Conditions: Systemic Lupus Erythematosus
Keywords: SELENA belimumab Lupus systemic lupus erythematosus PGA BLys SLE Flare Index continuation phase III BILAG extension efficacy SRI B cell SLEDAI safety Asia B lymphocyte
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 142
Healthy volunteers: no

Brief summary:
This study provides subjects who complete the BEL113750 study and subjects who complete the open-label extension of HGS1006-C1115 (referred to as C1115) Study in Japan the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their standard of care SLE therapy.

Detailed description:
This is a multicentre, continuation study of belimumab plus standard of care (SOC) in SLE subjects who completed the Phase III BEL113750 protocol in Northeast Asia or who completed the open-label extension of the HGS1006-C1115 protocol in Japan. This study provides subjects who complete the BEL113750 study the option of continuing treatment with belimumab (10 mg/kg intravenously every 4 weeks) for those randomized to belimumab, or the option to begin treatment with belimumab for those randomized to placebo, as an add-on to their SOC SLE therapy. Subjects participating in this continuation protocol will continue to be monitored for safety and efficacy, as measured by the SLE responder index. 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 4 weeks. 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.

Arms:
arm 1: Belimumab 10 mg/kg administered intravenously every 4 weeks. All study subjects will receive standard SLE therapies during the study. Subjects will continue to receive belimumab treatment until such time 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.

Interventions: intervention 1: Belimumab
Intervention descriptions: intervention 1: 10 mg/kg administered intravenously over 1 hour every 4 weeks

Protocol document:
Prot_001.pdf: 
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.
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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 


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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


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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 


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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


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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


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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


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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


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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


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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


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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


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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).


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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.  


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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.


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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 


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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 


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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 


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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, 


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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 


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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 


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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.


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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:


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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.


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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 


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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 


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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.  


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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.


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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


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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


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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. 


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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


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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.


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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.


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
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.


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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.


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
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


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
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:


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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 


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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


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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.


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
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.


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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 


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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% 


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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


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
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


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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


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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), 


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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 


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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.


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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


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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


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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. 


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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 


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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 


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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.


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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.


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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.


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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, 


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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. 




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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 
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MG, Abramovicz,D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gül A, Levy 
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Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, 
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Shida, Y, Takahashi N, Sakamoto T, Ino H, Endo A, Hirama T. The pharmacokinetics 
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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.


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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.


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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.


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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.


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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.  


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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 


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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.


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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


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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.    


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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.


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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.  


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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 


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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 


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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 


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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)


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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).


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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


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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.


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
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.


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
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 


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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. 


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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.


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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.


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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.


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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.


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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,  


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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. 


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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). 


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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.


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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)


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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.


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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.  


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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).


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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-


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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.


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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. 


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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


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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 


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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 


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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 


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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

SAP_000.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
BEL114333
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for GSK1550188 Study 
BEL114333.  A multicentre, 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
Effective Date 
:
31-MAY-2019
Description :

The purpose of this RAP is to describe the planned analyses and output to be 
included in the final Clinical Study Report for Protocol BEL114333, which was a 
continuation study of belimumab in Japan and Korea subjects with systemic lupus 
erythematosus (SLE) who completed the phase III study BEL113750 in Northeast-
Asia or who completed the open-label extension of HGS1006-C1115 in Japan (in 
this document referred to as GSK study number BEL112341).  

This RAP is intended to describe the evaluation of the long-term safety and efficacy 
of belimumab in subjects with SLE in Japan and Korea, following completion of 
BEL113750 and BEL112341. 

This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable.
Author(s):
Author
Date
Lead
Principal Statistician, Immuno-Inflammation, Clinical Statistics
Co-Author
Senior Clinical Development Director, Immuno-Inflammation, 
Clinical
Copyright 2019 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
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The GlaxoSmithKline group of companies
BEL114333
2
RAP Team Review Confirmations
(Method: E-mail)
Reviewer
Date
31-MAY-2019
SERM Director, Immuno-Inflammation, GCSP
31-MAY-2019
Programming Manager, Immuno-Inflammation
29-MAY-2019
Clinical Pharmacology Manager, CPMS
30-MAY-2019
Project Physician Lead, Immuno-Inflammation
30-MAY-2019
Medical Writing Manager, Immuno-Inflammation, Clinical 
Development
28-MAY-2019
Clinical Development Manager, Immuno-Inflammation, PCPS
30-MAY-2019
Principal Clinical Data Scientist, Immuno-Inflammation, PCPS
Clinical Statistics and Clinical Programming Line Approvals
(Method: Pharma TMF eSignature):1
Approver
Date
31-MAY-2019
Director, Immuno-Inflammation, Clinical Statistics
31-MAY-2019
Director, Immuno-Inflammation, Clinical Programming
1     As described in the file note sign off was by email on 31-May-2019.  Details are 
found in the file note in TMF.
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CONFIDENTIAL
BEL114333
3
TABLE OF CONTENTS
PAGE
1.
REPORTING & ANALYSIS PLAN SYNOPSIS.........................................................7
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................9
2.1.
Changes to the Protocol Defined Statistical Analysis Plan ............................9
2.2.
Study Objective(s) and Endpoint(s).............................................................11
2.3.
Study Design ..............................................................................................14
2.4.
Statistical Hypotheses.................................................................................15
2.4.1.
Treatment Comparisons ..............................................................15
3.
PLANNED ANALYSES...........................................................................................17
3.1.
Interim Analyses .........................................................................................17
3.1.1.
Safety Reviews............................................................................17
3.2.
Final Analyses ............................................................................................17
4.
ANALYSIS POPULATIONS ...................................................................................17
4.1.
Protocol Deviations.....................................................................................18
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................19
5.1.
General Data Considerations......................................................................20
6.
STUDY POPULATION ANALYSES........................................................................23
6.1.
Overview of Planned Analyses ...................................................................23
6.2.
Overview of Planned Demography & Baseline Characteristics 
Analyses.....................................................................................................24
6.2.1.
Demography................................................................................25
6.2.1.1.
Baseline Disease Characteristics ...............................25
7.
SAFETY ANALYSES .............................................................................................27
7.1.
Overview of Planned Medications and Exposure Analyses.........................27
7.1.1.
Concomitant Medications.............................................................27
7.1.1.1.
Concomitant Medication Collapsing Rules..................28
7.1.2.
SLE Medications..........................................................................29
7.1.3.
Maximum Daily Prednisone Equivalent Corticosteroid 
Daily Dose Category....................................................................29
7.1.4.
Shifts in Prednisone Average Daily Dose from Baseline ..............29
7.1.5.
Extent of Exposure and Study Drug Administration......................30
7.2.
Overview of Planned Adverse Event Analyses............................................31
7.2.1.
Adverse Events............................................................................32
7.2.2.
Adverse Event Summaries...........................................................33
7.3.
Overview of Planned Adverse Events of Special Interest............................34
7.3.1.
Adverse Events of Special Interest ..............................................35
7.4.
Overview of Planned Laboratory, Immunogenicity and Vital Signs 
Summaries .................................................................................................37
7.4.1.
Clinical Laboratory Evaluations....................................................38
7.4.2.
Laboratory Parameters by Visit....................................................39
7.4.3.
Worst laboratory toxicity grade post-baseline...............................39
7.4.4.
Shift in Laboratory toxicity grade post-baseline............................39


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7.4.5.
Laboratory Reference Range Shifts.............................................39
7.4.6.
Immunogenicity............................................................................40
8.
EFFICACY ANALYSES..........................................................................................42
8.1.
Overview of SRI and Secondary Efficacy Endpoints ...................................42
8.1.1.
SRI Response Rate .....................................................................42
8.1.2.
SELENA SLEDAI 4 Point Reduction from Baseline...................43
8.1.3.
PGA No Worsening .....................................................................43
8.1.4.
BILAG No New 1A/2B Organ Domain Scores..............................43
8.1.5.
Number of Days of Daily Prednisone 7.5 mg/day and/or 
Reduced by 50% from Baseline...................................................43
8.1.6.
Time to First Severe SFI Flare.....................................................44
8.2.
Overview of Other Efficacy Endpoints.........................................................45
8.2.1.
SELENA SLEDAI Change from Baseline.....................................45
8.2.2.
SLICC/ACR Damage Index..........................................................46
8.2.3.
Physician’s Global Assessment Change from Baseline ...............46
8.2.4.
Time to First SFI Flare .................................................................46
8.2.5.
Number of SFI Flares and Rates .................................................47
8.2.6.
Time to First 1A/2B BILAG Flare..................................................47
8.2.7.
Time to First BILAG A Flare.........................................................47
8.2.8.
Time to First Renal Flare .............................................................47
8.2.9.
Proteinuria Percent Change from Baseline ..................................49
8.2.10.
Proteinuria shifts..........................................................................49
8.2.11.
Prednisone Percent Change from Baseline .................................50
8.2.12.
Prednisone Dose 7.5 mg/day for Subjects with an 
Average Daily Dose > 7.5 mg/day at Baseline .............................50
8.2.13.
Prednisone Dose > 7.5 mg/day for Subjects with an 
Average Daily Dose 7.5 mg/day at Baseline .............................50
9.
BIOMARKER ANALYSES......................................................................................51
9.1.
Overview of Planned Biomarker Analyses ..................................................51
9.1.1.
Percent change from baseline .....................................................52
9.1.2.
Immunoglobulin (IgG, IgA and IgM) below LLN............................52
10. REFERENCES.......................................................................................................53
11. APPENDICES ........................................................................................................54
11.1.
Appendix 1: Time & Events.........................................................................55
11.1.1.
BEL114333 Protocol Defined Time & Events...............................55
11.1.1.1.
Open-label Year 1 ......................................................55
11.1.1.2.
Open-Label Additional Years......................................58
11.1.2.
Parent Study Protocol Defined Time & Events.............................60
11.1.2.1.
BEL113750 - Double-Blind Phase ..............................60
11.1.2.2.
BEL112341 (HGS1006-C1115) ..................................64
11.1.2.2.1.
BEL112341 - Double-blind Phase...........64
11.1.2.2.2.
BEL112341 - Open-Label Phase ............67
11.2.
Appendix 2: Assessment Windows .............................................................69
11.2.1.
Year Intervals ..............................................................................69
11.2.2.
Belimumab Visits .........................................................................70
11.3.
Appendix 3: Adverse Event Collapsing Rules and Assignment of 
Adverse Events to Study Year ....................................................................73
11.3.1.
Adverse Event Collapsing............................................................73


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BEL114333
5
11.3.2.
Assigning Adverse Events to Study Year.....................................74
11.4.
Appendix 4: Data Display Standards & Handling Conventions....................75
11.4.1.
Study Treatment & Sub-group Display Descriptors ......................75
11.4.2.
Baseline Definition.......................................................................75
11.4.2.1.
Baseline SLE Disease Duration..................................76
11.4.2.2.
Total Number of ACR Criteria at Baseline ..................76
11.4.2.3.
SLE Flares at Baseline ...............................................76
11.4.2.4.
Derivations and Handling of Missing Baseline 
Data ...........................................................................76
11.4.3.
Reporting Process & Standards...................................................77
11.5.
Appendix 5: Derived and Transformed Data ...............................................79
11.5.1.
General........................................................................................79
11.5.2.
Study Population..........................................................................80
11.5.3.
Safety ..........................................................................................80
11.5.4.
Efficacy........................................................................................84
11.5.4.1.
SELENA SLEDAI Disease Assessment Scale............84
11.5.4.2.
BILAG.........................................................................86
11.5.4.3.
Physician’s Global Assessment (PGA) Score.............97
11.5.4.4.
SLICC/ACR Damage Index ........................................97
11.5.4.5.
SLE Flare Index..........................................................99
11.5.4.6.
Spot Urine Protein Creatinine Ratio Conversion .......101
11.5.5.
Biomarkers ................................................................................102
11.5.5.1.
B Cell Subsets..........................................................102
11.6.
Appendix 6: Premature Withdrawals & Handling of Missing Data .............107
11.6.1.
Premature Withdrawals and Completion....................................107
11.6.2.
Handling of Missing Data...........................................................107
11.6.2.1.
Handling of Missing and Partial Dates ......................107
11.6.2.2.
Handling of Missing Data for Statistical 
Analysis....................................................................108
11.7.
Appendix 7: Methods for Handling Centres...............................................109
11.7.1.
Methods for Handling Centres ...................................................109
11.8.
Appendix 8: Examination of Covariates, Subgroups & Other Strata..........110
11.8.1.
Handling of Other Strata and Covariates....................................110
11.8.2.
Handling of Subgroups ..............................................................110
11.9.
Appendix 9: Laboratory Parameters & Adverse Events Grading 
Tables.......................................................................................................111
11.9.1.
Laboratory Values......................................................................111
11.9.2.
Adverse Event and Laboratory Value Severity Grade 
Tables........................................................................................112
11.10. Appendix 10: PSAP Sections for AESI Reporting .....................................120
11.11. Appendix 11: Abbreviations & Trade Marks ..............................................132
11.11.1. Abbreviations.............................................................................132
11.11.2. Trademarks ...............................................................................133
11.12. Appendix 12: List of Data Displays............................................................134
11.12.1. Data Display Numbering............................................................134
11.12.2. Mock Example Shell Referencing ..............................................134
11.12.3. Study Population Tables............................................................135
11.12.4. Safety Tables.............................................................................138
11.12.5. Safety Figures............................................................................146
11.12.6. Efficacy Tables ..........................................................................148
11.12.7. Efficacy Figures .........................................................................151
11.12.8. Biomarker Tables.......................................................................153


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BEL114333
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11.12.9. Biomarker Figures .....................................................................155
11.12.10.ICH Listings ...............................................................................156
11.12.11.ICH Listings (Efficacy/Biomarkers).............................................160
11.13. Appendix 13: Example Mock Shells for Data Displays ..............................161


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The GlaxoSmithKline group of companies
BEL114333
7
1.
REPORTING & ANALYSIS PLAN SYNOPSIS
Overview
Key Elements of the RAP
Purpose

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol BEL114333, which was a 
continuation study of intravenous (IV) belimumab in Japan and Korea subjects 
with systemic lupus erythematosus (SLE) who completed the Phase III study 
BEL113750 in Northeast-Asia (China, Japan, Korea) or who completed the 
Phase III subcutaneous (SC) open-label extension of HGS1006-C1115
(Japanese subjects only).
In this document, HGS1006-C1115 is referred to as GSK study number 
BEL112341.
The complete results for all countries for study BEL112341 (using the SC 
formulation) and BEL113750 DB study have been previously reported.

The study (BEL114333) included Japan and Korea, while the OL extension of 
study BEL113750 included China, of which the study design was similar.  Thus, 
the reporting of OL data will be similar for both studies.
Due to process changes in China, the clinical trial permit for a separate OL 
extension was not available in time for China double-blind subjects to 
smoothly transition into study BEL114333 without interruption.

Per protocol amendment 3, study BEL114333 was extended to allow Japanese
subjects to enter, who had completed the 6 month OL extension of BEL112341, 
after receiving 52 weeks of blinded SC treatment on study BEL112341. 

The BEL114333 study RAP is intended to describe the evaluation of the long-
term safety and efficacy of belimumab in subjects with SLE in Japan and Korea.
Protocol

The BEL114333 RAP is based on the following study documents:

Protocol amendment 3 (Dated: 16/MAY/2014) of study BEL114333 (GSK
Document No. YM2010/00145/03).

Final Case Report Form (eCRF) Version 3 (dated: 17/NOV/2017).

Program Safety Analysis Plan (PSAP) for GSK1550188 Version 6 (October 02 
2018).  Note: for reporting purposes the most current version of the PSAP and 
associated MedDRA version at the time of the database release (DBR) will be 
used.  Sections of the PSAP that are relevant to reporting are given in the 
BEL114333 RAP, Appendix 10: PSAP Sections for AESI Reporting.
Primary 
Objective

The primary objective of BEL114333 is to evaluate long-term safety and 
tolerability of belimumab in subjects with SLE in Japan and Korea. 
Primary 
Endpoint

Multiple safety endpoints (SAEs, AEs, AESIs, haematology and clinical 
chemistry parameters, immunogenicity, vital signs).
Study 
Design

BEL114333 provides Japan and Korea subjects who completed study 
BEL113750 and Japan subjects who completed the open-label extension of 
BEL112341 with the option of receiving IV belimumab, as an add-on to their


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The GlaxoSmithKline group of companies
BEL114333
8
Overview
Key Elements of the RAP
standard of care SLE therapy. In this document, BEL113750 and BEL112341 
are collectively referred to as the ‘parent’ studies. All eligible subjects will 
receive IV belimumab 10 mg/kg every 4 weeks irrespective of their randomised 
treatment (placebo vs. belimumab) in the parent study. 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 provide data on long-term safety and
efficacy of belimumab in Japan and Korea.

This study is being closed as belimumab commercial supply is now available in 
Japan and Korea, and the study has met the protocol-defined criteria for 
stopping.   
Planned 
Analyses

Safety and efficacy endpoints will be assessed using counts (percentages) and 
summary statistics.

The data will be reported by years of belimumab treatment beginning at the first 
dose of belimumab, which will include subjects who received belimumab 
treatment during the parent study. See Section 2.4.1. 
Analysis 
Populations

All Japan and Korea subjects who enrolled in study BEL114333 and received at 
least one dose of open-label (IV) belimumab treatment.
Hypothesis

No formal statistical hypothesis testing.  Data from all subjects as one total 
belimumab treatment group will be presented.  Any comparisons between 
parent study randomised treatment groups will be purely descriptive.  See 
Section 2.4.1.


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9
2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.
Table 1
Changes to Protocol Defined Analysis Plan
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Study Completion Status
Section 3.1. Study Design
Study completion is defined as:

IV belimumab becomes 
commercially available in the 
respective countries.

Upon the decision of the sponsor 
to close/terminate the study. 
Definition has been revised to 
include “the subject transferred 
to a different protocol”.
The BEL114333 protocol intent 
was to include this additional 
criterion. Similar definition is 
contained within the BEL113750 
OL (China only) Phase of the 
protocol.
Safety
Section 8.1.3 Safety 
The frequency of AEs will be 
tabulated by treatment groups, 
according to the treatment 
assignment during the respective DB 
phase of study BEL113750 or
BEL112341 (C1115).  
Although the adverse events in 
this section were initially 
intended to be summarised by 
parent study randomised 
treatment groups, the safety 
data will actually be shown as 
one total belimumab group.
Similar approach to other Long-
Term Continuation (LTC) 
studies, allowing meaningful 
comparisons between study 
BEL114333 and the LTC 
studies.
Section 8.1.3 Safety 
The number of subjects with AEs and 
the incidence rate of AEs will be 
summarised in each 6-month time 
interval.  
Adverse events will be 
summarised by year interval.
For consistency with the LTC 
studies.
Section 8.1.3 Safety 
AE of Special Interest (AESI) will 
also be summarised. 
AESI (serious and non-serious) 
of scientific and medical interest 
specific for GSK are being 
reported across the Benlysta 
program.
Section 8. Data Analysis and 
Statistical Considerations.
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.
Not required. 
The data base will be locked 
once all subjects have 
completed their last visit of 
BEL114333. All data will be 
included in the BEL114333 
CSR. 


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10
Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
Efficacy
Section 8.1.1. Primary Efficacy 
Analysis and Section 8.1.2 Analysis 
of Additional Efficacy and Biomarkers
Subjects who received subcutaneous 
(SC) belimumab in the BEL112341
study before joining the BEL114333 
study will be evaluated separately.
Although the efficacy data for 
BEL112341 subjects in this 
section were to be analysed 
separately, the data will be 
combined with the data from 
subjects who received IV 
belimumab in the BEL113750 
parent study.  
There are no clinically significant 
differences in the results 
between these studies in terms 
of which formulation was used.  
Hence, the data from these 25 
SC subjects can be aggregated 
with the subjects who received 
the IV formulation, unless 
otherwise stated. *
Section 6.2.1.2 Secondary [Efficacy] 
Endpoints
Baseline will be defined as study Day 
0 of the respective studies 
BEL113750 or BEL112341. 
For subjects randomised to 
placebo during the parent study
BEL113750, baseline will be 
defined as study Day 0 of the 
study BEL114333.
For subject randomised to 
placebo in the parent study
BEL112341, baseline will be 
defined as study Day 0 of the 
open-label extension of 
BEL112341.
For consistency with the LTC 
studies, baseline is defined as 
the last available value prior to 
the initiation of treatment with 
belimumab. No additional 
analyses are planned as 
mentioned in the protocol, for 
placebo.
  
Section 6.2.1.1 Primary Endpoint
The SRI response is defined as the 
primary efficacy endpoint. 
The primary SRI response 
endpoint will be regarded as a 
key secondary endpoint for the 
study BEL114333. 
The primary objective of the 
study BEL114333 is safety. 
Efficacy is considered as a 
secondary outcome.
Section 6.2.1.2 Secondary [Efficacy] 
Endpoints
PGA and BILAG components of 
the SRI response endpoint were
added.
Additional analyses are being 
reported to enable the long-term 
data to be further evaluated. 
Section 6.2.1.2 Secondary [Efficacy] 
Endpoints
Number of days of daily prednisone 
dose 7.5 mg/day and/or reduced by 
25% from baseline over time.
The threshold of a 25% 
reduction has been revised to 
50%.
For consistency with the 
BEL113750 parent study 
definition of this endpoint.  This 
endpoint was not considered in 
the parent study BEL112341.
Section 6.2.1.3 Other [Efficacy] 
Endpoints
Duration of primary response [SRI] 
assessed every 24 weeks.
This endpoint has been 
removed. 
Because the investigator has 
much more freedom in 
prescribing concomitant 
medications during the OL 
continuation study BEL114333, 
this could potentially confound 
evaluating the duration of the 
SRI response.  
Section 6.2.1.3 Other [Efficacy] 
Endpoints
The following efficacy endpoints 
were added:

Change and percent 
Additional analyses are being 
reported to enable the long-
term, data to be further 


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Protocol
Reporting & Analysis Plan
Statistical Analysis Plan
Statistical Analysis Plan
Rationale for Changes
change from baseline in 
SELENA SLEDAI.

SLICC/ACR Damage Index 
Worsening from baseline.
evaluated.
Section 6.2.1.3 Other [Efficacy] 
Endpoints
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 criteria (not shown here) in 
2 or more consecutive visits during 
the study. See RAP, Section 8.2.8, 
for details of the criteria.
The renal flare definition has 
been revised for study 
BEL114333, as the occurrence 
of one or more of the following 
criteria (not shown here) at a 
single visit in which 
assessments are performed.
Assessments every 6 months 
during study BEL114333 will not 
allow the use of the same 
definition of renal flares as in the 
respective parent studies, which 
requires assessments to be 
performed at 2 or more 
consecutive monthly visits.
Section 8.1 Data Analysis 
Considerations
Although the efficacy data will 
be tabulated by parent study 
randomised treatment groups, 
as mentioned in the protocol, the 
graphical displays will be shown 
for the total Safety population
only.
The graphs align with the 
interpretation of response over 
time rather than comparisons 
between treatment groups.
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints
Evaluate long-term safety and tolerability 
of belimumab in subjects with SLE in 
Japan and Korea 
The endpoints below will be used to assess this study 
objective.
Adverse events (AEs)

Frequency and percentage of subjects with events.

Event rates adjusting for person-years on study agent.
Laboratory Parameters

Observed and Change from Baseline by visit.

Laboratory reference shifts from baseline by visit.

Laboratory toxicity worsening of at least two grades from 
baseline by study year

Grade 3 or 4 laboratory abnormalities by visit and study 
year.
Immunogenicity

Immunogenic response (anti-belimumab anti-bodies) by 
visit and study year.
Biomarkers


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Objectives
Endpoints

Percent change from baseline in immunoglobulins, auto-
antibodies, and complement levels by visit.

Immunoglobulin values below the lower limit of normal by 
visit and study year.

Percent change from baseline in absolute B cell subsets.
Secondary Objectives
SRI and Other Secondary Endpoints
Evaluate the long-term efficacy of 
belimumab in subjects with SLE in Japan 
and Korea

SRI response rate at each scheduled visit when complete 
efficacy evaluations occur (e.g., Week 24 and Week 48 
for each year). An SRI 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

No new BILAG A organ domain score or 2 new 
BILAG B organ domain scores compared with 
baseline at the time of assessment. 

Percent of subjects with 4 point reduction from baseline 
in SELENA SLEDAI score assessed every 24 weeks

Percent of subjects with No Worsening in PGA compared 
to baseline (added to the RAP)

Percent of subjects with No new BILAG A organ domain 
or 2 new BILAG B organ domain scores compared to 
baseline (added to the RAP)

Number of days of daily prednisone dose 7.5 mg/day 
and/or reduced by 50% from baseline over time.

Time to first severe SLE Flare Index (SFI) flare assessed 
over time.
Other Efficacy Endpoints
Disease Activity

Absolute change and percent change from baseline in 
SELENA SLEDAI (added to the RAP)

Change in Systemic Lupus International Collaborating 
Clinics (SLICC)/ACR Damage Index assessed every 24 
weeks.

SLICC/ACR Damage Index Worsening from baseline 
(added to the RAP).

Percent change from baseline in PGA assessed every 24 
weeks.
Flares

Time to first SFI flare assessed over time.

Time to first 1A/2B BILAG flare assessed over time.

Time to first BILAG A flare assessment over time.
Organ-specific measures

Renal flare rate and time to first renal flare assessed over 


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Objectives
Endpoints
time.

Percent change from baseline 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.


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2.3.
Study Design
Overview of Study Design and Key Features
Design
Features

Multicentre, open-label, continuation study of intravenous (IV) belimumab plus 
standard of care in Japan and Korea subjects with SLE who completed the 
Phase III study BEL1123750 in Northeast-Asia or who completed the Phase III 
study SC open-label extension of BEL112341 (Japan subjects only).
o The complete results for all countries for BEL112341 (using the SC 
formulation) and study BEL113750 have been previously reported.

Subjects in Japan and Korea randomised to placebo in the parent study 
BEL113750 began IV belimumab in BEL114333. Those initially randomised to 
belimumab in the parent study BEL113750 will continue IV belimumab. 

Subjects in Japan randomised to placebo in parent study BEL112341 began 
SC belimumab in the open-label phase extension of BEL112341 and then 
changed to IV belimumab in BEL114333.  Those initially randomised to SC 
belimumab in the parent study BEL112341 changed to IV belimumab at the 
start of BEL114333.

Subjects no longer receiving belimumab after their exit visit are expected to 
return for follow up visits. A 6 month FU visit was included for Japan in order to 
obtain B cells. However, immunogenicity draws at the 6 month FU visit were 
only obtained if there were positive immunogenicity results at the prior 16 week 
FU visit.  Korean subjects were not required to collect B cells at the 6 month 
FU visit.  Korea however only had 6 month FU visits scheduled for those 
subjects with prior positive immunogenicity results at the 16 week FU visit.
Dosing

Belimumab 10 mg/kg IV infused over 1 hour every 28 days as add-on therapy 
to standard of care.


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Overview of Study Design and Key Features

The first dose in BEL114333 must be given 4 weeks (minimum of 2 weeks, 
maximum of 8 weeks) after the last IV dose for subjects enrolled from the 
parent study BEL113750. For subjects from the SC parent study BEL112341, 
the first IV dose in BEL114333 is targeted for 1 week after the last dose of SC 
belimumab (scheduled for Week 23 in the OL extension part of BEL112341).

