A Multi-center, Randomized, Placebo-Controlled Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Patients With Systemic Lupus Erythematosus
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: GlaxoSmithKline

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The GlaxoSmithKline group of companies
BEL114055
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
A Multi-center, Randomized Parallel Group, Placebo-Controlled 
Double-Blind Trial to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of Belimumab, a Human Monoclonal Anti-
BLyS Antibody, Plus Standard Therapy in Pediatric Patients 
with Systemic Lupus Erythematosus (SLE)
Compound Number:
GSK1550188
Development Phase:
II
Effective Date:
02-NOV-2020
Protocol Amendment Number:  08
Author (s):
(Immuno-Inflammation & Fibrosis, Global Clinical Operations; 
(Development Biostatistics);
(Immunology and Fibrosis, 
Clinical Sciences),
(Safety Evaluation & Risk Management, Development 
Global Medical);
(Immunology and Fibrosis, Clinical Sciences),
(Immuno-Inflammation & Fibrosis, Global Clinical Operations);
(Safety Evaluation & Risk Management, Development Global Medical),
(Medical Writing, Global Clinical Operations).
Copyright 2020 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
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Revision Chronology
GlaxoSmithKline Document 
Number
Date
Version
2010N108742_09
2020-NOV-02
Amendment No. 8
Protocol Amendment 07 had been distributed but not submitted to Health Authorities 
and IRB/ECs in all participating countries. Clarification was requested on the exact 
number of allowable consecutive missed study IP infusions. The wording was 
modified in Amendment 08 to make this clear.
The protocol amendment revision chronology has been reversed so the most recent is 
documented first.
Withdrawal Criteria and Treatment Compliance updated:

Up to 4 consecutive infusions may be missed without requirement to 
withdraw the subject if any of the doses are missed due to COVID-19 related 
reasons.
Where not yet approved the changes in Protocol Amendment 07 should be reviewed 
together with Protocol Amendment 08.
Change in Sponsor Signatory.
Change in laboratory performing immunogencity testing, correction of the shipping 
arrangements to the central laboratory which is daily, clarification that the approximate 
blood collection volume is 10mL per participant and documentation regarding the 
assay methodology.
Minor typographical errors corrected.
2010N108742_08
2020-JUN-09
Amendment No. 7
This amendment adjusts the protocol in response to the COVID-19 pandemic.  The 
purpose of this amendment is to increase the number of infusions of study agent that 
can be missed without requirement for withdrawal if this is due to a COVID-19 related 
reason. This flexibility is in accordance with guidance from regulatory agencies, while 
maintaining trial and data integrity. 
Withdrawal Criteria and Treatment Compliance updated:

4 or more consecutive infusions may be missed without requirement to 
withdraw the subject if one or more of the doses are missed due to COVID-19 
related reasons.
Dose interruption

Guidance to review resumption of IP administration with the Medical Monitor 
where dosing is interrupted due to a subject having tested positive or displays 
COVID-19 symptoms.

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Other changes:
Update to authors including organization names and Medical Monitors.
UK Sponsor address updated.
Results from Part A of the study added to Introduction.
Footnote added clarifying start of annual assessments in Part C.
Minor typographical errors and formatting issues corrected and administrative changes 
added.
2010N108742_07
2016-DEC-12
Amendment No. 6
Updated Author information
Updated Medical Monitor information
Updated site address 
Total study target amended to ‘at least 70’ from 100 subjects. 
Estimates for sample size re-estimation add to the protocol. 
Target for subjects less than 13 years old amended to at least 14 from 20. 
Target for Cohort 2 amended from 12 to “at least 10”.
PedsQL amended in time and events table such that it is instructed to be taken at Day 
0.
Anti-dsDNA; C3/C4 added to time and events table for 6 month visits in Part B.
Deleted immunogenicity sample collection once a subject has left the study.
Collect additional PK samples in the subjects in Japan at the first 12 week and 6 month 
visit in Part B
Minor typographical errors corrected
Clarification of reporting of AEs, SAEs, and AESI
Change in Part C from “non-belimumab phase” to “safety follow up phase”
2010N108742_06
2015-APR-22
Amendment No. 5
Country Specific Amendment for Russian Federation: Restart of study treatment after 
liver event is not applicable to Investigator sites in Russia.
Updated phone number of back-up Medical Monitor.
2010N108742_05
2014-Nov-03
Amendment No. 4

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Changed the Screening inclusion criterion SELENA SLEDAI to ≥ 6.
Changed randomization strata for Cohort 3 to stratification by age and SELENA 
SLEDAI 6-12 and ≥13.
Added requirement that 50% of subjects will be recruited with SS score of ≥8.
Changed exclusion #4 intravenous (IV) cyclophosphamide within 60 days of Day 0.
Added allowance for stable Grade 3 lymphopenia with exclusion #24.
Updated GSK liver chemistry stopping criteria and added of study drug restart criteria
Clarification of laboratory tests needed to complete SS and BILAG assessments. 
Added immunogenicity testing in Part C.
Clarification of NSAIDs use in Part A
Minor typographical errors corrected
2010N108742_04
2014-FEB-18
Amendment No. 3
Amendment No: 03 pertaining to all sites:
Update to safety information on PML and Delayed Hypersensitivity Reaction.
Changed the exclusion for high dose steroid use from 90 days to 60 days prior to 
baseline. 
Clarification of treatment failure and study withdrawal criteria
Clarification of procedure for destruction of investigational product and used vials.
Added a home pregnancy test and follow up phone call at 16 Week post last dose.
Extended visit window in Part B and Part C
Minor typographical and formatting errors corrected.
2010N108742_03
2013-JAN-31
Amendment No. 2
Country Specific Amendment for Russian Federation: only subjects 12 years of age 
may participate.
Amendment 02 pertaining to all sites includes the following changes: 
Exclusion Criterion #1 excludes if B cell targeted therapy is within 1 year of Day 0 and 
Exclusion #23 omitting HCV confirmation RIBA assay.
Allow extra visits for collection of large blood sample collection 
Addition of 3 hours observation post infusion for first 3 infusions in Part B.
The investigational product may be delivered in either 100 mL or 250mL of saline.
Minor typographical errors corrected.
2010N108742_02
2012-FEB-21
Amendment No. 1
Update Author information
Update Medical Monitor information
Additional pharmacokinetic samples for children not in Cohort 1 or 2
Addition of three hours observation post infusion
Update to Time and Events Table including immunogenicity, vaccine titer procedure 

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and physical assessments
Update Other Secondary Endpoints Addition of Study Conclusion criteria 
Minor typographical errors corrected
2010N108742_01
2011-AUG-24
Original

2 November 2020
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SPONSOR INFORMATION PAGE
Clinical Study Identifier:
BEL114055
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Telephone: +44 (0)208 047 5000
GlaxoSmithKline
Research and Development
1250 South Collegeville Road
Collegeville, PA 19146-0989, USA
Telephone: +001 610 917 7000
GlaxoSmithKline
Five Moore Drive 
P.O. 13398
Research Triangle Park, NC 27709-3398, USA
Telephone: + 001-919-483-2100
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline Affiliate 
Company (or designee). Where applicable, the details of the Sponsor and contact person 
will be provided to the relevant regulatory authority as part of the clinical trial 
submission.
Sponsor Serious Adverse Events (SAE) Contact Information: 
Case Management Group, Global Clinical Safety and Pharmacovigilance (GCSP)
Email: US.NAPS@gsk.com
United States Food and Drug Administration Identifying Number(s): IND 009970 
(Human Genome Sciences, Inc)
EudraCT number: 2011-000368-88

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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol amendment 8
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...........................................................................................13
PROTOCOL SUMMARY...............................................................................................16
1.
INTRODUCTION....................................................................................................21
1.1.
Disease Background...................................................................................21
1.2.
Rationale ....................................................................................................25
1.2.1.
Dose Rationale ............................................................................26
1.3.
Part A Results Summary.............................................................................27
2.
OBJECTIVES.........................................................................................................29
3.
INVESTIGATIONAL PLAN.....................................................................................30
3.1.
Study Design ..............................................................................................30
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA.......................................34
4.1.
Number of Subjects ....................................................................................34
4.2.
Inclusion Criteria.........................................................................................34
4.3.
Exclusion Criteria........................................................................................37
4.4.
Withdrawal Criteria .....................................................................................40
5.
STUDY TREATMENTS..........................................................................................41
5.1.
Study Agent and Other Study Treatment ....................................................41
5.2.
Treatment Assignment................................................................................44
5.3.
Blinding.......................................................................................................44
5.4.
Unblinding...................................................................................................44
5.5.
Product Accountability ................................................................................45
5.6.
Treatment Compliance................................................................................45
5.6.1.
Permitted Medications and Non-Drug Therapies..........................45
5.6.1.1.
Anti-malarials..............................................................45
5.6.1.2.
Steroids......................................................................46
5.6.1.2.1.
Systemic Steroids for SLE-related 
Disease Activity ......................................46
5.6.1.2.2.
Intra-articular Injections ..........................47
5.6.1.2.3.
Steroids for Reasons Other Than 
SLE Disease Activity...............................47
5.6.1.2.4.
Tapering or Restoration/Restart of 
Steroids ..................................................48
5.6.1.2.5.
Treatment of SLE Flares with 
Steroids ..................................................48
5.6.1.3.
Other Immunosuppressive/Immunomodulatory 
Agents........................................................................48
5.6.1.4.
Nonsteroidal Anti-inflammatory Drugs 
(NSAIDs)....................................................................49
5.6.2.
Prohibited Medications and Non-Drug Therapies.........................50
5.7.
Treatment after the End of the Study ..........................................................51
5.7.1.
Study Conclusion.........................................................................51

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5.8.
Treatment of Study Treatment Overdose....................................................51
6.
STUDY ASSESSMENTS AND PROCEDURES .....................................................51
6.1.
Critical Screening and Baseline Assessments ............................................64
6.2.
Efficacy.......................................................................................................65
6.2.1.
SELENA SLEDAI.........................................................................65
6.2.1.1.
SELENA SLEDAI Score .............................................65
6.2.1.2.
Laboratory Tests for SELENA SLEDAI and 
BILAG.........................................................................66
6.2.1.3.
Guidelines for Scoring Proteinuria for SELENA 
SLEDAI ......................................................................66
6.2.1.3.1.
Scoring for Proteinuria for 
Eligibility and at Screening......................67
6.2.1.3.2.
Scoring for Proteinuria at Day 0 
and Subsequent Study Visits..................67
6.2.1.4.
SELENA SLEDAI Flare Index.....................................68
6.2.1.5.
Physician’s Global Assessment (PGA) .......................68
6.2.1.6.
Parent ’s Global Assessment (ParentGA)...................68
6.2.2.
Pediatric Rheumatology International Trials 
Organization/ACR (PRINTO/ACR Juvenile SLE Response 
Evaluation)...................................................................................69
6.2.3.
BILAG..........................................................................................69
6.2.4.
Pediatric SLICC/ACR Damage Index...........................................70
6.3.
Safety .........................................................................................................70
6.3.1.
Liver Chemistry Stopping and Monitoring Criteria ........................71
6.3.1.1.
Required Actions and Follow up Assessments 
following ANY Liver Stopping Event ...........................72
6.3.2.
Increased Monitoring Criteria with Continued Therapy.................73
6.3.2.1.
Required Actions and Follow Up Assessments 
for Increased Monitoring with Continued 
Therapy......................................................................74
6.3.3.
Study Treatment Restart..............................................................74
6.3.4.
IgG Stopping Criteria ...................................................................75
6.3.5.
Independent Data Monitoring Committee.....................................75
6.3.6.
Adverse Events............................................................................76
6.3.6.1.
Definition of an AE......................................................76
6.3.6.2.
Definition of a SAE .....................................................77
6.3.7.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs.........................................................78
6.3.8.
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs...............................................78
6.3.9.
Suicidality Assessment ................................................................79
6.3.10.
Possible Suicidality Related Questionnaire (PSRQ).....................80
6.3.11.
Investigator Evaluation of Adverse Events...................................80
6.3.12.
Pregnancy ...................................................................................80
6.3.13.
Time Period and Frequency of Detecting AEs and SAEs.............81
6.3.14.
Prompt Reporting of Serious Adverse Events and Other 
Events to GSK.............................................................................81
6.3.14.1.
Regulatory reporting requirements for SAEs ..............82
6.3.15.
Laboratory Evaluations ................................................................83
6.3.16.
Infusion-related Reactions and Hypersensitivity Reactions ..........83
6.3.17.
Immunosuppression, Infections, and Malignancies......................84

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6.3.18.
Vital Signs, Height and Weight.....................................................85
6.3.19.
Physical Examination...................................................................85
6.3.20.
Other Safety Outcomes ...............................................................86
6.3.20.1.
Immunogenicity ..........................................................86
6.4.
Health Outcomes........................................................................................86
6.4.1.
Pediatric Quality of Life Inventory - Generic Core 
(PedsQL) .....................................................................................86
6.4.2.
Pediatric Quality of Life Multidimensional Fatigue Scale ..............87
6.5.
Pharmacokinetics .......................................................................................87
6.6.
Pharmacodynamics ....................................................................................89
6.6.1.
Biomarker(s)................................................................................89
6.6.2.
Test for Functional Antibodies......................................................90
6.6.3.
Vaccine Response.......................................................................90
6.7.
Pharmacogenetics......................................................................................90
7.
DATA MANAGEMENT ...........................................................................................91
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS...................................91
8.1.
Hypotheses.................................................................................................91
8.2.
Study Design Considerations......................................................................91
8.2.1.
Sample Size Considerations........................................................91
8.2.2.
Sample Size Sensitivity................................................................91
8.2.3.
Sample Size Re-estimation..........................................................92
8.3.
Data Analysis Considerations .....................................................................92
8.3.1.
Analysis Populations....................................................................92
8.3.2.
Analysis Data Sets.......................................................................93
8.3.3.
Analysis strategy and timing ........................................................93
8.3.4.
Interim Analysis ...........................................................................93
8.3.5.
Key Elements of Analysis Plan ....................................................94
8.3.5.1.
Laboratory Data for Disease Activity Scales ...............95
8.3.5.2.
Efficacy Analyses .......................................................95
8.3.5.2.1.
Primary Efficacy Endpoint.......................96
8.3.5.2.2.
Major Secondary Efficacy 
Endpoints ...............................................97
8.3.5.3.
Safety Analyses..........................................................98
8.3.5.3.1.
Extent of Exposure .................................98
8.3.5.3.2.
Adverse Events and Disease 
Related Events .......................................99
8.3.5.3.3.
Laboratory Parameters...........................99
8.3.5.3.4.
Vital Signs ..............................................99
8.3.5.3.5.
Immunogenicity ....................................100
8.3.5.4.
Pharmacokinetic Analyses........................................100
8.3.5.5.
Pharmacogenetic Analyses ......................................100
8.3.5.6.
Biological Markers ....................................................100
9.
STUDY CONDUCT CONSIDERATIONS .............................................................101
9.1.
Posting of Information on Clinicaltrials.gov................................................101
9.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ......................................................................................101
9.3.
Quality Control (Study Monitoring) ............................................................101
9.4.
Quality Assurance.....................................................................................102
9.5.
Study and Site Closure .............................................................................102

