after the last dose of belimumab.
To:
If a subject experiences a clinically significant, potentially life-threatening (Grade 4) AE
that in the clinical judgement of the investigator is possibly, probably or definitely related 
to belimumab then treatment with belimumab will be discontinued.  The subject should 
be withdrawn from the study and followed at regularly scheduled monthly study visits as 
required until resolution of the AE(s) and must also return for follow-up at the EXIT 
visit 4 weeks after the last dose of belimumab, and the follow-up visit 16 weeks after 
the last dose.  For any subject who had an anti-belimumab antibody response at the 
16-week follow-up visit (or last study visit at which immunogenicity was assessed if 
the 16-week follow-up immunogenicity sample is not available), an attempt will be 
made to obtain a serum sample for anti-belimumab antibodies at least 6 months 
after the last dose of study agent.  From subjects at selected sites only, B-cell subsets 
will be collected at the EXIT visit and at approximately 6 months after the last dose 
of study agent. 
Rationale:  Clarify that the 6 month visit post last dose will be for subjects who had an 
anti-belimumab antibody response at the 16-week follow-up visit (or last study visit at 
which immunogenicity was assessed if the 16-week follow-up immunogenicity sample is 
not available, and for B-cell subsets labs for subjects at selected sites).  
Change 8:  Study Assessments and Procedures, Time and Events Table
This change affects Section 6, Time and Events Table, Table 2 (Year 1) and Table 3 
(Additional Years), Exploratory Lab Assessments, B cell Markers
Add:
Add “X” at Week 48 to Time and Events Table exploratory lab assessment B cell marker 
row in both Table 2 (Year 1) and Table 3 (Additional Years)

YM2010/00145/03
CONFIDENTIAL
BEL114333
111
Rationale:  Addition of B-cell subsets collected at Week 48 while subjects participate in 
the extension study will allow monitoring of B-cell subsets at selected sites on a yearly 
basis. 
Change 9:  Study Assessments and Procedures
This change affects Section 6, Time and Events Table, Table 2 (Year 1), Exploratory Lab 
Assessment Immunogenicity row at 6 month follow-up visit column and Footnote 9
Change from:
“X” at 6 month follow-up visit column and Immunogenicity row
To:
“X9A”
And:
Footnote:
9.  Immunogenicity testing includes quantifying the amount of belimumab present in the 
samples using the belimumab PK assay.  For all subjects, a serum sample for anti-
belimumab antibodies will be obtained at least 6 months after the last dose or upon 
completion of the study.   
To:
9.  Immunogenicity testing includes quantifying the amount of belimumab present in the 
samples using the belimumab PK assay.  For all subjects, a serum sample for anti-
belimumab antibodies will be obtained at least 6 months after the last dose or upon 
completion of the study.  
9AFor any subject who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 
16-week follow-up immunogenicity sample is not available), an attempt will be made 
to obtain a serum sample for anti-belimumab antibodies at least 6 months after the 
last dose of study agent.
Rationale:  Clarity is added to the Time and Events table with these changes.  Subjects 
participating in this open-label extension study no longer need to remain blinded.  Only 
subjects who had an anti-belimumab antibody response at the 16-week follow-up visit (or 
last study visit at which immunogenicity was assessed if the 16-week follow-up 
immunogenicity sample is not available) will have attempts made to obtain a serum 
sample for anti-belimumab antibodies at least 6 months after the last dose of study agent.

YM2010/00145/03
CONFIDENTIAL
BEL114333
112
Change 10:  Study Assessments and Procedures
This change affects Section 6, Time and Events Table, Table 2 (Year 1 ), end of Footnote 
10
Change from:
Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, 
CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ 
plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells).
To:
Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, 
CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ 
plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells).  Note:  B-cell subsets to be drawn at selected sites only.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects. 
Change 11:  Study Assessments and Procedures
This change affects Section 6, Time and Events Table, Table 3 (Additional Years), 
Exploratory Lab Assessments Immunogenicity row and Footnote 8
Change from:
“X” at 6 month follow-up visit column and Immunogenicity row
To:
“X8A”
And:
Footnote:
1. 8.  Immunogenicity testing includes quantifying the amount of belimumab present in 
the samples using the belimumab PK assay.  For all subjects, a serum sample for anti-
belimumab antibodies will be obtained at least 6 months after the last dose or upon 
completion of the study. 
To:
8.  Immunogenicity testing includes quantifying the amount of belimumab present in the 
samples using the belimumab PK assay.  For all subjects, a serum sample for anti-
belimumab antibodies will be obtained at least 6 months after the last dose or upon 
completion of the study.  