If a subject misses 3 or more consecutive infusions during BEL114333, they 
should be withdrawn from the study. 
Time & 
Events

Refer to Appendix 1: Time & Events
Treatment 
Assignment

Open-label – all subjects will receive IV belimumab
Interim 
Analysis

None
2.4.
Statistical Hypotheses
Since this is an open-label continuation, no formal statistical hypothesis testing will be 
performed.  Any comparisons between the parent study randomised treatment groups will 
be purely descriptive.
2.4.1.
Treatment Comparisons
All subjects will be treated with open-label IV belimumab for the duration of the study 
BEL114333. The analyses will be performed on data from all subjects as one total 
belimumab treatment group by year of belimumab treatment.
As subjects started to receive belimumab treatment in the parent study, or the open-label 
extension of the parent study BEL112341, or the open-label study BEL114333, different 
time points to start of belimumab treatment will be used to define subject follow up in the 
analysis. See Figure 1.
Analyses will be based on all available follow-up from the first dose of belimumab 
treatment through to study end.
Additional safety (e.g., labs), efficacy and study population summaries will be presented 
by parent study randomised treatment groups (belimumab vs placebo); however, these 
comparisons will be descriptive in nature.  For the remainder of the document, parent 
randomised treatment group will be used to refer to the treatment to which a subject was 
randomised in the parent study, irrespective of formulation.


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Figure 1
First Belimumab Dose/Baseline Definition


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3.
PLANNED ANALYSES
3.1.
Interim Analyses
To date, no interim analyses pertaining to open-label safety data has been required to 
support regulatory submission activities for Japan, Korea and China.
3.1.1.
Safety Reviews
The SRT regularly performs in stream data looks of the pooled open-label data from 
BEL114333, Japan and Korea subjects, and BEL113750, China subjects, to monitor the 
safety of these studies.  These reviews are based on data from all subjects as one 
belimumab treatment group.  
Additionally, the SRT performs in stream adjudication of subject-level data for Adverse 
Events of Special Interest (AESIs; serious and non-serious).   See Appendix 10: PSAP 
Sections for AESI Reporting.. 
3.2.
Final Analyses
Korean sites in BEL114333 were closed in 2015 (per the protocol-defined stopping 
criteria) because of approval and the commercial availability of Benlysta in Korea. The 
last subject visit in Korea was 27 April 2015.
The data base can be locked since all Japan and Korea subjects have completed their last 
visits of BEL114333.  All Japanese subjects completed their latest visit, as appropriate, 
up to 6-month post-treatment follow-up visit.  The 6-month FU serves as the last subject 
last visit.  The last subject visit in Japan was on 13 September 2018.
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All subjects have completed the study as defined in the protocol.
2.
All required database cleaning activities have been completed and final database 
release and database freeze has been declared by Data Management.
4.
ANALYSIS POPULATIONS
All Subjects

Japan and Korea subjects who were randomised in the 
DB 52-week parent study BEL113750.  Additionally,
participation in BEL114333 was extended to Japanese
subjects in the parent study BEL112341, of which 30 
subjects were randomised at the beginning of 
BEL112341 (but only 27 remained to enter the open-
portion of BEL112341). A total of 25 of these 27 
subjects elected to join BEL114333; the other 2 did not 
elect to join BEL114333.  

This population, and all subsequently defined 

Enrolment and 
Population level 
displays for patient 
disposition


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populations below, will be based on data from all 
subjects as one total belimumab treatment group.  
Additional summaries will be presented by the parent 
randomised treatment groups.  See Section 2.4.1.  
Screened 

All subjects in the All Subjects population who 
completed the parent studies BEL113750 (Japan and 
Korea) or BEL112341 (Japan only) and were eligible to 
enrol in BEL114333.

Study Population
Enrolled

All subjects who enrolled in BEL114333. 

Disposition-level 
displays
Safety

All subjects in the Enrolled population who received at 
least one IV dose of belimumab during BEL114333. 
Analyses will be based on all available follow-up from 
the first dose of belimumab treatment through to study 
end.  See Section 2.4.  As such exposure data to 
belimumab will be included for subjects who received 
their first dose in the parent study, and subsequently 
enrolled in BEL114333.  
Note: although the OL analysis for Japan and Korea will 
be based on the Safety population, the definition is the 
same as the Efficacy population used for China (which 
excluded subjects from one site).  

Safety/Efficacy
analyses and 
displays
Refer to Appendix 12: List of Data Displays which details the population used for each display.
4.1.
Protocol Deviations

Important protocol deviations (including deviations related to study inclusion/
exclusion criteria, conduct of the trial, patient management or patient assessment) 
will be summarised and listed.  Note, only important protocol deviations that 
occurred during BEL114333 will be reported.  

Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan Version 3 (dated: 
June 21, 2017).  
–
Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset. 
–
This dataset will be the basis for the summaries and listings of protocol 
deviations.

A separate summary and listing of all inclusion/exclusion criteria deviations for 
BEL114333 will also be provided. This summary will be based on data as recorded 
on the inclusion/exclusion page of the eCRF.


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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS
Table 2 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions. 
Table 2
Overview of Appendices
Section
Component
11.1
Appendix 1: Time & Events
Section 11.1.1: BEL114333 Protocol Defined Time & Events
Section 11.1.2:  Parent Study Protocol Defined Time & Events
11.2
Appendix 2: Assessment Windows
Section 11.2.1:  Year Intervals
Section 11.2.2:  Belimumab Visits
11.3
Appendix 3: Adverse Event Collapsing Rules and Assignment of Adverse Events to 
Study Year
Section 11.3.1:  Adverse Event Collapsing
Section 11.3.2:  Assigning Adverse Events to Study Year
11.4
Appendix 4: Data Display Standards & Handling Conventions
Section 11.4.1:  Study Treatment & Sub-group Display Descriptors
Section 11.4.2:  Baseline Definition
11.5
Appendix 5: Derived and Transformed Data
Section 11.5.1:  General
Section 11.5.2:  Study Population
Section 11.5.3:  Safety
Section 11.5.4:  Efficacy
Section 11.5.5: Biomarkers
11.6
Appendix 6: Premature Withdrawals & Handling of Missing Data
Section 11.6.1:  Premature Withdrawals and Completion
Section 11.6.2:  Handling of Missing Data
11.7
Appendix 7: Methods for Handling Centres
11.8
Appendix 8: Examination of Covariates, Subgroups & Other Strata
Section 11.8.1:  Handling of Other Strata and Covariates
Section 11.8.2:  Handling of Subgroups
11.9
Appendix 9: Laboratory Parameters & Adverse Events Grading Tables
Section 11.9.1:  Laboratory Parameters
Section 11.9.2:  Adverse Event and Laboratory Value Severity Grade Tables
11.10
Appendix 10: PSAP Sections for AESI Reporting.


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5.1.
General Data Considerations

This is a multi-centre study in Japan and Korea. There are no planned adjustments 
made for multiple centres or regions.

As no formal hypotheses are being tested, there are no planned adjustments for 
multiple comparisons or multiplicity. 

As all subjects will be treated with belimumab and there are no hypothesis tests, no 
additional strata or covariates will be employed in the analyses.  Subgroups will be 
defined for further exploration of the data in a descriptive fashion.

Reporting of data is by year of belimumab treatment beginning on the date when 
subjects received their first dose of belimumab, irrespective of the formulation
(Section 2.4.1 and Section 11.2.1).  

Baseline is defined as the last available value prior to the initiation of treatment with 
belimumab and will henceforth be referred to as ‘Belimumab baseline’. See Appendix 
4: Data Display Standards & Handling Conventions for more details on baseline 
definitions.

For summaries performed by belimumab visit, placebo subjects are aligned based on 
start of exposure to belimumab (see Section 11.2.2 for details of the visit mapping). 
Note, for BEL114333, subjects randomized to belimumab in the parent study were 
off-set by an additional 4 weeks compared to the open-label visit schedule, in order to 
complete the final assessments at the parent study Week 52 visit.  Therefore, the 
mapping was adjusted in order to align the ensuing open-label visits. This was 
achieved by mapping the parent study Week 52 visit to the Belimumab Visit Year 1 
Week 48 (and dropping the parent study Week 48).  Ongoing open-label visits will 
always align.
Note, for subjects ongoing in BEL114333 at the time of study end, there is one year 
off-set between the parent randomised treatment groups until the last dose was 
administered in March 2018.  Data for the last year will be limited to the belimumab 
group.  

There is a single data base that captures both parent study (i.e. DB phase of 
BEL113750) and open-label data for study BEL113750.  The dividing line between 
parent study and open-label data is determined by the Day 365 visit.  Any new data 
after this visit is regarded as open-label.  
Note, after the database was frozen for the parent study analysis (DB data), technical 
limitations required the entire data base to be open in order to enter open-label 
information. Thus, sites had the ability to also change data pertaining to the parent 
study.  

A complete BEL113750 database extraction will be performed (because the 
DB data will be used in the open-label analyses). Note, there are differences 
between the prior DB data extraction by a different vendor/format and the 
open-label data. The complete extraction will enable all the data to be 
compatible.     


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
The complete extraction will be able to include any additional parent study 
information (e.g., SAEs, concomitant meds) entered by sites at any time from 
the start of the parent study, and will be included in aggregate reporting.   
Note any additional SAEs will also be mentioned separately in the open-label 
phase CSR.  
The same database captures data for BEL114333.  Similarly, the BEL114333 sites 
had the ability to also change data pertaining to the parent study BEL113750, per the 
above

From the complete database, a selected data extraction of the BEL114333 data 
will be performed

The DB data for Japan and Korea subjects will be extracted from the complete 
BEL113750 data (previously used for the BEL113750 – China OL analysis).  
Lastly, the BEL112341 Japan subjects who entered BEL114333 will have all relevant 
data extracted from the complete BEL112341 database. 
All relevant belimumab data from the parent studies and study BEL114333 will be 
aggregated.
   
Unless otherwise stated, the following statistics will be used to summarise the data:

Continuous Variables: n, mean, standard deviation (SD), median, 25th & 75th
percentiles, minimum and maximum.

Categorical Variables: n, frequency counts and percentages. 
Unless otherwise stated, the following rules will be implemented: 

Summaries by Visit: Only scheduled visits will be presented (i.e. that correspond 
to the timings of the open-label visits for BEL114333). Otherwise data not shown 
here will be displayed in listings, and used in derivations such as “any time post-
baseline” summaries for laboratory data, time to event, etc.  Exit visits will be 
slotted to the next 6 monthly scheduled visit for that year for efficacy endpoints
(or next 12 monthly scheduled visit for SLICC). Otherwise, data will be 
summarised per the nominal visit. 

Due to the additional 6 month OL extension for SC subjects entering BEL114333, 
there is a 6 month off-set in the data capture between the parent studies.  As a 
result, for SLICC, immunoglobulins and B cell subsets, captured on an annual 
basis in BEL114333, the data captured at each analysis visit stratifies by parent 
study. As such these endpoints will be tabulated by parent study, and the data will 
not be aggregated.

Summaries by belimumab Treatment: Data will be mapped to the year by 
windowing starting at the time of first belimumab treatment.


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
Listings: If endpoints reported, data will be presented in listings as required.

Figures: error bars will be displayed.
Unless otherwise stated, no imputation for missing values will be conducted. 


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6.
STUDY POPULATION ANALYSES
The study population analyses will be based on the Safety population, unless otherwise 
specified.
6.1.
Overview of Planned Analyses
Table 3 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 12: List of Data Displays.
Table 3
Overview of Planned Study Population Analyses
Display Type
Data Displays Generated
Table
Figure
Listing
Subject Disposition
Subject Enrolment (All Subjects Population)
Y [1] [2]
Enrolment by Site
Y [1]
Belimumab Treated Subject-Years on Study
Y [3]
Subject Disposition (All Enrolled Subjects Population)
Y [4]
Reasons for Study Withdrawal
Y [5]
Study Completion Status per Protocol
Y [6]
Y [7]
Time to Withdrawal Prior to Study Closing
Y [8]
Y [8]
Subject Completion Status per Protocol by Year Interval
Y [9]
Inclusion/Exclusion Criteria
Inclusion/Exclusion Criteria Deviations 
(All Enrolled Subjects Population)
Y [1]
Y
Protocol Deviations
Subjects with Important Protocol Deviations
(All Enrolled Subjects Population)
Y [1]
Y
NOTES :

T = tables, F = Figures, L = Listings, Y = Yes display generated.
[1]
Summarised by parent randomised treatment group and the total population. 
[2]
Summarises No. (%) of Japan and Korea subjects randomised & completed parent study BEL113750, and 
those subjects who were enrolled and included in the Safety population for BEL114333.  Additionally, Japan 
subjects from BEL112341 are also summarised.  
[3]
Summarises person-years and cumulative person-years for time on belimumab treatment by year interval and 
parent randomised treatment group, and person-years for at any time post-baseline up to a subject’s final 
contact.  See Section 11.5.1 for definition of final contact.
[4]
Summarises subject disposition per End of Treatment CRF page as determined by the investigator. Note, the 
CRF page does not include an option for selecting study completion. Thus, all subjects were indicated as being 
withdrawn.   
[5]
Listing indicates reasons and time of withdrawal per End of Treatment CRF page (see footnote 4).
[6]
Summarises study completion status per protocol (completed, death, withdrawn [and reasons for withdrawal]).  
See Section 11.6.1 for definition of study completion.
[7]
Listing indicates subject completion status (see footnote 6) and whether subjects are included in analysis 
populations.
[8]
Kaplan-Meier plot of time (in days) to withdrawal (see footnote 6 for definition of withdrawal) and associated 
summary table. See Section 11.5.1 for derivation of time to withdrawal. Note: subjects who died or completed 
the study per the protocol, will be censored.
[9]
Summarises No. (%) of subjects starting each year interval, and of those, the number completed, died and 
withdrawn [and reason for withdrawal], or ongoing in the study at the end of that year interval. Will be 
summarised using frequencies and percent.  The denominator for each year will be the number of subjects who 
started each year of treatment.


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6.2.
Overview of Planned Demography & Baseline 
Characteristics Analyses
Table 4  provides an overview of the planned demography and baseline characteristics 
analyses, with full details of data displays being presented in Appendix 12: List of Data 
Display.
Table 4
Overview of Planned Demography & Baseline Characteristics & 
Medical History Analyses
Display Type
Data Display’s Generated
Table
Listing
Demography & Baseline (BL) Characteristics
Demographics & BL Characteristics 
Y 
Y (x6) [3]
Demographics & BL Characteristics by Age Group (< 65 vs ≥ 65 years)
Y (x2) [1]
Demographics & BL Characteristics by Sex (Male vs Female) 
Y (x2) [1]
Demographics & BL Characteristics by BL SELENA SLEDAI (≤9 vs ≥10) 
Y (x2) [1]
Summary of Age Ranges (All Enrolled Subjects Population)
Y
Race and Racial Combination Details (All Enrolled Subjects Population)
Y
Y
Medical History
Medical History
Y [4]
Baseline Disease Activity
Baseline Disease Activity
Y
Baseline Disease Activity by Age Group (< 65 vs ≥ 65 years)
Y (x2) [1]
Baseline Disease Activity by Sex (Male vs Female) 
Y (x2) [1]
Baseline Disease Activity by BL SELENA SLEDAI (≤9 vs ≥10) 
Y (x2) [1]
Other Baseline
Allowable SLE Medication Usage at Baseline
Y
ACR Classification Criteria at Parent Study Baseline
Y
SELENA SLEDAI Organ & Item Involvement at Baseline
Y
BILAG Grade by Organ Domain at Baseline
Y
Complement Levels at Baseline
Y
Autoantibody Levels at Baseline
Y
Immunoglobulin Levels at Baseline
Y [2]
B Cells at Baseline (Japan Only)
Y


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NOTES:

BL= Baseline, T = Tables, L = Listings, Y = Display Generated, (xN) = Number of separate displays generated
[1]
Separate displays generated for each sub-group level.
[2]
Parameters summarised: IgG, IgM and IgA. 
[3]
Separate listings generated for [A] Demographic Characteristics [B] Anti-dsDNA, ANA, Complement Levels and 
SLE Medication Use [C] Disease Duration, PGA, SLICC/ACR Damage Index and Proteinuria Results [D] SELENA 
SLEDAI Results [E] BILAG Index Results [F] SLE Flare Index.
[4]
Medical history data were collected at screening of the parent studies. The baseline definitions for the parent 
randomised treatment groups are different for the open-label analysis. See Figure 1. Thus, for subjects who were 
randomised to placebo in the parent study, any AEs with end dates prior to the first open-label belimumab dose 
(i.e. either in BEL112341 open-label extension or BEL114333), will be included as medical history terms. For 
subjects who were randomised to belimumab in the parent study, any AEs that started before the first belimumab 
dose in the parent study, will be included as medical history terms; any AEs that started on or after the first 
belimumab dose with end dates during the parent study will be summarised as AEs.
6.2.1.
Demography
Baseline measurements for subjects are defined in Section 11.4.2. Data presentations will 
be summarized by parent randomized treatment group and overall.
Descriptive statistics will be used to summarize the continuous demographic and baseline 
characteristics of age at start of belimumab treatment (years), height (cm), weight (kg), 
BMI (kg/m2).
Counts (%) of the following categorical demographic and baseline characteristics will be 
presented:  sex, race, race category, ethnicity.
The summary of demographic and baseline characteristics will be repeated for subgroups, 
where the subgroup categories are defined in Appendix 8: Examination of Covariates, 
Subgroups & Other Strata.
6.2.1.1.
Baseline Disease Characteristics
A summary of baseline disease activity will be provided, including counts and 
percentages for categorical endpoints defined in Table 5.
Descriptive statistics for the continuous scores will be presented for SELENA-SLEDAI, 
PGA and SLICC/ACR Damage Index.  The summary of baseline disease activity will be 
repeated for subgroups.  Refer to Appendix 8: Examination of Covariates, Subgroups & 
Other Strata.
Table 5
Baseline Disease Endpoints
Endpoint
Categories
BILAG Organ Domain Involvement
At least 1A or 2B, At least 1A, At least 1B, No A or B [1]
SELENA-SLEDAI
≤ 9 or ≥10
SLE Flare Index
No flare, At least 1 flare, At least 1 severe flare [2]
PGA 
0 to 1, >1 to 2.5 or > 2.5
SLICC/ACR Damage Index
0, 1 or >1
Baseline Proteinuria (measured by spot 
urine protein creatinine ratio mg/mg)
≤ 0.5 or > 0.5
Subcategories of > 0.5 mg/mg: >0.5 to < 1, 1 to < 2 or ≥ 2


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26
NOTES:
[1]
“No A or B” is to mean “Neither A nor B”, equivalently, “No A and No B”, and not “No A or No B”.  A footnote 
should be added to the SAS output.
[2]
See Section 11.4.2.3 for derivation of flare categories.
Table 6 provides indicators of baseline disease activity that will also be summarized.
Table 6
Baseline Indicators of Disease Activity
Baseline Indicator
Categories & Summaries at Baseline
SLE Disease Duration (yrs)

Summary statistics
ACR Classification Criteria

Count (%) with each symptom present and total at 
baseline, and total number of ACR criteria met. 
NOTE: ACR classification is collected at screening of the 
respective parent studies, and therefore based on parent 
study screening assessment.
SELENA-SLEDAI category

Count (%) for each organ domain and item present.
BILAG

Count (%) of each A – E score by organ domain.
Autoantibody Levels (anti-dsDNA, ANA)

Count (%) for negative and positive (Anti-ds DNA: ≥30 
IU/ml & ANA ≥0.80 Index [BEL113750] or ANA ≥ 80 Titer 
[BEL112341]) 

Summary statistics for positive Anti-dsDNA and positive 
ANA.
Complement Levels (C3, C4)

Summary Statistics.

Low, Normal, and High C3
o
C3 count (%) of low (< 90 mg/dL), normal, and 
high (> 180 mg/dL)

Low, Normal, and High C4
o
C4 count (%) of low (< 10 mg/dL), normal, and 
high (> 40 mg/dL).
Immunoglobulin Levels (IgG, IgA, and 
IgM [g/L])

Summary statistics.

Count (%) below the lower limit of normal (LLN) and above 
upper limit of normal (ULN).  See Section 11.5.5 for 
definitions.
Allowable SLE Medication Usage

Counts (%) by class for: Steroid only, Immunosuppressant 
only, Anti-malarial only, Steroid and Immunosuppressant 
only, Steroid and Anti-malarial only, Immunosuppressant 
and Anti-malarial only, Steroid, Immunosuppressant and 
Anti-malarial only.

Counts (%) for preferred term within drug class (Steroid, 
Other Immunosuppressant/immunomodulatory Agents, 
Anti-malarial, NSAIDs and Aspirin).
Average daily prednisone dose (mg/day) 
at baseline

Summary statistics.

Counts (%) for dose categories: 0, >0 to 7.5, >7.5 to 40 
and >40 mg/day


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7.
SAFETY ANALYSES
The safety analyses will be based on the Safety population, unless otherwise specified.  
7.1.
Overview of Planned Medications and Exposure Analyses
Table 7 provides an overview of the planned analyses of medications and exposure, with 
full details of data displays being presented in Appendix 12: List of Data Displays.  
Table 7
Overview of Planned Medications & Exposure
Display Type
Absolute
Summary
Individual
T
F
L
Medications
Concomitant Medications by ATC Level 1 & ATC Level 4 Term
Y 
Y [1]
Concomitant Medications by ATC Level 4 & Preferred Term
Y 
Y [1]
Concomitant Procedures/Surgery
Y
SLE Medication Use by Year Interval
Y
Prednisone and Other Corticosteroids by Year Interval
Y [2]
Prednisone Dose Shifts from BL by Visit
Y
Y
Exposure
Study Drug Exposure
Y 
Y
Study Drug Administration
Y
NOTES:

BL = Baseline, T = Table, F = Figure, L = Listing, Y = Yes display generated, (xN) = number of separate displays 
generated.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represent L related to any displays of individual subjects observed raw data.
[1]
Listing by ATC code 1 and 4, Preferred and verbatim term.
[2]
Maximum Daily Prednisone Equivalent Corticosteroid Daily Dose Category
7.1.1.
Concomitant Medications

Concomitant medications are defined as medications that started on or before the first 
dose of belimumab treatment, which continued during the belimumab treatment 
period, or medications that started after the first belimumab dose. See Section 11.6.2
for details of handling missing and partial dates. 

Summaries will be performed by the parent randomised treatment group and the total 
Safety population.

Concomitant medications in BEL114333 will be coded and reported based on the 
current version of the GSK Drug Dictionary (version 1.6) at the time of study 
reporting (study BEL114333). To comply with fulfilling any PMDA regulations, the 
concomitant medications will also be coded using the WHO-DRUG dictionary.  
Outputs using the WHO-DRUG dictionary will be produced on request.


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NOTE: the same version of the GSK Drug Dictionary which was used at the time of 
reporting the parent studies will be used for this current reporting (BEL113750, 
version 1.4; BEL112341, version 1.3).  Any major coding discrepancies between
different versions of GSK Drug can be addressed in a CSR appendix, if necessary.  
o
WHO coded medications will not be provided for BEL112341 because the 
BEL112341 reporting predates the PMDA regulations requiring WHO 
coded data. The BEL112341 data were only coded using GSK DRUG at 
the time of reporting (CSR effective date 26 Sep 2016).  WHO coded 
medications will be provided for BEL113750.
Note: medications which do not have pharmacological properties are not coded to
ATC descriptions, and therefore, will be assigned programmatically to an ATC Level 
1 term of “PHARMACOLOGICAL PROPERTIES CANNOT BE REFERENCED”. 
These medications are identified by a blank ATC Level 1 term (CMATC1).
For summaries performed by ATC Level 4, medications that have no ATC Level 4 
term, will be summarised according to the lowest ATC level categorisation based on 
the level of specificity of the medication therapeutic action.

Listings of concomitant medications will be presented. 
7.1.1.1.
Concomitant Medication Collapsing Rules

Concomitant medications were collected in both the parent studies and study 
BEL114333.

Due to the ongoing nature of some concomitant medications at the end of the parent 
study, some medications occur in both the parent study and study BEL114333.

The following table shows where medications reside by their relationship to the 
parent study exit date or Year 1 Day 0 visit of the BEL114333 study.
Medication Occurrence
Database
CM starts and ends on/before parent study Exit Visit.
Parent study only
CM starts on/before Exit Visit in the parent study and ends either 
on/after Year 1 Day 0 of BEL114333, or after the Exit Visit but 
before Year 1 Day 0 of BEL114333 (where there is a gap 
between these visits). 1
Parent study and BEL114333 2
CM starts after Exit Visit of the parent study and ends before Year 
1 Day 0 of BEL114333 (where there is a gap between these 
visits). 
BEL114333 only 
CM starts after Exit Visit of the parent study and ends on/after 
Year 1 Day 0 of BEL114333 (where there is a gap between these 
visits). 
BEL114333 only
CM starts and ends on/after Year 1 Day 0 of BEL114333.
BEL114333 only 


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1 Records to be collapsed.
2 Ongoing concomitant medications (CM) in the parent study BEL112341 were entered by site in the BEL114333 eCRF.  Ongoing 
CMs in the parent study BEL113750 were programmatically added to the BEL114333 data transfer.    

Medications that occur in both the parent study and BEL114333 will be collapsed 
based on the following dataset attributes: GSK Drug Preferred Term, medication start 
date, dose, unit, frequency, route and reason/indication. 
o
Medication end date should reflect the final date in BEL114333, as 
appropriate.
7.1.2.
SLE Medications

Corticosteroids, anti-malarials, other immunosuppressive/immunomodulatory agents, 
NSAIDs and Aspirin will be categorized based on the coded preferred terms, and 
summarized by yearly interval using frequencies (%).

For summaries, all corticosteroids taken during belimumab treatment are converted to 
a prednisone equivalent dose (mg/day).  This then can be used for the derivation of 
average daily dose, see Appendix 5: Derived and Transformed Data.

Use of prednisone or other corticosteroids during the study were collected as a 
running log with other concomitant medications, and will be summarized using dose 
level categories: 0, > 0 to 7.5 or > 7.5 to 40, and > 40 mg/day.
7.1.3.
Maximum Daily Prednisone Equivalent Corticosteroid Daily Dose 
Category
Prednisone equivalent corticosteroid daily dose will be mapped to belimumab visits 
occurring at Year 1 Day 0, as well as weeks 24 and 48 for each year per the definitions in 
Appendix 5: Derived and Transformed Data.
Maximum prednisone equivalent corticosteroid daily dose will be summarised within the 
year intervals.
Categories reported as 
[1] No prednisone use (0 mg prednisone equivalent)
[2] > 0 to 7.5 mg prednisone equivalent
[3] > 7.5 to 40 mg prednisone equivalent
[4] > 40 mg prednisone equivalent
[5] Unknown
7.1.4.
Shifts in Prednisone Average Daily Dose from Baseline
Shifts from average daily dose category at baseline will be summarised using frequencies 
and percentages, and be presented by the parent randomised treatment group and the total 
Safety population, for each visit.
Categories reported as 
[1] No prednisone use (0 mg prednisone equivalent)


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[2] > 0 to 7.5 mg prednisone equivalent
[3] > 7.5 to 40 mg prednisone equivalent
[4] > 40 mg prednisone equivalent
[5] Unknown
No imputation will be performed for missing data.
7.1.5.
Extent of Exposure and Study Drug Administration

The extent of exposure to IV belimumab treatment through end of study will be
assessed by examining the duration of exposure to belimumab in days and the total 
number of infusions a subject received. First and last infusion dates will be used, 
regardless of any intermittently missed infusions.