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9.6.
Records Retention....................................................................................102
9.7.
Provision of Study Results to Investigators, Posting to the Clinical 
Trials Register and Publication .................................................................103
9.8.
Independent Data Monitoring Committee (IDMC) .....................................103
10. REFERENCES.....................................................................................................104
11. APPENDICES......................................................................................................112
11.1.
Appendix 1: Pharmacogenetic Research ..................................................112
11.2.
Appendix 2: Country Specific Requirements.............................................116
11.3.
Appendix 3: American College of Rheumatology (ACR) Criteria for 
SLE...........................................................................................................117
11.4.
Appendix 4: Liver Safety Criteria...............................................................118
11.4.1.
Liver Stopping Event Algorithm..................................................118
11.4.2.
Liver Monitoring Event Algorithm with Continued Therapy 
for ALT≥3xULN but <8xULN ......................................................119
11.5.
Appendix 5: Clinical Laboratory Tests.......................................................120
11.6.
Appendix 6: SELENA SLEDAI Disease Assessment Scales.....................129
11.7.
Appendix 7: SLE Flare Index ....................................................................130
11.8.
Appendix 8: Physician’s Global Disease Assessment...............................131
11.9.
Appendix 9: Parent’s Global Disease Assessment....................................132
11.10. Appendix 10: BILAG Index Assessment ...................................................133
11.11. Appendix 11: Pediatric SLICC/ACR Damage Index ..................................135
11.12. Appendix 12: Columbia Suicide Severity Rating Scale C-SSRS ...............139
11.13. Appendix 13: Possible Suicidality-Related Questionnaire .........................167
11.14. Appendix 14: Pediatric Quality of Life Inventory - Generic Core 
Scale (PedsQL) ........................................................................................169
11.15. Appendix 15: Pediatric Quality of Life Multidimensional Fatigue 
Scale (PedsQL Fatigue)............................................................................170
11.16. Appendix 16: Protocol Amendment 01 Changes.......................................174
11.17. Appendix 17: Country Specific Protocol Amendment 02 Changes ............194
11.18. Appendix 18: Protocol Amendment 02 Changes.......................................195
11.19. Appendix 19: Protocol Amendment 03 - Summary of Changes.................202
11.20. Appendix 20: Protocol Amendment 04 - Summary of Changes.................210
11.21. Appendix 21: Country Specific Protocol Amendment 05 Changes ............219
11.22. Appendix 22: Protocol Amendment 06 Changes.......................................220
11.23. Appendix 23: Protocol Amendment 07 Changes.......................................224
11.24. Appendix 24: Protocol Amendment 08 Changes.......................................227

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LIST OF ABBREVIATIONS
aCL
Anticardiolipin
ACR
American College of Rheumatology
AE
Adverse Event
ALT
alanine aminotransferase
ANA
anti-nuclear antibody
ANCOVA
Analysis of Covariance
AS
All subjects
AST
aspartate aminotransferase
BILAG
British Isles Lupus Assessment Group 
BLyS
B lymphocyte Stimulator
CBC
Complete blood count
C-SSRS
Columbia Suicide Severity Rating Scale
CNS
Central Nervous System
COVID-19
Coronavirus SARS-CoV-2 (COrona Virus Disease -2019)
CPK
Creatinine phosphokinase
CrCl
Creatinine clearance
CRF
Case report form
CVA
Cerebrovascular accident
dL
Deciliter
DRE
Disease Related Event
dsDNA
double stranded deoxyribonucleic acid 
eCRF
electronic case report form
ECG
electrocardiogram
ELISA
enzyme linked immunosorbent assay
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
HIV
Human immunodeficiency virus
HMG CoA
3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A
hpf
High power field
IA
Intraarticular
IB
Investigator’s Brochure
IDMC
Independent Data Monitoring Committee
IEC
Independent ethics committee
IgA
Immunoglobulin A
IgG
Immunoglobulin G
IgM
Immunoglobulin M
IL-6
Interleukin-6

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IM
Intramuscular
INR
International Normalized Ratio
IRB
Institutional Review Board
ITT
Intention to Treat
IUD
intrauterine device
IV
Intravenous
IVIG
Intravenous immunoglobulin
IVRS
Interactive voice response system
IWRS
Interactive web-based response system
kg
Kilogram
LDH
lactate dehydrogenase
LOCF
Last observation carried forward
MedDRA
Medical Dictionary for Drug Regulatory Activities
mg
Milligram
mL
Milliliter
MMF
Mycophenolate mofetil
MRI
Magnetic Resonance Imagery
MSDS
Materials Safety Data Sheet
NR
Non-responder
NSAIDs
non-steroidal anti-inflammatory drugs
ParentGA
Parent’s Global Assessment
PedsQL
Pediatric Quality of Life Inventory – Generic Core Scale
PedsQL-Fatigue
Pediatric Quality of Life Multidimensional Fatigue Scale
PCR
polymerase chain reaction
PGA
Physician’s Global Assessment
PGx
Pharmacogenetics
PO
By mouth (per os)
PRINTO
Pediatric Rheumatology International Trials
Organization
PSRQ
Possible Suicidality-Related Questionnaire
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
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
SOC
System Organ Classes
SPM
Study Procedures Manual
SRM
Study Reference Manual

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SRI
SLE Responder Index
SRT
Safety Review Team
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
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
BENLYSTA (belimumab)
PASS 2005
LYMPHOSTAT-B

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PROTOCOL SUMMARY
Rationale
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and the 
effects on quality of life of 10 mg/kg (or pediatric exposure adjusted dose) of belimumab 
administered intravenously (IV) compared to placebo in pediatric subjects 5 to 17 years 
of age with systemic lupus erythematosus (SLE) on a background of standard of care 
therapy.  This study has a 52-week, randomized, double-blind, placebo-controlled phase 
followed by an open label continuing phase for up to 10 years for subjects that qualify.  
Additionally, subjects who withdraw from treatment at any time during the study will be 
assessed in a long term follow-up period where safety evaluations and limited disease 
activity assessments will be performed for up to 10 years. 
Objectives

Evaluate the safety and tolerability of belimumab in the pediatric SLE 
population

Evaluate the pharmacokinetics of belimumab in the pediatric SLE population.

Evaluate the efficacy of belimumab in the pediatric SLE population

Evaluate the effects of belimumab on the quality of life in the pediatric SLE 
population.
Study Design
This is a multi-center study to evaluate the safety, efficacy and pharmacokinetics of 
belimumab plus background standard therapy in at least 70 pediatric subjects 5 years to 
17 years of age with active systemic lupus erythematosus (SLE).  The study will consist 
of three separate phases:  

Randomized, placebo-controlled, double-blind 52-week treatment phase (Part 
A)

Long term belimumab open label safety follow up for any subject who 
completes Part A (Part B)

Long term safety follow up phase for subjects who withdraw from Part A or  
Part B at any time (Part C)
Part A is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, 
safety, and pharmacokinetics of 10 mg/kg belimumab intravenous (IV) in pediatric 
subjects with active SLE (SELENA SLEDAI score 6).  In this study, at least 70 subjects 
will be randomized in three cohorts with Cohort 3 stratified by age (5-11 years vs. 12-17 
years) and screening SELENA SLEDAI scores (6-12 vs. ≥13).  Cohorts 1 and 2 will be 
randomized in a 5:1 ratio, and Cohort 3 subjects will be randomized in a 1:1 ratio to 
receive belimumab or placebo for 48 weeks on a background of standard of care.  Cohort 
1 will consist of the first 12 subjects, age 12 to 17 years.  No further enrolment of the 
study will proceed until after the PK of this cohort is evaluated.  Once the PK and safety 
profile of Cohort 1 is evaluated and any potential dose adjustments are determined as a 

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result of this analysis, additional subjects 12-17 years of age will then be enrolled in 
Cohort 3.  In addition, at this point, at least 10 subjects 5-11 years of age at the dose 
determined from the PK analysis of Cohort 1.  Once the PK and safety profile of Cohort 2 
is evaluated and any potential dose adjustments are determined as a result of this analysis, 
additional subjects 5-11 years of age will then be enrolled in Cohort 3.
Belimumab will be infused over a minimum of 1 hour on Days 0, 14, 28, and then every 
28 days through the Week 48 (Day 336) visit.  All subjects will continue to receive their 
standard SLE therapy with progressive restrictions on the changes that are permitted 
throughout the 52-week randomized period.   Enrolment will be staggered to allow PK 
analysis of the first 2 age cohorts (Cohorts 1 and 2).
Safety monitoring and PK analysis from the initial 12 subjects will be used to confirm or 
adjust the belimumab dose for the remaining subjects enrolling in Cohort 2 and 3.

Cohort 1:  The first 12 subjects, age 12 to 17 years of age will be randomized in 
a 5:1 ratio to belimumab 10 mg/kg (n=10) or placebo (n=2) on a background of 
standard of care for 48 weeks.  After all 12 subjects in Cohort 1 have received at 
least 8 weeks of treatment, safety and PK analysis will be conducted.  Cohort 1 
subjects will continue in the treatment period while the Study Team progresses 
the PK analysis, but no other subjects will enrol until the PK analysis is 
completed. If the belimumab dose is adjusted because of the PK analysis, the 
Cohort 1 subjects will continue the study with the adjusted dose. Enrolment will 
be initiated for Cohort 2 (at least 10 of the first subjects age 5 to 11 years) and 
Cohort 3 (subjects age 12-17 years) after the Cohort 1 PK analysis is completed.

Cohort 2:  At least 10 of the first subjects aged 5 to 11 years will be randomised 
in a 5:1 ratio to belimumab (10 mg/kg confirmed or adjusted dose) or placebo 
for 48 weeks on a background of standard of care.  After all subjects in Cohort 2 
have received at least 8 weeks of treatment, safety and PK analysis will be 
conducted.  Administration of study agent in Cohort 2 will continue while safety 
monitoring and PK analysis progresses, but no additional subjects ages 5-11 
years will enrol in the study until the safety and PK analysis is completed.  If the 
belimumab dose is adjusted, the Cohort 2 subjects age 5 to 11 years will 
continue with the dose-adjusted blinded treatment. 

Cohort 3: This cohort will consist of at least 48 subjects aged 5 to 17 years old.  
These subjects will be randomised in a 1:1 ratio to belimumab (10 mg/kg 
confirmed or adjusted dose) or placebo on a background of standard of care for 
52 weeks.  Randomization will be stratified by age group and screening 
SELENA SLEDAI scores (6-12 vs. ≥ 13).  Subjects aged 12 to 17 years will 
begin enrolment after Cohort 1 enrolment PK analysis is completed. Subjects 
aged 5 years to 11 years will begin enrolment after Cohort 2 safety and PK 
analysis is completed. 
Younger children (5-11 years old) will not be randomized to treatment in Cohort 3 until 
reviews of Cohort 1 and 2 have taken place, but they may be identified for potential 
inclusion at any time.  

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Two separate dose assessment meetings will be held in which members of the GSK 
Safety Review Team (SRT) will review the safety, tolerability and preliminary PK data 
obtained from Cohorts 1 and Cohorts 2, respectively.  The objective of these meetings 
will be to either confirm the initial dose or to adjust the dose if a substantial difference in 
exposure is observed compared to adult Phase 3 PK data based on 10 mg/kg dosing.  An
assessment of any safety signal may also factor into the decision to confirm or adjust the 
initial dose.  The SRT will review the available blinded safety, key biomarker and PK 
data and a recommendation by consensus will be made regarding dose confirmation or 
adjustment and the initiation of the subsequent cohorts.  The PK analysis and 
recommendation regarding dose confirmation or adjustment will be reviewed by the 
IDMC. Final decisions will be made by the sponsor considering the recommendation 
from the IDMC and independent pharmacokineticist.  The Study Team will remain 
blinded to treatment during these dose assessments.  Decisions regarding dose 
confirmation or adjustment will be summarized and distributed to study team members, 
investigators, the IDMC, and IRBs, and/or regulatory authorities according to local 
regulations.
A target enrolment of at least 70 subjects will be randomized.  In Cohorts 1 and 2,
subjects will be randomized in a 5:1 ratio (belimumab:placebo), and the remaining 
subjects (at least 48) in Cohort 3 will be randomized in a 1:1 allocation ratio.  Therefore, 
at least 42 subjects will be randomized to belimumab and 28 to placebo. The study will 
also enrol at least 14 subjects who are younger than 13 years of age. Enrolment will 
ensure that at least 50% of the randomised subjects will have presented with SELENA 
SLEDAI ≥ 8 at screening.
Subjects may withdraw or discontinue from the study at any time for any reason.  All 
subjects withdrawing from Part A of the study will return for an exit visit 4 weeks after 
their last dose of study agent, and then continue in the safety follow-up period (Part C) 
where safety evaluations and limited disease activity assessments will be performed for 
up to 10 years from the first administration of study agent or open label belimumab.  
Subjects choosing not to continue in Part A or participate in Part B and do not wish to be 
monitored in the safety follow-up period (Part C), will return for a safety follow-up visit 
approximately 8 weeks following their last dose of study agent. Additional withdrawal 
criteria are presented in Section 4.4.
Subjects completing the randomized, double-blind, placebo-controlled phase of the study 
may continue to Part B of the study, the open label safety follow up and receive monthly 
belimumab treatment.  
The study sponsor will remain blinded to subjects’ treatment until all data from the 
Part A of the study are locked and the data are unblinded.  Clinical sites will remain 
blinded until after the results of Part A are publicly disclosed.
Part B: Open Label Belimumab Continuation
Subjects who complete 48 weeks of belimumab or placebo on a background of standard 
of care and the Week 52 assessments, regardless of treatment assignment, may progress 
to Part B of the study, the open-label belimumab continuation phase. In this phase, all 
subjects will receive belimumab (10 mg/kg or adjusted dose) at monthly infusion 

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visits. The Week 52 administration will be considered the 1st administration of the open-
label continuation phase. Safety will be assessed at each monthly visit, and disease 
activity assessments will be performed every 6 months.  Subjects will continue in Part B 
of the study for up to 10 years from the first administration of belimumab. However, the 
study will conclude earlier if all subjects continuing belimumab treatment have received 
at least 5 years of treatment with belimumab (Part B or a combination of Part A and Part 
B) and if there are 15 or fewer subjects continuing to receive belimumab in the study (See 
Section 5.7.1 Study Conclusion). Any subject who withdraws during the continuation 
phase will return for an exit visit at 4 weeks after their last dose and proceed to Part C, 
safety follow-up phase.  Subjects choosing to discontinue from the study and not be 
monitored in the safety follow-up period (Part C), will return for a follow-up visit 
approximately 8 weeks following their last dose of open label belimumab.
Part C: Safety Follow-up Phase
Part C will include any subject who discontinues study agent from Part A or open label 
belimumab from Part B.  These subjects will return for safety follow up visits in Part C 
monthly for 3 months and then annually after their last dose of study agent or open label 
belimumab.  In Part C safety evaluations and limited disease activity assessments will be 
performed for up to 10 years from the first administration of study agent or open label 
belimumab.  However, the study will conclude earlier if all subjects continuing 
belimumab treatment have received at least 5 years of treatment with belimumab (Part B 
or a combination of Part A and Part B) and if there are 15 or fewer subjects continuing to 
receive belimumab in the study (See Section 5.7.1 Study Conclusion). For subjects that 
withdraw from the study 8 weeks or less from the last administration of IV belimumab, 
an 8 Week Follow-up Visit (and a 16 Week Follow-up Visit post administration for 
female subjects of child-bearing potential) must be performed and recorded in the IVR 
system and the eCRF. An Exit Visit may be conducted by phone for any subject who 
withdraws completely from the study while in Part C.
Independent Data Monitoring Committee (IDMC)
An IDMC comprised of experts in paediatric rheumatology, paediatric pharmacology, 
paediatric ethics and a statistician, none of whom are affiliated with the sponsor, will be 
organized to monitor the study as it progresses.  A charter will be developed to govern 
the activities of this committee. The IDMC will conduct its first safety and PK data 
review after the first cohort has been treated through the Week 8 (Day 56) visit, or within 
4 months of the treatment of the first subject enrolled in Cohort 1, whichever is earlier. If 
the earlier time point of within 4 months of the first subject enrolled is met, the IDMC
will review the available safety data only. The IDMC will continue to meet, at a 
minimum, approximately every 6 months from the first meeting until the last subject 
concludes Part A, the randomized treatment period of the study.  After each meeting, the
IDMC will generate a report of data reviewed and if applicable, recommendations made.  
Investigators will be notified of the outcome of each IDMC meeting. Notification of local 
EC/IRB of the IDMC review outcomes will be at the discretion and requirements of local 
regulations.

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Study Endpoints/Assessments for Part A
The primary efficacy endpoint is SLE Responder Index (SRI) response rate at Week 
52 which 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.
Major Secondary endpoints: 
1.
Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation 
criteria for improvement in juvenile SLE using two different PRINTO/ACR Juvenile 
SLE Response Evaluation definitions of improvement
a.
At least 50% improvement in any 2 of 5 endpoints below and no more than 1 of 
the remaining worsening by more than 30% 
b.
At least 30% improvement in 3 of 5 endpoints below and no more than 1 of the 
remaining worsening more than 30%. 
I.
Percent change in Parent’s Global Assessment (ParentGA) at Week 52.
II.
Percent change in Physician’s Global Assessment (PGA) at Week 52.
III.
Percent change in SELENA SLEDAI score at Week 52.
IV.
Change in PedsQL physical functioning domain at Week 52
V.
Percent change in 24 hour proteinuria at Week 52 (g/24hour equivalent by 
spot urine protein to creatinine ratio).
2.
Proportion of subjects with a sustained SRI response 
3.
Proportion of subjects with a sustained ParentGA response
4. Safety of belimumab
5. PK comparison with Adult PK
6. PedsQL Multidimensional Fatigue Scale
For Parts B and C, endpoints will include assessment of safety and disease activity as 
detailed in the Time and Events Table (Table 2).  