YM2010/00145/03
CONFIDENTIAL
BEL114333
113
8AFor any subject who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 
16-week follow-up immunogenicity sample is not available), an attempt will be made 
to obtain a serum sample for anti-belimumab antibodies at least 6 months after the 
last dose of study agent.
Rationale:  Clarity is added to the Time and Events table with these changes.  Subjects 
participating in this open-label extension study no longer need to remain blinded.  Only 
subjects who had an anti-belimumab antibody response at the 16-week follow-up visit (or 
last study visit at which immunogenicity was assessed if the 16-week follow-up 
immunogenicity sample is not available) will have attempts made to obtain a serum 
sample for anti-belimumab antibodies at least 6 months after the last dose of study agent.
Change 12:  Study Assessments and Procedures
This change affects Section 6, Time and Events Table, Table 3 (Additional Years), end of 
Footnote 9
Change from:
Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, 
CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ 
plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells).
To:
Biological Markers include FACS of peripheral lymphocytes: B lymphocytes (CD20+, 
CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated, CD20+/138+ 
plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells).  Note:  B-cell subsets to be drawn at selected sites only.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects.
Change 13:  Procedures (Day 0)
This change affects Section 6.1.1, Procedures (Day 0), Blood Samples bullet, end of B-
cell subsets sub-bullet
Change from:

B-cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ activated,  
CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+
plasma cells).

YM2010/00145/03
CONFIDENTIAL
BEL114333
114
To:

B-cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+ 
activated,  CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset 
and CD20-/138+ plasma cells) at selected sites.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead 
of all subjects.   
Change 14:  Safety
This change affects Section 6.3, Safety, 3rd bullet point
Change from:

B Cell Markers assessed at the EXIT visit and at approximately 6 months after the
last dose of study agent.  Samples will be collected pre-dose where taken at dosing 
visits.  Blood samples for measurement of B-cell subsets will be collected from 
subjects at selected sites only.
To:

B Cell Markers assessed at the Week 48 visit, EXIT visit,  and at approximately 6 
months after the last dose of study agent.  Samples will be collected pre-dose where 
taken at dosing visits.  Blood samples for measurement of B-cell subsets will be 
collected from subjects at selected sites only.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of 
all subjects.  Addition of B-cell subsets collected at Week 48 while subjects participate in 
the extension study will allow monitoring of B-cell subsets at selected sites on a yearly 
basis. 
Change 15:  Safety
This change affects Section 6.3, Safety, 4th bullet point
Change from:

Immunogenicity over each 24 week period, at the Exit visit and the 16 week follow-
up visit for subjects who withdraw prior to completion of the 52-week treatment 
period.  A serum sample for anti-belimumab antibodies will be obtained 
approximately 6 months after the last dose of study agent. Any anti-belimumab 
antibody positive sample will be tested for neutralization. 
To:

Immunogenicity over each 24 week period, at the Exit visit and the 16 week follow-
up visit for subjects who withdraw prior to completion of the 52-week treatment 
period.  An attempt will be made to obtain a serum sample for anti-belimumab 
antibodies at least 6 months after the last dose of study agent  for any subject 
who had an anti-belimumab antibody response at the 16-week follow-up visit 
(or last study visit at which immunogenicity was assessed if the 16-week follow-