Duration of exposure to IV belimumab (in days) will be calculated for each subject, 
as:
Extent of Exposure (days) =
Date of last exposure to IV treatment + 28 – Date of first exposure to IV treatment
where

the first IV belimumab dose either occurred during the parent study BEL113750 
(for subjects randomized to belimumab in BEL113750) or during BEL114333 
(for everyone else).

the last IV belimumab dose occurred during BEL114333 for everyone.  For any 
subjects who died within the 28 days after infusion, duration of exposure will be 
censored at the date of death.

Only complete dates will be used when calculating duration of exposure. 

Summary statistics will be produced for the duration of exposure.
NOTE: subjects from the parent study BEL112341 received SC belimumab prior to 
joining BEL14333.  Their total duration to exposure is the sum of the exposure to 
both IV and SC (see details of exposure calculation for SC belimumab below).

Summary statistics of the total number of infusions.
o
Additionally, the total number of infusions will also be summarized using 
counts and percentages using the following categories: 1 to 9, 10 to 19, 20
to 29, 30 to 39, 40 to 49, 50 to 59 and >60 (if applicable). 
NOTE: for BEL112341 subjects only.  The extent of exposure to SC belimumab during 
the parent study BEL112341 prior to joining BEL114333, will be assessed by examining 
the duration of exposure to SC belimumab in days and the total number of injections a 
subject received. First and last injection dates will be used, regardless of any 
intermittently missed injections.


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
SC belimumab was administered weekly by injection.  Duration of exposure to SC 
belimumab (in days) will be calculated for each subject, as:
Extent of Exposure (days) =
Date of last exposure to SC treatment + 7 – Date of first exposure to SC treatment
where

the first SC belimumab dose either occurred during the DB portion of the parent 
study BEL112341 (for subjects randomized to belimumab in BEL112341) or the 
open-label portion of the parent study BEL112341 (for subjects randomized to 
placebo in BEL112341). 

the last SC belimumab dose occurred during the open-label portion of 
BEL112341 for everyone. 

Only complete dates will be used when calculating duration of exposure. 

Summary statistics will be produced for the total number of injections.  
o
Additionally, the total number of injections will also be summarized using 
counts and percentages using the following categories: 1 to 23, 24 to 76, 
and >76 (if applicable).  
7.2.
Overview of Planned Adverse Event Analyses
Table 8 provides an overview of the planned Adverse Event analyses, with full details of 
data displays being presented in Appendix 12: List of Data Displays. Data from all 
subjects as one treatment belimumab group will be presented. 
Table 8
Overview of Planned Adverse Events Analyses
Endpoint
Absolute
Summary
Individual
T
F
L
AE Summary by Year Interval
Y
Cumulative AE Incidence Over Time
Y [4]
Adverse Events by SOC
AE by SOC 
Y
Serious AE by SOC
Y
Severe AE by SOC
Y
Study Drug Related AE by SOC
Y
AE Leading to PD of Study Drug or WD from Study by SOC
Y
Adverse Event Rates by SOC
AE Rate by SOC 
Y
Serious AE Rate by SOC
Y
Severe AE Rate by SOC
Y
Study Drug Related AE Rate by SOC
Y


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Endpoint
Absolute
Summary
Individual
T
F
L
AE Leading to PD of Study Drug or WD from Study Rate by SOC
Y
Adverse Events by SOC & PT
AE by SOC & PT 
Y
Y [2]
Serious AE by SOC & PT
Y
Y [2]
Severe AE by SOC & PT
Y
Study Drug Related AE by SOC & PT
Y
AE Leading to PD of Study Drug or WD from Study by SOC & PT
Y
Y [3]
Subject Numbers by Individual AE by SOC & PT
Y [2]
Relationship between AE SOC, PT and Verbatim Text
Y [2]
Adverse Events by SOC & PT (Subgroups)
AE by Age Group (< 65 vs 65 Years), SOC and PT
Y (x2) [1]
AE by Gender (Male vs Female), SOC and PT
Y (x2) [1]
AE by BL SELENA SLEDAI (≤9 vs ≥10), SOC & PT
Y (x2) [1]
Adverse Events: Non-Serious, Serious & Fatal Serious by SOC & PT
Fatal Serious Adverse Events
Y [2]
Non-Fatal Serious Adverse Events
Y [2]
Reason for Considering as a Serious Adverse Event 
Y
Most Common (10%) Non-Serious Drug Related Adverse Events
Y
Most Common (2%) Serious Drug Related Adverse Events
Y
Common (5%) Non-Serious Adverse Events by SOC and PT (FDAAA)
Y
Serious Adverse Events by SOC and PT (FDAAA)
Y
Adverse Events by PT
AE by PT 
Y
Serious AE by PT
Y
Severe AE by PT
Y
Study Drug Related AE by PT
Y
AE Leading to PD of Study Drug or WD from Study by PT
Y
Adverse Events by Maximum Severity
AE by SOC & Maximum Severity
Y
AE by SOC, PT & Maximum Severity
Y
NOTES:

BL = Baseline, PD = Permanent Discontinuation, WD = Withdrawal, T = Table, F = Figures, L = Listings, Y = Yes 
display generated, (xN) = Number of separate displays generated.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
Separate displays generated for each level of the subgroup.
[2]
Listing generated by SOC, PT and Verbatim Term.
[3]
Listing generated for AE results in study drug discontinuation.
[4]
Kaplan-Meier figure showing each AE category (all, related, serious, severe).
7.2.1.
Adverse Events

Data from all subjects as one belimumab group will be summarised.


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
All adverse event tables will show the data by year interval at the start of an AE, and
include a summary over the total post-baseline period.  Year interval is defined in 
Appendix 2: Assessment Windows.

Any AEs that started prior to the first IP administration in the parent study will not be 
reported. See Section 6.2, footnote 4 in Table 4 for relevance for such AEs as past 
medical history terms. Only treatment-emergent adverse events will be summarised.
o
Treatment-emergent AEs are defined as follows:

AEs that started on or after the first dose of belimumab treatment.

For those subjects who were randomised to placebo in the parent 
study, ongoing AEs that started before the first open-label belimumab 
dose (in either BEL112341 open-label extension or BEL114333) and 
worsened (severity, seriousness, relatedness) at any point during the 
open-label treatment.
o
Ongoing AEs that started before the first open-label belimumab dose which 
did not worsen during the open-label treatment (for those subjects who were 
randomised to placebo during the parent study) will not be considered 
treatment-emergent, but will be listed.    

Listings will be generated by the parent randomized treatment group (see Table 8). 
All treatment-emergent AEs as defined above will be listed plus any ongoing AEs 
that started before the first belimumab dose (for subjects randomised to placebo in the 
parent study) that were not considered treatment-emergent. AEs that started in each 
parent study will be flagged.

The hierarchical relationship between MedDRA SOCs, PTs and verbatim text will be 
displayed as a listing for all AEs.  

Adverse events in BEL114333 will be coded to the current MedDRA dictionary 
version at the time of study reporting (version 22.0).   
NOTE: the same version of the MedDRA dictionary which was used at the time of 
reporting the parent studies will be used for this current reporting (BEL113750, 
version 21.1; BEL112341, version 18.0). Any major coding discrepancies between 
different versions of MedDRA can be addressed in a CSR appendix, if necessary.  
7.2.2.
Adverse Event Summaries

An overall summary of AEs will be presented showing the number (%) of subjects 
with at least one of the following: AE, related AEs, SAE, severe AE, AE resulting in 
study treatment discontinuation, and deaths.

The number of events and the number (%) of subjects who had at least one treatment-
emergent AE will be summarized for each category of AE listed in Table 9. 
Table 9
Adverse Events Categories
AE’s
Summary Category


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By SOC
By SOC & PT
By PT 
All
YES
YES
YES
Serious
YES
YES
YES
Study Drug Related
YES
YES
YES
Severe
YES
YES
YES
Leading to permanent discontinuation of study
YES
YES
YES
Non-Serious Drug Related 
YES
Serious Drug Related Adverse Events
YES
SOC = System Organ Class, PT = Preferred Term

The table for AEs by SOC and PT will be repeated for subgroups. See Appendix 8: 
Examination of Covariates, Subgroups & Other Strata for more details.

The tables for AEs by SOC will also be reported for event rates (see below for 
derivation).

Summaries of AE incidence, by SOC and maximum severity will also be provided.  
For these displays, the number (%) of subjects will be summarized as mild, moderate 
or severe, based on the maximum severity observed across all PTs within the SOC for 
a given subject. AEs that have missing severity will be excluded from the summaries.

A Kaplan-Meier figure of cumulative incidence (at least one) of treatment-emergent 
AE by category (all, related, serious, severe) will be created relative to the first dose 
of belimumab and censored at the last visit date/contact. 

Listings of AEs will be presented (see Table 8). A listing of AEs in the Infections and 
Infestations SOC for those subjects with a Grade 3 or Grade 4 IgG toxicity at baseline 
and/or at any time post-baseline, will also be produced.
Adverse Event Rates

The event rate will be calculated as the number of events per 100 person-years.  The 
last contact date for AE reporting is the date of the latest scheduled visit where 
AE/SAE were assessed, as appropriate, up to the 16 week FU visit. 
Event Rate = 100* Number of Events / Subject Years
Overall 
Subject 
Years
∑All Subjects in Population [(Last Contact Date – 1st Belimumab Treatment Date + 1)]
365
NOTE: This will be the denominator for the “Any Time Post Baseline” column.
Subject 
Years in 
Year k
∑All Subjects in Population (End of Interval Day – Start of Interval Day + 1)
365
7.3.
Overview of Planned Adverse Events of Special Interest
Table 10 provides an overview of the planned Adverse Event analyses, with full details 
of data displays being presented in Appendix 12: List of Data Displays.


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Table 10
Overview of Planned Adverse Events of Special Interest
Endpoint
Absolute
Summary
Individual
T
L
Adverse Events of Special Interest (AESI)
Overall AESI by Category
Y
Y [1]
Malignant Neoplasm AESI by Category & PT
Y
Post-Infusion Systemic Reaction AESI by Category & PT
Y
Serious Post-Infusion Systemic Reaction AESI by Category & PT
Y
Infection AESI by Category & PT
Y
Serious Infection AESI by Category & PT
Y
Infection AESI Leading to PD Discontinuation of Study Drug or WD from Study by 
Category & PT
Y
Depression/Suicide/Self-injury AESI by Category & PT
Y
Deaths by Category & PT
Y
Adverse Events of Special Interest (AESI) Rates
Overall AESI Rates by Category
Y
Malignant Neoplasm AESI Rates by Category & PT
Y
Post-Infusion Systemic Reaction AESI Rates by Category & PT
Y
Serious Post-Infusion Systemic Reaction AESI Rates by Category & PT
Y
Infection AESI Rates by Category & PT
Y
Serious Infection AESI Rates by Category & PT
Y
Infection AESI Leading to PD Discontinuation of Study Drug or WD from Study 
Rates by Category & PT
Y
Depression/Suicide/Self-injury AESI Rates by Category & PT
Y
NOTES:

T = Table, L = Listing, Y = Yes display generated, (xN) = Number of separate displays generated.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
Listing generated by AESI Category, SOC, PT and Verbatim Term.
7.3.1.
Adverse Events of Special Interest
AESI have already been identified by the GSK Safety Review Team (SRT).  This 
information will be provided for analysis purposes via an adjudication spreadsheet, and 
therefore, does not need to be re-derived from the raw data.  For a broader description, 
see Appendix 10: PSAP Sections for AESI Reporting.
The reporting of AESIs is defined below.
An overall summary of the incidence of AESI will be tabulated, and presented by study 
year and “any time post-baseline”.  Rate of events per 100 person-years will also be 
reported.  Further summaries of the preferred terms assigned to each AE special interest 
category will be provided.  


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A listing of all AESIs will be produced.
The categorizations for the adverse events of special interest groups are:
Malignant Neoplasms

Malignancies Excluding non-melanoma skin cancer (NMSC)

Malignancies Including NMSC

Solid Tumour

Hematologic

Skin (All)

NMSC

Excluding NMSC

Tumours of unspecified malignancy adjudicated as malignant per GSK
Post-Infusion Systemic Reactions (PISR)

PISR per Anaphylactic Reaction Customized MedDRA Query (CMQ) narrow 
search

PISR per Anaphylactic Reaction CMQ broad search

PISR per Anaphylactic Reaction CMQ algorithmic search

Serious Anaphylaxis per Sampson Criteria per GSK adjudication

Serious Acute PISR/Hypersensitivity per GSK adjudication

Serious Acute PISR Excluding Hypersensitivity per GSK adjudication

Serious Acute Hypersensitivity Reactions per GSK adjudication

Serious Delayed Acute Hypersensitivity Reactions per GSK adjudication

Serious Delayed Non-Acute Hypersensitivity Reactions per GSK adjudication
All Infections of Special Interest (All and Serious, separately)

All opportunistic infections (OI) per GSK adjudication

OI per GSK adjudication excluding Tuberculosis and Herpes Zoster

Active Tuberculosis

Non-Opportunistic

Opportunistic

Herpes Zoster

Non-Opportunistic

Opportunistic

Recurrent

Disseminated

Sepsis
Depression*/suicide/self-injury (All and Serious, separately)

Depression* (excluding suicide and self-injury)

Suicide/self-injury

Serious suicide/self-injury per GSK adjudication

Suicidal Behaviour

Completed Suicide

Suicidal Ideation


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
Self-injurious Behaviour without Suicidal Intent
* Including mood disorders and anxiety.
Deaths
7.4.
Overview of Planned Laboratory, Immunogenicity and Vital 
Signs Summaries
Table 11 provides an overview of the planned Laboratory, Immunogenicity, 
Immunoglobulins and Vital Signs summaries by parent randomised treatment group, with 
further details of data displays being presented in Appendix 12: List of Data Displays.
Table 11
Overview of Planned Laboratory, Immunogenicity and Vital Signs
Summary
Individual
T
F
L
Laboratory Parameters (by Visit)
Lab Parameters Visit Values
Y (x5) [1] [2]
Y (x5) [1]
Y (x6) [3]
Lab Parameter Change from BL
Y (x5) [1] [2]
Y (x5) [1]
Worst Laboratory Toxicity Grade (by Year Interval)
Worst Lab Toxicity Grade
Y (x6) [3]
Worst Lab Toxicity Grade by At least 2 Grades from BL
Y (x6) [3]
Grade 3 & 4 Lab Toxicity Results
Y (x6) [3]
Laboratory Reference Range Shifts
Lab Reference Shifts from BL
Y (x6) [3]
Hepatobiliary (Liver)
Liver Events
Y (x3) [4]
Immunogenicity
Immunogenicity Response by Visit
Y
Y
Immunogenicity Response by Year Interval
Y
Vital Signs
Vital Signs Visit Values
Y
Y
Pregnancies
On-study Pregnancies per End of Treatment CRF
Y
NOTES:

BL = Baseline, T = Table, F = Figure, L = Listing, Y = Yes display generated, (xN) = Number of separate displays
generated

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
Separate displays generated for [A] Haematology, [B] Liver Function, [C] Electrolytes, [D] Other Chemistries,
[E] Immunoglobulins.
[2]
A combined display will be generated for Absolute and Change from baseline for each laboratory parameter.
[3]
Separate displays generated for [A] Haematology, [B] Liver Function, [C] Electrolytes, [D] Other Chemistries,
[E] Urinalysis, [F] Immunoglobulins. Note: immunoglobulin data will be summarised separately by parent study.  
See Section 5.1.
[4]
Separate displays generated for [A] Liver Assessment, [B] Liver Biopsy Details, [C] Liver Imaging.


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7.4.1.
Clinical Laboratory Evaluations

Laboratory parameters which are continuous numeric values will be analyzed using 
summary statistics, and those with categorical results will be summarized using 
frequencies and percentages.  

Analyses will be performed based on the observed data. Only central laboratory data 
will be summarized.

Refer to Appendix 5: Derived and Transformed Data for handling of laboratory 
values that are above or below the lower limit of quantification.

Listings will be generated for all laboratory results, and additionally for Grade 3 or 
Grade 4 laboratory toxicity results.

Baseline is defined as described in Section 11.4.2 and a list of laboratory parameters 
collected and definition of the toxicity grades provided in Appendix 9: Laboratory 
Parameters & Adverse Events Grading Tables. 
o
Note: UREA is collected in BEL114333/BEL113750 and BUN is collected in 
BEL112341. “Urea (mmol/L) & BUN (mmol/L)” will be displayed as a single 
parameter in tabular summaries of laboratory parameters and a footnote added 
to highlight that different tests were performed in the different studies. 
o
Note: Bilirubin direct data were not collected during the parent study for 
BEL112341 subjects; thus, because of missing data at baseline and post-
baseline visits for the first 6 months of belimumab treatment (and data for the 
subsequent 12 months is limited to the placebo group), these subjects will be 
excluded from this summary. 

Toxicities will be reported as derived by the GSK EDU, as protocol toxicity grading 
was applied (or as assigned programmatically in the ADaM dataset creation, for 
lymphocytes, spot urine protein creatinine ratio and urine RBC).  Note: toxicity data 
for partial thromboplastin time and prothrombin time will not be summarised because 
the data were only collected in the parent study. However, PT/PTT at baseline will be 
displayed in tabular summaries of laboratory parameters (see Section 7.4.2).
Additionally, for potassium, glucose, calcium and sodium, toxicities are bi-directional 
(i.e. high or low directions) and both will be summarised by name of the toxicity.

Potassium: hypokalemia, hyperkalemia

Glucose: hypoglycemia, hyperglycemia

Calcium: hypocalcemia, hypercalcemia

Sodium: hyponatremia, hypernatremia
For example, calcium will have two toxicity sections, one for hypocalcemia and one 
for hypercalcemia and mapped to their high or low as

RESULT < (LLN+ULN)/2 = “Hypo” toxicity

RESULT > (LLN+ULN)/2 = “Hyper” toxicity.


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7.4.2.
Laboratory Parameters by Visit

Summaries will be presented by parent randomized treatment group, and total Safety 
population. 
o
Note: immunoglobulin data will be summarized for subjects from each parent 
study separately. 

The absolute values and the change from baseline for each analyte will be 
summarized using descriptive statistics, at each belimumab visit.

Line graphs will display the time course for each analyte, separately for the absolute 
value and the change from baseline.
7.4.3.
Worst laboratory toxicity grade post-baseline

Toxicity grading for each analyte will be summarized. This reflects the worst grade 
for each analyte across all subjects and all assessments for each year interval and at 
any time post-baseline.  The display will summarize the number (%) of subjects for 
each of the toxicity grades. 
7.4.4.
Shift in Laboratory toxicity grade post-baseline

Toxicity grade shifts from baseline of 2 grades for each analyte will be summarized
for each year interval and at any time post-baseline.  The display will summarize the 
number (%) of subjects with at least one 2 grade shift as well as the specific shift 
categories:  Grade 0 to 2, Grade 0 to 3, Grade 0 to 4, Grade 1 to 3, Grade 1 to 4, and 
Grade 2 to 4.

See Appendix 2: Assessment Windows for handling of the post-last dose 16 Week 
follow-up visit.  
7.4.5.
Laboratory Reference Range Shifts

Summaries will be presented by parent randomized treatment group, and total Safety 
population. 

Laboratory reference range shifts will be summarized only for laboratory tests 
without toxicity grades. 

A laboratory value that is outside of normal range will be considered abnormal 
(above or below).  

Shifts relative to the normal range will be summarized for each analyte, at each 
belimumab visit, as follows: 
o
‘n’ represents the number (%) of subjects with a low, high or normal value at 
the specified visit.
o
For subjects with a low value at the specified visit, the shift categories relative 
to baseline are shown as either remained low, or normal/high to low.
o
For subjects with a high value at the specified visit, the shift categories 
relative to baseline are shown as either remained high, or normal/low to high.


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o
For subjects with a normal value at the specified visit, the shift categories 
relative to baseline are shown as either remained normal, or high to normal, or 
low to normal.  
7.4.6.
Immunogenicity

Serum samples for anti-belimumab anti-body measurements were obtained from 
subjects per the protocol.
o
Immunogenicity testing in BEL114333 subjects used a tiered approach.  The 
binding assay (to detect the presence of anti-drug antibodies) consisted of 3-
testing steps: screening, confirmation and titer.  At each scheduled visit, the 
screening assessment was performed resulting in a positive (above screening 
cut point) or negative (below screening cut point) result.  Samples testing 
potentially positive in the screening assay were then tested in the confirmation 
assay. Samples then testing positive in the confirmation assay (above 
confirmation cut point) were considered confirmed and reported as positive; 
samples with a result below the confirmation cut point were reported as 
negative for the binding assay.  Samples with a confirmed positive result were 
also run in the titration assay, and a titer value reported.  In addition, samples 
testing positive for the binding assay were also tested in the neutralization 
assay (to determine if ADA were neutralizing), which also produced a result 
of positive or negative. 
o
Binding confirmatory assay results will be categorized for analysis as

negative, 

persistent positive (defined as a positive immunogenic response on at 
least 2 consecutive assessments post-first dose of belimumab or a 
single positive result at the final assessment), or

transient positive (defined as a single post-first dose of belimumab
positive immunogenic response that does not occur at the final 
assessment)
Note: For the placebo cohort who proceeded to the open-label and received 
belimumab, the baseline result for the open-label analysis is defined as the last 
assessment prior to the start of belimumab treatment.  The baseline result was 
assessed from the sample collected prior to the first dose of belimumab. The first 
positive post-dose assessment would be a transient positive, and if followed by a 
positive result in the next assessed sample, the result is considered persistent.

Immunogenicity response (negative, persistent positive, transient positive) will be 
summarized by the parent randomized treatment group, and total Safety population, 
for each belimumab visit (including Week 16 FU and Month 6 FU visits).  Note, 
collection of samples for immunogenicity testing at the Month 6 FU visit is reserved 
for subjects with a prior positive immunogenicity result such as from the Week 16 FU 
visit. Any Month 6 FU visit result for subjects having had a prior positive result will 
be summarized. 
Additionally, the immunogenicity response will be summarized for any time post 
baseline in which a subject will be counted once only, based on the highest binding 


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confirmatory assay result (lowest to highest result: Negative, Transient Positive, 
Persistent Positive).

Immunogenicity response post-first dose will also be summarized by year interval in 
which the latest value in the year interval will be reported (usually Week 48 visit, but 
when not available, Week 24 or Exit visit value will be used).

A summary of all (including baseline) immunogenicity results based on the highest
binding confirmatory assay result will be produced by parent randomized treatment 
group, and the total Safety population.  If a subject had Negative and Positive 
confirmatory results during the entire study period, they will be included in the 
Positive category.

A quartile assessment of the titer value will not be performed due to the low number 
of positive results.


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8.
EFFICACY ANALYSES
The efficacy analyses will be based on the Safety population, unless otherwise specified. 
Further details of efficacy endpoints are provided in Appendix 5: Derived and 
Transformed Data.
8.1.
Overview of SRI and Secondary Efficacy Endpoints
Table 12 provides an overview of the planned analyses for the SRI and secondary 
efficacy endpoints, with further details of data displays being presented in Appendix 12: 
List of Data Displays.
Table 12
Overview of Planned Efficacy Analyses
Endpoint
Summary
Individual
T
F
L
SRI Response
SRI Response
Y
Y
Y
SELENA SLEDAI [1]
SELENA SLEDAI 4 Point Reduction from BL
Y
Y
Y
PGA [1]
PGA No Worsening (Increase of < 0.30 points from BL)
Y
Y
Y
BILAG [1]
BILAG No New 1A/2B Organ Domain Scores
Y
Y
Y
Prednisone
Number of days of daily prednisone 7.5 mg/day and/or reduced by 
50% from BL
Y
Y
SFI Flare
Time to First Severe SFI Flare
Y
Y
Y
NOTES:

BL = Baseline, T = Table, F = Figure, L = Listing, Y = Yes display generated, (xN) = Number of separate displays
generated

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
Component endpoints of the composite SRI response.
8.1.1.
SRI Response Rate
The proportion of subjects achieving an SRI response will be summarised by parent 
randomised treatment group, and the total Safety population, for each belimumab visit
(every Week 24 and Week 48 visit).  Total Safety population data will be displayed 
graphically using a line graph.
The SRI 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


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
No new British Isles Lupus Assessment Group of SLE Clinics (BILAG) A organ 
domain score or 2 new BILAG B organ domain scores compared with baseline at the 
time of assessment.
Note: This third bullet is more clearly written as, “No new British Isles Lupus 
Assessment Group of SLE Clinics (BILAG) A organ domain score and at most 1
new BILAG B organ domain score compared with baseline at the time of 
assessment.”
8.1.2.
SELENA SLEDAI 4 Point Reduction from Baseline
The proportion of subjects with a reduction from baseline of ≥4 points in SELENA 
SLEDAI score will be summarised by parent randomised treatment group, and the total 
Safety population, for each belimumab visit (every Week 24 and Week 48 visit).  Total 
Safety population data will be displayed graphically using a line graph.
8.1.3.
PGA No Worsening
Scoring of the PGA scale ranges from 0-3, where 0 indicates no disease activity.
The proportion of subjects with no worsening in PGA (defined as an increase < 0.30
points from baseline, using the re-scaled score 0-3 scale) will be summarised by parent 
randomised treatment group, and the total Safety population, for each belimumab visit
(every Week 24 and Week 48 visit).  Total Safety population data will be displayed 
graphically using a line graph.  
8.1.4.
BILAG No New 1A/2B Organ Domain Scores
The proportion of subjects with no new BILAG A and at most 1 new BILAG B organ 
domain scores (No New 1A/2B) compared to baseline at the time of the assessment, will 
be summarised by parent randomised treatment group, and the total Safety population, for 
each belimumab visit (every Week 24 and Week 48 visit).  Total Safety population data 
will be displayed graphically using a line graph.  
8.1.5.
Number of Days of Daily Prednisone 7.5 mg/day and/or 
Reduced by 50% from Baseline
The number of days of daily prednisone dose 7.5 mg/day and/or reduced by 50% from 
baseline will be summarised at each Week 24 and 48 belimumab visit (in every year) and 
at any time post-baseline. Only subjects receiving a prednisone dose > 7.5 mg/day at the 
baseline visit will be included.  
For subjects who have attended Week 24 and 48 belimumab visits (in every year), the 
number of days from first day of belimumab (given on the baseline visit) of daily 
prednisone dose 7.5 mg/day and/or reduced by 50% compared to the baseline visit will 
be summarised, using descriptive statistics.