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1.
INTRODUCTION
1.1.
Disease Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by 
autoantibody production and abnormal B lymphocyte function [Pisetsky, 2001].  Due to 
the heterogeneity of SLE, its diagnosis may be difficult to make.  Regardless of age of 
onset or the time of diagnosis, SLE subjects share many immunogenetic and serologic 
similarities [Barron, 1993]. There are, however, several important laboratory and clinical 
features associated with childhood-onset SLE that are different from adult-onset SLE 
[Brunner, 2008; Costallat, 1994; Tucker, 1995]. 
Like other rheumatic diseases of childhood, SLE is not identical to that of adults 
[Lehman, 2007]. Compared with adult SLE, children with SLE have more active disease 
both at the time of diagnosis and over time. SLE in children is associated with more rapid 
accrual of damage, and has a higher degree of morbidity compared with SLE in adult 
populations [Brunner, 2008; Tucker, 2008]. Several studies suggest that
glomerulonephritis is more prevalent in childhood-onset than adult-onset SLE [King, 
1977; Barron, 1993; Fish, 1977]. In addition, adolescent-onset SLE subjects have a 
significantly higher occurrence of neurological involvement at the time of diagnosis 
[Tucker, 2008].
Age of Onset and Incidence
In most adult SLE subjects, symptoms appear on average between 29 and 32 years of age 
[Jimenez, 2003, Cevera, 1993]. For childhood SLE there is no strict definition with 
regard to onset. The onset of SLE is almost never seen before the age of 5 [Petty, 2005], 
with only very rare and anecdotal cases. A recent case series from France in children 
which looked at the clinical and laboratory manifestations of the disease at onset, showed 
the mean subject age at onset of childhood SLE to be 11.5 years. [Bader Meunier, 2005].
In a recent review [Pluchinotta, 2007], 13 subjects were identified with signs and 
symptoms of infantile lupus’ (2 years old).  This infantile lupus was likely caused by 
transfer of maternal antibodies from mothers with SLE.  A recent study based on a chart 
review of SLE subjects at a Rheumatology Unit of the Department of Pediatrics at an 
Italian hospital [Pluchinotta, 2007], identified 2 subjects diagnosed under the age of 2 
years, 11 subjects aged 2 to 9 years and 29 subjects aged 10 to 15 years at diagnosis. A 
cross-sectional survey of a sample of 90 pediatric clinics in France for SLE in children up 
to the age of 16 found a total of 155 cases, with a median age at onset of 12 years, the 
youngest subject diagnosed at 18 months and 2 further children diagnosed under the age 
of 5 years [Bader Meunier, 2005]. A chart review at the Pediatric Rheumatology Division 
of a New York Hospital identified 3 SLE subjects diagnosed under the age of 5 years, 20 
subjects aged 5 to 9 years and 82 subjects aged 10 to 19 years [Lehman, 1989].  A study 
in Israel [Uziel, 2007] ascertained all SLE cases with disease onset prior to the age of 18 
years in the country. A total of 102 children were identified with 81% females. The mean 
age at diagnosis was 13 years, with 16 children (12 females) being younger than age 11 at 
diagnosis; the youngest being 7. A study in a children’s hospital in Toronto 
[Brunner, 2002] ascertained all childhood-onset SLE over an 8-year period and identified 

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a total of 66 subjects, with an average age at onset of 13 years, the youngest being 4 years 
old. A further study investigated childhood SLE cases in three tertiary care centers in 
Italy and Brazil [Bandeira, 2006] and identified 57 subjects with disease onset prior to the 
age of 18 years. The mean age at diagnosis was 11 with the youngest age at 6 years.
In the PRINTO series containing 557 from 40 different countries the mean age at onset 
was 12±2.9 years with 268 with age at onset < 12 years and 55 < 8 years. [Ruperto, 2005, 
Ruperto, 2006]
The true incidence and prevalence of childhood SLE remain unknown [Singsen, 1998]. 
The reported estimates in the literature are based on only a very small number of cases 
and hence are subject to considerable variability and uncertainty. As a very rough 
estimate, the incidence for the age groups that approximate the group 12-18 years appears 
to be in the range of 1-4/100,000/year for both sexes combined, with an even 
considerably lower incidence in subjects < 12 years. The SLE prevalence could be 
estimated to be in the range of about 2-6/100,000 for children ≥ 12 years, again with a 
drastically lower prevalence for children below that age.  
A study in the population of Iceland [Gudmundsson, 1990] over a 10-year period found 
no cases in children aged 9 years and 3 cases (incidence 3/100,000) in females and 1 
case (1/100,000) in males aged 10-14 years. A study in the arctic region of Norway 
[Nossent, 2001] found 4 cases aged 15 years (incidence 0.5/100,000) over an 8-year 
period. A Spanish study [Lopez, 2003] identified 1 female case (prevalence 1.9/100,000) 
in the age group 0-14 years. A study using a GP records database in the UK [Nightingale, 
2007] identified 1 male case (prevalence 1.3/100,000) in the age group 0-9 years and 11 
female cases (10.6/100,000) and 2 male cases (1.8/100,000) in the 10-19 age group. A 
second study using the same database [Somers, 2007] estimated an incidence of < 
0.5/100,000 for the ages 0-9 and 0.5-1/100,000 for the ages 10-14 years. Other studies 
reported 6 cases under the age of 18 in Northern Ireland, UK [Gourley, 1997] and 2 cases 
under 19 years of age in Vilnius, Lithuania [Dadoniene, 2006]. These cases were likely to 
have been older than 11 years at diagnosis. A study in Nottingham, UK [Hopkinson, 
1993] found no cases for the ages 0-9 years and 1 female case (incidence 2.5/100,000) in 
the age group 10-19 over a 2-year period. Two US studies [Somers, 2007; Naleway, 
2005] investigated SLE in those younger than 20 years old with results indicating that 
SLE is unlikely to occur under the age of 12 years. 
The Iceland study [Gudmundsson, 1990] estimated an incidence of 4/100,000/year for the 
age group 15-19, while the UK GPRD study [Somers, 2007] shows an incidence of 
2/100,000/year for the same age group. The UK Nottingham study estimates an incidence 
of 2.5/100,000/year for females aged 10-19 years. The prevalence was reported as 
12.9/100,000 for females for the ages 0-19 in the Lithuania study [Dadoniene, 2006], 
10.6 and 1.8/100,000 for females and males aged 10-19 respectively in the UK GPRD 
study [Nightingale, 2007] and 20.4 and 0/100,000 in the US Wisconsin study 
[Naleway, 2005] for the same age-gender groups.
Taken together, from all of this information, it appears that the onset of SLE in children 
generally appears at an age of 10 to 11 years, with only rare cases in children younger 
than that, but virtually almost never below an age of 5.

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Disease Diagnosis
The diagnosis of SLE in the pediatric population is hampered by the same issues as the 
diagnosis of SLE in adults, i.e. there is still considerable uncertainty and ongoing 
discussion to define general and globally accepted diagnostic criteria for SLE in both 
adults and children. For adult clinical trials, the ACR Criteria for the Classification of 
Systemic Lupus Erythematosus are often used, which suggest that for the purpose of 
identifying subjects in clinical studies, a person shall be said to have SLE if any 4 or 
more of the 11 criteria are present, serially or simultaneously, during any interval of 
observation [Tan, 1982; Hochberg, 1997].
Due to the heterogeneity of SLE, its diagnosis may be difficult to make in a general 
pediatric or community setting. However, regardless of age of onset or of the time of 
diagnosis, SLE subjects share many immunogenetic and serologic similarities 
[Barron, 1993]. There are, however, several important laboratory and clinical features 
associated with childhood-onset SLE (i.e., before age 16) that are different from adult-
onset SLE [Brunner, 2008; Costallat, 1994; Tucker, 1995]. 
Serologically, anti-dsDNA, anti-Sm and anti-RNP antibodies and a low C3 are more 
prevalent in juvenile-onset than in adult-onset SLE [Tucker, 1995; Press, 1996; 
Reichlin, 1999]. However, complement, ANA, anti-dsDNA, aCL, and lupus anti-
coagulant antibodies are not significantly different in children of any age group.
Treatment
The clinical evidence of effective treatment of childhood rheumatic diseases including 
SLE is generally based on anecdotal reports [Lehman, 1997]. Generally, children are 
treated with the same agents used in the adult population.  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, methotrexate, leflunomide, 
thalidomide, 6-mercaptopurine) [Reveille, 2001; Petri, 2001; Ruiz-Irastorza, 2001; 
Chatham, 2001; Wallace, 2002; Brocard, 2005; Houssiau, 2004]. In the US, 
corticosteroids, hydroxychloroquine, and aspirin have been approved for SLE; no drug 
has been approved for the treatment of lupus in over 50 years.  Likewise, no drug has yet 
been approved across the entirety of the EU for the treatment of SLE. However, 
prednisolone, azathioprine and hydroxychloroquine have been authorised to treat SLE in 
various EU member states. 
All these therapies, whether approved or used off-label, 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 or azathioprine are 
immunosuppressive, resulting in increased risk of serious infections and certain cancers. 
Headache, dizziness, loss of appetite, upset stomach, diarrhea, stomach pain, vomiting 
and skin rash which are the side effects of hydroxychloroquine are not life-threatening, 
nevertheless they are responsible for the decreased quality of life of SLE subjects which 

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is of importance as all SLE treatments are chronic, since there is currently no cure for 
SLE. 
Supporting information on treatment of the pediatric population from clinical trials is also 
rather limited as most clinical trials for SLE are conducted in adults. Small case series 
involving B-cell depletion therapy such as rituximab in children with SLE have been 
published [Podolskaya, 2008; Marks, 2007; El-Hallak, 2007]. To date, the use of 
rituximab in SLE both in adult and pediatrics populations remains off-label. Clinical 
trials in juvenile SLE are being undertaken currently; yet performing clinical trials in 
juvenile SLE remains a challenge because of the small number of eligible subjects and 
the heterogeneity of the disease [Ruperto, 2004]. 
Study Drug Background
Belimumab (also known as LymphoStat-B™; BENLYSTA™) is a B-lymphocyte 
stimulator (BLyS)-specific inhibitor that blocks the binding of soluble BLyS, a B-cell 
survival factor, to its receptors 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. Belimumab reduces, but does not deplete, B-cells.  The lack of severe depletion of 
B-cells across all subsets supports the hypothesis that belimumab modulates B-cells and 
has the potential to preserve cells that respond to foreign or abnormal self antigens.  
Belimumab administered IV at a dose of 1 or 10 mg/kg compared with placebo was 
studied in two Phase 3 studies in adult subjects (N= 1,684) with active (SELENA 
SLEDAI 6), autoantibody-positive (ANA or anti-dsDNA) SLE who were receiving 
standard therapy (including steroids, antimalarials, and immunosuppressants).  In both 
studies, belimumab 10 mg/kg demonstrated superior efficacy as measured by response 
rate at Week 52 using the SLE Responder Index (SRI), the primary efficacy endpoint in 
each trial.  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 in adult subjects with SLE is also associated 
with reduction in autoantibodies and increases (normalization) of complement levels.  
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. 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 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, 

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common in subjects 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 
subjects 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.
In conjunction with functional differentiation of immune cells and the maturation of 
lymph node architecture from infancy through early childhood and adolescence, there is a 
progressive increase in general cytokine mRNA and protein expression with age 
[Härtel, 2005]. The bone marrow in children has more hemopoietic cellular content and 
less fat than adults. Within the bone marrow, transitional and naïve B-cells undergo 
proliferation and differentiation to become immunoglobulin secreting B-cells and long-
lived plasma cells. Bone marrow multipotent mesenchymal stromal cells enhance naïve 
B-cell proliferation and differentiation in a similar manner in both normal healthy donors 
and pediatric SLE subjects [Timonen, 2003; Traggiai, 2008]. The effect of belimumab 
upon B-cell survival would be expected to be similar between adults and children, 
although the sensitivity and extent of apoptosis is unknown. The implications for immune 
system function and potential long-term effects are unknown for the pediatric population.  
In general, the action of belimumab is expected to be the same in the adult and in the 
pediatric SLE population. 
Further information on the safety and efficacy of belimumab is provided in the 
Investigator Brochure (IB).
1.2.
Rationale
Recent and past studies consistently show that adult and pediatric SLE subjects have 
increased serum BLyS levels [Hong, 2009; Cheema, 2001; Petri, 2008; Wang, 2008]. 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 that involves an antagonist to 
BLyS may have therapeutic benefit in SLE. In addition, this therapeutic strategy of 
utilising a BLyS specific inhibitor, belimumab, proved successful with the positive 
results from two pivotal adult lupus studies.  In general, pediatric SLE subjects have 
more severe disease and thus higher disease activity index on average than adults. Adult 
SLE subjects who presented with more active disease performed better with 
belimumab. It is theorized based on this, that belimumab will have a beneficial effect in 
the pediatric SLE population.

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The Phase III clinical studies of belimumab demonstrated positive benefit/risk in the 
adult population. Marketing authorisation of belimumab for adults was granted in the EU 
on 13 July 2011 and belimumab received marketing approval from the FDA on 09 March 
2011. Belimumab is currently approved in the United States, all European Union 
Member States, as well as in over 20 countries. As a result of demonstration of positive 
benefit risk in the adult SLE population it is reasonable to expect a similar safety and 
efficacy profile in juvenile SLE. Additionally, no authorised pediatric medicinal 
products for SLE exist on the market.   Additionally, this trial fulfils the post-approval 
regulatory requirements to conduct a pediatric study.
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and 
quality of life of belimumab administered intravenously (IV) compared to placebo in 
pediatric subjects with systemic lupus erythematosus (SLE) receiving background 
standard therapy.
1.2.1.
Dose Rationale
The belimumab 10 mg/kg dose was selected based on the safety, efficacy and 
pharmacokinetic data from the two pivotal Phase 3 studies in adults with SLE. This dose 
will be confirmed or adjusted based on PK and safety assessments for each age group as 
described in Section 3.1. 
In the pivotal Phase 3 studies of belimumab in adult subjects with SLE, two doses were 
studied, 1 mg/kg and 10 mg/kg.  Although both belimumab 1mg/kg and 10mg/kg doses 
were active, the 10mg/kg dose was proposed for the pediatric trial because only the 
10mg/kg dose achieved the primary efficacy endpoint in both Phase 3 adult studies.  
Moreover, in the Phase 3 adult studies several clinical measures of improvement 
including the primary efficacy endpoint at Week 52 (including all sensitivity analyses), 
SELENA SLEDAI reductions, severe flare risk reduction, and complement normalization 
generally favored the 10 mg/kg dose. While steroid reductions tended to favor 1 mg/kg 
belimumab, fewer subjects receiving 10 mg/kg belimumab required increases in steroids 
over time. Additionally, there appeared to be a greater dose response in subjects with 
high disease and serological activity than in subjects with lower activity. Since pediatric 
subjects typically present with higher disease activity, the additional benefit of 10 mg/kg 
versus 1 mg/kg dosing is expected to be larger in children compared to the general adult 
population.  There was no apparent dose-response in the safety profile of belimumab in 
adult subjects, with both doses being generally well-tolerated, further supporting the 
selection of 10 mg/kg belimumab as the recommended dose in combination with standard 
therapies. The 10 mg/kg dose is approved in the United States, all European Union 
Member States, as well as in over 20 countries for the treatment of adult subjects with 
active, autoantibody-positive SLE.
BLyS-mediated clearance of belimumab did not appear to play a substantial role in the 
pharmacokinetics for 1 to 20 mg/kg dosing in adult SLE subjects, likely due to the large 
molar excess of serum belimumab relative to circulating BLyS levels even at trough 
concentrations for the lowest dose. Since circulating BLyS level were found to be similar 
in pediatric compared to adult subjects, there is no reason to change the adult dose in 
children based on differential target expression.