YM2010/00145/03
CONFIDENTIAL
BEL114333
115
up immunogenicity sample is not available).   Any anti-belimumab antibody 
positive sample will be tested for neutralization. 
Rationale:  Subjects participating in this open-label extension study no longer need to 
remain blinded.  Only subjects who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available) will have attempts made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.
Change 16:  Sample Collection and Handling
This change affects Section 6.3.13.1, Sample Collection and Handling, first paragraph
Change from:
Serum samples will be collected for belimumab immunogenicity assays prior to dosing at 
Day 0, and Weeks 24 and 48 of Year 1 and Year 2, etc., and at the Exit visit, 16 week and 
6 month follow-up visits.  
To:
Serum samples will be collected for belimumab immunogenicity assays prior to dosing at 
Day 0, and Weeks 24 and 48 of Year 1 and Year 2, etc., and at the Exit visit, and 16 
week follow-up visit. and 6 month follow-up visits.  An attempt will be made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last 
dose of study agent for any subject who had an anti-belimumab antibody response 
at the 16-week follow-up visit (or last study visit at which immunogenicity was 
assessed if the 16-week follow-up immunogenicity sample is not available).
Rationale:  Subjects participating in this open-label extension study no longer need to 
remain blinded.  Only subjects who had an anti-belimumab antibody response at the 16-
week follow-up visit (or last study visit at which immunogenicity was assessed if the 16-
week follow-up immunogenicity sample is not available) will have attempts made to 
obtain a serum sample for anti-belimumab antibodies at least 6 months after the last dose 
of study agent.
Change 17:  Biomarkers
This change affects Section 6.4, end of last bullet point
Change from:

Percent change in absolute B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–
naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells) at the 
Exit visit and 6 month  Follow-up.

YM2010/00145/03
CONFIDENTIAL
BEL114333
116
To:

Percent change in absolute B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–
naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells) at the 
Exit visit and 6 month  Follow-up at selected sites.
Rationale:  Clarify that B-cell subsets will be collected only at selected sites instead of
all subjects. 

YM2010/00145/03
CONFIDENTIAL
BEL114333
117
Protocol Amendment 01
Protocol amendment 01 applies to all countries and sites.
Description of Changes
Changes are highlighted in bold.
Change 1:  Protocol Summary, Study Design
This change affects Protocol Summary, Study Design, paragraph 6.
Change from:
Subjects recruited into this study will continue to receive treatment with belimumab until 
such time as belimumab becomes commercially available in a subject’s country of 
participation, or until either the subject's physician withdraws the subject from the study 
or upon the decision by the sponsor to discontinue further development of belimumab for 
SLE.
To:
Subjects recruited into this study will continue to receive treatment with belimumab until 
such time as belimumab becomes commercially available in a subject’s country of 
participation, or the subject elects to participate in another belimumab continuation 
study for SLE, or until either the subject's physician withdraws the subject from the 
study or upon the decision by the sponsor to discontinue further development of 
belimumab for SLE.
Rationale:  Sentence inadvertently omitted
Change 2:  Inclusion Criteria
This change affects Section 4.2, Inclusion Criterion #3, after last bullet point