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8.1.6.
Time to First Severe SFI Flare
SFI flare data are collected at scheduled visits where only one flare may be recorded. The 
frequency of these flare assessments vary and will be collected in accordance to their 
respective timings (Section 11.1).  Additional flares occurring between scheduled 
assessments during study BEL114333 were collected using an additional SLE flare log.  
(Note: only the flare data were collected but no visit information) and flares will be 
assigned to the next scheduled visit for flares.
Time to the first severe SFI flare during belimumab treatment will be summarised by the 
parent randomised treatment group, and the total Safety population.  
Note, for this study, analyses of SFI flares will be conducted based on the modified SLE 
flare index (modified excludes severe flares from the SELENA SLEDAI assessment that 
were triggered only by an increase in SELENA SLEDAI score to > 12, see Section
11.5.4.5).
Only post-baseline flares will be considered in these analyses. Flares (not subjects) 
occurring on the first belimumab dose date should be removed from the analysis dataset 
prior to determining the first flare.
Time to the first severe SFI flare is calculated as the number of days from the first dose of
belimumab treatment up to the first severe flare event (event date – first dose date of 
belimumab + 1).  The disposition of subjects is defined as follows:
Subject Disposition
Event Met
Event Date
Subject has a severe SFI flare
Subject has a severe SFI flare during the 
study
Yes
Date of first severe SFI flare
Subject does not have a severe SFI flare
Subject withdraws from the study
No
Censored at last available date where flare is 
assessed
Subject dies during the study
No
Censored at date of death.
Subject who completes the study *
No
Censored at last available date where flare is 
assessed
* As per the protocol. Includes subjects who transferred to study BEL116027, or who were still participating in the study 
at the time of the sponsor decision to close the study.
The display will summarise the number and percentage of subjects with a severe SFI flare 
as well as the Kaplan-Meier estimate of the median, 25th and 75th percentiles of days to 
first severe SFI flare. For subjects who experienced a severe SFI flare, the display will 
summarise the median, 25th and 75th percentiles, minimum and maximum time to the first 
severe SFI flare from baseline, by parent randomised treatment group, and the total 
Safety population.
A cumulative incidence curve for time to first severe SFI flare will be produced for the 
total Safety population, using Kaplan-Meier methods.  The time of the first severe SFI 


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flare from baseline through to each belimumab visit at Week 24 and Week 48 of each 
year will be summarised.
8.2.
Overview of Other Efficacy Endpoints
Table 13 provides an overview of the planned analyses of other efficacy endpoints, with 
further details of data displays being presented in Appendix 12: List of Data Displays.
Table 13
Overview of Planned Other Efficacy Analyses
Endpoint
Summary
Individual
T
F
L
Disease Activity
SELENA SLEDAI Change from BL
Y [1]
Y
SELENA SLEDAI % Change from BL
Y [1]
Y
SLICC/ACR Damage Index Observed and Change from BL
Y [1] [2]
Y
SLICC/ACR Damage Index Worsening
Y [2]
PGA % Change from BL
Y [1]
Y
Flares
Time to First SFI Flare
Y
Y
Number of Severe SFI Flares (and rate per 100 PY)
Y
Number of SFI Flares (and rate per 100 PY) 
Y
Time to First 1A/2B BILAG Flare
Y
Y
Time to First BILAG A Flare
Y
Y
Organ-Specific Measures
Time to First Renal Flare
Y
Y
Proteinuria % Change from BL (among subjects with BL proteinuria)
Y [1]
Y
Proteinuria Shifts from BL
Y
Prednisone
Prednisone % Change from BL
Y [1]
Y
Prednisone Dose Reduced to 7.5 mg/day (among subjects with BL 
dose > 7.5 mg/day)
Y
Y
NOTES:

BL = Baseline, T = Table, F = Figure, L = Listing, Y = Yes display generated, (xN) = Number of separate displays
generated

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
A combined display will be generated for Absolute and Change from baseline for each laboratory parameter.
[2]
Data summarised separately by parent study.  See Section 5.1.
8.2.1.
SELENA SLEDAI Change from Baseline
The absolute values, the change, and the percent change from baseline in SELENA 
SLEDAI scores will be summarised using descriptive statistics, and presented by parent 
randomised treatment group and the total Safety population, for each belimumab visit


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(every Week 24 and Week 48 visit). In summaries, decreases will reflect improvement in 
the assessment.
Data will be displayed graphically over time using a line graph for the total Safety 
population.  Separate plots will be produced for the mean change from baseline (SE) 
and mean percent change from baseline in SELENA SLEDAI score.
8.2.2.
SLICC/ACR Damage Index

The absolute values and change from baseline in SLICC/ACR Damage Index will be 
summarised using descriptive statistics, and presented by the parent randomised 
treatment group, for each belimumab visit. This data will be presented separately for 
subjects from each parent study.      

The SLICC/ACR Damage Index increases over time, and once an item is scored it 
continues to be scored at all subsequent assessments, even if the subject subsequently 
recovers. 
o
Due to incorrect scoring, the database contains a small number of subjects who 
have at least one decrease in SLICC/ACR Damage Index since baseline.
o
Where the error occurred at closed sites, data management were unable to query 
and correct the error.
o
Due to these incorrect assessments, a worst score observation carried forward 
(WOCF) approach will be used at the item level for the SLICC/ACR Damage 
Index items.  These WOCF values will then be used to calculate the total score 
which will be the value summarized and displayed for reporting.

The number and percentage of subjects with a worsening in their SLICC/ACR 
Damage Index score compared with baseline (change score > 0) will be summarized.  
See Appendix 5: Derived and Transformed Data for the derivation of SLICC/ACR 
Damage Index score including Worst Observation Carried Forward (WOCF).
8.2.3.
Physician’s Global Assessment Change from Baseline
The absolute values and percent change from baseline in PGA will be summarised using 
descriptive statistics, and presented by the parent randomised treatment group and total 
Safety population, for each belimumab visit (every Week 24 and Week 48 visit).  Total 
Safety population data will be displayed graphically using a line graph.  The plot will 
show the mean change from baseline (SE) over time.    
See Appendix 5: Derived and Transformed Data for the derivation.
8.2.4.
Time to First SFI Flare
A SFI flare is defined as a mild/moderate or severe flare per the modified SELENA 
SLEDAI SLE Flare Index.  Analyses of the first SFI flare will use the same methodology 
as for severe SFI flares (see Section 8.1.6).


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8.2.5.
Number of SFI Flares and Rates
The number of SFI flares (each for severe flares and any flares) will be summarised at 
any time post-baseline, and presented by the parent randomised treatment group and the 
total Safety population. Rates of flares per 100 person-years will also be reported.  
The table will display the total number of SFI flares (each for severe flares and any 
flares), total person-years of follow-up for SFI flare assessments, and the rate of flare 
events per 100 person-years.  See Section 11.5.4.5 for the derivation of the SFI flare rate.
8.2.6.
Time to First 1A/2B BILAG Flare
A 1A/2B BILAG flare is defined as at least 1 new BILAG A or 2 or more new BILAG B 
organ domain scores compared to baseline. Note, a BILAG assessment needs to be 
performed to determine if there is a change in organ domains.  Every 6 month BILAG 
assessments in BEL114333 will not allow the same reporting as in the parent study
(every 4 weeks).   
Time to first 1A/2B BILAG flare is calculated as the number of days from first dose of 
belimumab treatment up to the first BILAG flare event (event date – first belimumab 
dose date + 1).  The event date is defined by the BILAG assessment date.  The 
disposition of subjects is defined as follows:  
Subject Disposition
Event Met
Event Date
Subject has a 1A/2B BILAG flare
Subject has a BILAG flare during the 
study
Yes
Date of first BILAG flare
Subject does not have a 1A/2B BILAG flare
Subject withdraws from the study
No
Censored at last available BILAG assessment
Subject dies during the study
No
Censored at date of death.
Subject completes the study *
No
Censored at last available BILAG assessment
* As per the protocol. Includes subjects who transferred to study BEL116027, or who were still participating in the 
study at the time of the sponsor decision to close/terminate the study
Analyses for the first 1A/2B BILAG flare will use the same methodology as for severe 
SFI flares (see Section 8.1.6).
8.2.7.
Time to First BILAG A Flare
A BILAG A flare is defined as at least 1 new BILAG A organ domain score compared to 
baseline.  Time to the first BILAG A flare will be summarised as per the BILAG 1A/2B 
flare endpoint (see Section 8.2.6).
8.2.8.
Time to First Renal Flare
Only time to first renal flare will be analysed. Although a renal flare rate was of interest 
at the time of the protocol design writing, renal flare rates have been relatively 


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uncommon, and do not provide much clinical value at this current time. Focus will be 
placed upon providing a summary of the first renal flare event.
Assessments every 6 months during BEL114333 will not allow the use of the same 
definition of renal flares as in the parent studies, which requires assessments to be
performed at two or more consecutive monthly visits. Thus, a renal flare is defined as the 
occurrence of one or more of the following criteria at a single (belimumab) visit at every 
Week 24 and Week 48, timepoints at which both protein creatinine ratio and lab 
assessments are scheduled in the protocol. Note, when identifying renal flares, data 
within the visit window at Week 24 and Week 48 visits will be considered. 
1. An 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 the baseline if the baseline value is > 1 g.
2. An increase in serum creatinine of >20 % or an increase of at least 0.3 mg/dL, 
accompanied by at least one of proteinuria (>1 g/24 hour equivalent), hematuria 
(4 red blood cells [RBCs]/high-power field [hpf]), cellular (RBC or WBC) 
casts.  The inclusion of ‘at least one of’ and ‘RBC or WBC’ casts is an addition to 
the protocol specified definition.  This addition has been included in the parent 
study BEL113750 RAP. 
3. Treatment-emergent, hematuria (11 to 20 RBCs/hpf) or an increase in hematuria 
by 2 grade 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].
To clarify criterion 2, [an increase in serum creatinine of > 20% OR an increase of at 
least 0.3 mg/dL], AND [proteinuria (> 1 g/24-hour equivalent) OR hematuria (4 red 
blood cells {RBCs}/high-power field {hpf}) OR cellular (RBC or WBC) casts].
To clarify criterion 3, [treatment-emergent, hematuria (11 to 20 RBCs/ hpf) OR (an 
increase in hematuria by 2 grades compared with baseline AND > 25% dysmorphic 
RBCs, glomerular in origin, exclusive of menses)], AND [0.8 g increase in 24-hour 
urinary protein levels (equivalent) OR new RBC casts].
Time to first renal flare is calculated as the number of days from first dose of belimumab 
treatment up to the first renal flare event (event date – first belimumab dose date + 1). 
The event date is defined by the scheduled laboratory assessment date.  The disposition 
of subjects is defined as follows:
Subject Disposition
Event 
Met
Event Date
Subject has a renal flare
Subject has a renal flare during the 
study
Yes
Date of first renal flare


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Subject does not have a renal flare
Subject withdraws from the study
No
Censored at last available date where all relevant 
parameters were assessed.
Subject dies during the study
No
Censored at date of death.
Subject completes the study *
No
Censored at last available date where all relevant 
parameters were assessed.
* As per the protocol.  Includes subjects who transferred to study BEL116027, or who were still participating in the 
study at the time of the sponsor decision to close/terminate the study
Analyses for the first renal flare will use the same methodology as for severe SFI flares 
(see Section 8.1.6).
8.2.9.
Proteinuria Percent Change from Baseline
Because no subjects had an actual 24 hour urine collection to assess proteinuria, the 
definition of proteinuria can be simplified to just using the spot urine PC ratio to assess 
the degree of proteinuria present at Week 24 and Week 48 (in every year). Proteinuria 
will be defined as a urine PC ratio > 0.5 mg/mg.  Note, the PC ratio reported in mg/mg is 
the 24 hour gram equivalent.
For subjects with proteinuria at baseline, the absolute value and percent change from 
baseline in urine PC ratio will be summarised using descriptive statistics, and presented 
by the parent randomised treatment group and overall, for each belimumab visit.
For this group of subjects having proteinuria at baseline, the data will be displayed 
graphically using a line graph.  The plot will show the mean percent change from 
baseline (SE) over time.
See Section 11.5.4.6 for the conversion of urine PC ratio from SI units to mg/mg.
8.2.10.
Proteinuria shifts
Proteinuria shifts as measured by spot urine PC ratio.
Urine PC ratio values will be summarised according to the following categories at 
baseline:  normal (0.5 mg/mg) or high (> 0.5 mg/mg). 
For each Week 24 and Week 48 belimumab visit (in every year), the data will be 
summarised by baseline status defined as normal or high.

For subject with a normal value at baseline, the shift categories at the specified 
visit are shown as either ‘No change’ or ‘Normal to High’.

For subjects with a high value at baseline, the shift categories at the specified visit 
are shown as either ‘No Change’ or ‘High to Normal’.
Additionally, the spot urine PC ratio values will be summarised based on shifts occurring 
any time while on treatment. 


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50

For subject with a normal value at baseline, the number (%) of subjects with at 
least one high post-baseline value will be presented as ‘Normal to High’; 
otherwise as ‘No Change’. 

For subjects with a high value at baseline, the number (%) of subjects with at least 
one normal post-baseline value will be presented as ‘High to Normal’; otherwise 
as ‘No Change’.
8.2.11.
Prednisone Percent Change from Baseline
The observed values and percent change from baseline in average daily prednisone dose 
will be summarised using descriptive statistics, and presented by the parent randomised 
treatment group and the total Safety population, for each Week 24 and 48 belimumab 
visit (in every year).
The derivation of average daily prednisone dose and conversion to the prednisone-
equivalent dose are provided in Section 11.5.3
Total Safety population data will be displayed graphically using a line graph.  The plot 
will show the mean percent change from baseline (SE) over time.    
8.2.12.
Prednisone Dose 7.5 mg/day for Subjects with an Average Daily 
Dose > 7.5 mg/day at Baseline
For subjects with an average daily prednisone dose > 7.5 mg/day at baseline, the 
proportion of subjects with an average daily prednisone dose reduced to 7.5 mg/day
will be summarised, and presented by the parent randomised treatment group, and 
overall, for each Week 24 and Week 48 belimumab visit (in every year).  
For this group of subjects having an average daily prednisone dose > 7.5 mg/day at 
baseline, the data showing reduction to 7.5 mg/day will be displayed graphically using 
a line graph.  The plot will show the proportion of subjects with this reduction (SE) 
over time.  
8.2.13.
Prednisone Dose > 7.5 mg/day for Subjects with an Average Daily 
Dose 7.5 mg/day at Baseline
For subjects with an average daily dose 7.5 mg/day at baseline, the proportion of 
subjects with an average daily prednisone dose increased to > 7.5 mg/day, will be 
summarised, and presented by the parent randomised treatment group, and the overall, for 
each Week 24 and Week 48 belimumab visit (in every year).  
For this group of subjects having an average daily prednisone dose 7.5 mg/day at 
baseline, the data showing elevation to > 7.5 mg/day will be displayed graphically using a 
line graph.  The plot will show the proportion of subjects with this increase (SE) over 
time.   


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9.
BIOMARKER ANALYSES
The biomarker parameters will be based on the Safety population, unless otherwise 
specified.
9.1.
Overview of Planned Biomarker Analyses
Table 14 provides an overview of the planned biomarker analyses, with further details of 
data displays being presented in Appendix 12: List of Data Displays.
Table 14
Overview of Planned Biomarker Analyses
Endpoint
Summary
Individual
T
F
L
Serum Immunoglobulin (IgG, IgM & IgA)
Lab Parameter Visit Values
Y [1] [4]
Lab Parameter % Change from BL
Y [1] [4]
Y
IgA, IgG, IgM below LLN by Visit
Y [4]
IgA, IgG, IgM below LLN by Year Interval
Y
Autoantibodies (anti-dsDNA)
Lab Parameter Visit Values
Y [1]
Y [2]
Lab Parameter % Change from BL
Y [1]
Y
Lab Parameter Visit Values for Subjects Positive at BL
Y [1]
Lab Parameter % Change from BL for Subjects Positive at BL
Y [1]
Y
Complement (C3, C4) Levels
Lab Parameter Visit Values
Y [1]
Y [2]
Lab Parameter % Change from BL
Y [1]
Y
Lab Parameter Visit Values for Subjects with Low Complement at BL
Y [1]
Lab Parameter % Change from BL for Subjects with Low 
Complement at BL
Y [1]
Y
B Cell Subsets [3]
Lab Parameter Visit Values
Y [1] [4]
Y
Lab Parameter % Change from BL
Y [1] [4]
Y
NOTES:

BL = Baseline, T = Table, F = Figure, L = Listing, Y = Yes display generated, (xN) = Number of separate displays
generated

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
[1]
A combined display will be generated for observed and change from baseline for each parameter. 
[2]
Combined into a single display. 
[3]
B cell data are collected only at ‘selected sites’ in which the selected sites were all Japan sites.  See Section 
11.5.5.1 for additional information. 
[4]
Data summarised separately by parent study.  See Section 5.1. 


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9.1.1.
Percent change from baseline
The absolute values and percent change from baseline in immunoglobulins, 
autoantibodies (anti-dsDNA), complement levels (C3 and C4), and B cell subsets (see 
Section 11.5.5.1) will be summarised using descriptive statistics, and presented by the 
parent randomised treatment group and the total Safety population. The frequency of 
these lab specimens vary and thus will be shown in accordance their respective timings
(see Section 11.1).
Total Safety population data will be displayed graphically using a line graph.  The plot 
will show the median percent change from baseline (interquartile range bars) over time.    
Note: For immunoglobulins and B cell subsets, the data will be presented separately for 
subjects from each parent study. 
Additionally, for anti-dsDNA, analyses will be performed among subjects who were 
positive at baseline; for complement levels, analyses will be performed among subjects 
with low values at baseline. See Section 11.5.5 for baseline classifications.
9.1.2.
Immunoglobulin (IgG, IgA and IgM) below LLN 
The number (%) of subjects with immunoglobulin (IgG, IgA and IgM) values below the 
lower limit of normal (LLN) will be summarised by the parent randomised treatment 
group, for each belimumab visit. This data will be presented separately for subjects from 
each parent study.  See Section 11.5.5 for LLN classifications.
Additionally, the immunoglobulin data for all subjects will be shown by year interval and 
at “any time post-baseline”.   See Section 11.5.5 for LLN classifications.


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53
10.
REFERENCES
Alarcón-Segovia D, Tumlin JA, Furie RA, McKay JD, Cardiel MH, Strand V, et al for 
the LJP 394 Investigator Consortium. LJP 394 for the prevention of renal flare in patients 
with systemic lupus erythematosus. Arthritis Rheum. 2003;48(2):442–54.
Division of Microbiology and Infectious Disease (DMID) Adult Toxicity Tables, May 
2001. http://www.naiaid.nih.gov/dmid/clinresearch/DMIDadulttox.doc.
Eibl MM, Rosen FS. Intravenous gamma globulin and plasmapheresis. In: Frank MM, 
editor. Samter’s Immunologic Disease (5th ed.). Boston: Little, Brown, 1995:1529-36.
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 transplant recipients. Transplantation. 2001;71(2):242-
6.
Hay EM, Bacon PA, Gordon C, et al. The BILAG index: a reliable and valid instrument 
for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 
1993;86:447-58.
Isenberg DA, Gordon C. From BILAG to BLIPS--disease activity assessment in lupus 
past, present and future. Lupus 2000; 9(9):651-4.
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.
Yee CS, Development and Validation of the BILAG 2004 Index for the Assessment of 
Disease Activity in Systemic Lupus Erythematosus. Doctoral Thesis submitted to the 
University of Birmingham, Rheumatology Research Group, Division of Infection and 
Immunology, School of Medicine, February 2008.


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11.
APPENDICES
Section
Appendix
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions
Section 11.1
Appendix 1: Time & Events
Section 11.2
Appendix 2: Assessment Windows
Section 11.3
Appendix 3: Adverse Event Collapsing Rules and Assignment of Adverse Events 
to Study Year
Section 11.4
Appendix 4: Data Display Standards & Handling Conventions

Study Treatment & Sub-group Display Descriptors

Baseline Definitions & Derivations

Reporting process & Standards
Section 11.5
Appendix 5: Derived and Transformed Data

General, Study Population & Safety

Efficacy

Biomarkers
Section 11.6
Appendix 6: Premature Withdrawals & Handling of Missing Data

Premature Withdrawals and Completion

Handling of Missing Data
Section 11.7
Appendix 7: Methods for Handling Centres
Section 11.8
Appendix 8: Examination of Covariates, Subgroups & Other Strata
Section 11.9
Appendix 9: Laboratory Parameters & Adverse Events Grading Tables
Section 11.10
Appendix 10: PSAP Sections for AESI Reporting.
Other RAP Appendices
Section 11.11
Appendix 11: Abbreviations & Trade Marks
Section 11.12
Appendix 12: List of Data Displays


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11.1.
Appendix 1: Time & Events
11.1.1.
BEL114333 Protocol Defined Time & Events
11.1.1.1.
Open-label 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 
PGA3
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


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BEL114333
56
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 Markers 10
X
X
X
X
Investigational 
Product
Belimumab 
Administration 11, 12
X*
X
X
X
X
X
X
X
X
X
X
X
X


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57
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.  Note: BEL112341 is referred to as ‘C1115’ in this time and events table.
*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 Protocol, 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 Protocol, 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 Protocol, 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’, Protocol, 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 Protocol, Section 6.3.11).
12. Subjects will remain under clinical supervision for 3 hours after completion of the first 2 infusions.  See Protocol, Section 5 and Protocol, Section 6.3.9. 


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58
11.1.1.2.
Open-Label 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 
Autoantibodies 4, 11
X
X
X
IgG 4, 7, 11
X
X
X
IgA & IgM 4, 7, 11
X
X


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59
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. Note: BEL112341 is referred to as ‘C1115’ in this time and 
events table.
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 Protocol, 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’, Protocol, 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 Protocol, 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.


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11.1.2.
Parent Study Protocol Defined Time & Events
11.1.2.1.
BEL113750 - Double-Blind Phase
Procedures
Screen
Random-
isation
Treatment in the Blinded Period
End of 
Therapy 
8    
Week 
FU
16 
Week 
FU
6 
Month 
FU
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Study Day
Up to
-35d
0
14
3d
28
3d
56
7d
84
7d
112
7d
140
7d
168
7d
196
7d
224 
7d
252
7d
280
7d
308
7d
336
7d
364 OR 
EXIT (4-
wks post 
dose) 1 
7d
8-wk 
Follow
-up 2 
7d
16-wk 
Follow-
up 16
7d
6
Month
Follow-
up
Study Week
Wk
-5
Wk 0
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Wk
56
Wk
64
6 
month
Written Informed Consent
X
Subject Demography
X
Medical History
X
SLE History
X
Therapy History
X
Physical Examination
X
Inclusion/Exclusion 
Criteria
X
X
Efficacy Assessments
Disease Activity Scales: 
SELENA SLEDAI, SLE 
Flare Index, BILAG and 
PGA 3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLICC/ACR Damage 
Index
X
X
Safety Assessments
Vital Signs 4, 5
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight, height 5, 6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 5
X
X
X


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61
Procedures
Screen
Random-
isation
Treatment in the Blinded Period
End of 
Therapy 
8    
Week 
FU
16 
Week 
FU
6 
Month 
FU
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Study Day
Up to
-35d
0
14
3d
28
3d
56
7d
84
7d
112
7d
140
7d
168
7d
196
7d
224 
7d
252
7d
280
7d
308
7d
336
7d
364 OR 
EXIT (4-
wks post 
dose) 1 
7d
8-wk 
Follow
-up 2 
7d
16-wk 
Follow-
up 16
7d
6
Month
Follow-
up
Study Week
Wk
-5
Wk 0
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Wk
56
Wk
64
6 
month
C-SSRS 5 See Protocol, 
Appendix 9 Baseline/
Screening. NOTE:  
“Baseline” does not refer 
to randomisation visit.  
X
C-SSRS 5 Since Last Visit.  
See Protocol, Appendix 
10 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-driven Physical 
Exam
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Record Concurrent 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess/Record Adverse 
Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory 
Assessments
Labs: HIV, Hepatitis B, C, 
and HBV DNA 7
X
Labs: Haematology & 
Modified Chem 20 (non-
fasting) 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis 8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Spot urine (protein to 
creatinine ratio) 9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ALT, AST, Total bilirubin
X 16


CONFIDENTIAL
BEL114333
62
Procedures
Screen
Random-
isation
Treatment in the Blinded Period
End of 
Therapy 
8    
Week 
FU
16 
Week 
FU
6 
Month 
FU
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Study Day
Up to
-35d
0
14
3d
28
3d
56
7d
84
7d
112
7d
140
7d
168
7d
196
7d
224 
7d
252
7d
280
7d
308
7d
336
7d
364 OR 
EXIT (4-
wks post 
dose) 1 
7d
8-wk 
Follow
-up 2 
7d
16-wk 
Follow-
up 16
7d
6
Month
Follow-
up
Study Week
Wk
-5
Wk 0
Wk
2
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
Wk
56
Wk
64
6 
month
Pregnancy Test 5, 10
S
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U16
Pharmacogenetic 
Sampling11
X
aCL Autoantibody
X
C3/C4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Anti-dsDNA 
Autoantibodies
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ANA Autoantibodies 
X
X
X
IgG 12
X
X
X
X
X
X
IgA & IgM 12
X
X
X
PT/ PTT
X
Exploratory Lab 
Assessments
Pharmacokinetic Sampling 
13
X
X
X
X
X
X
Immunogenicity 5, 14
X
X
X
X
X
X
BLyS Protein 5
X
B cell Markers 15
X
X
X
X
X
X
X
Investigational Product
Investigational product 
Administration17
X
X
X
X
X
X
X
X
X
X
X
X
X
X
See Footnotes on next page


CONFIDENTIAL
BEL114333
63
1.
The Exit (Day 364) visit will occur approximately 4 weeks after the last dose of investigational product.  For subjects completing all 48 weeks of treatment in the blinded period and 
continuing into the open-label period, this visit will also serve as their 1st (i.e., Day 0 OL [Open-Label]) visit of the open-label period and 1st dose of investigational product for the 
open-label period will be administered. Dosing information will be recorded in the Day 0 OL CRF of the open-label period.
2.
The 8-week follow-up visit is to occur approximately 8 weeks after last dose of investigational product, only if the subject does not enter the open-label period.
3.
Refer to Protocol, Section 6.2.2.3 for guidelines for scoring proteinuria for SELENA SLEDAI and BILAG evaluation.
4.
Vital signs include temperature, sitting blood pressure and heart rate. 
5.
Complete prior to dosing.
6.
If the subject’s weight changes by more than 5% from the Day 0 weight, the weight at the current visit should be used for calculating the dose to be administered. Height 
measured only at screening.
7.
HIV, Hepatitis B surface antigen, anti-HBc, anti-HBs, HBV DNA, and hepatitis C antibody (if hepatitis C antibody positive, a hepatitis C RIBA immunoblot or PCR assay should be 
reflexively performed on the same sample to confirm the results).   Note: For China subjects, if HBc result is reactive, the sample drawn for HBV DNA will be tested for viral DNA; 
otherwise, the sample will be destroyed). Subjects in China with positive hepatitis C screening results will be excluded without confirmatory hepatitis C testing; see Protocol,
Appendix 2.
8.
Urinalysis at screening will include drug screen.
9.
A 24-hour urine may be done as an additional assessment if clinically indicated (e.g., renal flare).  
10. Serum pregnancy test (S) required at screening. Results of urine pregnancy test (U) at subsequent visits, if required, must be available prior to dose. See ‘Critical Baseline 
Assessments’, Protocol, Section 6.1 for definition of those exempted from subsequent pregnancy testing.
11. PGx sampling: PGx informed consent must be obtained prior to any blood being taken for PGx research. Samples should be drawn prior to dosing. 
12. Serum immunoglobulin isotypes: IgG, IgM, IgA.
13. Pharmacokinetic sampling: Before the start of infusion on Days 0, 56, and 364 (only if entering the open-label period and at a selected China site); immediately after the end of 
infusion on Days 14 and 168; at any time during the visit at Day 364 (if not entering the open-label period at selected China sites) or during the 8-week follow-up visit.
14. All subjects withdrawing early or who do not enter the open-label period will have a blood sample taken at least 6 months after the final dose of investigational product.
15. 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).
16. This ‘16-week’ follow up visit is to occur approximately16 weeks after the last dose of investigational product.  ALT, AST, Total bilirubin, and urine pregnancy tests (for female 
subjects) will be drawn for all subjects who exit the blinded period prior to completion, and only for subjects who complete the blinded period, but who do not enter the open-label 
period.
17. Subjects will remain under clinical supervision for 3 hours after completion of the first 2 infusions.  See Protocol, Section 5.1 and Protocol, Section 6.3.11. 