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Adult Phase 3 PK data based on weight normalized dosing for subjects with similar BMI 
values show little dependency of exposure on weight compared to the variability 
originating from other factors. This lends further support to use the adult weight 
normalized dose of 10 mg/kg in the initial juvenile treatment group
Based on this assessment subjects 12 years and older are expected to have similar 
belimumab exposure than adults with weight normalized dosing. For younger subjects 
somewhat lower exposures are expected with 10 mg/kg dosing, due to the body size 
dependencies observed for adult PK data, the expected lower average BMI in the 
pediatric group and possibly other developmental differences between adults and 
juveniles affecting therapeutic antibody clearance. 
Previous clinical experience for other IgG monoclonal antibodies has shown that weight 
normalized dosing resulted in similar exposures in juveniles compared to adults and 
depending on disease and tested weight range similar or lower exposures in younger 
children [Stiehm, 2000, Kovarik, 2002; Baldassano, 2003; Pescovitz, 2008].  
As described in Section 3.1, PK data in the initial subjects of both staggered age groups 
will be monitored to separately assess any substantial dependencies of exposure on body 
size or age and whether these warrant any dose changes to achieve a similar exposure as 
for adults with 10 mg/kg dosing in any of the two age groups.
1.3.
Part A Results Summary
BEL114055 is the first randomized placebo-controlled trial to test for treatment effect on 
disease activity outcomes in pediatric SLE. BEL114055 is a three-part study. In Part A 
(52-week double-blind treatment phase), participants were randomized to receive IV 
belimumab or placebo in addition to standard of care SLE therapy. Participants who 
completed Week 52 of Part A were eligible to participate in Part B, a 10-year open-label 
continuation phase. Participants discontinuing study agent in Part A or Part B were 
eligible for enrollment into Part C, the long-term safety follow-up phase. Parts B and C 
are ongoing. Part A was completed in January 2018. Due to the rarity of SLE in children 
and the resulting recruitment challenges, BEL114055 was not powered by design, and 
therefore no hypothesis testing was performed. Of the 93 participants enrolled in 
BEL114055, 40 participants were randomized to placebo and 53 participants to IV 
belimumab in Part A. Thirteen participants were 5 to 11 years of age and 80 participants 
were 12 to 17 years of age at the time of screening. Within the limits of the 1-year data 
analyzed to date, the risk/benefit profile of IV belimumab 10 mg/kg in pediatric SLE 
patients appears consistent with that of the adult patient population.
Similar to the pivotal adult IV [Furie, 2011; Navarra, 2011] and SC [Stohl, 2017] studies, 
the primary endpoint for Part A of BEL114055 was the SRI at Week 52. A major 
secondary endpoint was the Week 52 PRINTO/ACR Juvenile SLE Response Evaluation 
(PRINTO), a novel pediatric-specific composite endpoint used for the first time in a 
placebo-controlled clinical trial. The PRINTO tool assessed percent improvement from 
baseline to Week 52 in the following five domains: 1) SELENA SLEDAI, 2) Physician’s 
Global Assessment, 3) Parent’s Global Assessment, 4) 24-hour proteinuria, and 5) 
Pediatric Quality of Life physical functioning. Other major secondary endpoints included 

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the individual PRINTO components, the proportion of participants with a sustained SRI 
response, and the proportion of participants with a sustained parent global assessment 
(parent GA) response. Risk of lupus flares was also assessed. 
From the double-blind (Part A) phase of BEL114055, the following results have been 
reported [Brunner, 2018]:

A numerical benefit of belimumab 10 mg/kg was shown over placebo for the 
primary efficacy endpoint of SRI response rate at Week 52. The treatment difference 
(belimumab vs. placebo) at Week 52 was consistent with those observed in adult IV 
belimumab studies and the results for SRI6 and sustained SRI response also favored 
belimumab.

The key secondary PRINTO/ACR endpoints indicated a greater benefit of 
belimumab with 4 of the 5 individual components (percent change in ParentGA, 
PGA, SELENA SLEDAI, and proteinuria) showing a numerical benefit of 
belimumab compared with placebo.

A higher percentage of belimumab participants had a sustained ParentGA response at 
Weeks 44-52 vs. placebo.

Participants in the belimumab group had a lower risk of experiencing a severe SFI 
flare compared with the placebo group.

More than 50% of pediatric participants exceeded the MCID for improvement in the 
PedsQL generic total score, with no difference between the belimumab and placebo 
groups.
Pharmacokinetics of IV Belimumab in Pediatric SLE Study Participants
Following IV administration of 10 mg/kg on Days 0, 14, and 28 and every 4 weeks 
thereafter, the approved adult SLE dosing regimen, belimumab exposures were similar 
between pediatric and adult SLE participants [GSK document number 2017N34326_00].
Steady-state geometric mean Cmax, Cmin, Cavg, and AUC values were, respectively, 
315, 50, 108 g/mL, and 3012 day g/mL in the overall pediatric population; 305, 42, 92 
g/mL, and 2569 day g/mL in the 5-11-year-old group, and 317, 52, 112 g/mL, and 
3126 day g/mL in the 12-17-year-old group compared to 311, 46, 100 g/mL, and 2811 
day g/mL in adults. The slightly decreased exposure in younger participants was 
expected due to their lower BMI and allometric principles.
Pharmacodynamics of IV Belimumab in Pediatric SLE Study Participants
Similar to results of adult IV [Stohl, 2012] and SC [Doria, 2018] studies, reductions in 
overall B cells, naive B cells, other B cell subsets, and immunoglobulins were observed 
following IV belimumab administration in pediatric participants in Part A of BEL114055 
[GSK document number 2017N34326_00].
Safety of IV Belimumab in Pediatric SLE Study Participants
In the double blind phase (Part A) of BEL114055, treatment with IV belimumab plus 
standard of care was generally well-tolerated. Overall, no new safety concerns were 

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identified during Part A, relative to the known safety profile of IV and SC belimumab in
adult SLE clinical trials as described in the current IB.
The proportion of participants withdrawn from Part A due to an adverse event was 12.5% 
of placebo participants compared with 5.7% of belimumab participants. Serious adverse 
events were reported in 35.0% of placebo participants compared with 17.0% of 
belimumab participants, and only lupus nephritis led to discontinuation in more than 
1 participant (2 [5%] placebo, 1 [1.9%] belimumab).
The most common AE reported in both treatment groups during the study was headache 
(27.5% placebo, 13.2% belimumab). AEs reported in >5% of belimumab-treated 
participants and at an incidence at least 3% greater than that observed with placebo were 
diarrhea, rash, neutropenia, and increased transaminases. 
The system organ class (SOC) with the highest incidence in both treatment groups was 
infections and infestations for AEs (70.0% placebo, 56.6% belimumab) and SAEs (12.5% 
placebo, 7.5% belimumab). Opportunistic infections, including active tuberculosis and 
herpes zoster, were not reported in the placebo group and one (1.9%) participant in the 
belimumab group had an opportunistic herpes zoster infection. There were no 
malignancies reported. During Part A, there were no deaths in the belimumab group and 
one subject in the placebo group died of acute pancreatitis.
2.
OBJECTIVES

Evaluate the safety and tolerability of belimumab in the pediatric SLE 
population

Evaluate the pharmacokinetics of belimumab in the pediatric SLE population.

Evaluate the efficacy of belimumab in the pediatric SLE population

Evaluate the effects of belimumab on the quality of life in the pediatric SLE 
population.

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3.
INVESTIGATIONAL PLAN
3.1.
Study Design
This is a multi-center study to evaluate the safety, efficacy and pharmacokinetics of 
belimumab plus background standard therapy in at least 70 pediatric subjects 5 years to 
17 years of age with active systemic lupus erythematosus (SLE).  The study will consist 
of three separate phases:

Randomized, placebo-controlled, double-blind 52-week treatment phase Part A

Long term belimumab open label safety follow up for any subject who 
completes Part A (Part B)

Long term safety follow up phase for subjects who withdraw from Part A or Part 
B at any time (Part C)
Part A is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, 
safety, and pharmacokinetics of 10 mg/kg belimumab intravenous (IV) in pediatric 
subjects with active SLE (SELENA SLEDAI score 6).  In this study, at least 70 subjects 
will be randomized in three cohorts with Cohort 3 stratified by age (5-11 years vs. 12-17 
years) and screening SELENA SLEDAI scores (6-12 vs. ≥ 13).  Cohorts 1 and 2 will be 
randomized in a 5:1 ratio, and Cohort 3 subjects will be randomized in a 1:1 ratio to 
receive belimumab or placebo for 48 weeks on a background of standard of care.  Cohort 
1 will consist of the first 12 subjects, age 12 to 17 years.  No further enrolment of the 
study will proceed until after the PK of this cohort is evaluated.  Once the PK and safety 
profile of Cohort 1 is evaluated and any potential dose adjustments are determined as a 
result of this analysis, additional subjects 12-17 years of age will then be enrolled in 
Cohort 3.  In addition, at this point, Cohort 2 will enrol at least 10 subjects 5-11 years of 
age at the dose determined from the PK analysis of Cohort 1.  Once the PK and safety 
profile of Cohort 2 is evaluated and any potential dose adjustments are determined as a 
result of this analysis, additional subjects 5-11 years of age will then be enrolled in 
Cohort 3.
Belimumab will be infused over a minimum of 1 hour on Days 0, 14, 28, and then every 
28 days through the Week 48 (Day 336) visit.  All subjects will continue to receive their 
standard SLE therapy with progressive restrictions on the changes that are permitted 
throughout the 52-week randomized period.  Enrolment will be staggered to allow PK 
analysis of the first 2 age cohorts (Cohorts 1 and 2).
Safety monitoring and PK analysis from the initial 12 subjects from Cohort 1 will be used 
to confirm or adjust the belimumab dose for the remaining subjects enrolling in Cohort 2 
and 3.

Cohort 1:  The first 12 subjects aged 12 to 17 years of age will be randomized 
in a 5:1 ratio to belimumab 10 mg/kg (n=10) or placebo (n=2) on a background 
of standard of care for 48 weeks.  After all 12 subjects in Cohort 1 have received 
at least 8 weeks of treatment, safety and PK analysis will be conducted.   Cohort 
1 subjects will continue in the treatment period while the Study Team progresses 
the PK analysis, but no other subjects will enrol until the PK analysis is 

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completed. If the belimumab dose is adjusted because of the PK analysis, the 
Cohort 1 subjects will continue the study with the adjusted dose. Enrolment will 
be initiated for Cohort 2 (at least the first 10 subjects age 5 to 11 years) and 
Cohort 3 (subjects age 12-17 years) after the Cohort 1 PK analysis is completed.

Cohort 2:  At least the first 10 subjects aged 5 to 11 years will be randomized in 
a 5: 1 ratio to belimumab (10 mg/kg confirmed or adjusted dose) or placebo for 
48 weeks on a background of standard of care.  After all subjects in Cohort 2 
have received at least 8 weeks of treatment, safety and PK analysis will be 
conducted.  Administration of study agent in Cohort 2 will continue while safety 
monitoring and PK analysis progresses but no additional subjects ages 5-11 will 
be enrolled into the study until after the safety and PK analysis have been 
completed.  If the belimumab dose is adjusted, the Cohort 2 subjects aged 5 to 
11 years will continue with the dose-adjusted blinded treatment. 

Cohort 3: This cohort will consist of at least 48 subjects aged 5 to 17 years old.   
These subjects will be randomized in a 1:1 ratio to belimumab (10 mg/kg 
confirmed or adjusted dose) or placebo on a background of standard of care for 
52 weeks.  Randomization will be stratified by age group and screening 
SELENA SLEDAI scores (6-12 vs. ≥ 13).  Subjects aged 12 to 17 years will 
begin enrolment after Cohort 1 enrolment PK analysis is completed.  Subjects 
aged 5 years to 11 years will begin enrolment after Cohort 2 safety and PK 
analysis is completed.  
Younger children (5-11 years old) will not be randomized to treatment until review of 
Cohorts 1 and 2 have taken place, but they may be identified for potential inclusion at 
any time.  
Two separate dose assessment meetings will be held in which members of the GSK 
Safety Review Team (SRT) will review the safety, tolerability and preliminary PK data 
obtained from Cohorts 1 and Cohorts 2, respectively.  The objective of these meetings 
will be to either confirm the initial dose or to adjust the dose if a substantial difference in 
exposure is observed compared to adult Phase 3 PK data based on 10 mg/kg dosing.  An 
assessment of any safety signal may also factor into the decision to confirm or adjust the 
initial dose.  The SRT will review the available blinded safety, key biomarker and PK 
data and a recommendation by consensus will be made regarding dose confirmation or 
adjustment and the initiation of the subsequent cohorts.  The PK analysis and 
recommendation regarding dose confirmation or adjustment will be reviewed by the 
IDMC.  Final decisions will be made by the sponsor considering the recommendation 
from the IDMC and independent pharmacokineticist. The Study Team will remain 
blinded to treatment during these dose assessments.  Decisions regarding dose 
confirmation or adjustment will be summarized and distributed to study team members, 
investigators, the IDMC and IRBs and/or regulatory authorities according to local 
regulations.
A target enrolment of at least 70 subjects will be randomized.  In Cohorts 1 and 2, 
subjects will be randomized in a 5:1 ratio (belimumab:placebo), and the remaining 
subjects (at least 48) in Cohort 3 will be randomized in a 1:1 allocation ratio.  Therefore, 

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at least 42 subjects will be randomized to belimumab and 28 to placebo. The study will 
also enrol at least 14 subjects who are younger than 13 years of age. Enrolment will 
ensure that at least 50% of the randomised subjects will have presented with SELENA 
SLEDAI ≥ 8 at screening.  
Subjects may withdraw or discontinue from the study at any time for any reason.  All 
subjects withdrawing from Part A of the study will return for an exit visit 4 weeks after 
their last dose of study agent, and then continue in the safety follow-up period (Part C) 
where safety evaluations and limited disease activity assessments will be performed for 
up to 10 years from the first administration of study agent or open label belimumab.  
Subjects choosing not to continue in Part A or participate in Part B and do not wish to be 
monitored in the safety follow-up period (Part C), will return for a safety follow-up visit 
approximately 8 weeks following their last dose of study agent. Additional withdrawal 
criteria are presented in Section 4.4.
Subjects completing the randomized, double-blind, placebo-controlled phase of the study 
may continue to Part B of the study, the open label safety follow up and receive monthly 
belimumab treatment.  
The study sponsor will remain blinded to subjects’ treatment until all data from the 
Part A of the study are locked and the data are unblinded.  Clinical sites will remain 
blinded until after the results of Part A are publicly disclosed.
Part B: Open Label Belimumab Continuation
Subjects who complete 48 weeks of belimumab or placebo on a background of standard 
of care and the Week 52 assessments, regardless of treatment assignment, may progress 
to Part B of the study, the open-label belimumab continuation phase.  In this phase, all 
subjects will receive belimumab (10 mg/kg or adjusted dose) at monthly infusion visits.  
The Week 52 administration will be considered the 1st administration of the open-label 
continuation phase. Safety will be assessed at each monthly visit, and disease activity 
assessments will be performed every 6 months.  Subjects will continue in Part B of the 
study for up to 10 years from the first administration of belimumab. However, the study 
may conclude earlier if all subjects continuing belimumab treatment have received at 
least 5 years of treatment with belimumab (Part B or a combination of Part A and Part B) 
and if there are 15 or fewer subjects continuing to receive belimumab in the study (See 
Section 5.7.1 Study Conclusion).  Any subject who withdraws during the continuation 
phase will return for an exit visit at 4 weeks after their last dose and proceed to Part C, 
safety follow-up phase. Subjects choosing to discontinue from the study and not be 
monitored in the safety follow-up period (Part C) will return for a follow-up visit 
approximately 8 weeks following their last dose of open label belimumab.
Part C Safety Follow-up Phase
Part C will include any subject who discontinues study agent from Part A or open label 
belimumab from Part B.  These subjects will return for safety follow up visits in Part C 
monthly for 3 months and then annually after their last dose of study agent or open label
belimumab.  In Part C safety evaluations and limited disease activity assessments will be 
performed for up to 10 years from the first administration of study agent or open label 

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belimumab.  However, the study may conclude earlier if all subjects continuing 
belimumab treatment have received at least 5 years of treatment with belimumab (Part B 
or a combination of Part A and Part B) and if there are 15 or fewer subjects continuing to 
receive belimumab in the study (See Section 5.7.1 Study Conclusion). For subjects that 
withdraw from the study 8 weeks or less from the last administration of IV belimumab, 
an 8 Week Follow-up Visit (and a 16 Week Follow-up Visit post administration for 
female subjects of child-bearing potential) must be performed and recorded in the IVR 
system and the eCRF.  An Exit Visit may be conducted by phone for any subject who 
withdraws completely from the study while in Part C.
Independent Data Monitoring Committee (IDMC)
An IDMC comprised of experts in paediatric rheumatology, paediatric pharmacology, 
paediatric ethics and a statistician, none of whom are affiliated with the sponsor, will be 
organized to monitor the study as it progresses.  A charter will be developed to govern 
the activities of this committee. The IDMC will conduct its first safety and PK data 
review after the first cohort has been treated through the Week 8 (Day 56) visit, or within 
4 months of the treatment of the first subject enrolled in Cohort 1, whichever is earlier. If 
the earlier time point of within 4 months of the first subject enrolled is met, the IDMC 
will review the available safety data only. The IDMC will continue to meet, at a 
minimum, approximately every 6 months from the first meeting until the last subject 
concludes Part A, the randomized treatment period of the study.  After each semiannual 
review meeting, the IDMC will generate a report of data reviewed and if applicable, 
recommendations made.  Investigators will be notified of the outcome of each IDMC 
meeting.  Notification of local EC/IRB of the IDMC review outcomes will be at the 
discretion and requirements of local regulations.   
Decisions regarding dose confirmation or adjustment as a result of the planned Cohort 1 
and Cohort 2 PK and safety analyses will be summarized and distributed to study team 
members, investigators, the IDMC, and IRBs and/or regulatory authorities according to 
local regulations.