YM2010/00145/03
CONFIDENTIAL
BEL114333
118
Add:
Note: MMF and other forms of mycophenolate affect the metabolism of oral 
contraceptives and may reduce their effectiveness. As such, women receiving 
mycophenolate who are using oral contraceptives for birth control should 
employ an additional method (e.g., barrier method).
Rationale:  MMF can affect the metabolism and effectiveness of oral contraceptives. 
Based on this, it is recommended that women receiving MMF who rely on oral 
contraceptives for birth control should be required to use an additional method to 
minimize the risk of pregnancy.
Change 3: Study Treatments; Investigational Products and Reference Therapy
This change affects Section 5, paragraph 10, regarding new information on post-infusion 
observation time for potential hypersensitivity reactions for the first two infusions.
Change from:
Subjects will be monitored during and after each infusion according to study sites’ 
guidelines or standard operating procedure for IV infusions.  This may include, but is not 
limited to, monitoring vital signs and observing for any untoward reactions. Trained 
rescue personnel and rescue medications/equipment should be available for a minimum 
of the first dose.
To:
In the post-marketing setting, delayed onset of symptoms of acute hypersensitivity 
reactions has been observed. Subjects should remain under clinical supervision for 
3 hours after completion of the first 2 infusions. Should symptoms of acute 
hypersensitivity occur, an extended period of monitoring may be appropriate, based 
on clinical judgment. Otherwise, subjects will be monitored during and after each 
infusion according to study sites’ guidelines or standard operating procedure for IV 
infusions.  This may include, but is not limited to, monitoring vital signs and observing 
for any untoward reactions.
Subjects should be made aware of the potential risk, the signs and symptoms of such 
reactions, and the importance of immediately seeking medical attention.  Trained 
rescue personnel and rescue medications/equipment should be available for a minimum 
of the first 2 doses.
Rationale: The protocol has been modified to require that subjects remain under clinical 
supervision for 3 hours after completion of the first 2 infusions. This change has been 
made to all upcoming trials of intravenous belimumab in adult subjects in order to
provide a longer period of post infusion monitoring and to prospectively collect more 
precise data on hypersensitivity reactions. A broad review of spontaneous safety reports 
received as of January 2012 identified 18 serious hypersensitivity reactions for an 
estimated reporting rate of 0.4%. Of these events, all occurred with the 1st or 2nd infusion 
(where infusion number is known, n=15) and the vast majority occurred during or shortly 
after completion of the infusion. Five cases appear to have been delayed in onset beyond 

YM2010/00145/03
CONFIDENTIAL
BEL114333
119
1 hour after completion of the infusion (n=3) or recurred after initial resolution of initial 
early symptoms (n=2). Given the nature of postmarketing reporting, details surrounding 
these events are limited and precise information with respect to time of onset of initial 
symptoms relative to the infusion is not available. This clinical trial, as well as other 
upcoming clinical trials, provides an opportunity to better characterize the 
hypersensitivity reactions observed with belimumab, including signs and symptoms and 
time to onset. The protocol-defined minimum monitoring period is applied only to the 
first 2 infusions because it is with these infusions that the vast majority of 
hypersensitivity reactions have been observed. For all subsequent infusions, subjects 
should be monitored during and for an appropriate period of time after infusion according 
to site procedures/clinical judgment.
This will also maintain the blind in the parent study BEL113750. 
Change 4:  Withdrawal Criteria
This change affects Section 4.4:  Withdrawal Criteria, second paragraph.
Remove:
“Sponsor request”
Rationale:  The intention of “Sponsor request” was to clarify subject withdrawals in the 
case report forms due to the unlikely administrative event of study termination changes to 
the clinical development plan.  The case report forms include “Study closed/Terminated” 
thus making “Sponsor request” redundant.
Change 5:  Study Assessments and Procedures, Time and Events Table (Year 1)
This change affects Section 6:  Study Assessments and Procedures, Table 2:  Time and 
Events Table (Year 1 only), Investigational Product, addition of Footnote 12, regarding 
new information on post-infusion observation time for potential hypersensitivity 
reactions for the first two infusions.
Add:
Footnote 12:  Subjects will remain under clinical supervision for three hours after 
completion of the first 2 infusions.  See Section 5 and Section 6.3.9. 
Rationale: The protocol has been modified to require that subjects remain under clinical 
supervision for 3 hours after completion of the first 2 infusions. This change has been 
made to all upcoming trials of intravenous belimumab in adult subjects in order to 
provide a longer period of post infusion monitoring and to prospectively collect more 
precise data on hypersensitivity reactions. A broad review of spontaneous safety reports 
received as of January 2012 identified 18 serious hypersensitivity reactions for an 
estimated reporting rate of 0.4%. Of these events, all occurred with the 1st or 2nd infusion 
(where infusion number is known, 15) and the vast majority occurred during or shortly 
after completion of the infusion. Five cases appear to have been delayed in onset beyond 
1 hour after completion of the infusion (n=3) or recurred after initial resolution of initial 