CONFIDENTIAL
BEL114333
64
11.1.2.2.
BEL112341 (HGS1006-C1115)
11.1.2.2.1. BEL112341 - Double-blind Phase
Procedures
52-week Treatment Period
Days 0 – 364 (Weeks 0 – 52)
Post-
Treatment
Follow-up 
Period B
Day 0 Visit
Day 28 Visit
± 7 day
Day 56 Visit
± 7 day
Day 84 Visit
± 7 day
Day 112 Visit
± 7 day
Day 140 Visit
± 7 day
Day 168 Visit
± 7 day
Day 196 Visit
± 7 day
Day 224 Visit
± 7 day
Day 252 Visit
± 7 day
Day 280 Visit
± 7 day
Day 308 Visit
± 7 day
Day 336 Visit
± 7 day
Day 364/Exit Visit 
subjects moving to 
OL phase A
1 d
Day 364/Exit Visit 
early termination or 
subjects not moving 
Day 364 for non-
completers F± 7 days
8 wk Follow-up Visit 
(8-wks post last dose) 
± 7 day B
Unscheduled
Visit C
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
1-4 
wks 
after 
last 
SC 
dose
Wk
52
SC administration of study 
agent*
X
Weekly (1 day) with final dose at Week 51
Clinical Assessments:
Weight 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-driven PE
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C-SSRS  Baseline/Screening
At Screening visit only (See Protocol, Section 6.1, Appendix 11, and Section 7.5)
C-SSRS Since Last Visit M
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Collect self-injection logs; 
record dosing in CRF
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Record All Concurrent 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLE Disease Activity Scales 
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLICC/ACR Damage Index
X
X
X
FACIT-Fatigue Scale E
X
X
X
X
X
X
X
X


CONFIDENTIAL
BEL114333
65
Procedures
52-week Treatment Period
Days 0 – 364 (Weeks 0 – 52)
Post-
Treatment
Follow-up 
Period B
Day 0 Visit
Day 28 Visit
± 7 day
Day 56 Visit
± 7 day
Day 84 Visit
± 7 day
Day 112 Visit
± 7 day
Day 140 Visit
± 7 day
Day 168 Visit
± 7 day
Day 196 Visit
± 7 day
Day 224 Visit
± 7 day
Day 252 Visit
± 7 day
Day 280 Visit
± 7 day
Day 308 Visit
± 7 day
Day 336 Visit
± 7 day
Day 364/Exit Visit 
subjects moving to 
OL phase A
1 d
Day 364/Exit Visit 
early termination or 
subjects not moving 
Day 364 for non-
completers F± 7 days
8 wk Follow-up Visit 
(8-wks post last dose) 
± 7 day B
Unscheduled
Visit C
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
1-4 
wks 
after 
last 
SC 
dose
Wk
52
Survival assessment F
X
Laboratory Assessments:
Pregnancy Test G
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Spot Urine Protein 
Creatinine Ratio 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PT/PTT
X
X
X
X
X
Hematology & Modified
Chem 20 (non fasting) H
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complement (C3/C4) and 
anti-dsDNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics I
X
X
X
X
X
X
X
X
X
Immunogenicity J
X
X
X
X
X
X
X
B cells
X
X
X
X
X
ANA
X
Extractable nuclear antigens 
(ENAs) K
X
X
X
X
X
Antiphospholipid antibodies 
(aCL, lupus anticoagulant, 
+/- beta-2-glycoprotein-1)
X
X
X
X
X
X
Serum Immunoglobulin (IgA, 
IgM, IgG)
X
X
X
X
X
X
X
X
X


CONFIDENTIAL
BEL114333
66
Procedures
52-week Treatment Period
Days 0 – 364 (Weeks 0 – 52)
Post-
Treatment
Follow-up 
Period B
Day 0 Visit
Day 28 Visit
± 7 day
Day 56 Visit
± 7 day
Day 84 Visit
± 7 day
Day 112 Visit
± 7 day
Day 140 Visit
± 7 day
Day 168 Visit
± 7 day
Day 196 Visit
± 7 day
Day 224 Visit
± 7 day
Day 252 Visit
± 7 day
Day 280 Visit
± 7 day
Day 308 Visit
± 7 day
Day 336 Visit
± 7 day
Day 364/Exit Visit 
subjects moving to 
OL phase A
1 d
Day 364/Exit Visit 
early termination or 
subjects not moving 
Day 364 for non-
completers F± 7 days
8 wk Follow-up Visit 
(8-wks post last dose) 
± 7 day B
Unscheduled
Visit C
Wk
4
Wk
8
Wk
12
Wk
16
Wk
20
Wk
24
Wk
28
Wk
32
Wk
36
Wk
40
Wk
44
Wk
48
Wk
52
1-4 
wks 
after 
last 
SC 
dose
Wk
52
BLyS Protein
X
Pharmacogenetic Sampling L
X
* The 1st (Day 0) and 2nd (Day 7 ± 1) day administration will be under supervision at the study site.
A This is Day 0 for subjects entering the open-label (OL) extension phase of the protocol. The visit window is 1 day 
B Subjects must complete an exit visit 1-4 weeks after their last dose of study agent and a follow-up visit 8 weeks after their last dose of study agent. Subjects who enter the open-label (OL) extension 
phase will complete the 8-week follow-up visit after their last dose of study agent in the open-label phase. Subjects who enroll in the continuation protocol do not need to complete the 8-week follow-up 
visit.
C Perform other assessments as clinically indicated.
D SLE Disease Activity Scales: SELENA SLEDAI, SLE Flare Index, BILAG, PGA.
E Must be completed by the subject prior to any study-related discussion with the investigator or study coordinator. The FACIT-Fatigue Scale will only be completed by subjects for whom a survey exists 
in the subject’s language. 
F Assessed only for subjects who withdraw from treatment prior to Week 52. Attempt should be made to follow subjects who have lost to follow-up.
G Serum pregnancy test is required at screening. Urine pregnancy tests are performed during the remainder of the study. See Protocol, Section 6.1 (Screening Procedures) for definition of those 
exempted from subsequent pregnancy testing.
H Refer to Protocol, Appendix 8 for a listing of laboratory assessments to be completed. PT/PTT will be assessed according to the separate line item for PT/PTT in this table.
I
Pharmacokinetic sampling: prior to the injection on Day 0, and at any time at Weeks 4, 8, 16, 24 and 52 and anytime during the 8-week follow-up and unscheduled visit. 
J For subjects not entering the open-label extension portion of the study who had a positive anti-belimumab antibody response at the 8 week follow-up visit (or last study visit at which immunogenicity was 
assessed if 8 week follow-up visit immunogenicity sample is not available), an attempt will be made to obtain an additional serum sample for anti-belimumab antibodies (see Protocol, Section 6.8).
K Will be measured in all subjects at Day 0 and samples will be collected at the time points specified; however, the assay will be run only on subjects with elevated titers of these autoantibodies at Day 0.


CONFIDENTIAL
BEL114333
67
L Pharmacogenetic sampling informed consent must be obtained prior to any blood being taken for PGx research. Sample should be drawn prior to dosing, or the sample may be taken at any time while 
the subject is participating in the clinical study
M C-SSRS Since Last Visit (see Protocol, Appendix 12) will be used at Day 0 and all subsequent visits. The C-SSRS Baseline/Screening form (see Protocol, Appendix 11) is only used at Screening.
11.1.2.2.2. BEL112341 - Open-Label Phase
Day 0 A
(1 day)
Day 28 Visit
± 7 day
Day 84 Visit
± 7 day 
Day 168 Visit 
7 days 
Exit visit for 
non-
completersB
8-wk Follow-
up Visit H
(8 wks post 
last dose) 
± 7 days 
Wk 4
Wk 12
Wk 24
SC administration of belimumab
XB
Weekly (+/- 1 day) with final dose at Week 23
Clinical Assessments:
Adverse Events 
See Day 364/Exit Visit 
in 52-Wk Treatment Period
X
X
X
X
X
Collect self-injection logs; record dosing in CRF
X
X
X
X
Record All Concurrent Medications 
X
X
X
X
X
Weight
X
X
Symptom-driven PE
X
X
SLE Disease Activity Scales C
X
X
SLICC/ACR Damage Index
X
X
FACIT-Fatigue ScaleD
X
X
Laboratory Assessments:
Urine Pregnancy Test E
X
X
X
X
X
Urinalysis
X
X
X
Spot Urine Protein Creatinine Ratio
X
X
PT/PTT
X
Hematology & Modified Chem 20 (non fasting) F
X
X
X
Complement (C3/C4) and anti-dsDNA
X
X
Serum Immunoglobulin (IgA, IgM, IgG)
X
X
X
B-Cells 
X
X
Immunogenicity G
X
X
See Footnotes on next page


CONFIDENTIAL
BEL114333
68
A Day 0 of the extension portion of the trial is the Week 52 study visit of the double-blind phase, and represents the first belimumab administration in the open-label phase for those subjects continuing on 
the 6-month open-label study (see Protocol, Table 6.1). The visit schedule is based on the schedule for the 52-week double-blind phase. The visit window is 1 day. 
B The exit visit is scheduled for Week 24, one week after the last dose of study agent. Subjects who discontinue study agent before Week 23 must complete an exit visit 1-4 weeks after the last dose of 
study agent 
C SLE Disease Activity Scales: SELENA SLEDAI, SLE Flare Index, BILAG, PGA. 
D Must be completed by the subject prior to any study-related discussion with the investigator or study coordinator. The FACIT-Fatigue Scale will only be completed by subjects for whom a survey exists 
in the subject’s language. 
E Home urine pregnancy test is performed by the subject every 4 weeks and results are called-in to the site except during scheduled visits, when urine pregnancy test is performed at the site. 
F Refer to Protocol, Appendix 8 for a listing of laboratory assessments to be completed. PT/PTT will be assessed according to the separate line item for PT/PTT in this table.
G For subjects who had a positive anti-belimumab antibody response at the 8 week follow-up visit (or last study visit at which immunogenicity was assessed if 8 week follow-up visit immunogenicity 
sample is not available), an attempt will be made to obtain an additional serum sample for anti-belimumab antibodies (see Protocol, Section 6.8). 
H   8-Week Follow-up visit is not required in subjects entering the separate continuation protocol.


CONFIDENTIAL
BEL114333
69
11.2.
Appendix 2: Assessment Windows
As baseline is defined as the last available value prior to the initiation of treatment with 
belimumab, windowing of the safety endpoints will be employed to align years of 
belimumab exposure between those who were originally randomized to belimumab and 
those originally randomized to placebo. 
11.2.1.
Year Intervals

To report subject disposition and AE assessments with similar durations of exposure 
to active belimumab treatment, assessments will be slotted into year intervals using a 
365-day calendar year.  

Few subjects are expected to have > 6 years exposure and therefore “Year 6+” will be 
extended to the last available visit.

For subjects who withdraw during an interval, the end date of their final interval will 
be set to their exit visit date. 

For summaries, the “Any Time Post-Baseline” includes the follow-up visits, where 
follow-up visits are excluded from the “Year 6+” year interval.

For laboratory assessments, the worst value/highest toxicity reported over the year 
interval will be used in the analyses.  Concomitant medications will be reported by 
what medications a subject is taking during the interval.  In addition, AEs will be 
reported by start date.  Subject disposition, worst value/highest toxicity laboratory 
assessments, concomitant medications, and AEs will be summarized according to the 
following year categories.  
Study Year
Belimumab Study Days
Start Day
End Day
Year 0-1
Day 1[1] First Treatment Date
Day 365
Year 1-2
Day 366
Day 730
Year 2-3
Day 731
Day 1095
Year 3-4
Day 1096
Day 1460
Year 4-5
Day 1461
Day 1825
Year 5-6
Day 1826
Day 2190
Year 6+
Day 2191
Maximum Study Day [2]
NOTES:
[1]
Protocols specify Day 0 as First Treatment, but due to CDISC standard implementation first treatment date will 
appear as Day 1 in the analyses.  Also, first treatment date refers to first belimumab treatment, regardless of 
originally randomized treatment.
[2]
Last visit date will be defined as the exit visit date where applicable. Subjects who do not have an exit visit date
and only a follow up date, the date of the follow up will be used. See Section 11.5.1 for more details. 


CONFIDENTIAL
BEL114333
70
11.2.2.
Belimumab Visits

For summaries performed by belimumab visit, placebo subjects are aligned based on 
start of exposure to belimumab.  

Baseline for both belimumab and placebo randomized subjects will be the last non-
missing value prior to or on the first treatment date, except for corticosteroid use, 
which is the last 7 days prior to treatment start date.

Visits will be aligned so that each visit represents equivalent exposure time to 
belimumab, regardless of parent study treatment, and will be mapped accordingly 
based on the endpoint and scheduled visits collected.
Belimumab 
Visit Name
BEL113750
BEL112341
Parent Randomized Study Treatment
Parent Randomized Study Treatment
Belimumab
Placebo
Belimumab
Placebo
Year 1 Day 0
PS Week 0
PS Week 52/
OL Year 1 Week 0
Day 0
Day 364/Exit
Year 1 Week 4
PS Week 4
OL Year 1 Week 4
PS Day 28
PS Day 28 OLE
Year 1 Week 8
PS Week 8
OL Year 1 Week 8
PS Day 56
Year 1 Week 12
PS Week 12
OL Year 1 Week 12
PS Day 84
PS Day 84 OLE
Year 1 Week 16
PS Week 16
OL Year 1 Week 16
PS Day 112
Year 1 Week 20
PS Week 20
OL Year 1 Week 20
PS Day 140
Year 1 Week 24
PS Week 24
OL Year 1 Week 24
PS Day 168
PS Day 168 OLE/ 
OL Year 1 Week 0
Year 1 Week 28
PS Week 28
OL Year 1 Week 28
PS Day 196
OL Year 1 Week 4
Year 1 Week 32
PS Week 32
OL Year 1 Week 32
PS Day 224
OL Year 1 Week 8
Year 1 Week 36
PS Week 36
OL Year 1 Week 36
PS Day 252
OL Year 1 Week 12
Year 1 Week 40
PS Week 40
OL Year 1 Week 40
PS Day 280
OL Year 1 Week 16
Year 1 Week 44
PS Week 44
OL Year 1 Week 44
PS Day 308
OL Year 1 Week 20
Year 1 Week 48
PS Week 52/OL 
Year 1 Week 0
OL Year 1 Week 48
PS Day 364/Exit
OL Year 1 Week 24
NOTE: PS Week 48 is not mapped to a belimumab visit due to issues within visit alignment for other visits and 
reporting of data but is used for any derivations.  See Section 5.1 for more details.
Year 2 Week 4
OL Year 1 Week 4
OL Year 2 Week 4
PS Day 28 OLE
OL Year 1 Week 28
Year 2 Week 8
OL Year 1 Week 8
OL Year 2 Week 8
OL Year 1 Week 32
Year 2 Week 12
OL Year 1 Week 12
OL Year 2 Week 12
PS Day 84 OLE
OL Year 1 Week 36
Year 2 Week 16
OL Year 1 Week 16
OL Year 2 Week 16
OL Year 1 Week 40
Year 2 Week 20
OL Year 1 Week 20
OL Year 2 Week 20
OL Year 1 Week 44
Year 2 Week 24
OL Year 1 Week 24
OL Year 2 Week 24
PS Day 168 OLE/ 
OL Year 1 Week 0
OL Year 1 Week 48
Year 2 Week 28
OL Year 1 Week 28
OL Year 2 Week 28
OL Year 1 Week 4
OL Year 2 Week 4
Year 2 Week 32
OL Year 1 Week 32
OL Year 2 Week 32
OL Year 1 Week 8
OL Year 2 Week 8
Year 2 Week 36
OL Year 1 Week 36
OL Year 2 Week 36
OL Year 1 Week 12
OL Year 2 Week 12
Year 2 Week 40
OL Year 1 Week 40
OL Year 2 Week 40
OL Year 1 Week 16
OL Year 2 Week 16
Year 2 Week 44
OL Year 1 Week 44
OL Year 2 Week 44
OL Year 1 Week 20
OL Year 2 Week 20
Year 2 Week 48
OL Year 1 Week 48
OL Year 2 Week 48
OL Year 1 Week 24
OL Year 2 Week 24


CONFIDENTIAL
BEL114333
71
Year 3 Week 4
OL Year 2 Week 4
OL Year 3 Week 4
OL Year 1 Week 28
OL Year 2 Week 28
Year 3 Week 8
OL Year 2 Week 8
OL Year 3 Week 8 
OL Year 1 Week 32
OL Year 2 Week 32
Year 3 Week 12
OL Year 2 Week 12
OL Year 3 Week 12
OL Year 1 Week 36
OL Year 2 Week 36
Year 3 Week 16
OL Year 2 Week 16
OL Year 3 Week 16
OL Year 1 Week 40
OL Year 2 Week 40
Year 3 Week 20
OL Year 2 Week 20
OL Year 3 Week 20
OL Year 1 Week 44
OL Year 2 Week 44
Year 3 Week 24
OL Year 2 Week 24
OL Year 3 Week 24
OL Year 1 Week 48
OL Year 2 Week 48
Year 3 Week 28
OL Year 2 Week 28
OL Year 3 Week 28
OL Year 2 Week 4
OL Year 3 Week 4
Year 3 Week 32
OL Year 2 Week 32
OL Year 3 Week 32
OL Year 2 Week 8
OL Year 3 Week 8
Year 3 Week 36
OL Year 2 Week 36
OL Year 3 Week 36
OL Year 2 Week 12 
OL Year 3 Week 12
Year 3 Week 40
OL Year 2 Week 40
OL Year 3 Week 40
OL Year 2 Week 16
OL Year 3 Week 16
Year 3 Week 44
OL Year 2 Week 44
OL Year 3 Week 44
OL Year 2 Week 20
OL Year 3 Week 20
Year 3 Week 48
OL Year 2 Week 48
OL Year 3 Week 48
OL Year 2 Week 24
OL Year 3 Week 24
Year 4 Week 4
OL Year 3 Week 4
OL Year 4 Week 4
OL Year 2 Week 28
OL Year 3 Week 28
Year 4 Week 8
OL Year 3 Week 8
OL Year 4 Week 8
OL Year 2 Week 32
OL Year 3 Week 32
Year 4 Week 12
OL Year 3 Week 12
OL Year 4 Week 12
OL Year 2 Week 36
OL Year 3 Week 36
Year 4 Week 16
OL Year 3 Week 16
OL Year 4 Week 16
OL Year 2 Week 40
OL Year 3 Week 40
Year 4 Week 20
OL Year 3 Week 20
OL Year 4 Week 20
OL Year 2 Week 44
OL Year 3 Week 44
Year 4 Week 24
OL Year 3 Week 24
OL Year 4 Week 24
OL Year 2 Week 48
OL Year 3 Week 48
Year 4 Week 28
OL Year 3 Week 28
OL Year 4 Week 28
OL Year 3 Week 4
OL Year 4 Week 4
Year 4 Week 32
OL Year 3 Week 32
OL Year 4 Week 32
OL Year 3 Week 8
OL Year 4 Week 8
Year 4 Week 36
OL Year 3 Week 36
OL Year 4 Week 36
OL Year 3 Week 12
OL Year 4 Week 12
Year 4 Week 40
OL Year 3 Week 40
OL Year 4 Week 40
OL Year 3 Week 16
OL Year 4 Week 16
Year 4 Week 44
OL Year 3 Week 44
OL Year 4 Week 44
OL Year 3 Week 20
OL Year 4 Week 20
Year 4 Week 48
OL Year 3 Week 48
OL Year 4 Week 48
OL Year 3 Week 24
OL Year 4 Week 24
Year 5 Week 4
OL Year 4 Week 4
OL Year 5 Week 4
OL Year 3 Week 28
OL Year 4 Week 28
Year 5 Week 8
OL Year 4 Week 8
OL Year 5 Week 8
OL Year 3 Week 32
OL Year 4 Week 32
Year 5 Week 12
OL Year 4 Week 12
OL Year 5 Week 12
OL Year 3 Week 36
Year 5 Week 16
OL Year 4 Week 16
OL Year 5 Week 16
OL Year 3 Week 40
Year 5 Week 20
OL Year 4 Week 20
OL Year 5 Week 20
OL Year 3 Week 44
Year 5 Week 24
OL Year 4 Week 24
OL Year 5 Week 24
OL Year 3 Week 48
Year 5 Week 28
OL Year 4 Week 28
OL Year 5 Week 28
OL Year 4 Week 4
Year 5 Week 32
OL Year 4 Week 32
OL Year 5 Week 32
OL Year 4 Week 8
Year 5 Week 36
OL Year 4 Week 36
OL Year 5 Week 36
OL Year 4 Week 12
Year 5 Week 40
OL Year 4 Week 40
OL Year 5 Week 40
OL Year 4 Week 16
Year 5 Week 44
OL Year 4 Week 44
OL Year 5 Week 44
OL Year 4 Week 20
Year 5 Week 48
OL Year 4 Week 48
OL Year 5 Week 48
OL Year 4 Week 24
Year 6 Week 4
OL Year 5 Week 4
OL Year 6 Week 4
Year 6 Week 8
OL Year 5 Week 8
OL Year 6 Week 8
Year 6 Week 12
OL Year 5 Week 12
OL Year 6 Week 12
Year 6 Week 16
OL Year 5 Week 16
OL Year 6 Week 16
Year 6 Week 20
OL Year 5 Week 20
OL Year 6 Week 20
Year 6 Week 24
OL Year 5 Week 24
OL Year 6 Week 24
Year 6 Week 28
OL Year 5 Week 28
OL Year 6 Week 28


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72
Year 6 Week 32
OL Year 5 Week 32
OL Year 6 Week 32
Year 6 Week 36
OL Year 5 Week 36
OL Year 6 Week 36
Year 6 Week 40
OL Year 5 Week 40
OL Year 6 Week 40
Year 6 Week 44
OL Year 5 Week 44
OL Year 6 Week 44
Year 6 Week 48
OL Year 5 Week 48
OL Year 6 Week 48
Year 7 Week 4
OL Year 6 Week 4
OL Year 7 Week 4
Year 7 Week 8
OL Year 6 Week 8 
Year 7 Week 12
OL Year 6 Week 12
Year 7 Week 16
OL Year 6 Week 16
Year 7 Week 20
OL Year 6 Week 20
Year 7 Week 24
OL Year 6 Week 24
Year 7 Week 28
OL Year 6 Week 28
Year 7 Week 32
OL Year 6 Week 32
Year 7 Week 36
OL Year 6 Week 36
Year 7 Week 40
OL Year 6 Week 40
Year 7 Week 44
OL Year 6 Week 44
Year 7 Week 48
OL Year 6 Week 48
Year 8 Week 4
OL Year 7 Week 4
PS = Parent Study, OLE = Open-label extension of BEL112341, OL = Open-label study BEL114333


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11.3.
Appendix 3: Adverse Event Collapsing Rules and 
Assignment of Adverse Events to Study Year
11.3.1.
Adverse Event Collapsing

Adverse events were collected in both the parent studies and study BEL114333. 

Due to the ongoing nature of some AEs at the end of the parent study, some AEs
originate in the parent study and continue into the BEL114333 study; however, such 
events will be counted once only.  

The following table shows where AEs reside by their relationship to the parent study 
exit date or Year 1 Day 0 visit of the BEL114333 study.
AE Occurrence
Database
AE starts and ends on/before parent study Exit Visit.
Parent study only.
AE starts on/before Exit Visit in the parent study and ends either 
on/after Year 1 Day 0 of BEL114333, or after the Exit Visit but 
before Year 1 Day 0 of BEL114333 (where there is a gap 
between these visits). 1
Parent study and BEL114333 2
AE starts after Exit Visit of the parent study and ends before Year 
1 Day 0 of the BEL114333 study (where there is a gap between 
these visits). 
BEL114333 only
AE starts after Exit Visit of the parent study and ends on/after 
Year 1 Day 0 of the BEL114333 study (where there is a gap 
between these visits).
BEL114333 only
AE starts and ends on/after Year 1 Day 0 of the BEL114333 
study.
BEL114333 only 
1Records to be collapsed.
2 Ongoing AEs in the parent study BEL112341 were entered by site in the BEL114333 eCRF.  Ongoing AEs in the parent study 
BEL113750 were programmatically added to the BEL114333 data transfer.

AEs that occur in both the parent study and study BEL114333 will be collapsed based 
on the following dataset attributes: MedDRA lower level term, AE start date, and
action taken with Investigational Product (IP).

AEs in both the parent study and BEL114333 should be considered one event if 
they match on the attributes noted above. Severity, Seriousness and Relationship 
to IP should reflect worst case between the two collapsed records. Outcome and 
end date should reflect the final outcome in BEL114333.   


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
Values from BEL112341 may be mapped as appropriate.  Note: AE Start Time 
was collected in BEL114333 but not in BEL112341, so the date part will be used 
for AE collapsing.
11.3.2.
Assigning Adverse Events to Study Year
The following rules will be used for allocating AEs to study year:

Each AE will be reported in the year it started.

AEs continuing for more than one treatment year will only be reported in the year 
they first occurred.

If distinct episodes (start and stop date) of an AE are reported in multiple years, 
the AE will be reported once in each study year in which the unique event began.
o
AEs with partial start and/stop dates will be assumed to have occurred on 
treatment unless there is evidence through comparison of partial dates to suggest 
otherwise. 
o
Where possible the non-missing information will be used to assign the AE to a 
study year, if the non-missing information is insufficient to assign the AE to a 
study year then the AE will be assigned to the earliest plausible study year. 

If the AE onset date is missing assume the start date was in Year 0-1. The event 
will be reported in Year 1 and “Any Time Post-Baseline.”

If the AE end date is missing assume the AE continued until the end of study. The 
AE will be reported in year of onset and “Any Time Post-Baseline.” 

AEs that begin and end on the first day of treatment will count in the Year 0-1 
period and for “Any Time Post-Baseline.”
Table 15
Example of Assigning AEs to Study Years
Scenari
o
Pre-Treatment
Year
0-1
Year
1-2
Year
2-3
Year
3-4
Year
4-5
After End of Treatment
A
B
C
D
NOTE: Arrow indicates the start and stop date of a single AE.
Scenari
o
Assignment of AE to Study Year
Any Time Post-Baseline
Year 0-1
Year 1-2
Year 2-3
Year 3-4
Year 4-5
A
No
No
No
No
No
No
B
Yes
Yes
No
No
No
No
C
Yes
Yes
No
No
No
No
D
Yes
No
Yes
No
No
No


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11.4.
Appendix 4: Data Display Standards & Handling 
Conventions
11.4.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
Parent Study 
Parent Study Display Group [1]
Belimumab 10 mg/kg IV
Belimumab
Placebo IV
Placebo
Belimumab 200 mg SC
Belimumab
Placebo SC
Placebo
NOTES:
[1]    The “Belimumab” group will consist of those on 10 mg/kg IV and 200 mg SC during the parent study PRIOR to 
joining BEL114333.  The “Placebo” group will consist of those on IV and SC during the parent study PRIOR to joining 
BEL114333.
11.4.2.
Baseline Definition
Belimumab baseline is defined as the last available value prior to the time of initiation of 
belimumab treatment.  See Figure 1.