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Figure 1
BEL114055 Study Schematic
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA
4.1.
Number of Subjects
A target enrolment of at least 70 subjects to descriptively evaluate the efficacy and safety 
of belimumab is planned. In the first two cohorts, subjects will be randomized in a 5:1 
ratio (belimumab:placebo), and the remaining subjects will be randomized in a 1:1 
allocation ratio.  
4.2.
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the study agent or other study treatment 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.
Because of the uncertainty of vaccine response in any immunosuppressed population, it is 
recommended that all vaccinations be up to date as per country specific guidelines prior 
to entry into this study.  Live vaccinations are not to be administered less than 30 days 
before first dose or while subjects are receiving study agent. 
In addition, consideration should be given to administration of certain vaccines, in 
particular pneumococcus and meningococcus, prior to entry if the country specific 
vaccine schedule would require them soon after study start.  

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Subjects eligible for enrolment in the study must meet all of the following criteria:
1.
Are 5 to 17 years of age.  
2.
Have or have had in series, 4 or more of the American College of Rheumatology 
(ACR) 11 criteria for the classification of SLE 
3.
Have active SLE disease defined as a SELENA SLEDAI score ≥ 6 at screening. 
4.
Have unequivocally positive autoantibody test results defined as an ANA titre ≥ 1:80 
and/or a positive anti-dsDNA (≥ 30 IU/mL) serum antibody test from 2 independent 
time points as follows:
•Positive test results from 2 independent time points within the study screening 
period. Screening results must be based on the study’s central laboratory results.
OR
•One positive historical test result and 1 positive test result during the screening 
period.

Historical documentation of a positive test of ANA (e.g., ANA by HEp-2 titre) or anti-
dsDNA (e.g., anti-dsDNA by Farr assay) must include the date and type of the test, the 
name of the testing laboratory, numerical reference range, and a key that explains values 
provided as positive vs. negative OR negative, equivocal/borderline positive).  Only 
unequivocally positive values as defined in the laboratory’s reference range are 
acceptable; borderline values will not be accepted.
5.
Are on a stable SLE treatment regimen.
“Stable treatment at baseline” consists of any of the following medications (alone or in 
combination) at a fixed dose for a period of at least 30 days prior to Day 0:

Corticosteroids (prednisone or prednisone equivalent up to 0.5 mg/kg/day):

For subjects on SLE combination therapy, their stable steroid dose must be fixed 
within the range of 0 to 0.5mg/kg/day (prednisone or prednisone equivalent)

For subjects whose only SLE treatment is steroids, their stable steroid dose must 
be fixed within the range of 0.1-0.5mg/kg/day.

For those subjects on alternating day doses of steroids, use the average of 2 daily 
doses to calculate the average daily steroid dose. 

Other immunosuppressive or immunomodulatory agents including methotrexate, 
azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, 
mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin 
inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-
mercaptopurine or thalidomide.

Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine)

Non-steroidal anti-inflammatory drugs (NSAIDs)

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Note:

Pre-existing SLE medications must be stable for at least 30 days prior to Day 0.

Corticosteroids may be added as new medications or their doses adjusted only 
up to 30 days prior to Day 0.

New SLE therapy other than corticosteroids must not be added within 60 days of 
Day 0.
6.
A sexually active female subject is eligible to enter the study if she is:  

Not pregnant or nursing; 

Of non-childbearing potential. Non-childbearing potential is defined as a pre-
menarcheal female who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue); or a female who has 
documentation (medical report verification) of a hysterectomy, has both ovaries 
surgically removed or tubal ligation; or

Of childbearing potential (i.e., with functional ovaries and no documented 
impairment of oviductal or uterine function that would cause sterility). This 
category includes those with oligomenorrhoea [even severe]. These must have a 
negative serum pregnancy test at screening, and agree to 1 of the following:
Complete abstinence from intercourse from 2 weeks prior to administration of the 1st
dose of study agent until 16 weeks after the last dose of study agent; or
Consistent and correct use of 1 of the following acceptable methods of birth control 
for 1 month prior to the start of the study agent and 16 weeks after the last dose of 
study agent:  

Implants of levonorgestrel or etonogestrel; 

Ethinyl estradiol/Etonogestrel vaginal ring;

Injectable progesterone; 

Any intrauterine device (IUD) with a documented failure rate of less than 1% 
per year;

Oral contraceptives (either combined or progesterone only); 

Double barrier method: condom and occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/suppository;

Transdermal 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: Mycophenolate mofetil (MMF) and other forms of mycophenolate affect the 
metabolism of oral contraceptives and may reduce their effectiveness. As such, women 

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receiving mycophenolate who are using oral contraceptives for birth control should 
employ an additional method (eg, barrier method). 
7.
Subject signs and dates a written age appropriate assent form (in accordance with 
applicable regulations) and the parent or legal guardian (or emancipated minor) that 
has the ability to understand the requirements of the study, provides written informed 
consent (including consent for the use and disclosure of research-related health 
information) that the subject will comply with the study protocol procedures 
(including required study visits). 
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:
1.
Have received treatment with belimumab (BENLYSTA) at any time
2.
Have received any of the following within 364 days of Day 0:

Treatment with any B-cell targeted therapy (e.g., rituximab, other anti-CD20 
agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor 
fusion protein [BR3], TACI-Fc)

Abatacept.

A biologic investigational agent 
3.
Have required 3 or more courses of systemic corticosteroids for concomitant 
conditions (e.g., asthma, atopic dermatitis) within 364 days of Day 0 (Topical or 
inhaled steroids are permitted).
4.
Have received intravenous (IV) cyclophosphamide within 60 days of Day 0.
5.
Have received any of the following within 90 days of Day 0:  

Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab).

Interleukin-1 receptor antagonist (anakinra).

Intravenous immunoglobulin (IVIG).

Plasmapheresis.
6.
Have received any of the following within 60 days of Day 0:

A non-biologic investigational agent. 

Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, 
(See Inclusion Criteria #5)

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Note: New inhaled steroids and new topical immunosuppressive agents (e.g., eye 
drops, topical creams) are allowed. Any NSAID use for 1 week is allowed.

High dose prednisone or equivalent (> 1.5 mg/kg/day) or any steroid injection 
(intramuscular, intraarticular or intravenous).
7.
Have received any of the following within 30 days of Day 0:

A live vaccine.  

A change in dose of a corticosteroid, other immunosuppressive/
immunomodulatory agent, anti-malarial, NSAID, (See Inclusion Criteria #5)
8.
Have active central nervous system (CNS) lupus (including seizures, psychosis, 
organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS 
vasculitis) requiring therapeutic intervention within 60 days of Day 0.
9.
Have required renal replacement therapy (e.g. hemodialysis, peritoneal dialysis) 
within 90 days of Day 0 or be currently on renal replacement therapy
10. Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz 
Formula of less than 30 ml/min.
11. Have acute severe nephritis defined as a significant worsening of renal disease (e.g., 
the presence of urinary sediments and other lab abnormalities) that, in the opinion of 
the study investigator, may lead to the subject requiring induction therapy with IV 
cyclophosphamide, MMF or high dose corticosteroids during the first 6 months of 
the trial.  
Note: clinically stable lupus nephritis which can be managed with medications allowed in 
the study will not exclude subjects from participating in the trial (nor will any maximum 
level of proteinuria exclude subjects).  Clinical assessment and medical management of 
nephritis will be at the discretion of the study investigator.
12. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or 
hematopoietic stem cell/marrow transplant.
13. Have 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) 
which, in the opinion of the principal investigator, could confound the results of the 
study or put the subject at undue risk.
14. Have a planned surgical procedure or a history of any other medical disease 
(e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous 
access) that, in the opinion of the principal investigator, makes the subject unsuitable 
for the study.
15. Have a history of malignant neoplasm within the last 5 years.  
16. Subjects 12 years of age who have evidence of serious suicide risk including any 
history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 

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or 5 on the Columbia Suicide Severity Rating Scale (Refer to Appendix 12) in the 
last 2 months or who in the investigator's judgment, pose a significant suicide risk. 
17. Have a history of a primary immunodeficiency
18. Have an IgA deficiency (IgA level < 10 mg/dL).
19. Have acute or chronic infections requiring management, as follows:

Currently on any suppressive therapy for a chronic infection (such as 
tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes 
zoster and atypical mycobacteria).

Hospitalization for treatment of infection within 60 days of Day 0.

Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, 
or anti-parasitic agents) for infection within 60 days of Day 0.
20. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol 
abuse or dependence within 364 days prior to Day 0.
21. Have a historically positive HIV test or test positive at screening for HIV.
22. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection based on the results of 
testing for HBsAg, anti-HBc and anti-HBs as follows:

Subjects positive for HBsAg are excluded

Subjects negative for HBsAg and anti-HBc antibody but positive for anti-HBs 
antibody are eligible to participate

Subjects negative for HBsAg and anti-HBs antibody but positive for anti-HBc 
antibody will require clarification of their status by testing for HB DNA which if 
positive will exclude the subject from participation.
Subjects with documented vaccination against Hepatitis B (primary and secondary 
immunization and booster) will be considered negative.
23. Hepatitis C: Positive test for Hepatitis C antibody confirmed on an additional blood 
sample by RNA PCR assay.  Subjects who are positive for Hepatitis C antibody and 
negative when the Hepatitis C RNA-PCR assay is performed on an additional sample 
will be eligible to participate. Subjects who are positive for Hepatitis C antibody and 
have a positive result for the HCV when the Hepatitis C RNA PCR assay is 
performed on the additional sample will not be eligible to participate. (Institution or 
country specific guidelines for blood sample volume limits must be followed in 
collection of the additional blood sample.)
24. Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale 
except for the following that are allowed:

Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.

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
Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and 
not related to liver disease or anti-coagulant therapy.

Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver 
disease or malnutrition.

Any grade proteinuria 

Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus 
hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes or viral 
hepatitis. If present, any abnormalities in the ALT and or AST must be ≤ Grade 
2.

Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 
leukopenia, due to SLE
25. Have a history of an anaphylactic reaction to parenteral administration of contrast 
agents, human or murine proteins or monoclonal antibodies.
26. Children in Care:  A Child in Care (CiC) is a child who has been placed under the 
control or protection of an agency, organisation, institution or entity by the courts, 
the government or a government body, acting in accordance with powers conferred 
on them by law or regulation.  The definition of a CiC can include a child cared for 
by foster parents or living in a care home or institution, provided that the 
arrangement falls within the definition above.  The determination of whether a child 
meets the definition of CiC should be made with the study centre staff in 
consultation with the responsible IRB/Ethics Committee.
4.4.
Withdrawal Criteria
Subjects may be withdrawn from study agent or from the study if at any time:

It is the wish of the subject (or their legally acceptable representative) for any 
reason.

The investigator judges it necessary due to medical reasons.
Every effort will be made, in the event that a subject does not choose to continue study 
agent or to continue to be seen in the clinic according the study schedule, for subjects to 
be followed, at a minimum, on an annual basis in the long term safety follow-up period.
Furthermore, subjects will be withdrawn from study agent and transitioned to Part C, 
the long term safety follow-up, if at any time:

Subject becomes pregnant.

In Part A or Part B, receives prohibited therapy (See Section 5.6.2) 

In Part A are deemed a treatment failure (see Section 5.6.1 and Section 5.6.2)

Experiences unacceptable toxicity

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
Misses 3 consecutive study agent infusions (Note: This changes to 4 missed 
consecutive infusions if any of the doses are missed due to COVID-19 related 
reasons).
In the event a participant tests positive for COVID-19, or if no testing is available 
and a participant exhibits symptoms consistent with COVD-19, dosing of belimumab 
should be withheld until symptoms resolve and contact the Medical Monitor to 
discuss reinitiating belimumab treatment if applicable.

Participates in another interventional trial.
5.
STUDY TREATMENTS
5.1.
Study Agent and Other Study Treatment
The trade name of the investigational product is BENLYSTA (belimumab).  The generic 
(USAN/INN) name is belimumab.
Belimumab is a recombinant, human, IgG1monoclonal antibody derived by affinity 
maturation of a parental antibody which itself was derived from screening a phage 
display library for high affinity binding to BLyS.  Belimumab is expressed in the NS0 
mouse myeloma cell line. The secreted belimumab is recovered from the growth medium 
and purified using a series of chromatography and filtration steps.
A summary of the investigational products in this study is presented in Table 1.
Table 1
Summary of Investigational Products in BEL114055
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, study agent 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 

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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 in normal saline after reconstitution, using a typical 
approved plastic intravenous administration set for the infusion.
Study agent 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.  
Maintenance of a temperature log (manual or automated) is required.  Access to and 
administration of the study agent will be limited to the investigator and authorised site 
staff.  Study agent must be dispensed or administered only to subjects enrolled in the 
study and in accordance with the protocol.
All used product vials should be destroyed locally according to local site regulations for 
the destruction of study agents, after the monitor has conducted a check of the product 
accountability log during the study.  At the end of the study, unused product vials will be 
returned to GSK or destroyed on site according to local regulation at the study closeout 
visit, after the monitor has conducted final product accountability and given the site 
approval to destroy or return all remaining supplies.
The 400 mg single use vial of active study agent will be reconstituted with 4.8 mL SWFI, 
to yield a final concentration of 80 mg/mL of belimumab. After reconstitution and 
dilution in normal saline, the material is stable for up to 8 hours at 2-8°C, or at room 
temperature.
The unblinded site pharmacist or unblinded designee will be responsible for receiving, 
preparing and dispensing study agent, but will be independent of all other study activities.
During the double-blind period all other study site personnel, the subject and the sponsor 
will remain blinded to the study agent received and to certain biomarkers and 
pharmacodynamic laboratory results. Separate monitors will be responsible for the 
clinical (blinded monitor) and study agent (unblinded monitor) aspects of the study
Subjects receiving belimumab will receive the study agent at a concentration of 10 mg/kg 
or at a modified dose depending on evaluation of data from Cohorts 1 and 2 as described 
above.
The calculated dose of study agent to be administered to the subject is determined in 
milligrams (mg) by the assigned treatment group and the subject's body weight in 
kilograms (kg) at each visit. The study agent should be delivered to all subjects in 
250 mL of saline solution. Alternatively, infusion bags with 100 mL saline solution may 
be considered providing that the resulting belimumab concentration in the infusion bag 
does not exceed 4 mg/mL. When the study agent is administered at a dose of 10 mg/kg, 
to maintain a belimumab concentration of 4mg/mL or less, use of the 100 mL bag may 
only be considered for the subjects whose body weight is <=40 kg. This weight threshold 
may change as a result of any changes in the dose level of the study agent determined by 
the evaluation of PK data.