YM2010/00145/03
CONFIDENTIAL
BEL114333
120
early symptoms (n=2). Given the nature of postmarketing reporting, details surrounding 
these events are limited and precise information with respect to time of onset of initial 
symptoms relative to the infusion is not available. This clinical trial, as well as other 
upcoming clinical trials, provides an opportunity to better characterize the 
hypersensitivity reactions observed with belimumab, including signs and symptoms and 
time to onset. The protocol-defined minimum monitoring period is applied only to the 
first 2 infusions because it is with these infusions that the vast majority of 
hypersensitivity reactions have been observed. For all subsequent infusions, subjects 
should be monitored during and for an appropriate period of time after infusion according 
to site procedures/clinical judgment.
This will also maintain the blind in the parent study BEL113750. 
Change 6:  Study Assessments and Procedures, Time and Events Table (Additional 
Years)
This change affects Section 6:  Study Assessments and Procedures, Table 2:  Time and 
Events Table (Additional Years),  Laboratory Assessments, addition of Footnote 11.
Add:
Footnote 11:  During “Additional Years”, investigators can obtain any of the same 
laboratory assessments that are mentioned for Year 1 (hematology, modified Chem 20, 
urinalysis, spot urine to creatinine ratio, urine pregnancy, C3, C4, anti-ds DNA 
autoantibodies, IgG, IgA, and IgM), as unscheduled laboratory tests at any time during 
Year 2 and beyond, if clinically indicated.  Any additional laboratory tests beyond this, if 
not related to the protocol, will be the responsibility of the investigator and subject.
Rationale:  Clarification for investigators that labs are not limited to only every 6 months 
in “Additional Years” and investigators are able to obtain supplemental labs in addition 
to the scheduled every 6 month labs as in “Year 1” at the discretion of the investigator as 
unscheduled labs.
Change 7:  Infusion-related Reactions and Hypersensitivity Reactions
This change affects Section 6.3.9:  Infusion-reactions and Hypersensitivity Reactions, 
regarding new information on post-infusion observation time for potential 
hypersensitivity reactions for the first two infusions.
Add:
In the post-marketing setting, delayed onset of symptoms of acute hypersensitivity 
reactions has been observed. Subjects should remain under clinical supervision for 3 
hours after completion of the first 2 infusions. Should symptoms of acute 
hypersensitivity occur, an extended period of monitoring may be appropriate, based on 
clinical judgment.  Subjects should be made aware of the potential risk, the signs and 
symptoms of such reactions, and the importance of immediately seeking medical 
attention. 
Rationale:  The protocol has been modified to require that subjects remain under clinical 
supervision for 3 hours after completion of the first 2 infusions. This change has been 
made to all upcoming trials of intravenous belimumab in adult subjects in order to 

YM2010/00145/03
CONFIDENTIAL
BEL114333
121
provide a longer period of post infusion monitoring and to prospectively collect more 
precise data on hypersensitivity reactions. A broad review of spontaneous safety reports 
received as of January 2012 identified 18 serious hypersensitivity reactions for an 
estimated reporting rate of 0.4%. Of these events, all occurred with the 1st or 2nd infusion 
(where infusion number is known, 15) and the vast majority occurred during or shortly 
after completion of the infusion. Five cases appear to have been delayed in onset beyond 
1 hour after completion of the infusion (n=3) or recurred after initial resolution of initial 
early symptoms (n=2). Given the nature of postmarketing reporting, details surrounding 
these events are limited and precise information with respect to time of onset of initial 
symptoms relative to the infusion is not available. This clinical trial, as well as other 
upcoming clinical trials, provides an opportunity to better characterize the 
hypersensitivity reactions observed with belimumab, including signs and symptoms and 
time to onset. The protocol-defined minimum monitoring period is applied only to the 
first 2 infusions because it is with these infusions that the vast majority of 
hypersensitivity reactions have been observed. For all subsequent infusions, subjects 
should be monitored during and for an appropriate period of time after infusion according 
to site procedures/clinical judgment.
This will also maintain the blind in the parent study BEL113750. 
Change 8:  Appendix 5:  Clinical Laboratory Tests
This change affects Section 11.5:  Appendix 5:  Clinical Laboratory Tests; Biological 
Marker:  BLyS protein, and Autoantibody:  aCL.
Remove:
BLyS protein and aCL
Rationale:  These 2 laboratory tests are not obtained in this extension study