For subjects who were randomised to receive belimumab treatment in the parent
study, ‘baseline’ is the last value prior to the first dose of belimumab received in 
the parent study. 
o
For most assessments, this will be the assessment conducted at the 
baseline visit, but it may be the screening visit if the baseline assessment is 
missing, or if the assessment was only scheduled to be performed at 
screening.
o
If the baseline values originally derived for the parent study analyses are 
found to be calculated from data occurring post treatment, those values 
will be re-derived or set to missing.

For subjects who were randomised to placebo in the parent study, ‘baseline’ is the 
last available value prior to the first open-label belimumab dose i.e. either in 
BEL112341 open-label extension or BEL114333.  For most assessments, this will 
be the assessment at the parent study DB Week 52 visit.  For some assessments,
not available or missing at Week 52, baseline will be the last available value prior 
to belimumab start date, whether in the parent study (back to the DB Week 48 
visit) or either in BEL112341 open-label extension or BEL114333. 

Baseline demographic characteristics not captured at the beginning of 
BEL112341 open-label extension or BEL114333, will be pulled from the baseline 
of the parent study. 


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11.4.2.1.
Baseline SLE Disease Duration

Baseline SLE Disease Duration in years is calculated as follows:
Date of First belimumab Treatment / Baseline Visit – (Date of SLE Diagnosis)+1
365.25
11.4.2.2.
Total Number of ACR Criteria at Baseline

ACR criteria were only collected at screening of the parent study, so all baseline 
values will be derived from parent study regardless of the randomized treatment 
group in the parent study. 

The total number of ACR criteria will be summed for a total possible score of 11.   

Subjects were required to have at least 4 to be eligible for the study.  

If sub-questions are present for a criterion, the sub-questions will be checked 
programmatically for the creation of the total score rather than the overall criterion 
score.
11.4.2.3.
SLE Flares at Baseline

Per the CRF page design, the assessment window for deriving categories at baseline 
of ‘No flare’, ‘At least one flare’, ‘At least one severe flare’ is the time interval 
between the last SLE assessment and ‘baseline’ (~4 weeks), defined as follows: 
o
For subjects randomized to belimumab in the parent study, the time interval is 
from screening to baseline of the parent study.
o
For subjects randomized to placebo in the parent study BEL113750, the time 
interval is from Week 48 to Week 52 of the parent study.
o
For subjects randomized to placebo in the parent study BEL112341, the time 
interval is Week 48 to Week 52 of the DB phase of BEL112341.
11.4.2.4.
Derivations and Handling of Missing Baseline Data
Definition
Reporting Details
Change from Baseline
= Post-Dose Visit Value – Baseline
% Change from Baseline
= 100 x [(Post-Dose Visit Value – Baseline) / Baseline]
NOTES :

Unless otherwise specified, the baseline definitions specified in Section 11.4.2 Baseline Definitions will be used 
for derivations for endpoints / parameters and indicated on summaries and listings.

Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing.

The baseline definition will be footnoted on all change from baseline displays.


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11.4.3.
Reporting Process & Standards
Reporting Process
Software

The currently supported versions of SAS software 9.3 or higher will be used.
Reporting Area
HARP Server
: US1SALX00259
HARP Area
: arprod\gsk1550188\bel114333\final_01
QC Spreadsheet
: arprod\gsk1550188\bel114333\final_01\documents
Note: \data_look_01 will be used for the run dry. 
Analysis Datasets 

Analysis datasets will be created according to CDISC standards. 

For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will be 
implemented for conversion from SI to SDTM.
Generation of RTF Files

RTF files will be generated for all tables in the final reporting delivery.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx)
o
4.03 to 4.23: General Principles
o
5.01 to 5.08: Principles Related to Data Listings
o
6.01 to 6.11: Principles Related to Summary Tables
o
7.01 to 7.13: Principles Related to Graphics 
Formats

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated.

Numeric data will be reported at the precision collected on the eCRF.

The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses:

Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.

The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate.

Reporting for Data Listings: 

Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1).

Unscheduled or unplanned readings will be presented within the subject’s listings.
Unscheduled Visits


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Reporting Standards

Unscheduled visits will be included in summary tables and/or figures in the ‘Any Time Post 
baseline’ time interval.  Otherwise, unscheduled visits will not be displayed in by visit 
summaries or figures. 

All unscheduled visits will be included in listings.
Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.


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11.5.
Appendix 5: Derived and Transformed Data
11.5.1.
General
Subject Identifier, Breaks in Treatment and Date of Last Visit
Subject Identifier

Subjects enrolled in BEL114333 from the parent study BEL113750 continued to use the same 
subject identifier as assigned in the parent study.  Note: the site identifiers used in the parent 
study BEL113750 were changed in BEL114333 in order to retain the same subject identifier.

Subjects enrolled in BEL114333 from the parent study BEL112341 were assigned subject 
identifiers ranging from 9001 to 9030.
Dose Interruption

The first dose in the study BEL114333 must be given 4 weeks (minimum of 2 weeks, maximum 
of 8 weeks) after the last IV dose for subjects enrolled from the parent study BEL113750. 

For subjects from the SC parent study BEL112341, the first IV dose in study BEL114333 is 
targeted for 1 week (+1 week window) after the last dose of SC belimumab (scheduled for 
Week 23 in the OL extension part of BEL112341).
Note: For the purposes of reporting, dose interruptions will be ignored and exposure will be treated 
as continuous. 
Date of Last Visit

Last visit date (in BEL114333) will be defined as the exit visit date, where available.  

For subjects who do not have an open-label exit visit date, and only have a follow up date, the 
following will be used to derive a last visit date in order of priority:
1.
Death Date if non-missing and prior to Disposition Date
2.
Disposition Date, if non-missing
3.
If last non-follow up visit is after last dose of belimumab, use the minimum of a) the last 
non-follow up visit date, or b) the last dose date + 28 days.
4.
If the last non-follow up visit is prior to the date of last dose, use the last dose date.

Time to withdrawal (in days) will be calculated for each subject as 
o
Time to Withdrawal = Date of Last Visit – First Dose Date of Belimumab + 1
  
Date of Last Contact

Final contact (in BEL114333) will be defined as the latest visit, as appropriate, up to the 6 
month FU visit (post-last dose of belimumab).


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Multiple Measurements at One Time Point

Subjects having both High and Low values for Normal Ranges at any post-baseline visits for 
safety parameters will be counted in both the High and Low categories of “Any visit post-
baseline” row of related summary tables. This will also be applicable to relevant Potential 
Clinical Importance summary tables.
Study Day

Calculated as the number of days from first dose date of belimumab treatment:

Ref Date = Missing                        → Study Day = Missing 

Ref Date < First Dose Date           → Study Day = Ref Date – First Dose Date    

Ref Data ≥ First Dose Date           → Study Day = Ref Date – (First Dose Date) + 1    
11.5.2.
Study Population
Demographics
Age

Full date of birth and age were collected at screening of the parent study, and will be available 
in the data transfer.

Analysis age in years will be derived from the full date of birth and the first dose date of 
belimumab treatment, and will be calculated in SAS as: 
                      INTCK (‘YEAR’, date of birth, first dose date, ‘C’) 

Birth date will be presented in listings as ‘YYYY’. 
Body Mass Index (BMI)

BMI (kg/m2) = weight (kg) / height (m)2 will be derived from height at screening visit of the 
parent study, and weight measured at the belimumab baseline.  
11.5.3.
Safety
Adverse Events, Laboratory, SLE Medication, Average Daily Steroid Dose
Adverse Events of Special Interest (AESI)

AESI have already been identified by the Safety Review Team (SRT) (via an enhanced 
MedDRA dataset) and any event specific updates will be applied via an adjudication 
spreadsheet.
Laboratory Parameters

For laboratory values that are above or below the lower limit of quantification, having only 
character values starting with “<” or “>”, numeric values will be derived using the following rules, 
where LRESSI in the character result in standard units, and LNRES is the numeric version of 
the result:
If LRESSI = ‘> x’ then LNRES = x + 1, where x is an integer 1.
If LRESSI = ‘> x.y’ then LNRES = x.y + 0.1, where x, y are integers.
If LRESSI = ‘> x.yz’ then LNRES = x.yz + 0.01, where x, y, z are integers.
etc


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Laboratory Parameters
If LRESSI = ‘< x’ then LNRES = x - 1, where x is an integer  1.
If LRESSI = ‘< x.y’ then LNRES = x.y - 0.1, where x, y are integers.
If LRESSI = ‘< x.yz’ then LNRES = x.yz - 0.01, where x, y, z are integers.
etc
SLE Medication Categories

Concomitant medications will be reviewed and may be assigned to one of five categories based 
on their GSK Drug Dictionary preferred terms (using the current version of GSK Drug at the time 
of reporting) for summarisation throughout the course of the study:  corticosteroid, anti-malarial, 
immunosuppressant, NSAID and Aspirin, and defined as:  
Medication category
Definition
Corticosteroid
ATC code starts with “H02” and route of administration is 
intravenous, intramuscular, subcutaneous, intradermal, intra-
articular or oral.
Anti-malarial
Preferred term includes QUINACRINE, QUININE, 
HYDROXYCHLOROQUINE, MEPACRINE or CHLOROQUINE.
Meds with the following routes of administration will be excluded: 
topical, vaginal, conjunctival, intranasal, inhaled, intra-ocular, 
intratracheal, epidural, intra-articular or other.
Immunosuppressant
ATC code starts with “L04A” or preferred term contains 
CYCLOPHOSPHAMIDE, MERCATOPURINE or METOTREXATE.
Meds with the following routes of administration will be excluded:
topical or conjunctival.
NSAID
ATC code of “M01A”.
Meds with the following routes of administration will be excluded: 
topical or conjunctival.
Aspirin
Coded term contains ACETYLSALICYCLIC ACID or 
ACETYLSALICYLATE LYSINE.
Meds with the following routes of administration will be excluded: 
topical or conjunctival.


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Average Daily Steroid Dose

Concomitant medications, including corticosteroids, were collected in both the parent studies 
and BEL114333. To determine average daily dose and for analysis of steroid use, all steroid 
dosages are converted to a prednisone equivalent dosage in milligrams.

The average daily prednisone dose considers all steroids taken systemically intravenously (IV), 
intramuscularly (IM), SC, intradermally, and orally for both SLE and non-SLE reasons.

At baseline, the average daily prednisone dose is the sum of all prednisone doses over 7 
consecutive days up to, but not including Day 0, divided by 7.

While on treatment, the average daily prednisone dose is the sum of all prednisone doses over 
7 consecutive days, including the day of interest, divided by 7, unless otherwise specified. 

This average dose will be categorised as 0, >0 to 7.5, >7.5 to 40, and >40 mg/day. The 
average daily prednisone dose will be calculated for weeks 24 and 48 for each year. 
Prednisone Equivalent Daily Dose Conversions

At data base lock, all preferred terms identified with an ATC code beginning with ‘H02’ will be 
reviewed to ensure a conversion factor exists for all terms with a systemic or intra-articular route 
of administration.

Similarly, all routes of administration for preferred terms 

Reported dose of systemic steroid is converted to prednisone equivalent dose using a 
conversion factor for each medication (refer to online calculator 
http://www.globalrph.com/corticocalc.htm).

Prednisone equivalent dose (mg/day) = 
Collected dose (mg) x Conversion Factor x Frequency Factor
Preferred Term
Conversion Factor for Prednisone-Equivalent Dose (mg)
BETAMETHASONE
8.333
BETAMETHASONE DIPROPIONATE
8.333
BETAMETHASONE SODIUM PHOSPHATE
8.333
BUDESONIDE
No conversion applied – nasal spray taken by 1 subject in 
BEL113750
CELESTONA BIFAS
7.5
CORTISONE
0.2
CORTISONE ACETATE
0.2
DEFLAZACORT
5/6
DEPO-MEDROL MED LIDOKAIN
1.25
DEXAMETHASONE
6.667
DEXAMETHASONE ACETATE
6.667
DEXAMETHASONE SODIUM PHOSPHATE
6.667
FLUOCORTOLONE
3
HYDROCORTISONE
0.25
HYDROCORTISONE ACETATE
0.25
HYDROCORTISONE SODIUM SUCCINATE
0.25
MEPREDNISONE
1.25


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METHYLPREDNISOLONE
1.25
METHYLPREDNISOLONE ACETATE
1.25
METHYLPREDNISOLONE SODIUM SUCCINATE
1.25
PARAMETHASONE
2.5  
PREDNISOLONE
1
PREDNISOLONE ACETATE
No conversion applied - conjunctival
PREDNISOLONE SODIUM PHOSPHATE
1
PREDNISOLONE SODIUM SUCCINATE
1
PREDNISONE
1
PREDNISONE ACETATE
1
TRIAMCINOLONE
1.25
TRIAMCINOLONE ACETATE
1.25
TRIAMCINOLONE ACETONIDE
1.25
Frequency Factors
Frequency
Factor
BID
2
BIW
2/7
OAM
1/30
ONCE
1
PRN
null
Q2H
12
Q2W
1/14
Q3H
8
Q3MO
1/84
Q3W
1/21
Q4H
6
Q4W
1/28
Q6H
4
Q8H
3
QAM
1
QD
1
QH
24
QHS
1
QID
4
QM
1/30
QOD
1/2
QPM
1
QW
1/7
QWK
1/7
TID
3
TIW
3/7
1 TIME PER WEEK
1/7
2 TIMES PER WEEK
2/7
3 TIMES PER WEEK
3/7


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EVERY 2 WEEKS
1/14
EVERY 4 WEEKS
1/28
EVERY WEEK
1/7
UNKNOWN
null
11.5.4.
Efficacy
11.5.4.1.
SELENA SLEDAI Disease Assessment Scale
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.


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11.5.4.2.
BILAG
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.


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Domain
Endpoint
1
2
3
4
5
6
7
8
Belimumab Visit
General
Mucocutaneous
Neurological
Musculoskeletal
Cardiovascular/ 
Respiratory
Vasculitis
Renal
Hematology
New A or New B 
Compared to 
Baseline
BILAG (SRI) 
component (No 
new A and at 
most 1 new B)
BILAG 1A/2B 
Flare (At least 
1 new A and/or 
at least 2 new 
B)
BILAG 1A 
Flare (At least 
1 new A)
Baseline
A
B
E
E
D
E
D
E
1A, 1B
Year 1 Week 24
A
B
E
E
D
E
D
E
-



Year 1 Week 48
B
B
E
E
D
E
D
E
-



Year 2 Week 24
A
B
E
C
B
E
D
E
1 new B



Year 2 Week 48
A
B
B
C
D
E
D
E
1 new B



Year 3 Week 24
D
B
B
C
B
E
D
E
2 new B

(1st event)

Year 3 Week 48
A
C
C
C
D
E
D
E
-



Year 4 Week 24
B
B
B
C
B
E
D
E
2 new B



Year 4 Week 48
A
A
C
C
D
E
D
E
1 new A


(1st event)
Year 5 Week 24
A
A
B
B
D
E
D
E
1 new A, 2 new B



Year 5 Week 48
D
A
A
C
B
E
D
E
2 new A, 1 new B



Year 6 Week 24
A
A
A
B
B
E
D
E
2 new A, 2 new B



Year 6 Week 48
A
A
B
B
B
E
D
E
1 new A, 3 new B





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11.5.4.3.
Physician’s Global Assessment (PGA) Score

The PGA is collected on a 10 cm visual analogue scale (VAS).

The standard scoring range for the PGA is 0 to 3, and the score will be rescaled for 
standard reporting by multiplying the collected score by 3/10.  This re-scaling is 
applied in the eCRF data extraction.
11.5.4.4.
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.


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11.5.4.5.
SLE Flare 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.


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11.5.4.6.
Spot Urine Protein Creatinine Ratio Conversion
Spot Urine Protein Creatinine Ratio
Conversion from mg/mmol to mg/mg (performed by central laboratory)

For analysis, spot urine protein creatinine ratio (PCR) will be reported in mg/mg (or equivalently, 
g/24h).

The SI unit for PCR is mg/mmol (which is the same as g/mol as stored in the database).

To convert lab values reported as mg/mmol to mg/mg, divide the lab value by 113.12


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Spot Urine Protein Creatinine Ratio

Example: (20 g/mol) / 113.12 = 0.1768 mg/mg
11.5.5.
Biomarkers
Biomarker Parameters
Anti-ds DNA

Positive: ≥30 IU/mL

Negative: <30 IU/mL
Complement Level C3 1

Low: <90 mg/dL

High: > 180 mg/dL
Complement Level C4 1

Low: < 10 mg/dL

High: > 40 mg/dL
Immunoglobulin G

Low: < 6.94 g/L

Normal/High: 6.94 g/L
Immunoglobulin A

Low: < 0.81 g/L

Normal/High: 0.81 g/L
Immunoglobulin M

Low: < 0.48 g/L

Normal/High: 0.48 g/L
1 The SI unit for C3, C4 is g/L.  For analysis, complement levels will be reported in mg/dL.  To convert lab values reported as g/L to 
mg/dL, multiply the lab value by 100.
11.5.5.1.
B Cell Subsets
B cell specimens were collected at selected sites which were all Japan sites.
The B cell subsets (as specified in the protocol) include:

CD20+

Naïve CD20+/27–

Memory CD20+/27+

Activated CD20+/69+

Plasmacytoid CD20+/138+


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
SLE subset CD19+/27BRIGHT/38BRIGHT

Plasma cells CD20-/138+
In addition, the following two B cell subsets have been added to the RAP:

Concentration of CD19+

Short-lived plasma subset CD27+BRIGHT/CD20-
Note: the parent study BEL113750 included the analysis of these two additional B cell 
subsets.  However, B cell samples were not analysed for the short-lived plasma subset in 
the parent study BEL112341; thus, because of missing data at baseline and post-baseline 
visits for the first 6 months of belimumab treatment (and data for the subsequent 12 
months is limited to the placebo group), no summary will be produced for this B cell 
subset for BEL112341 subjects. However, available short-lived plasma B cell subset data 
will be listed. 
Reporting of B Cells subsets
CD19+, CD20+, naïve and memory B Cell subsets (collectively known as “common B
cell” subsets) are reported in counts per microliter (uL).   Activated, plasmacytoid, SLE 
subset, plasma and short-lived plasma b cells (collectively known as “rare B cell” 
subsets) are reported in counts per millilitre (mL).
Table 16 includes the variables, labels and details of derivations to be used in the 
reporting of the B cell subsets.


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Table 16
Variables, labels and details of derivations to be used in the reporting of the B cell subsets
ADaM Lab
Derivation for Normalization and/or Conversion of B cell subsets
Test Code
SDTM Lab Test Code (LBTESTCD)
Protocol specified B cell subset
B cell subset label for displays
(LBTESTCD)
BEL114333 and BEL113750 1
BEL112341
Common B cells
CD19+
CD19 (/uL)
CD19
CD19 requires conversion to /uL
CD19 reported as /uL
CD20+
CD20 (/uL)
CD20
CD20 requires conversion to /uL
CDZ037 reported as /uL
Naïve CD20+/27-
Naïve CD19+CD20+CD27- (/uL)
CDX136
CDX136 requires conversion to /uL
CDZ035 reported as /uL
Memory CD20+/27+
Memory CD19+CD20+CD27+ (/uL)
CDX137
CDZ137 requires conversion to /uL
CDZ034 reported as /uL
Rare B cells
Activated CD20+/69+
Activated CD19+CD20+CD69+ 
Normalised (COUNT/mL)
CDX141N
CDX155E, CD19E from Plasma 
Panel and CD19 concentration from 
TBNK Panel
CDZ005EV, CD19EVC from Plasma 
Panel and CD19 concentration from 
TBNK Panel 1
Plasma CD20-/138+
Plasma CD19+CD20-CD138+ Normalised 
(COUNT/mL)
CDX143N
CDX143E, CD19E from Plasma 
Panel and CD19 concentration from 
TBNK Panel
CDZ007EV, CD19EVC from Plasma 
Panel and CD19 concentration from 
TBNK Panel 1
Plasmacytoid CD20+/138+
Plasmacytoid CD19+CD20+CD138+ 
Normalised (COUNT/mL)
CDX145N
CDX145E, CD19E from Plasma 
Panel and CD19 concentration from 
TBNK Panel
CDZ002EV, CD19EVC from Plasma 
Panel and CD19 concentration from 
TBNK Panel 1
Short-lived Plasma 
CD27+BRIGHT/CD20-
Short-lived Plasma CD19+CD20-CD27b+ 
Normalised (COUNT/mL)
CDX154N
CDX154E, CD19E from Plasma 
Panel and CD19 concentration from 
TBNK Panel
NA
SLE subset CD19+/27BRIGHT/38BRIGHT
SLE Subset 
CD19+CD38b+CD27b+Lymph Normalised 
(COUNT/mL)
CDX156N
CDX156E, CD19E from Plasma 
Panel and CD19 concentration from 
TBNK Panel
CDZ024EV, CD19EVC from Plasma 
Panel and CD19 concentration from 
TBNK Panel 1
1 The derivation for the normalisation of rare B cell subsets should use the CD19 Concentration from the TBNK flow panel.  BEL113750 the TBNK method was used but the method was incorrectly 
reported as PLASMA by the central lab (and cannot be corrected as BEL113750 has met DBF).  BEL112341 the method is not specified, but it is confirmed that TBNK was used. 


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B cell unit conversions and Normalization of Rare B cell Subsets
The Benlysta program standard is to report common B cells (CD19, CD20, naïve and 
memory) in counts per microliter (uL).
Common B cells are not normalized but they must be converted to uL for reporting. To 
convert values reported from GI/L (= 109 / L) to count per uL (= cells / mm3), multiple 
the value by 103 or 1000.
Example: (0.25 GI/L) x (1000) = 250 / uL  
Rare B cell subsets are reported in counts per millilitre (mL).  Rare B cell subsets 
reported in GI/L will be converted to cells / ml using the following formula:
Normalized count/mL = [(rare cell events) / (CD19+ events)] * (CD19+ count/uL) * 1000
Note: the CD19+ B cell event count should be taken from the same flow panel as the B 
cell subset being converted in the derivation. The CD19+ concentration should be taken 
from the TBNK panel and converted to count/uL prior to the normalisation and 
conversion of the rare B cell subset.
Example: Normalization and conversion of Plasma CD20-CD138+ to count/mL
Given:

Plasma CD20-CD138+ number of events = 16

CD19+ number of events on Plasma panel = 10250

CD19+ concentration on TBNK panel =  0.35 GI/L
Then:
Plasma CD20-CD138+ Normalized (count/mL) = (16 / 10250) * (0.35*1000) * 1000 = 546.34 count/mL


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11.6.
Appendix 6: Premature Withdrawals & Handling of Missing 
Data
11.6.1.
Premature Withdrawals and Completion
Element
Reporting Detail
General

All subjects were indicated as withdrawn from study BEL114333 based on the 
design of the end of treatment CRF page.  

Study completion (i.e. as specified in the protocol) is defined as
o
the subject was still participating in the study at the time belimumab 
became commercially available in Japan and Korea * or
o
the subject transferred to a different protocol (as indicated by a reason 
for withdrawal of Investigator Discretion), or 
o
upon the decision by the sponsor to close/terminate the study (as 
indicated by a reason for withdrawal of Study/Closed Terminated).
* the study is now being closed as PMDA approved Benlysta, and subjects have 
been transitioned from study supplied belimumab over to commercially available 
Benlysta.  The KFDA approved Benlysta in 2015.  

There will be no adjustments for missing results (i.e. LOCF) due to subject 
withdrawal prior to study termination.

All subjects are expected to return for an exit visit. Subjects no longer receiving 
belimumab after their exit visit are expected to return for follow up visits.  See 
Section 2.3 for more details. 

All available data will be listed and all available planned data will be included in 
summary tables and figures, unless otherwise specified.
11.6.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data are not provided, leading to blank 
fields on the collection instrument:
o
These data will be indicated by the use of a “blank” in subject listing 
displays. Unless all data for a specific visit are missing in which case the 
data is excluded from the table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to 
be missing data and should be displayed as such.
Outliers

Any subjects excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
11.6.2.1.
Handling of Missing and Partial Dates
Element
Reporting Detail
General
Partial dates will be displayed as captured in subject listing displays.


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Element
Reporting Detail
SLE 
Duration

If only year of SLE diagnosis is known, day and month will be set to 01 January.

If month and year are known, but not the day, the day will be set to 01. 
Adverse 
Events

The EDC does not allow partial dates to be entered for AE start and stop dates. 

Completely missing start or end dates will remain missing, with no imputation 
applied. Consequently, time to onset and duration of such events will be missing.

AEs with missing start dates will be considered as treatment-emergent. 
Concomitant 
Medications

The EDC allows partial dates to be entered for medication start dates (but the 
Year must be present). Partial dates cannot be entered for medication end dates. 

For reporting, missing or partial start and/or end dates will remain missing, with no 
imputation applied.
o
Medications with partial or missing start dates will be considered as
concomitant unless there is evidence through comparison of partial dates 
to suggest otherwise.  For example, if the day is missing, then the month
and year will be compared to the month and year of the first dose of 
belimumab, and if the month and year are the same or later, the 
medication will be considered concomitant.
o
Medication with missing end dates will be considered ‘ongoing’.
11.6.2.2.
Handling of Missing Data for Statistical Analysis
Element
Reporting Detail
General

The efficacy endpoints will be summarised using observed case data, for all 
subjects in the Safety population, unless otherwise stated.

Assessments not done will remain as missing.
SLICC/ACR 
Damage 
Index

The Index is cumulative, once an item is scored it should continue to be scored 
for all subsequent assessments (see Section 11.5.4.4).

Where an assessment is completed (at least one item was marked or a total 
score of 0 was recorded), items left unchecked on the SLICC/ACR, and not 
previously checked, will be considered as “not present” (rather than missing), 
and assigned an item score of 0 in the analysis dataset (see Section 11.5.4.4).
SELENA 
SLEDAI

Where an assessment is completed (at least one item was marked or a total 
score of 0 was recorded), items left unmarked on the SELENA SLEDAI will be 
considered as “not present” (rather than missing), and assigned an item score of 
0 in the analysis dataset (see Section 11.5.4.1).
BILAG

As OL BILAG assessments are every 6 months vs monthly for the DB part of the 
parent studies, items left unmarked on the questionnaire will not be imputed. 
See Section 11.5.4.2, for the derivation of organ domain scores with missing 
data.


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11.7.
Appendix 7: Methods for Handling Centres
11.7.1.
Methods for Handling Centres
The data will be analysed on a combined-centre basis per the parent studies. No subjects 
transferred between centres in BEL114333. 


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11.8.
Appendix 8: Examination of Covariates, Subgroups & Other 
Strata
11.8.1.
Handling of Other Strata and Covariates
As all subjects, will receive IV belimumab treatment and there are no hypothesis tests, no 
additional strata or covariates will be employed in the analyses.  Subgroups will be 
defined for further exploration of the data in a descriptive fashion.
11.8.2.
Handling of Subgroups
The demographics, baseline disease characteristics, and AE endpoint summaries will also 
be performed within the following subgroups. 
Category
Covariates and / or Subgroups
Age
< 65 years and 65 years
Gender
Male and Female
Baseline SELENA SLEDAI
9 and 10
NOTES :

Age and baseline SELENA SLEDAI at first dose of belimumab treatment.