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The reconstituted belimumab will be diluted in 250 mL or 100 mL normal saline for IV 
infusion.  An amount of normal saline, equal to the calculated amount of product to be 
added, should be removed from the 250 mL or 100 mL infusion bag prior to adding the 
product.  After adding the reconstituted product, gently invert the bag to mix the solution.  
The prepared study agent should be infused over 1 hour. 
Placebo will be 250 mL or 100 mL normal saline for IV infusion.  To prevent unblinding, 
the injection membrane on the infusion bag should be punctured with an injection needle.  
The dose of study agent 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.
The treatment groups consist of an active treatment arm (belimumab) and a placebo arm, 
with all treatment groups receiving background standard therapy.  Once randomized, 
subjects will be dosed with study agent on Days 0, 14, 28 and then every 28 days through 
Day 336 (Week 48), resulting in a total of 14 doses.  Dosing from Part B of the study will 
be monthly for up to a total of 120 doses on belimumab.
Subjects will be monitored during all infusions. Subjects will remain under clinical 
supervision for 3 hours after completion of the first 3 infusions in Part A and for 3 hours 
after completion of the first 3 infusions in Part B the open label portion 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.  If symptoms of acute hypersensitivity occur, an extended period of monitoring 
may be appropriate, based on clinical judgment.  Trained personnel and rescue 
medications/equipment should be available during infusion visits.  
Sites are encouraged to follow their standard practices to manage any untoward infusion 
reactions noted during the infusion period. Subjects and parents/legal guardian should be 
made aware of the potential risk, the signs and symptoms of such reactions, and the 
importance of immediately seeking medical attention.
Refer to the Pharmacy Manual for detailed instructions on the preparation, administration 
and storage of study agent.
If a subject experiences a clinically significant AE that, in the clinical judgment of the 
investigator, is possibly, probably or definitely related to study agent, 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 study agent should be 
discontinued.  
If a subject experiences a clinically significant, potentially life-threatening (Grade 4) AE 
that in the clinical judgment of the investigator is possibly, probably or definitely related 
to study agent then treatment with study agent will be discontinued.  The subject should 
be withdrawn from the study and followed at regularly scheduled monthly study visits as 

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required until resolution of the AE(s), and must also return for follow-up visit 8 weeks 
after the last dose of study agent.
5.2.
Treatment Assignment
Subjects will be assigned to study treatment in accordance with the randomization 
schedule.  Once a randomization number has been assigned to a subject, it cannot be 
assigned to any other subject in the study.
Subjects will be randomized centrally using the Interactive Voice Response System
(IVRS)/ Interactive Web Response System (IWRS).  This was a telephone-based system 
now used more as a web-based system which will be used by the Investigator or designee 
to register the subject, randomize the subject and receive medication assignment 
information.  Subjects in Cohort 1 and Cohort 2 will be randomized in a 5:1 ratio and 
Cohort 3 will be randomized in a 1:1 ratio to 1 of 2 treatment groups: Belimumab (10 
mg/kg or adjusted dose) or placebo.  Details of how to use the IVRS/IWRS to register 
and randomize subjects will be provided in the SPM/SRM.
The investigator or designee will obtain the subject's treatment container assignment for 
use by the unblinded pharmacist or pharmacy designee to prepare and dispense the 
treatments.  Subjects will be identified by the unique subject number assigned at 
screening that will remain constant for the duration of the study.  Each investigator will 
be supplied with sufficient supplies to conduct the trial.  Additional treatments will be 
supplied as needed to the sites.  Although study agent will be stored at the site, the 
Investigator (or designee) must register in the IVRS/IWRS to obtain study agent 
assignments.
5.3.
Blinding
To maintain the integrity of the blind:

The pharmacist or designee involved in the preparation of the intravenous 
injections of study agent will be unblinded to the treatment allocation of each 
subject at that site.   The separate site pharmacist or designee will also be the 
person responsible for receiving and dispensing study agent, but independent of 
all other study activities.

Once diluted, in a saline bag as described above belimumab will be identical in 
appearance to placebo and will be administered by a blinded member of the site 
staff.  All other study site personnel, the subject and the sponsor will remain 
blinded to the study agent received and to certain biomarkers and 
pharmacodynamic laboratory results
5.4.
Unblinding
The investigator or treating physician may unblind a subject’s treatment assignment only 
in the case of an emergency, when knowledge of the study treatment is essential for the 
appropriate clinical management or welfare of the subject.  Whenever possible, the 
investigator must first discuss options with the GSK Medical Monitor or appropriate 
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impractical, the investigator must notify GSK as soon as possible, but without revealing 
the treatment assignment of the unblinded subject, unless that information is important 
for the safety of subjects currently in the study.  The date and reason for the unblinding 
must be recorded in the appropriate data collection tool.
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
treatment assignment for any subject with an SAE. If the SAE requires that an expedited 
regulatory report be sent to one or more regulatory agencies, a copy of the report, 
identifying the subject’s treatment assignment, may be sent to clinical investigators in 
accordance with local regulations and/or GSK policy.
5.5.
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 study 
agent 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.
5.6.
Treatment Compliance
Subject compliance with intravenous administration of study medication/placebo will be 
documented by the administering pharmacist and/or other qualified study personnel in the 
site records.  A subject will be withdrawn if they have missed 3 consecutive study agent 
infusions (4 consecutive infusions if any of these are missed due to COVID-19).
5.6.1.
Permitted Medications and Non-Drug Therapies
All concomitant medications taken during the study will be recorded in the eCRF. For all 
medication types explicitly described in this section, complete information must be 
recorded on the concomitant medications page.
Subjects must be on a stable SLE treatment regimen for at least 30 days prior to Day 0.  
New SLE medications other than corticosteroids must not be added within 60 days prior 
to Day 0.  Corticosteroids may be added as new medications or their doses adjusted only 
up to 30 days prior to Day 0.
Once the subject is randomized and receives the first dose of study agent on Day 0, the 
investigator may adjust concurrent medications (add, eliminate, change dose 
level/frequency) as clinically required; however, in Part A changes in certain medications 
(as outlined below) may result in the subject being defined as a treatment failure and will 
require withdrawal from Part A of the study and transition to Part C. 
5.6.1.1.
Anti-malarials

A new anti-malarial (eg, hydroxychloroquine, chloroquine, quinacrine) may be 
started between Day 0 and the Day 112 (Week 16) visit.

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
The dose of an anti-malarial may be reduced during the course of the study. The dose 
of an anti-malarial may be increased as clinically required, up to the Day 112 (Week 
16) visit.

After the Day 112 (Week 16) visit, any increase in dose of an anti-malarial over the 
baseline (Day 0) or Day 112 (Week 16) visit dose, whichever is higher, will declare 
the subject a treatment failure.

Starting any new anti-malarial treatment after the Day 112 (Week 16) visit will 
declare the subject a treatment failure.

An antimalarial treatment will be considered new if the subject did not receive an 
antimalarial at any time during the Day 0 to Day 112 (Week 16) treatment interval.

An anti-malarial may be replaced by another anti-malarial due to documented 
toxicity or lack of availability at any time during the study.

The allowable doses of anti-malarial drugs* are:

Hydroxychloroquine –up to 400 mg/day.

Chloroquine – up to 500 mg/day.

Quinacrine – up to 100 mg/day.

Compounded anti-malarials – no individual component may exceed the 
maximum dose above.
*Clinical loading dose is permitted for initiation or replacement.
NOTE: The use of anti-malarials for either SLE management or malarial prophylaxis is 
permitted.
5.6.1.2.
Steroids
In this section, total systemic steroid dose is defined as the average daily dose of all 
steroids taken IV, IM, SC, intradermally and orally for both SLE and non-SLE reasons.  
At baseline, the average daily dose of steroids is the sum of steroid dose over 7 
consecutive days up to, but not including Day 0, divided by 7.  While on treatment, the 
average daily dose of steroids is the sum of steroid dose over any 7 consecutive days 
divided by 7 in the respective time window.
5.6.1.2.1.
Systemic Steroids for SLE-related Disease Activity

The total dose of systemic steroids as defined above may be increased as clinically 
required during the first 6 months of the trial, (i.e., until the Day 168 [Week 24] 
visit), but must return to within 25% or 5 mg over the baseline (Day 0) dose, 
whichever is higher, by the Day 168 (Week 24) visit.

A subject who fails to return to within 25% or 5 mg over the baseline (Day 0) dose, 
whichever is higher, by the Day 168 (Week 24) visit will be considered a treatment 
failure. The calculation of the 7-day average steroid dose to determine whether a 
subject is a treatment failure will begin on the day after the visit.

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
After Day 168 (Week 24) visit, an increase > 25% or > 5 mg over the baseline (Day 
0) dose, whichever is higher, for SLE activity will deem the subject a treatment 
failure.

Within 8 weeks before the Day 364 (Week 52) visit, no new increase over the 
baseline (Day 0) or Day 308 (Week 44) visit dose, whichever is higher, is allowed. 
5.6.1.2.2.
Intra-articular Injections

Subjects may receive intraarticular (IA) injections between baseline (Day 0) and the 
Day 308 (Week 44) visit.

A subject who receives any intraarticular injection(s) within 8 weeks before the Day 
364 (Week 52) visit will be defined as a treatment failure.
5.6.1.2.3.
Steroids for Reasons Other Than SLE Disease Activity
Inhaled and topical steroids are allowed throughout the course of the study.  The 
following time specific restrictions apply to steroid formulations which are not inhaled or 
topical.
From Day 0 to the Day 168 (Week 24) Visit:
Steroids may be given for reasons other than SLE disease activity (such as asthma, 
contact dermatitis) as clinically indicated until Day 168 (Week 24) visit.
From Day 168 to 308 (Week 24 to 44) Visits:
Steroids may be given for reasons other than SLE disease activity from the Day 168 
(Week 24) visit until the Day 308 (Week 44) visit at any dose/duration that does not 
result in a total steroid dose (for SLE and non-SLE reasons) > 25% or > 5 mg, whichever 
is higher, over the baseline dose.  In addition, steroids (prednisone or prednisone 
equivalent) for non-SLE reasons may be given at the investigator’s discretion short-term 
at higher doses but not to exceed the maximum doses described below.
Up to 750 mg (prednisone or prednisone equivalent) for 1day,
and/or
Up to 100 mg/day (prednisone or prednisone equivalent) for 2-3 days ,
and/or
Up to 40 mg/day (prednisone or prednisone equivalent) for 4-7 days.
The duration of high dose steroid use for reasons other than SLE must not exceed 7 days, 
after which time, tapering should begin.  The total steroid dose must be tapered to within 
25% or 5 mg over the baseline dose, whichever is higher, within 30 days of the 1st dose 
of a course of steroids.  In addition, the steroid dose must be tapered to within 25% or 5 
mg over the baseline dose, whichever is higher, by the Day 308 (Week 44) visit.

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From the Day 308 to Day 364 (Week 44 to 52) Visits:
After the Day 308 (Week 44) visit, no new steroids are allowed for reasons other than 
SLE activity that result in a total daily steroid dose > 25% or > 5 mg, whichever is 
higher, over the baseline total steroid dose.  A subject will be considered a treatment 
failure for any steroid use 8 weeks before the Day 364/Exit (Week 52) visit that does not 
meet this criterion.
5.6.1.2.4.
Tapering or Restoration/Restart of Steroids
One of the objectives of this trial is to evaluate the ability of belimumab to reduce 
juvenile SLE disease activity.  Premature or rapid reduction in steroids may confound 
interpretation of study results and could induce a flare.  However, it is understood that an 
important goal of therapy is to reduce steroids with clinical improvement maintained, 
given their associated morbidity.  As such, subjects who have clinically significant 
improvement of SLE disease activity for at least 4 weeks may, at the investigator’s 
discretion, reduce the steroid dose targeting a reduction to 7.5 mg/day or lower.  If the 
subject continues to have stable or improving disease activity after 4 weeks on a reduced 
dose, then the investigator may consider reducing the dose again.  During attempts to 
wean subjects from steroid use altogether, alternating dosages are permitted to help guard 
against Addisonian crises.  Caution should be exercised when discontinuing steroids 
before the Day 364/Exit (Week 52) given the potential to induce a flare and thereby 
confound the study results.
If a subject has had worsening SLE disease activity, then a 12-week period of stable or 
improving disease activity should be observed before considering a clinically significant 
steroid dose reduction.  (Note: The investigator may always apply their clinical judgment 
as to whether a dose reduction is appropriate.)
Subjects who have their prednisone or prednisone equivalent tapered may have their dose 
increased up to the maximum allowed as defined in Section 5.6.1.2.1 and Section 
5.6.1.2.3.
5.6.1.2.5.
Treatment of SLE Flares with Steroids
If a subject has an SLE flare requiring an increase in steroid dose before the Day 168 
(Week 24) visit, the investigator should consider the guidelines prepared for the ACR, for 
steroid dose/duration of induction therapy [Ad, 2004].  The subject must return to within 
25% or 5 mg over the baseline (Day 0) steroid dose, whichever is higher, on or before the 
Day 168 (Week 24) visit or they will be considered a treatment failure.  If a subject’s 
dose is increased > 25% or > 5 mg over the baseline dose, whichever is higher, any time 
after the Day 168 (Week 24) visit, they are also considered a treatment failure. 
5.6.1.3.
Other Immunosuppressive/Immunomodulatory Agents
One of the primary objectives of this trial is to evaluate the ability of belimumab to 
reduce SLE disease activity.  Premature or rapid reduction in 
immunosuppressant/immunomodulatory agents may confound interpretation of study 
results and could induce a flare.

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
Starting any new immunosuppressive/immunomodulatory agent after Day 0 will 
cause the subject to be declared a treatment failure.

The dose of existing immunosuppressive/immunomodulatory agents may be 
increased, as clinically required, up to the Day 112 (Week 16) visit.

After the Day 112 (Week 16) visit, any increase in dose over the baseline (Day 0) or 
Day 112 (Week 16) visit dose, whichever is higher, will cause the subject to be 
declared a treatment failure.
The allowable doses for immunosuppressives at baseline (Day 0) and during the study:

Azathioprine – up to 300 mg/day.

6-mercaptopurine – up to 300 mg/day.

Mycophenolate mofetil (PO)/ mycophenolate mofetil hydrochloride (IV) – up to      
4 g/day.

Mycophenolate sodium (PO) – up to 2.88 g/day.

Methotrexate –up to 25 mg/week.

Oral cyclophosphamide – up to 2.5 mg/kg/day.

Cyclosporine – up to 4 mg/kg/day*.

Tacrolimus – up to 0.2 mg/kg/day*.

Sirolimus – up to 2 mg/day*.

Thalidomide – up to 200 mg/day.

Leflunomide – up to 40 mg/day*.

Mizoribine – up to 150 mg/day. 
An immunosuppressive/immunomodulatory agent may be replaced with 1 of the agents 
above due to documented toxicity or lack of availability.  For other immunosuppressive 
agents not listed above, the investigator must contact the Medical Monitor for approval.
*Clinical loading dose is permitted when replacing 
immunosuppressive/immunomodulatory agents. Monitor blood levels as clinically 
indicated.
New topical immunosuppressive agents [e.g., eye drops, topical creams] are allowed after 
Day 0.
5.6.1.4.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Since NSAIDs may affect efficacy parameters (e.g., arthritis) and may affect renal 
function (NSAID nephropathy), the use of these agents should be initiated and stabilised 
prior to the screening visit.

NSAIDs may be given as clinically indicated until the Day 308 (Week 44) visit.

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
For subjects who have received an NSAID between Day 0 and Day 308, the existing 
NSAID can continue at a stable dose after Day 308.

For subjects who never received an NSAID between the Day 0 and Day 308 (Week 
44) visit, starting a new NSAID after the Day 308 (Week 44) visit will declare the 
subject a treatment failure unless the NSAID is given for < 1 week.

An NSAID may be replaced with another NSAID due to documented toxicity or lack 
of availability.

Anti-thrombotic doses of aspirin are permitted at any time during the study  
Paracetamol (acetaminophen) is primarily an analgesic and lacks the anti-inflammatory 
properties of other NSAIDs. The use of paracetamol is recommended when possible to 
treat non-SLE related conditions, in the absence of a pre-existing hepatic function 
deficiency.
5.6.2.
Prohibited Medications and Non-Drug Therapies
Subjects who start prohibited medications or therapies at any time during Part A, the 
double blind placebo controlled portion of the study will be considered treatment failures 
and nonresponders for primary efficacy analysis.  These subjects must have study agent 
discontinued and will be placed into Part C, the safety follow up phase. 
In Part B the belimumab open label safety follow-up, subjects who start prohibited 
medications or therapies will be considered a protocol violation and will have study 
treatment (belimumab) discontinued.  These subjects will be placed into the Part C safety 
follow-up period.
The following medications and therapies are prohibited at any time during Part A of 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.