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11.9.
Appendix 9: Laboratory Parameters & Adverse Events 
Grading Tables
11.9.1.
Laboratory Values
Hematology
Urinalysis
Modified Chem-20
Total white blood cell count
(leukocytes) *
Differential:
Absolute Neutrophils *
o Segmented Neutrophils
o Band Neutrophils
o Myelocytes 
o Metamylocytes 
o Promyelocytes 
Lymphocytes *
Monocytes
Eosinophils
Basophils
Hemoglobin *
Hematocrit
Red blood cell count
Platelet count *
Prothrombin time * 1
Partial thromboplastin time * 1
Protein *
Glucose
Ketones
Occult blood
Microscopic examination
including:
WBC per hpf
RBC per hpf *
Dysmorphic RBC
Casts (specified by type eg,   
RBC, WBC)
Spot Urine 
Protein:creatinine ratio *
Electrolytes:
Sodium *
Potassium *
Magnesium *
Chloride
Carbon dioxide
Calcium adjusted for 
Albumin *
Inorganic Phosphate *
Enzymes:
SGOT (AST) *
SGPT (ALT) *
Alkaline Phosphatase *
GGT *
LDH
Other:
Creatinine *
Blood urea nitrogen 3
BUN/creatinine ratio 3
Bilirubin, direct 2
Bilirubin, total *
Protein, total
Albumin *
Uric acid *
Glucose *
Estimated Creatinine 
Clearance/GFR 
(Cockroft-Gault)
Biological Markers 
Immunoglobulins
PK/Immunogenicity
Serum Complement (C3 and C4)
B cell subtypes
Autoantibodies
Anti-dsDNA
ANA 1
Serum immunoglobulin IgG *, IgM, IgA
Anti-belimumab antibodies 
* Lab parameters with toxicity grading.
1  Only collected in the parent study.
2  Bilirubin, direct was not collected in the parent study BEL112341.
3  Urea was collected in BEL114333/BEL113750 and BUN was collected in BEL112341.  Display “Urea (mmol/L) & BUN (mmol/L)” 
as a single parameter and add a footnote to highlight that different tests were performed in the different studies.  


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11.9.2.
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


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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


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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


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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)
*(Goldfarb, 2001; Yamini, 2001; Eibl, 1995).                                                                                                                                               Modified from DMID Adult Toxicity Tables, 2001


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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


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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
  Dipstick
  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


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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


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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


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11.10.
Appendix 10: PSAP Sections for AESI Reporting
Section 15: Adverse Events of Special Interest
AESI are defined using preferred terms from the current version of MedDRA. The intent 
is to update these definitions semi-annually using the newest MedDRA version. Preferred 
terms used in the current and prior versions of MedDRA can be found in Section 17.
Section 15.1: Malignant neoplasms
Malignant neoplasms are identified using the sub-SMQs of Malignant or unspecified 
tumours (20000091), malignancy related conditions (20000092), haematological 
malignant tumours (20000227), non-haematological malignant tumours (20000228), 
haematological tumours of unspecified malignancy (20000229) and non-haematological 
tumours of unspecified malignancy (20000230) under the current version of MedDRA. 
The sub-SMQ of Malignant or unspecified tumours contains two further subcategories: 
“Malignant Tumours” and “Tumours of unspecified malignancy.” Tumours of 
unspecified malignancy will be reviewed by GSK and identified as malignant or non-
malignant for reporting.
Malignancies other than those in the “Tumours of unspecified malignancy” category will 
be categorized as hematologic, skin, or solid, based on a CMQ developed by the MAH 
(Section 17.1). In addition, the following customizations have been made (generally since 
MedDRA v19.1).
The following terms have been added as hematological tumour types:
Marginal zone lymphoma recurrent
Epstein Barr virus positive mucocutaneous ulcer
Primary gastrointestinal follicular lymphoma
Transformation to acute myeloid leukaemia
FIP1L1/PDGFR alpha fusion kinase positive
Acute bilineal leukaemia
Primary breast lymphoma
The following terms have been added as a solid tumour type:
Malignant meningioma metastatic
Astroblastoma
Langerhans cell sarcoma
Nasopharyngeal cancer metastatic
Phosphaturic mesenchymal tumour


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Squamous cell breast carcinoma
Gleason grading score
Oncotype test
Malignant urinary tract obstruction
Sarcomatoid carcinoma
Cystadenocarcinoma pancreas
Paracancerous pneumonia
Chromophobe renal cell carcinoma
Gastrointestinal adenocarcinoma
Pleuropulmonary blastoma
Primary pulmonary melanoma
Dysplastic naevus
ALK gene rearrangement positive
Breast tumour excision
NMP22 test abnormal
The following terms have been added as a skin tumour type:
Naevoid melanoma
Trichoblastic carcinoma
The following terms have been added as a tumour of unspecified malignancy:
Mismatch repair cancer syndrome
Skin neoplasm bleeding
Intestinal metastasis
Maternal cancer in pregnancy
Microsatellite instability cancer
Pulmonary tumour thrombotic microangiopathy
Tumour cavitation
Tumour hyperprogression
Paraneoplastic myelopathy
Carcinogenicity
BRAF V600E mutation positive
Paraneoplastic thrombosis 


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In addition, the preferred term “Malignant neoplasm progression” was moved from 
“Non-haematological Malignant Tumour” SMQ in MedDRA Version 20.1 to 
“Malignancy Related Conditions” SMQ in MedDRA Version 21.0, and was further 
customized to be a tumour of unspecified malignancy.
The following terms have been removed from the SMQ:
Paraneoplastic glomerulonephritis (as it is a complication of malignancy)
Lymphoma cutis
Mucinous cystadenocarcinoma of pancreas
Serous cystadenocarcinoma of pancreas
Secondary cerebellar degeneration
Bone marrow infiltration
Pseudoachalasia
Malignant exophthalmos
Tumour obstruction
Tumour psuedoprogression
Paraneoplastic arthritis
Tumour pruritus
Oncogenic osteomalacia
Neurogenic tumour
Non-melanoma skin cancer (NMSC) will be categorized using a CMQ developed by the 
Marketing Authorization Holder (MAH) (Section 17.1).
Note beginning with MedDRA v20.0 in 2017, there will be two new sub-SMQs of 
Hematological Malignancies. These do not result in any changes to how malignant 
neoplasms are identified.
Post-study malignancies that are captured in ARGUS prior to CSR approval, but are not 
captured in the clinical database, will be described within the CSR text but cannot be 
included in statistical post-text displays. Post-study malignancies are not adjudicated by 
the SRT.
Additionally, for the BEL115467 “BASE” study, any malignancies that are reported 
annually (in the Year 2-5 post-treatment follow-up) via malignancy status updates in the 
CRF and not captured in ARGUS, will not be adjudicated by the SRT.


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Section 15.2: Post-infusion/injection systemic reactions
Post-infusion/injection systemic reactions will be identified using a customization of the 
Anaphylactic Reaction SMQ (20000021). This SMQ includes a broad list of preferred 
terms including symptoms of systemic injection/infusion reactions and hypersensitivity 
reactions and anaphylaxis. For the Anaphylactic Reaction query, 4 categories of preferred 
terms are considered, including a set of core anaphylactic terms (Category A), upper 
airway/respiratory terms (Category B), angioedema/urticaria/pruritus/flush terms 
(Category C), and cardiovascular/hypotension terms (Category D).
The customizations of the SMQ involve terms in Categories A, B and C: 

Category A has been modified to include the following additional terms: “Infusion-
related reaction”, “Drug hypersensitivity”, “Hypersensitivity”, and “Urticarial 
vasculitis”.

Category B has been modified to include the following additional terms:
“Oropharyngeal oedema” and “Pharyngeal oedema”. 

Category C has been modified to include the following additional terms: “Fixed 
eruption”, “Drug eruption” and “Lipoedema”.
GSK has also removed eight terms that are not relevant for an analysis of hypersensitivity 
reactions to belimumab (“Anaphylactic transfusion reaction”, “Dialysis membrane 
reaction”, “Cyanosis”, “Nasal obstruction”, “Ocular hyperaemia”, “Tachypnoea”, 
“Hereditary angioderma with C1 est” and “Acquired C1 inhibitor deficiency”).

Anaphylactic transfusion reaction is an adverse event associated with a blood 
transfusion, not related to study medication. 

Dialysis membrane reaction is associated with adverse events related to kidney 
transplants and dialysis, not related to study medication.

Cyanosis, nasal obstruction, ocular hyperaemia, tachypnoea, hereditary angioderma 
with C1 est, acquired C1 inhibitor deficiency are adverse events generally not 
associated with post-infusion/injection systemic reactions.
The terms “Injection site urticaria”, “Eye pruritis”, and “Procedural shock” are part of the 
Anaphylactic Reaction SMQ but were inadvertently excluded (identified during PSAP 
Version 6 update). These terms will be included when the next MedDRA version i.e. 
MedDRA Version 21.1. is released.
Algorithmic Search Criteria
The post-infusion/injection systemic reactions per Anaphylactic Reaction SMQ 
algorithmic search are defined as follows:
Subjects must have the following associated with the same infusion/injection: 
a.
at least 1 AE coding to a Category A preferred term or


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b.
2 AEs, 1 coding to a Category B preferred term and the other coding to a Category C 
preferred term or
c.
2 AEs, 1 coding to a Category D preferred term and the other coding to either a 
Category B preferred term or to a Category C preferred term.
For the algorithmic search, if any event at a given infusion/injection meets the definition 
under criteria a, b or c, then all events in Categories A, B, C and D associated with that 
injection/infusion will be considered AESI.
GSK SRT will review all serious events identified via the broad search using a 21-day 
window from the start of an infusion/injection (see PSAP Section 8.3.2 for the definition 
of the assessment windows), and adjudicate these events as post-infusion/injection 
systemic reactions or hypersensitivity reactions per the criteria in Section 16.2. Therefore, 
the window for the narrow, broad and algorithmic searches of AE and SAE data from the 
clinical database for SRT reporting (PSAP Section 13.3) is 21 days to correspond to the 
window for adjudication. Adverse events with partial or missing start dates will be 
included unless there is evidence through comparison of partial dates to suggest 
otherwise.
Note, for CSR reporting, narrow, broad, and algorithmic searches of AE and SAE data 
will be run using a 3-day window from the start of an infusion/injection.
Sampson Criteria
Sampson et al define anaphylaxis as a severe, potentially fatal, systemic allergic reaction 
that occurs suddenly after contact with an allergy-causing substance. In addition, one of 
the following 3 criteria must be met: (1) acute onset of illness with involvement of skin or 
mucosal tissue, accompanied with either respiratory compromise, reduced blood pressure, 
or hypotension-related symptoms of end-organ dysfunction (2) reduced blood pressure 
associated with a known allergen or (3) two or more of the following that occur rapidly 
after exposure to an allergen: a) involvement of skin-mucosal tissue b) respiratory 
compromise c) reduced blood pressure d) persistent GI symptoms. 
With the exception of GI symptoms, all symptoms required to assess anaphylaxis per 
Sampson criteria would be identified by Broad Anaphylaxis SMQ or the Anaphylactic 
Reaction SMQ algorithmic. Therefore, any events falling under the below criteria will be 
adjudicated by SRT prior to database release to determine if serious anaphylaxis per 
Sampson criteria is met.
Possible cases of serious anaphylaxis per Sampson criteria will be identified as follows:
a.
Any Infusion/Injection-related Reaction per Anaphylactic Reaction SMQ broad 
search SAE which occurs during the first 24 hours after the start of an 
infusion/injection.
b.
Any AE or SAE in the “Gastrointestinal disorders” SOC that coincides with the 
event that meets the criterion in a) above.


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c.
Any anaphylaxis and hypersensitivity reactions per Anaphylactic Reaction SMQ 
algorithmic search SAE which occurs during the first 24 hours after the start of an 
infusion/injection.
Section 15.3: Infections
The infections of special interest are described below.
Section 15.3.1: Opportunistic Infections
Opportunistic infections will be identified using a broad CMQ developed by the MAH
(Section 17.1). Any events falling under these preferred terms will be adjudicated by 
GSK to determine if criteria are met for an opportunistic infection, per the criteria in 
Section 16.3.
Section 15.3.2: Mycobacterium Tuberculosis
Tuberculosis events will be identified using a CMQ developed by the MAH (Section 
17.1). Any events falling under these preferred terms will be adjudicated by GSK to 
determine if criteria are met for an opportunistic infection (Section 16.3).
Section 15.3.3: Herpes Zoster
Herpes Zoster events will be identified using a CMQ developed by the MAH (Section 
17.1). Additional manual adjudication by GSK will identify events that are recurrent or 
disseminated (Section 16.3).
Section 15.3.4: Pneumonia
Pneumonia events will be identified using a CMQ developed by the MAH (Section 17.1). 
Pneumonia events will not be reported separately, but are being flagged in the event 
further evaluation is necessary.
Section 15.3.5: Sepsis
Sepsis events will be identified using a CMQ developed by the MAH (Section 17.1 ).
Section 15.4: Depression/suicide/self-injury
Section 15.4.1: Depression (excluding suicide and self-injury)
Depression events will be identified using a CMQ including the preferred terms from the 
depression (excluding suicide and self injury) SMQ (20000167) plus additional terms 
added by the MAH (Section 17.1).
Section 15.4.2: Suicide and Self-Injury
Suicide and self-injury events will be identified using the SMQ (20000037) plus 
additional terms added by the MAH (Section 17.1).


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Section 15.5: Fatalities
All fatalities that are reported while a subject is eligible for SAE reporting will be 
identified in the clinical database and subsequently adjudicated by the GSK SRT into a 
general category of death (Section 16.5).
Post-study fatalities that are captured in ARGUS prior to CSR approval, but are not 
captured in the clinical database, will be described within the CSR text but cannot be 
included in statistical post-text displays. Post-study fatalities are not adjudicated by the
SRT.
Additionally, for the BEL115467 “BASE” study, any fatalities that are reported annually 
(in the Year 2-5 post-treatment follow-up) via survival status updates in the CRF and not 
captured in ARGUS, will not be adjudicated by the SRT. 
Section 16: GSK SRT Adjudication of Adverse Events of Special 
Interest
Adverse events of special interest (AESI) are identified per the preferred terms(Section 
17.1) and other criteria described in Section 15. The following AESI are adjudicated in-
stream at the subject level by GSK during regular SRT meetings or during quarterly 
adjudication, and then prior to database release for CSR reporting purposes, per the 
criteria described below.
In-stream review/adjudication of AESI is conducted as follows: 

Review/Adjudication of AESI in ARGUS
Safety Evaluation and Risk Management (SERM) lists all events in ARGUS each 
month for SRT to review.  AESIs are adjudicated at SRT meetings and entered onto 
Excel spreadsheets maintained by SERM.  These spreadsheets are cumulative and 
contain events for all belimumab studies (clinical trials, post-marketing studies and 
spontaneous reports). SERM refer to these as “Cumulative AESI spreadsheets”.  
SERM use these spreadsheets to tabulate the numerators used for PBRER/DSUR 
rates (see PSAP Section 7.6).  The numerators are typically updated shortly after the 
Data Lock Point, and updated numerators are then used for PBRER/DSUR updates.  
The numerators are tracked in spreadsheets referred to as “AESI numerator 
spreadsheets”.
Review/Adjudication of AESI in the Clinical Database
The SRT central programming team sends spreadsheets of AESIs based upon the CRF 
(Clinical Database) to SERM for periodic in-stream review. These spreadsheets contain 
AEs and SAEs and are study specific. SERM enter adjudication based on the SRT 
adjudication (“Cumulative AESI spreadsheets”) and checks for missing serious AESIs 
between ARGUS and the Clinical Database.  SERM send the clinical data derived 


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spreadsheets to the study specific Medical Monitor, who adjudicates the non-serious 
events. Once updated, the spreadsheets are returned to the SRT central

programming team and are used to create the SRT output for the next periodic in-
stream review.
In addition, as part of individual study close-out procedures, the adjudications should be 
finalized as follows:

Just preceding database freeze (DBF), allowing time to send queries or update the 
eCRF/database as necessary prior to DBF, and are used in the CSR.

Between DBR and Source Database Lock (as required) to provide final confirmation 
of adjudications and ensure there are no new AESI or relevant data changes to 
adjudicated events since the pre-DBR adjudication. This would be a requirement for 
declaring database freeze (DBF).
Note, at study close-out, the study programming team is responsible for generating 
spreadsheets of AESIs based upon the clinical data, in consult with the SRT central 
programming team, and liaising with SERM to finalise the adjudication. Refer to the SRT 
team site for more information: SRT/Team Documents/SRT documentation/ 
AESI/Belimumab_ADAE_AEANAL AESI Adjudication Variables Process.doc.
Section 16.1: Malignancies
All malignancies identified via the terms in Section 17.1 will be reviewed by GSK SRT. 
The classification of malignancies as solid tumor, hematological, and skin will be 
reviewed against the verbatim term to confirm an appropriate and accurate preferred term 
has been assigned, or to recommend follow-up with the investigator for additional 
specificity on the verbatim term. In addition, malignancies that are flagged more than 
once, e.g., based on a term for both a diagnostic procedure and a diagnosis, will be 
adjudicated as one event.
Tumors of unspecified malignancy, as identified per the terms in Section 17.1, will be 
reviewed clinically by the GSK SRT for reporting. In general, non-serious events in the 
tumours of unspecified malignancy with insufficient information will be categorized as 
not malignant. Serious adverse events with insufficient information will be categorized as 
either not malignant or malignant based on the type of tumor and likelihood the tumor 
type is malignant (e.g., thyroid nodules are common in SLE patients and are generally not 
malignant; tumor types with higher likelihood for malignancy would be assumed to be 
malignant).
Section 16.2: Serious hypersensitivity and post-infusion/injection systemic reactions
GSK SRT will review all serious cases identified from the Broad Anaphylaxis SMQ as 
described in Section 15 and Section 17.1, applying clinical judgment to determine if the 
preferred terms are indicative of a hypersensitivity or post-infusion/injection reaction. 
Time to onset after an infusion/injection and details provided in the clinical narratives 
with respect to the nature and likely cause of the events are taken into consideration. The 
GSK SRT adjudicates serious hypersensitivity reactions into a category based primarily 
on time to onset: acute (onset < 24 hours), delayed acute (onset 2-3 days), or delayed, 


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non-acute (onset 4-21 days). In addition to time to onset, description of associated 
symptoms is taken into account for this categorization. In studies where subjects are
receiving weekly injections, any delayed, non-acute reactions will typically occur in the 
interval 4-7 days later, but may occur up to 21 days later following a missed injection or 
after the last injection.
In addition, possible cases of serious anaphylaxis per Sampson criteria will be identified 
per the criteria in Section 15. Any events falling under these criteria will be adjudicated 
by GSK prior to database release to determine if serious anaphylaxis per Sampson criteria 
is met.
Section 16.3: Potential opportunistic infections
Opportunistic infections (OIs) will be identified using a list of preferred terms (Section 
17.1), designed to cast a wide net for events potentially indicative of an opportunistic 
infection. Any identified events will be adjudicated by the GSK SRT to determine if 
criteria are met for an opportunistic infection. Targeted follow-up is sought for events 
with insufficient information. In general, potential OIs that are non-serious with 
insufficient information to adjudicate will be considered non-opportunistic. Potential OI 
SAEs with insufficient information to adjudicate will be considered opportunistic. See 
below for a list of agreed upon pathogens and infections considered to be opportunistic 
for the purpose of adjudication.
Pathogens and Infections Considered Opportunistic:

Acinetobacter infection

Aspergillosis

Blastomycosis, extrapulmonary

Candidiasis of esophagus, bronchi, trachea or lungs

Capnocytophaga infection

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis infection, chronic intestinal (greater than 1 month duration)

CMV disease other than liver, spleen, or nodes

Herpes simplex – bronchitis, pneumonitis, or esophagitis

Herpes Zoster (adjudication details are below)

Histoplasmosis disseminated or extrapulmonary

Human polyomavirus infection

Isosporiasis, chronic intestinal (greater than one month duration)

Listeriosis

Mycobacterium avium complex or M. Kansasii, disseminated or extrapulmonary

Nocardiosis 

Other non-tuberculous mycobacterium (NTM) infections (other species or 
unidentified species), disseminated or extrapulmonary*

Polyomavirus (JC virus or BK virus) associated nephropathy (including PML)

Pneumocystis jiroveci infection

Toxoplasmosis of brain


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* Extra pulmonary NTM infections are generally considered an OI unless the affected 
extra pulmonary area followed a wound or trauma.
In addition, GSK SRT will review all SAEs, including those coded under preferred terms 
not listed in Section 17.1, and utilizing the supplemental/narrative information, will 
adjudicate the SAEs as OI if warranted based on medical judgment. 
Other Infections of Interest but not generally considered opportunistic:

Mycobacterium tuberculosis (adjudication details are below)

Salmonella sepsis - there may be rare exceptions in which the presentation is 
atypical, which will be considered on a case-by-case basis by the SRT.

Hepatitis B

Hepatitis C
Herpes Zoster
Herpes Zoster events will be identified per terms in Section 17.1. Adjudication by GSK 
SRT will identify events that are recurrent or disseminated. Herpes Zoster is considered 
disseminated if there is involvement of other organs other than the skin or if skin lesions 
(1) cross the midline of the body or (2) are in non-adjacent dermatomes or (3) are located 
in more than three adjacent dermatomes. Herpes zoster is considered an opportunistic 
infection if it is adjudicated as recurrent or disseminated. However, there may be some 
uncommon occurrences of a herpes zoster case that is adjudicated as an OI but is neither 
recurrent or disseminated.
Mycobacterium Tuberculosis
Tuberculosis (TB) cases are reviewed by the GSK SRT to determine if a case is an OI. 
The following principles are applied: Pulmonary TB in an endemic area is not considered 
an OI. Pulmonary TB in an non-endemic area would be considered an OI unless the 
subject had close contact with a person infected with TB. Extra pulmonary TB is 
generally considered an OI unless the affected extra pulmonary area followed a wound or 
trauma.
Section 16.4: Suicide/self-injury
Suicide and self-injury SAEs will be identified using the preferred terms identified in
Section 17.1 and subsequently adjudicated into the following categories:
Adjudicated Category
Suicidal Behaviour
Completed Suicide
Suicidal Ideation
Self-Injurious Behaviour without Suicidal Intent


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In addition, GSK SRT will review all SAEs, including those coded under preferred terms 
not listed in Section 17.1, and utilizing the supplemental/narrative information, will 
adjudicate the SAEs as suicide/self-injury if warranted based on medical judgment. 
Section 16.5: Fatalities
All fatalities that are reported while a subject is eligible for SAE reporting will be 
identified in the clinical database and subsequently adjudicated by the GSK SRT into a 
general category of death.
All fatalities will be adjudicated into one of the following categories:
Adjudicated Category of Death
SLE-Related
Infectious
Vascular
Gastrointestinal
Respiratory
Malignancy
Hypersensitivity
Suicide
Surgical Complication
Unknown
Hematologic
Trauma
Additional ‘categories of death’ may be added in the future should a fatality not clearly 
fit into one of the ‘categories’ listed above. The ‘categories’ will not change unless 
agreed upon by the GSK SRT.  
Section 17: AESI Preferred term definitions under current and prior 
versions of MedDRA
The AESI definitions under the current version of MedDRA are found via the IMMS 
pathname in Section 17.1. Prior AESI definitions under legacy versions of MedDRA are 
found in the subsequent sections.
Section 17.1: MedDRA v21
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_21.csv
Section 17.2: MedDRA v20.1
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_201.csv
Section 17.3: MedDRA v20.0


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/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_20.csv
Section 17.4: MedDRA v19.1
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_191.csv
Section 17.5: MedDRA v19.0
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_19.csv
Section 17.6: MedDRA v18.1
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_181.csv
Section 17.7: MedDRA v18.0
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_18.csv
Section 17.8: MedDRA v17.1
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_171.csv
Section 17.9: MedDRA v17.0
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_17.csv
Section 17.10: MedDRA v16.1
The AESI definitions were not updated for MedDRA v16.1.
Section 17.11: MedDRA v16.0
/Study File/GSK1550188/_Project/Meta Analysis/PSAP/AESI_16.csv


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11.11.
Appendix 11: Abbreviations & Trade Marks
11.11.1.
Abbreviations
Abbreviation
Description
ADaM
Analysis Data Model
ACR
American College of Rheumatology
AE
Adverse Event
AESI
Adverse Event of Special Interest
ANA
Anti-nuclear antibody
Anti-dsDNA
Anti-double-stranded DNA
ATC
Anatomical Therapeutic Chemical
BILAG
British Isles Lupus Assessment Group of SLE Clinics
BMI
Body Mass index
BUN
Blood Urea Nitrogen
C3 / C4
Complement 3 / Complement 4
CDISC
Clinical Data Interchange Standards Consortium
CNS
Central Nervous System
CPMS
Clinical Pharmacology Modelling & Simulation
CRF
Case Report Form
CSR
Clinical Study Report
DB
Double Blind
DP
Decimal Places
eCRF
Electronic Case Record Form
GSK
GlaxoSmithKline
hpf
High-power Field
IDSL
Integrated Data Standards Library
IgA, IgG, IgM
Immunoglobulin A, G, M
IM
Intramuscular
IV
Intravenous
LLN
Lower Limit of Normal
LOC
Last Observation Carries Forward
LTC
Long Term Continuation (studies)
MedDRA
Medical Dictionary for Regulatory Activities
NMSC
Non-melanoma skin cancer
OL
Open-Label
PDMP
Protocol Deviation Management Plan
PGA
Physician’s Global Disease Assessment
PK
Pharmacokinetic
PSAP
Program Safety Analysis Plan
PT
Preferred Term
QC
Quality Control
RAP
Reporting and Analysis Plan
RBC
Red Blood Cell
SAC
Statistical Analysis Complete


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Abbreviation
Description
SAE
Serious Adverse Event
SD
Standard Deviation
SDTM
Study Data Tabulation Model
SE
Standard Error
SELENA
Safety of Estrogen in Lupus National Assessment
SFI
SLE Flare Index
SLE
Systemic Lupus Erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease Activity Index
SLICC
Systemic Lupus International Collaborating Clinics
SMQ
Standardized MedDRA Query
SOC
System Organ Class
SOP
Standard Operation Procedure
SRI
SLE Response Index
SRT
Safety Review Team
TFL
Tables, Figures & Listings 
ULN
Upper Limit of Normal
VAS
Visual Analogue
WOCF
Worst Observation Carried Forward
yrs
Years
11.11.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
ADVAIR
SAS
WinNonlin


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11.12.
Appendix 12: List of Data Displays
11.12.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.1 to 1.32
Safety
2.1 to 2.86
2.1 to 2.14
Efficacy
3.1 to 3.29
3.1 to 3.16
Biomarker
5.1 to 5.11
5.1 to 5.8
Section
Listings
ICH Listings (Safety)
1 to 56
Other Listings
11.12.2.
Mock Example Shell Referencing
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Section 11.13: Example Mock Shells for Data Displays.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Efficacy/Biomarker
EFF_Fn
EFF_Tn
EFF_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL / TST ID / Example Shell’ or ‘Programming Notes’ column as 
‘[Non-Standard] + Reference.’