Participation in a study using 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, 
certolizumab, tocilizumab, golimumab).

Other biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist).

Intravenous immunoglobulin (IVIG).

IV cyclophosphamide (oral cyclophosphamide is permitted).

Plasmapheresis, leukapheresis.
For Part B, the belimumab open label safety follow up portion of the study, the above 
rules also apply with the exception of IV cyclophosphamide, which is permitted in the 
open label safety follow up.  It should be noted that the potential risks of combining 
belimumab with cyclophosphamide should be factored into the decision to utilize IV 
cyclophosphamide.

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Finally, for Part C, the safety follow-up phase, there are no prohibited medications. 
Live Vaccines:  Live vaccines are not permitted in the study. Subjects who require a live 
vaccine during the study should have study agent discontinued prior to receiving the live 
vaccine.
5.7.
Treatment after the End of the Study
Subjects who complete 48 weeks of treatment and the final 52-week evaluation (Part A) 
will be eligible to participate in Part B, the open label extension period of the study, and 
receive belimumab.  
During Part B, the investigator may adjust concurrent medications (add, eliminate, 
change dose level/frequency) as clinically appropriate in response to improving or 
worsening disease activity. However, subjects who violate the prohibited medication 
rules (Section 5.6.2) will have belimumab discontinued and subjects placed in Part C.  
Investigators are encouraged to consider the guidance provided in Section 5.6.1.2.3
regarding corticosteroid reduction during periods of stable SLE disease. The American 
College of Rheumatology (ACR) draft guidance regarding steroid dosing and tapering in 
response to SLE flare is provided in Appendix 7 SLE Flare Index. The reason for altering 
any immunosuppressant therapy (e.g., toxicity associated with the medication, 
fluctuations in disease activity, etc) must be recorded on the appropriate eCRF. 
The investigator is responsible for ensuring that consideration has been given to care of 
the subject’s medical condition in Part C and post-study.
5.7.1.
Study Conclusion
The long term follow up portion of the study (Part B and Part C) is planned for a total of 
up to 10 years. However, the study will conclude earlier if all subjects continuing 
belimumab treatment have received at least 5 years of treatment with belimumab and if 
there are 15 or fewer subjects continuing to receive belimumab in the study. 
5.8.
Treatment of Study Treatment Overdose
The dose of belimumab considered 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 judgment in treating the 
symptoms of a suspected overdose.
6.
STUDY ASSESSMENTS AND PROCEDURES
Study assessments and procedures will include the following and are detailed in the Time 
and Events Table 2 and Study Procedures Manual:

Demographic information including gender, ethnic origin, race, date of birth.

Medical history.

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
Complete physical examination, including height and weight 

Vital signs including temperature, sitting blood pressure, and heart rate

Confirm classification of SLE disease (based on ACR criteria) by reviewing 
previously documented clinical records.

Blood samples for: 

Haematology.

Modified Chem 20 (non-fasting).  (CPK MUST be done for subjects with 
myositis in order to score SELENA SLEDAI/BILAG)

Serum pregnancy test - l – defined as a pre-menarcheal female who has not yet
entered puberty as evidenced by lack of breast development (palpable glandular 
breast tissue); or a female who has documentation (medical report verification) 
of a hysterectomy, has both ovaries surgically removed or tubal ligation.

HIV antibody, Hepatitis B surface antigen, anti-HBc, anti-HBs and Hepatitis C 
antibody testing.

Prothrombin time (PT), partial thromboplastin time (PTT )

Complement C3, C4

Serum Immunoglobulin isotypes (IgG, IgM, IgA)

ANA and anti-dsDNA autoantibodies

aCL autoantibodies  

PK sampling 

Immunogenicity 

Functional antibodies

BLyS protein 

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).

Urine sample for:

Routine urinalysis 

Spot urine for macroscopic/microscopic/proteinuria assessments

Disease activity scales:

SELENA SLEDAI (See ‘Guidelines for Scoring Proteinuria’)

At Screening, confirm SLE disease is active, defined as SELENA SLEDAI 
score ≥ 6 

Physician’s Global Assessment (PGA)

Parent Global Assessment (ParentGA)

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
SLE Flare Index

BILAG

Pediatric SLICC/ACR Damage Index

PRINTO/ACR Juvenile SLE Response Evaluation

Pediatric Quality of Life Inventory (PedsQL)

PedsQL-Multidimensional Fatigue Scale

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Table 2
Time and Events Table
Procedures
Part A
Double-Blind Treatment Period 
Days 0-364 (Weeks 0-52)
Post 
Treatment 
Follow-up
Unschedule
d Visit 3
Study Day
Screenin
g Period 
-35 days
Day 
0
D
ay 
14

3 
da
ys
Da
y 
28
3 
day
s
Day 
56
7 
day
s
Day 
84
7 
day
s
Day 
112
7 
day
s
Day 
140
7 
day
s 
Day 
168
7 
day
s
Day 
196
7 
day
s
Day
224
7 
day
s
Day
252
7 
day
s
Day
280
7 
day
s
Day
308
7 
day
s
Day 
336
7 
day
s
Day 
364 
or 
Exit 
(4 
wks 
post 
dose
)17 
days
8-Week
Follow-up
7 days 2
16 
Week 
Follow
-Up
7 
days19
Study Week
Wk 
0
W
k 
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
Written Informed 
Consent + 
Assent 
x
Subject 
Demography
x
Medical History
x
Inclusion/Exclusi
on Criteria
x
Efficacy Assessments
Disease Activity Scales  
SELENA 
SLEDAI15
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
SLE Flare Index
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
PRINTO/ACR
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
BILAG15
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physician GA
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Parent GA
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x

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Procedures
Part A
Double-Blind Treatment Period 
Days 0-364 (Weeks 0-52)
Post 
Treatment 
Follow-up
Unschedule
d Visit 3
Study Day
Screenin
g Period 
-35 days
Day 
0
D
ay 
14

3 
da
ys
Da
y 
28
3 
day
s
Day 
56
7 
day
s
Day 
84
7 
day
s
Day 
112
7 
day
s
Day 
140
7 
day
s 
Day 
168
7 
day
s
Day 
196
7 
day
s
Day
224
7 
day
s
Day
252
7 
day
s
Day
280
7 
day
s
Day
308
7 
day
s
Day 
336
7 
day
s
Day 
364 
or 
Exit 
(4 
wks 
post 
dose
)17 
days
8-Week
Follow-up
7 days 2
16 
Week 
Follow
-Up
7 
days19
Pediatric SLICC/ 
ACR Damage 
Index
x
x
x
Quality of Life16
PedsQL16
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
PedsQL-
Fatigue16
x
x
x
x
x
x
x
x
x
x
Safety Assessments
Concomitant 
Medication
x
x
x
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
x
x
Vital Signs 4,5 
x
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
x
12-Lead ECG 
x
C-SSRS 
(12 years of 
age) Baseline/
Screening 
x

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Procedures
Part A
Double-Blind Treatment Period 
Days 0-364 (Weeks 0-52)
Post 
Treatment 
Follow-up
Unschedule
d Visit 3
Study Day
Screenin
g Period 
-35 days
Day 
0
D
ay 
14

3 
da
ys
Da
y 
28
3 
day
s
Day 
56
7 
day
s
Day 
84
7 
day
s
Day 
112
7 
day
s
Day 
140
7 
day
s 
Day 
168
7 
day
s
Day 
196
7 
day
s
Day
224
7 
day
s
Day
252
7 
day
s
Day
280
7 
day
s
Day
308
7 
day
s
Day 
336
7 
day
s
Day 
364 
or 
Exit 
(4 
wks 
post 
dose
)17 
days
8-Week
Follow-up
7 days 2
16 
Week 
Follow
-Up
7 
days19
C-SSRS – Since 
Last Visit
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
Serious Adverse 
Events
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
Laboratory Assessments
Hematology 7
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Chemistry 
(Modified 20 
non-fasting) 7
x
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 to 
creatinine ratio)8
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
PGx Sampling 12
x
Pregnancy Test 
5,9,19
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x

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Procedures
Part A
Double-Blind Treatment Period 
Days 0-364 (Weeks 0-52)
Post 
Treatment 
Follow-up
Unschedule
d Visit 3
Study Day
Screenin
g Period 
-35 days
Day 
0
D
ay 
14

3 
da
ys
Da
y 
28
3 
day
s
Day 
56
7 
day
s
Day 
84
7 
day
s
Day 
112
7 
day
s
Day 
140
7 
day
s 
Day 
168
7 
day
s
Day 
196
7 
day
s
Day
224
7 
day
s
Day
252
7 
day
s
Day
280
7 
day
s
Day
308
7 
day
s
Day 
336
7 
day
s
Day 
364 
or 
Exit 
(4 
wks 
post 
dose
)17 
days
8-Week
Follow-up
7 days 2
16 
Week 
Follow
-Up
7 
days19
PK Sampling 10,11
x
x
x
x
x
x
x
x
Immunogenicity
x
x
x
x
x
x
BLys Protein
x
C3/C4; CRP
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
B-Cells
x
x
x
x
x
x
x
anti-dsDNA
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Auto-antibodies 
13,
x
x
aCL13
x
IgA, IgG and 
IgM14
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Functional 
Antibodies 18
x
x
x
Vaccine Antibody 
Titer 18

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Procedures
Part A
Double-Blind Treatment Period 
Days 0-364 (Weeks 0-52)
Post 
Treatment 
Follow-up
Unschedule
d Visit 3
Study Day
Screenin
g Period 
-35 days
Day 
0
D
ay 
14

3 
da
ys
Da
y 
28
3 
day
s
Day 
56
7 
day
s
Day 
84
7 
day
s
Day 
112
7 
day
s
Day 
140
7 
day
s 
Day 
168
7 
day
s
Day 
196
7 
day
s
Day
224
7 
day
s
Day
252
7 
day
s
Day
280
7 
day
s
Day
308
7 
day
s
Day 
336
7 
day
s
Day 
364 
or 
Exit 
(4 
wks 
post 
dose
)17 
days
8-Week
Follow-up
7 days 2
16 
Week 
Follow
-Up
7 
days19
PT/PTT
x
Study 
Treatment
Administer Study 
Treatment 17
x
x
x
x
x
x
x
x
x
x
x
x
x
x
only 
if 
goin
g 
into 
Part 
B
Randomization
x
IVRS
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x

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Time and Events Table – Open-Label and Follow-up Periods
Procedures
Part B
Open-Label Continuation
Part C
10 Year Post Infusion Safety Follow-up
Assessment 
Every 
4 weeks  
± 7days
Additional 
Assessments 
Every 6
Months/Yearly
7 days
Exit Visit2 and 
8-Week Post 
Treatment
Follow-up
7 days 2
16 Week Post 
Treatment 
Follow Up 
phone call 
7 days 19
Assessment Every 
4 weeks ± 7 days for the First 3 
Months^
Assessments Every Year† 
28 days after last infusion#
Efficacy Assessments
Disease Activity 
Scales: 
SELENA, 
SLEDAI,SLE 
Flare Index, 
BILAG, 
Physician GA, 
Parent GA15
x
x
Pediatric 
SLICC/ACR 
Damage Index16
x
x
x
PedsQL 16
x
x
x
PedsQL-
Multidimensional 
Fatigue16
x
x
x
Safety Assessments
Concomitant 
Medication
X
x
x
x
Symptom Driven 
Physical 
Examination
X
x
x
x
Vital Signs 
X
x
x
x

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Procedures
Part B
Open-Label Continuation
Part C
10 Year Post Infusion Safety Follow-up
Assessment 
Every 
4 weeks  
± 7days
Additional 
Assessments 
Every 6
Months/Yearly
7 days
Exit Visit2 and 
8-Week Post 
Treatment
Follow-up
7 days 2
16 Week Post 
Treatment 
Follow Up 
phone call 
7 days 19
Assessment Every 
4 weeks ± 7 days for the First 3 
Months^
Assessments Every Year† 
28 days after last infusion#
Weight and 
Height5,6
X
x
x
x
Adverse Events
(AEs) 
X
X*
x
x
Serious AEs
(SAEs) and  AEs 
of Special 
Interest (AESIs)
X
X*
x
x
x*
Laboratory 
Assessments
Hematology
x
x
x
x
Chemistry 
(Modified 20 
non-fasting) 
x
x
x
x
B-cells
X
X
X
Immunogenicity
X
X
X**
Anti-dsDNA; 
C3/C4
X
IgA, IgG and 
IgM14
X
X
X
X
X
Spot Urine 
(protein to 
creatinine ratio)8
X
X
Pregnancy Test 
5,9,19
X
X
X
X

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Procedures
Part B
Open-Label Continuation
Part C
10 Year Post Infusion Safety Follow-up
Assessment 
Every 
4 weeks  
± 7days
Additional 
Assessments 
Every 6
Months/Yearly
7 days
Exit Visit2 and 
8-Week Post 
Treatment
Follow-up
7 days 2
16 Week Post 
Treatment 
Follow Up 
phone call 
7 days 19
Assessment Every 
4 weeks ± 7 days for the First 3 
Months^
Assessments Every Year† 
28 days after last infusion#
PK Sampling 20
X
(Japan only,
at only 
week12 / 3 
month visit 
of first year)
X
(Japan only, at 
only 6 month 
visit of first 
year)
Study 
Treatment
Administer Study 
Treatment 17
X
IVRS
X
X
X
X
X
X
* Adverse events of special interest (including serious and non-serious events) will be collected every 6 months in Part B and annually in Part C (See Section 8.3.5.3.2 for definition 
of Adverse Events of Special Interest)
^ For subjects that withdraw from the study 8 weeks or less from the last administration of IV belimumab, an 8 Week Follow-up Visit (and a 16 Week Follow-up Visit post 
administration for female subjects of child-bearing potential) must be performed and recorded in the IVR system and the eCRF.
† Note the first annual visit occurs 9 months after the 3rd monthly visit in Part C and every 12 months thereafter.
# Exit visit for any subject who withdraws completely from Part C after the first 3 month period may be conducted as a phone contact to close out the study.
** Serum sample for anti-belimumab antibodies only required at first monthly visit in Part C (approximately 8 weeks after last dose)

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Time and Events Table – (Continued)
1.
The Exit (Day 364) visit will occur approximately 4 weeks after the last dose of study agent. For subjects completing all 48 weeks of treatment 
and continuing into the safety follow-up with belimumab portion of the protocol (Part B) or safety follow up (Part C), this visit will also serve as 
their 1st (i.e., Day 0) visit of the open label safety follow up of the study. Only subjects who will continue in Part B will have study drug 
administered at the Day 364/Week 52 visit after the completion of all Day 364/Week 52 assessments.
2.
Subjects stopping treatment in Part A or Part B will return in 4 weeks from last dose for an Exit visit.  For subjects withdrawn from Part A or Part 
B of the study and who are not continuing into Part C, a follow-up visit will occur approximately 8 weeks after last dose of study agent 
(belimumab in the case of the open label period).
3.
Other assessments may be performed as clinically indicated.
4.
Vital signs include temperature, sitting blood pressure, and pulse.
5.
Complete prior to dosing.
6.
The subject’s weight at the current visit should be used for calculating the dose to be administered.
7.
Refer to Appendix 5 Clinical Laboratory Tests for a listing of laboratory assessments to be completed.  
8.
A 24-hour urine may be done if clinically indicated (e.g., renal flare).  
9.
Serum pregnancy test required at screening for all females of childbearing potential. Results of urine pregnancy test at subsequent visits, if 
required, must be available prior to dose. See Section 6.1 (Screening Procedures) for definition of those exempted from subsequent pregnancy 
testing.
10. Cohort 1 and Cohort 2: Days 0, 14/Wk2, 28/Wk4, 56/Wk8 - Before the start of infusion, 5 minutes and 2 hours after the end of infusion; Days 2, 
7, 16, 21 - Anytime during visit; Day 168/wk24 - 0-4 hours after the end of infusion; Day 364/Wk52 and 8 week follow-up visit - Any time 
during visit before start of infusion (if applicable). Cohort 3 PK sample schedule: Day 0, 14, 28 – Before the start of infusion and 0-4 hrs after the 
end of infusion; Day 56 – Before the start of infusion; Day 168/wk24 – 0-4 hrs after the end of infusion; Day 364/wk52 and 8 week follow-up 
visit – any time during visit before start of infusion (if applicable). [see Table 3 and Table 4 in Section 6.5]
11. Cohort 1 (12-17yrs) subjects (N=12) and Cohort 2 (5-11 yrs) (at least 10 subjects) will be subject to more frequent sampling for PK and intense 
observation during the study are also detailed in Section 6.5, Table 3 of the protocol. 
12. PGx informed consent must be obtained prior to any saliva being taken for PGx research. Refer to Section 9 and Appendix 1 Pharmacogenetic 
Research. Samples should be drawn prior to dosing but may be taken at anytime during the course of the study.
13. Autoantibodies include: ANA, aCL (IgM, IgG, IgA isotypes), anti-ribosomal P and anti-Sm. Autoantibodies 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. 
14. Serum immunoglobulin isotypes: IgG, IgM, IgA.
15. Refer to Section 6.2.1.3 for guidelines for scoring proteinuria for SELENA SLEDAI evaluation.
16. Subjects ≥ 8 years of age will complete the PedsQL and PedsQL Fatigue directly. For subjects aged 5-7 years, a parent/guardian will complete 
the Parent Report version of the PedsQL and PedsQL Fatigue on their child’s behalf.  Must be completed prior to any study-related discussion 
with the investigator or study coordinator.
17. Study agent is to be administered to all randomized subjects for 48 weeks in Part A.  Subjects completing the double-blind period (Part A) will 
continue in the open-label, long term continuation portion of the protocol for up to 10 years.  The Day 364/Week 52 visit of Part A will serve as 
the 1st visit of Part B. Only subjects who will continue in Part B will have study drug administered at the Day 364/Week 52 visit after the 
completion of all Day 364/Week 52 assessments.
18. Blood sample for functional antibodies on all subjects. Vaccine antibody titer test will be completed on subjects who receive a vaccine during the 
treatment period of this study. A blood sample to measure the pre-vaccination titer will be obtained during a study visit closest to the time prior to 
the planned vaccination In cases where blood may not be drawn immediately before vaccination, the baseline (Day 0) blood sample will be used 
as a reference for pre-vaccination titer. A post-vaccine titer will be drawn on the next study visit if it has been at least 21 to 60 days post-
immunization.