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11.12.3.
Study Population Tables
Study Population : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
Subject Disposition
1.1.
All Subjects
POP_T1
Subject Enrolment
1.2.
Safety
POP_T2
Enrolment by Site
1.3.
Safety
POP_T3
Belimumab Treated Person-Years on Study
1.4.
All Enrolled 
Subjects
POP_T4
Subject Disposition Per End of Treatment CRF
Prioritise for SAC deliverable
1.5.
Safety
POP_T5
Subject Completion Status Per Protocol
1.6.
Safety
POP_T6
Subject Completion Status Per Protocol by Year Interval
1.7.
Safety
POP_T7
Time to Withdrawal for Those Subjects Who Exited Prior to 
Study Closing 
Inclusion / Exclusion Criteria
1.8.
All Enrolled 
Subjects
POP_T8
Summary of Inclusion/Exclusion Criteria Deviations
Protocol Deviations
1.9.
All Enrolled 
Subjects
POP_T9
Subjects with Important Protocol Deviations
Demography & Baseline Characteristics
1.10.
Safety
POP_T10
Demographic and Baseline Characteristics
Prioritise for SAC deliverable
1.11.
Safety
POP_T10
Demographic and Baseline Characteristics by Age Group (< 65 
years)


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Study Population : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
1.12.
Safety
POP_T10
Demographic and Baseline Characteristics by Age Group (>= 65 
years)
1.13.
Safety
POP_T10
Demographic and Baseline Characteristics by Gender (Male)
1.14.
Safety
POP_T10
Demographic and Baseline Characteristics by Gender (Female)
1.15.
Safety
POP_T10
Demographic and Baseline Characteristics by Baseline SELENA 
SLEDAI (<= 9)
1.16.
Safety
POP_T10
Demographic and Baseline Characteristics by Baseline SELENA 
SLEDAI (>= 10)
1.17.
All Enrolled 
Subjects
POP_T11
Summary of Age Ranges at Baseline
EudraCT
1.18.
All Enrolled 
Subjects
POP_T12
Race and Racial Combination Details
Prioritise for SAC deliverable
Baseline Disease Activity
1.19.
Safety
POP_T13
Baseline Disease Activity
1.20.
Safety
POP_T13
Baseline Disease Activity by Age Group (< 65 years)
1.21.
Safety
POP_T13
Baseline Disease Activity by Age Group (>= 65 years)
1.22.
Safety
POP_T13
Baseline Disease Activity by Gender (Male)
1.23.
Safety
POP_T13
Baseline Disease Activity by Gender (Female)
1.24.
Safety
POP_T13
Baseline Disease Activity by Baseline SELENA SLEDAI (<= 9)
1.25.
Safety
POP_T13
Baseline Disease Activity by Baseline SELENA SLEDAI (>= 10)
Other Baseline Data
1.26.
Safety
POP_T14
Allowable SLE Medication Usage at Baseline


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Study Population : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
1.27.
Safety
POP_T15
ACR Classification Criteria at Parent Study Baseline
Data collected at DB parent study 
screening visit. 
1.28.
Safety
POP_T16
SELENA SLEDAI Organ and Item Involvement at Baseline
1.29.
Safety
POP_T17
BILAG Grade by Organ Domain at Baseline
1.30.
Safety
POP_T18
Complement Levels at Baseline
Parameters = C3, C4
1.31.
Safety
POP_T19
Autoantibody Levels at Baseline
Parameters = anti-dsDNA, ANA
1.32.
Safety
POP_T20
Immunoglobulin Levels at Baseline
Parameters = IgG, IgA, IgM


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11.12.4.
Safety Tables
Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
Medications
2.1.
Safety
SAFE_T1
Concomitant Medications by ATC Level 1 and ATC Level 4 
Term
2.2.
Safety
SAFE_T1
Concomitant Medications by ATC Level 4 and Preferred Term
2.3.
Safety
SAFE_T2
SLE Medication by Year Interval
2.4.
Safety
SAFE_T3
Shifts from Baseline in Daily Prednisone Equivalent Steroid 
Dose by Belimumab Visit
Exposure
2.5.
Safety
SAFE_T4
Study Drug Exposure
Adverse Events by SOC
2.6.
Safety
SAFE_T5
Adverse Events Summary by Year Interval
2.7.
Safety
SAFE_T6
Adverse Events by SOC
2.8.
Safety
SAFE_T6
Serious Adverse Events by SOC
2.9.
Safety
SAFE_T6
Severe Adverse Events by SOC
2.10.
Safety
SAFE_T6
Study Drug Related Adverse Events by SOC
2.11.
Safety
SAFE_T6
Adverse Events Leading to Permanent Discontinuation of Study 
Drug or Withdrawal from Study by SOC
Adverse Events Rates by SOC
2.12.
Safety
SAFE_T7
Adverse Event Rates per 100 Person-Years by SOC
1
2.13.
Safety
SAFE_T7
Serious Adverse Event Rates per 100 Person-Years by SOC
1
2.14.
Safety
SAFE_T7
Severe Adverse Event Rates per 100 Person-Years by SOC
1


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.15.
Safety
SAFE_T7
Study Drug Related Adverse Event Rates per 100 Person-Years
by SOC
2.16.
Safety
SAFE_T7
Adverse Events Leading to Permanent Discontinuation of Study 
Drug or Withdrawal from Study Rates per 100 Person-Years by 
SOC
Adverse Events by SOC and PT
2.17.
Safety
SAFE_T8
Adverse Events by SOC and PT
Prioritise for SAC deliverable
2.18.
Safety
SAFE_T8
Serious Adverse Events by SOC and PT
2.19.
Safety
SAFE_T8
Severe Adverse Events by SOC and PT
2.20.
Safety
SAFE_T8
Study Drug Related Adverse Events by SOC and PT
2.21.
Safety
SAFE_T8
Adverse Events Leading to Permanent Discontinuation of Study 
Drug or Withdrawal from Study by SOC and PT
Adverse Events by SOC and PT (Subgroups)
2.22.
Safety
SAFE_T8
Adverse Events by Age Group (< 65 Years), SOC and PT
2.23.
Safety
SAFE_T8
Adverse Events by Age Group (65 Years), SOC and PT
2.24.
Safety
SAFE_T8
Adverse Events by Gender (Male), SOC and PT
2.25.
Safety
SAFE_T8
Adverse Events by Gender (Female), SOC and PT
2.26.
Safety
SAFE_T8
Adverse Events by Baseline SELENA SLEDAI (9), SOC and 
PT 
2.27.
Safety
SAFE_T8
Adverse Events by Baseline SELENA SLEDAI (10), SOC and 
PT 
Adverse Events: Non-Serious and Serious by SOC and PT (for Disclosure)


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.28.
Safety
SAFE_T8
Most Common Non-Serious Drug Related Adverse Events 
(10% incidence in any interval) by SOC and PT
PLS
2.29.
Safety
SAFE_T8
Most Common Serious Drug Related Adverse Events (2% 
incidence in any interval) by SOC and PT
PLS – 2% cut-off to be used for dry run, 
may revise for final 
2.30.
Safety
SAFE_T9
Most Common (5%) Non-Serious Adverse Events by SOC 
and PT (Number of Subjects and Occurrences)
FDAAA – prioritise for SAC deliverable
2.31.
Safety
SAFE_T10
Serious Adverse Events by SOC and PT (Number of Subjects 
and Occurrences)
FDAAA – prioritise for SAC deliverable
Adverse Events by PT
2.32.
Safety
SAFE_T8
Adverse Events by PT
2.33.
Safety
SAFE_T8
Serious Adverse Events by PT
2.34.
Safety
SAFE_T8
Severe Adverse Events by PT
2.35.
Safety
SAFE_T8
Study Drug Related Adverse Events by PT
2.36.
Safety
SAFE_T8
Adverse Events Leading to Permanent Discontinuation of Study 
Drug or Withdrawal from Study by PT
Adverse Events by Maximum Intensity
2.37.
Safety
SAFE_T11
Adverse Events by SOC and Maximum Severity
2.38.
Safety
SAFE_T12
Adverse Events by SOC and PT and Maximum Severity
Adverse Events of Special Interest
2.39.
Safety
SAFE_T13
Adverse Events of Special Interest by Category
2.40.
Safety
SAFE_T14
Malignant Neoplasm Adverse Events of Special Interest by 
Category and PT


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.41.
Safety
SAFE_T14
Post-Infusion Systemic Reaction Adverse Events of Special 
Interest by Category and PT
2.42.
Safety
SAFE_T14
Serious Post-Infusion Systemic Reaction Adverse Events of 
Special Interest by Category and PT
2.43.
Safety
SAFE_T14
Infection Adverse Events of Special Interest by Category and PT
2.44.
Safety
SAFE_T14
Serious Infection Adverse Events of Special Interest by 
Category and PT
2.45.
Safety
SAFE_T14
Infection Adverse Events of Special Interest Leading to 
Permanent Discontinuation of Study Drug or Withdrawal from 
Study by Category and PT
2.46.
Safety
SAFE_T14
Depression/Suicide/Self-injury Adverse Events of Special 
Interest by Category and PT
2.47.
Safety
SAFE_T14
Deaths by Category and PT
Adverse Events of Special Interest Rates
2.48.
Safety
SAFE_T15
Adverse Events of Special Interest Rates per 100 Person-Years 
by Category
2.49.
Safety
SAFE_T16
Malignant Neoplasm Adverse Events of Special Interest Rates
per 100 Person-Years by Category and PT
2.50.
Safety
SAFE_T16
Post-Infusion Systemic Reaction Adverse Events of Special 
Interest Rates per 100 Person-Years by Category and PT
2.51.
Safety
SAFE_T16
Serious Post-Infusion Systemic Reaction Adverse Events of 
Special Interest Rates per 100 Person-Years by Category and 
PT


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.52.
Safety
SAFE_T16
Infection Adverse Events of Special Interest Rates per 100 
Person-Years by Category and PT
2.53.
Safety
SAFE_T16
Serious Infection Adverse Events of Special Interest Rates per 
100 Person-Years by Category and PT
2.54.
Safety
SAFE_T16
Infection Adverse Events of Special Interest Leading to 
Permanent Discontinuation of Study Drug or Withdrawal from 
Study Rates per 100 Person-Years by Category and PT
2.55.
Safety
SAFE_T16
Depression/Suicide/Self-injury Adverse Events of Special 
Interest Rates per 100 Person-Years by Category and PT
Laboratory
2.56.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Hematology
2.57.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Liver Function
2.58.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Electrolytes
2.59.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Other Chemistries
2.60.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Immunoglobulins (Subjects from Parent Study 
BEL113750)
2.61.
Safety
SAFE_T17
Laboratory Results (Observed and Change from Baseline) by 
Belimumab Visit:  Immunoglobulins (Subjects from Parent Study 
BEL112341)
Worst Laboratory Toxicity Grade (by Year Interval)


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.62.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: Hematology
2.63.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: Liver Function
2.64.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: Electrolytes
2.65.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: Other 
Chemistries
2.66.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: Urinalysis
2.67.
Safety
SAFE_T18
Worst Laboratory Toxicity Grade by Year Interval: 
Immunoglobulins
2.68.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Hematology
2.69.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Liver Function
2.70.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Electrolytes
2.71.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Other Chemistries
2.72.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Urinalysis
2.73.
Safety
SAFE_T19
Laboratory Toxicity Grade Worsening of at Least 2 Grades from 
Baseline by Year Interval: Immunoglobulins
Laboratory Reference Range Shifts (by Visit)
2.74.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Hematology


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Safety : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.75.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Liver Function
2.76.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Electrolytes
2.77.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Other Chemistries
2.78.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Urinalysis
2.79.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Immunoglobulins (Subjects from Parent Study 
BEL113750)
2.80.
Safety
SAFE_T20
Laboratory Reference Range Shifts from Baseline by 
Belimumab Visit: Immunoglobulins (Subjects from Parent Study 
BEL112341)
Immunogenicity
2.81.
Safety
SAFE_T21
Immunogenic Response by Belimumab Visit
2.82.
Safety
SAFE_T22
Immunogenic Response by Year Interval
2.83.
Safety
SAFE_T23
Immunogenic Summary
See 3750 DB, DS Table 3.73
Vital Signs
2.84.
Safety
SAFE_T24
Vital Signs by Belimumab Visit
2.85.
Safety
SAFE_T24
Weight (kg) by Belimumab Visit (Subjects from Parent Study 
BEL113750)
2.86.
Safety
SAFE_T24
Weight (kg) by Belimumab Visit (Subjects from Parent Study 
BEL112341)


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11.12.5.
Safety Figures
Safety : Figures
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.1.
Safety
SAFE_F1
Time to Withdrawal for Subjects Who Exited Prior to Study 
Closing [1]
2.2.
Safety
SAFE_F2
Cumulative Adverse Event Incidence Over Time
Laboratory
2.3.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Haematology
2.4.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Liver Function
2.5.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Electrolytes
2.6.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Other Chemistries
2.7.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Immunoglobulins
(Subjects from Parent Study BEL113750)
2.8.
Safety
SAFE_F3
Laboratory Results by Belimumab Visit: Immunoglobulins 
(Subjects from Parent Study BEL112341)
2.9.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Hematology
2.10.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Liver Function
2.11.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Electrolytes
2.12.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Other Chemistries
2.13.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Immunoglobulins (Subjects from Parent Study BEL113750)


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Safety : Figures
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
2.14.
Safety
SAFE_F3
Laboratory Results Change from Baseline by Belimumab Visit: 
Immunoglobulins (Subjects from Parent Study BEL112341)


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11.12.6.
Efficacy Tables
Efficacy : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
SRI and Secondary Efficacy Endpoints
3.1.
Safety
EFF_T1
SRI Response by Belimumab Visit
3.2.
Safety
EFF_T1
SELENA SLEDAI (4 Point Reduction from Baseline) by 
Belimumab Visit
3.3.
Safety
EFF_T1
PGA No Worsening (Increase of < 0.30 points from Baseline) by 
Belimumab Visit
3.4.
Safety
EFF_T1
BILAG No New 1A/2B Organ Domain Scores Compared to 
Baseline by Belimumab Visit
3.5.
Safety
EFF_T2
Number of Days of Daily Prednisone 7.5 mg/day and/or 
Reduced by 50% from Baseline, Among Subjects with Baseline 
Daily Prednisone Dose > 7.5 mg/day
3.6.
Safety
EFF_T3
Time to First Severe SFI Flare
3.7.
Safety
EFF_T4
Number of Subjects with At Least One Severe SFI Flare by 
Belimumab Visit
Other Efficacy Endpoints:  Disease Activity
3.8.
Safety
EFF_T5
SELENA SLEDAI (Observed and Change from Baseline) by 
Belimumab Visit
3.9.
Safety
EFF_T5
SELENA SLEDAI (Observed and Percent Change from 
Baseline) by Belimumab Visit
3.10.
Safety
EFF_T5
SLICC/ACR Damage Index (Observed and Change from 
Baseline) by Belimumab Visit (Subjects from Parent Study 
BEL113750)


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Efficacy : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
3.11.
Safety
EFF_T5
SLICC/ACR Damage Index (Observed and Change from 
Baseline) by Belimumab Visit (Subjects from Parent Study 
BEL112341)
3.12.
Safety
EFF_T1
SLICC/ACR Damage Worsening (Change > 0) from Baseline by 
Belimumab Visit (Subjects from Parent Study BEL113750)
3.13.
Safety
EFF_T1
SLICC/ACR Damage Worsening (Change > 0) from Baseline by 
Belimumab Visit (Subjects from Parent Study BEL112341)
3.14.
Safety
EFF_T5
PGA (Observed and Percent Change from Baseline) by 
Belimumab Visit
Other Efficacy Endpoints: Flares
3.15.
Safety
EFF_T3
Time to First SFI Flare
3.16.
Safety
EFF_T4
Number of Subjects with At Least One SFI Flare by Belimumab 
Visit
3.17.
Safety
EFF_T6
Total Number of Severe SFI Flares (Rate per 100 Person-Years)
3.18.
Safety
EFF_T6
Total Number of SFI Flares (Rate per 100 Person-Years)
3.19.
Safety
EFF_T3
Time to First 1A/2B BILAG Flare
3.20.
Safety
EFF_T4
Number of Subjects with At Least One 1A/2B BILAG Flare by 
Belimumab Visit
3.21.
Safety
EFF_T3
Time to First BILAG A Flare
3.22.
Safety
EFF_T4
Number of Subjects with At Least One BILAG A Flare by 
Belimumab Visit
Other Efficacy Endpoints: Organ-Specific Measures
3.23.
Safety
EFF_T3
Time to First Renal Flare


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Efficacy : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
3.24.
Safety
EFF_T4
Number of Subjects with At Least One Renal Flare by 
Belimumab Visit
3.25.
Safety
EFF_T5
Proteinuria (Observed and Percent Change from Baseline) by 
Belimumab Visit, Among Subjects with Baseline Proteinuria
3.26.
Safety
EFF_T8
Proteinuria Shifts from Baseline by Belimumab Visit
Other Efficacy Endpoints: Prednisone
3.27.
Safety
EFF_T5
Prednisone (mg/day) (Observed and Percent Change from 
Baseline) by Belimumab Visit
3.28.
Safety
EFF_T1
Daily Prednisone Dose Reduced to 7.5 mg/day by Belimumab 
Visit, Among Subjects with Baseline Prednisone Dose > 7.5 
mg/day
3.29.
Safety
EFF_T1
Daily Prednisone Dose Increased to > 7.5 mg/day by Belimumab 
Visit, Among Subjects with Baseline Prednisone Dose 7.5 
mg/day


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11.12.7.
Efficacy Figures
Efficacy : Figures
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
SRI and Secondary Efficacy Endpoints
3.1.
Safety
EFF_F1
SRI Response by Belimumab Visit
3.2.
Safety
EFF_F1
SELENA SLEDAI (4 Point Reduction from Baseline) by 
Belimumab Visit
3.3.
Safety
EFF_F1
PGA No Worsening (Increase of < 0.30 points from Baseline) by 
Belimumab Visit
3.4.
Safety
EFF_F1
BILAG No New 1A/2B Organ Domain Scores Compared to 
Baseline by Belimumab Visit
3.5.
Safety
EFF_F2
Time to First Severe Flare
Other Efficacy Endpoints: Disease Activity
3.6.
Safety
EFF_F3
SELENA SLEDAI Percent Change from Baseline by Belimumab 
Visit
3.7.
Safety
EFF_F3
SELENA SLEDAI Change from Baseline by Belimumab Visit
3.8.
Safety
EFF_F3
PGA Percent Change from Baseline by Belimumab Visit
Other Efficacy Endpoints: Flares
3.9.
Safety
EFF_F2
Time to First SFI Flare
3.10.
Safety
EFF_F2
Time to First 1A/2B BILAG Flare
3.11.
Safety
EFF_F2
Time to First BILAG A Flare
Other Efficacy Endpoints: Organ-Specific Measures
3.12.
Safety 
EFF_F2
Time to First Renal Flare


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Efficacy : Figures
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
3.13.
Safety
EFF_F3
Proteinuria Percent Change from Baseline by Belimumab Visit,
Among Subjects with Baseline Proteinuria
Other Efficacy Endpoints: Prednisone
3.14.
Safety
EFF_F3
Prednisone Percent Change from Baseline by Belimumab Visit
3.15.
Safety
EFF_F1
Daily Prednisone Dose Reduced to 7.5 mg/day by Belimumab 
Visit, Among Subjects with Baseline Prednisone Dose > 7.5 
mg/day
3.16.
Safety
EFF_F1
Daily Prednisone Dose Increased to > 7.5 mg/day by Belimumab 
Visit, Among Subjects with Baseline Prednisone Dose 7.5 
mg/day


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11.12.8.
Biomarker Tables
Biomarker : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
Immunoglobulin (IgG, IgA, IgM)
5.1.
Safety
EFF_T5
Immunoglobulin (Observed and Percent Change from Baseline) 
by Belimumab Visit (Subjects from Parent Study BEL113750)
5.2.
Safety
EFF_T5
Immunoglobulin (Observed and Percent Change from Baseline) 
by Belimumab Visit (Subjects from Parent Study BEL112341)
5.3.
Safety
SAFE_T25
Immunoglobulin Levels below the Lower Limit of Normal (LLN) 
by Belimumab Visit (Subjects from Parent Study BEL113750)
5.4.
Safety
SAFE_T25
Immunoglobulin Levels below the Lower Limit of Normal (LLN) 
by Belimumab Visit (Subjects from Parent Study BEL112341)
5.5.
Safety
SAFE_T26
Immunoglobulin Levels below the Lower Limit of Normal (LLN) 
by Year Interval
Autoantibodies (anti-dsDNA)
5.6.
Safety
EFF_T5
Anti-dsDNA (IU/mL) (Observed and Percent Change from 
Baseline) by Belimumab Visit
5.7.
Safety
EFF_T5
Anti-dsDNA (IU/mL) (Observed and Percent Change from 
Baseline) by Belimumab Visit, for Subjects Positive at Baseline
Complement (C3, C4) Levels
5.8.
Safety
EFF_T5
Complement Levels (Observed and Percent Change from 
Baseline) by Belimumab Visit
5.9.
Safety
EFF_T5
Complement Levels (Observed and Percent Change from 
Baseline) by Belimumab Visit, for Subjects with Low 
Complement at Baseline 


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Biomarker : Tables
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
B Cell Subsets
5.10.
Safety
EFF_T5
B Cell Subsets (Observed and Percent Change from Baseline) 
by Belimumab Visit (Japanese Subjects from Parent Study 
BEL113750)
5.11.
Safety
EFF_T5
B Cell Subsets (Observed and Percent Change from Baseline) 
by Belimumab Visit (Japanese Subjects from Parent Study 
BEL112341)


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11.12.9.
Biomarker Figures
Biomarker : Figures
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Priority]
Immunoglobulin (IgG, IgA, IgM)
5.1.
Safety
EFF_F3
Immunoglobulin Percent Change from Baseline by Belimumab 
Visit (Subjects from Parent Study BEL113750)
5.2.
Safety
EFF_F3
Immunoglobulin Percent Change from Baseline by Belimumab 
Visit (Subjects from Parent Study BEL112341)
Anti-dsDNA
5.3.
Safety
EFF_F3
Anti-dsDNA Percent Change from Baseline by Belimumab Visit
5.4.
Safety
EFF_F3
Anti-dsDNA Percent Change from Baseline by Belimumab Visit, 
for Subjects Positive at Baseline
Complement (C3, C4) Levels
5.5.
Safety
EFF_F3
Complement Levels Percent Change from Baseline by
Belimumab Visit
5.6.
Safety
EFF_F3
Complement Levels Percent Change from Baseline by 
Belimumab Visit, for Subjects with Low Complement at Baseline
B Cell Subsets
5.7.
Safety
EFF_F3
B Cell Subsets Percent Change from Baseline by Belimumab 
Visit (Japanese Subjects from Parent Study BEL113750)
5.8.
Safety
EFF_F3
B Cell Subsets Percent Change from Baseline by Belimumab 
Visit (Japanese Subjects from Parent Study BEL112341)


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11.12.10. ICH Listings
ICH : Listings
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
Subject Disposition
1.
All Screened 
Subjects
SAFE_L1
Subject Disposition
2.
All Enrolled
Subjects
SAFE_L2
Reasons for Study Withdrawal
3.
All Screened 
Subjects
SAFE_L3
Reasons for Screen Failure
Inclusion / Exclusion Criteria
4.
All Enrolled 
Subjects
SAFE_L4
Inclusion or Exclusion Criteria Not Met
Protocol Deviations
5.
All Enrolled 
Subjects
SAFE_L5
Important Protocol Deviations
Baseline Demographic Characteristics
6.
Safety
SAFE_L6
Demographic Characteristics
7.
All Enrolled
Subjects
SAFE_L7
Race
8.
Safety
SAFE_L8
Baseline Characteristics: Anti-dsDNA, ANA, Complement Levels 
and SLE Medication Use
9.
Safety
SAFE_L9
Baseline Characteristics: Disease Duration, PGA, SLICC/ACR 
Damage Index and Proteinuria Results
10.
Safety
SAFE_L10
Baseline Characteristics: SELENA SLEDAI


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ICH : Listings
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
11.
Safety
SAFE_L11
Baseline Characteristics: BILAG Index Results
12.
Safety
SAFE_L12
Baseline Characteristics: SLE Flare Index
Medical History
13.
Safety
SAFE_L13
Medical History
Medications
14.
Safety
SAFE_L14
Concomitant Medications
15.
Safety
SAFE_L15
Concomitant Procedures/Surgery
16.
Safety
SAFE_L16
Daily Prednisone Equivalent Dose
17.
Safety
SAFE_L17
Study Drug Exposure
18.
Safety
SAFE_L18
Study Drug Administration
Adverse Events
19.
Safety
SAFE_L19
Subject Numbers for Individual Adverse Events
20.
Safety
SAFE_L20
All Adverse Events
21.
Safety
SAFE_L20
Serious Adverse Events
22.
Safety
SAFE_L20
Fatal Serious Adverse Events
23.
Safety
SAFE_L20
Non-Fatal Serious Adverse Events
24.
Safety
SAFE_L20
Adverse Events Leading to Permanent Discontinuation of Study 
Drug
25.
Safety
SAFE_L20
Infections and Infestations SOC Adverse Events for Subjects 
with a Grade 3 or Grade 4 IgG Toxicity
26.
Safety
SAFE_L21
Adverse Events of Special Interest


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ICH : Listings
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
27.
Safety
SAFE_L22
Relationship Between Adverse Event System Organ Classes, 
Preferred Terms, and Verbatim Text
28.
Safety
SAFE_L23
Reasons for Considering as a Serious Adverse Event
Laboratory
29.
Safety
SAFE_L24
Laboratory Results: Hematology
30.
Safety
SAFE_L24
Laboratory Results: Liver Function
31.
Safety
SAFE_L24
Laboratory Results: Electrolytes
32.
Safety
SAFE_L24
Laboratory Results: Other Chemistries
33.
Safety
SAFE_L24
Laboratory Results: Urinalysis
34.
Safety
SAFE_L24
Laboratory Results: Immunoglobulins
35.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: Hematology
36.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: Liver Function
37.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: Electrolytes
38.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: Other 
Chemistries
39.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: Urinalysis
40.
Safety
SAFE_L25
Grade 3 or Grade 4 Laboratory Toxicity Results: 
Immunoglobulins
41.
Safety
SAFE_L26
Liver Assessment
42.
Safety
SAFE_L27
Liver Biopsy Details
43.
Safety
SAFE_L28
Liver Imaging
Immunogenicity


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ICH : Listings
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
44.
Safety
SAFE_L29
Immunogenicity Results
Vital Signs
45.
Safety
SAFE_L30
Vital Signs


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11.12.11. ICH Listings (Efficacy/Biomarkers)
ICH : Listings
No.
Population
Example Shell
Title
Programming Notes
Final
Deliverable 
[Stage]
Disease Activity
46.
Safety
EFF_L1
SRI Results Relative to Baseline [1]
47.
Safety
EFF_L2
SELENA SLEDAI Results
48.
Safety
EFF_L3
Physician’s Global Assessment (PGA) Results
49.
Safety
EFF_L4
BILAG Results
50.
Safety
EFF_L5
SLICC/ACR Damage Index Results
51.
Safety
EFF_L6
SLE Flare Index Results
Biomarkers
52.
Safety
EFF_L7
Autoantibody and Complement Level Results 
53.
Safety
EFF_L7
B Cell Results
Pregnancies
54.
Safety
SAFE_L31
On-Study Pregnancies
AE/Post 16 Week Follow-up Visit
55.
Safety
SAFE_L14
Concomitant Medications Starting After the 16 Week Follow-up
56.
Safety
SAFE_L20
Adverse Events Starting After the 16 Week Follow-up Visit


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11.13.
Appendix 13: Example Mock Shells for Data Displays
Refer to the separate mock example shell document.