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19. A home pregnancy test will be provided to all female subjects of child bearing potential. These subjects will be contacted by phone 
approximately 16 weeks after the last dose of belimumab to obtain the results of the test. AEs/SAEs will not be actively solicited, but SAE(s) 
reported by the subject during this call will be reported to the Drug Safety designee on the SAE worksheet.
20. For subjects enrolled in Japan only, additional PK samples (before the start of infusion and 0-4 hours after the end of infusion) will be taken at 
the week 12 (3 month) and at the first 6 month visit only in Part B .

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6.1.
Critical Screening and Baseline Assessments
All screening assessments must be performed within 35 days prior to the baseline visit. 
The ANA/anti-ds DNA autoantibody screening assessments may be repeated once during 
the 35-day window from screening to the baseline visit if a positive historical test is not 
being used to supplement the screening visit result to meet Inclusion criteria 4 
(Section 4.2) 
Screening assessments at Visit 1 (Week -5/Day -35) or Randomization assessments at 
Visit 2 (Week 0/Day 0) as detailed in Table 2 will comprise the following:

Demographic information including gender, ethnic origin, race, date of birth.

Medical history.

Complete physical examination, including height, weight (further details are 
provided in Section 6.3.19 and Section 6.3.18).

Vital signs including temperature, sitting blood pressure, and heart rate (further 
details are provided in Section 6.3.18).

12-lead ECG at screening

Confirm classification of SLE disease (based on ACR criteria) by reviewing 
previously documented clinical records.

Blood samples for: 

Haematology

Modified Chem 20 (non-fasting).  (CPK MUST be done for subjects with 
myositis in order to score SELENA SLEDAI/BILAG)

Serum pregnancy test - for all women with an intact uterus, unless exempted 
from pregnancy testing (ie, of non-childbearing potential – females who are pre-
menarcheal, 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 tubal ligation).

HIV antibody, Hepatitis B surface antigen, anti-HBc, anti-HBs and Hepatitis C 

Prothrombin time (PT), partial thromboplastin time (PTT )

Biological markers (Complement C3, C4)

Serum Immunoglobulin isotypes (IgG, IgM, IgA)

ANA and anti-dsDNA autoantibodies

aCL autoantibodies

PK sampling 

Immunogenicity

Functional antibodies

Vaccine Antibody titer assessment

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
BLyS protein 

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).

Urine sample for:

Routine urinalysis.

Drug screen.

Spot urine for macroscopic/microscopic/proteinuria assessments.

Disease activity scales:

SELENA SLEDAI (See ‘Guidelines for Scoring Proteinuria’ Section 6.2.1.3.1).
•
At screening, confirm SLE disease is active, defined as SELENA SLEDAI 
score 6.

Physician’s Global Assessment (PGA).

SLE Flare Index.

BILAG. 

Pediatric SLICC/ACR Damage Index.

PRINTO/ACR Juvenile SLE Response Evaluation 

Pediatric Quality of Life Inventory (PedsQL) 

PedsQL-Multidimensional Fatigue Scale
6.2.
Efficacy
6.2.1.
SELENA SLEDAI
All site staff scoring SELENA SLEDAI are required to pass proficiency tests before 
carrying out assessments to ensure consistency across centres.
6.2.1.1.
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.

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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 are slightly modified, but the organ systems and 
weighted scores are the same as the SLEDAI.  The maximum theoretical score for the 
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 6.2.1.2), measurement of anti-dsDNA, C3, C4, 
haematology, and urinalysis, and for subjects with myositis, CPK.  Guidelines for scoring 
proteinuria are provided in Section 6.2.1.3. 
SELENA SLEDAI will be assessed in Part A at screening and prior to dosing at Day 0, 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/or Exit, 8 week follow-up (Part 
A) and every 6 months in Part B and 8 week follow-up (Part B).
A copy of the index is provided in Appendix 6 SELENA SLEDAI Disease Assessment 
Scales.
6.2.1.2.
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; KDOQI 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 [KDOQI Clinical Practice Guidelines for 
Chronic Kidney Disease, 2002].  Therefore, GFR estimated by the Schwartz formula or 
Cockroft-Gault formula will be used in the BILAG disease activity index.  The procedure 
for calculation of GFR using the Schwartz formula or Cockroft-Gault formula will be 
provided in the Study Procedure Manual. The age appropriate formula should be used. 
6.2.1.3.
Guidelines for Scoring Proteinuria for SELENA SLEDAI
The following guidelines should be followed for scoring for proteinuria in the SELENA 
SLEDAI disease activity index.

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6.2.1.3.1.
Scoring for Proteinuria for Eligibility and at Screening
In order to be assigned 4 points for proteinuria at screening, the screening spot urine 
proteinuria assessment must show:

Proteinuria > 1 g/24 hour equivalent (irrespective of previous value).
OR

New onset or recurrent proteinuria > 0.5 g/24 hour equivalent or a > 0.5 g/24 hour 
equivalent increase above the previously documented 24-hour proteinuria or 
equivalent value obtained within 26 weeks of the screening value.  If the screening 
value is 1 g/24 hour equivalent and there are no previous assessments of 24-hour 
proteinuria or spot urine protein to creatinine ratio available within 26 weeks for a 
given subject, 4 points cannot be given for proteinuria on the SELENA SLEDAI 
index, unless a 2nd assessment is done during the screening period of the study (ie, 
before Day 0).
6.2.1.3.2.
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 (ie, 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 (ie, 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.

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6.2.1.4.
SELENA SLEDAI Flare Index
The SLE Flare Index (SFI) categorises 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 or prednisone equivalent dosage.

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. 
In this study a modification of the SFI will be used in which a severe flare will not be 
counted if it is triggered only by an increase in SELENA SLEDAI score.
A copy of the SLE Flare Index is provided in Appendix 7 SLE Flare Index
6.2.1.5.
Physician’s Global Assessment (PGA)
The PGA is a 10 cm visual analogue scale (VAS), anchored at 0 (none) and 3 (severe), 
designed for the physician to indicate the subject’s overall disease activity at a particular 
visit as 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) by the GSK statistician to obtain a 
value between 0.00 and 3.00.
PGA will be assessed at screening and prior to dosing at Day 0, Weeks 4, 8, 12, 16, 20, 
24, 28, 32, 36, 40, 44, 48, and 52/or Exit, 8 week follow-up (Part A) and every 6 months 
in Part B and 8 week follow-up (Part B). 
A copy of the PGA VAS is provided in Appendix 8 Physician’s Global Disease 
Assessment.
6.2.1.6.
Parent ’s Global Assessment (ParentGA)
The Parent’s Global Assessment (ParentGA) assesses the subject’s overall well-being at 
the moment rated on a 21-numbered circle visual analog scale (VAS; 0 - very well, 10 -
very poorly). The ParentGA will be assessed at screening and prior to dosing at Day 0, 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/or Exit, 8 week follow-up (Part 
A) and every 6 months in Part B and 8 week follow-up (Part B).
A copy of the ParentGAVAS is provided in Appendix 9 Parent’s Global Disease 
Assessment: Parent’s Global Disease Assessment.

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6.2.2.
Pediatric Rheumatology International Trials Organization/ACR 
(PRINTO/ACR Juvenile SLE Response Evaluation)
The Pediatric Rheumatology International Trials Organization (PRINTO)/American 
College of Rheumatology (ACR) criteria for evaluation of juvenile SLE include objective 
measures for assessing clinical improvement. The five PRINTO/ACR Juvenile SLE 
Response Evaluation lupus lupus disease activity measures include assessments in the 
following domains: Physician’s Global Assessment of overall disease activity utilizing a 
10-cm visual analog scale (VAS); Parent’s Global Assessment of the subject’s overall 
well-being (21 circle VAS); 24 hour proteinuria to measure renal involvement; SELENA-
SLEDAI to measure disease activity; and the PedsQL Generic Core physical functioning 
domain  The individual measurements will be assessed at screening and prior to dosing 
at Day 0, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/or Exit, 8 week 
follow-up and every 6 month in the open label safety follow up (Part B), 8 week follow-
up visit (Part B). 
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 screening and prior to dosing at Day 0, Weeks 4, 8, 12, 
16, 20, 24, 28, 32, 36, 40, 44, 48, and 52//Exit visit, 8 week follow-up (Part A), and every 
6 months and 8 week follow-up in Part B.
A copy of the BILAG index is provided in Appendix 10 BILAG Index Assessment. 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.
Pediatric SLICC/ACR Damage Index
The pediatric Systemic Lupus International Collaborative Clinics/American College of 
Rheumatology (SLICC/ACR) Damage Index is a modification of the validated 
instrument developed to assess the accumulated damage in subjects with SLE, resulting 
from either the disease process or its sequelae.  
The SLICC/ACR Damage Index can identify changes in damage seen in subjects with 
both active and inactive disease and records damage occurring in subjects with SLE 
regardless of its cause [Ginsberg, 1983; 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 subject
populations included in studies, and as an outcome measure for therapeutic trials and 
studies of prognosis [Ginsberg, 1983; Gladman, 1996].
The pediatric modified SLICC/ACR Damage Index consists of 41 items in 12 different 
organ systems.  In addition to the items included in the SLICC/ACR Damage Index, the 
modified index includes assessments to evaluate growth failure and delayed puberty 
which are believed important in the assessment of damage in juvenile SLE [Gutiérrez, 
2006].
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 [Ginsberg, 1983; 
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. 
Pediatric SLICC/ACR Damage Index will be assessed at Day 0 and the/52/or Exit visit 
and 8 week follow-up visit in Part A; every 6 months in Part B and 8 week follow-up 
visit (Part B); and annually in Part C. 
A copy of the pediatric SLICC/ACR Damage Index is provided in Appendix 11 Pediatric 
SLICC/ACR Damage Index [Hay, 1993; Isenberg, 2000].
6.3.
Safety
For Part A, the safety assessments will be as follows:

Adverse Event (including infusion-related and hypersensitivity reactions, infections 
and malignancies) reported throughout the 52-week treatment period and 8 week 
follow-up.

Haematological and clinical chemistry parameters (including urinalysis) throughout 
the 52-week treatment period and 8 week follow-up.

Vital signs (i.e., pulse rate and systolic and diastolic blood pressure) throughout the 
52-week treatment period and 8 week follow-up.

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
Physical examination

Suicidality assessment (for subjects 12 years of age) 

Immunogenicity during the 52-week treatment period and 8 week follow-up.  A 6 
month follow-up assessment will be included for all subjects that have a positive 
anti-belimumab antibody response at the 8 week follow-up assessment.

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 
the course of the study based on newly available data to ensure appropriate safety 
monitoring.  IRB/IEC will be informed of any safety issues that require alteration of 
the safety monitoring scheme.
6.3.1.
Liver Chemistry Stopping and Monitoring Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
subject safety and evaluate liver event etiology in alignment with the FDA premarketing 
clinical liver safety guidance [James, 2009; Le Gal, 2005].
Liver Chemistry Stopping Criteria- Liver Stopping Event
ALT-absolute
ALT 8xULN
ALT Increase
ALT 5xULN but <8xULN  persists for 2 weeks
ALT 3xULN but <5xULN  persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR2
ALT 3xULN and INR>1.5, if INR measured
Cannot Monitor
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks
Symptomatic3
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to  liver injury or hypersensitivity
1) Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2) All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold 
value stated will not apply to subjects receiving anticoagulants.
3) New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia).

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6.3.1.1.
Required Actions and Follow up Assessments following ANY Liver 
Stopping Event
ACTIONS:

Immediately discontinue study treatment

Report the event to GSK within 24 hours

Complete the liver event CRF and complete SAE data collection tool if the 
event also meets the criteria for an SAE (All events of ALT 3xULN and 
bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if 
INR measured which may indicate severe liver injury (possible ‘Hy’s Law’), 
must be reported as an SAE (excluding studies of hepatic impairment or 
cirrhosis); INR measurement is not required and the threshold value stated will 
not apply to subjects receiving anticoagulants)

Perform liver event follow up assessments

Monitor the subject until liver chemistries resolve, stabilize, or return to within 
baseline (see MONITORING below)
Do not restart/rechallenge subject with study treatment unless allowed per protocol and 
GSK Medical Governance approval is granted (refer to [Appendix 4]).
MONITORING
For bilirubin or INR criteria:

Repeat liver chemistries (include ALT, AST, alkaline phosphatase, bilirubin) 
and perform liver event follow up assessments within 24 hours

Monitor subjects twice weekly until liver chemistries resolve, stabilize or return 
to within baseline

A specialist or hepatology consultation is recommended
For All other criteria:

Repeat liver chemistries (include ALT, AST, alkaline phosphatase, bilirubin) 
and perform liver event follow up assessments within 24-72 hours

Monitor subjects weekly until liver chemistries resolve, stabilize or return to 
within baseline
FOLLOW UP ASSESSMENTS

Viral hepatitis serology (includes: 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 
(or if unavailable, obtain heterophile antibody or monospot testing); Hepatitis E 
IgM antibody)

Blood sample for pharmacokinetic (PK) analysis, obtained within approximately 
one to two weeks after last dose (PK sample may not be required for subjects 

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known to be receiving placebo or non-GSK comparator treatments.)  Record the 
date/time of the PK blood sample draw and the date/time of the last dose of 
study treatment 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 creatine 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 liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications on the concomitant medications report 
form including acetaminophen, herbal remedies, other over the counter 
medications

Record alcohol use on the liver event alcohol intake case report form
For bilirubin or INR criteria:

Anti-nuclear antibody, anti-smooth muscle antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total immunoglobulin G (IgG or gamma 
globulins).

Serum acetaminophen adduct HPLC assay (quantifies potential acetaminophen 
contribution to liver injury in subjects with definite or likely acetaminophen use 
in the preceding week [James, 2009]). NOTE: not required in China 

Liver imaging (ultrasound, magnetic resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms.
6.3.2.
Increased Monitoring Criteria with Continued Therapy
If met see required actions below:

If ALT 5xULN and <8xULN and bilirubin <2xULN without symptoms 
believed to be related to liver injury or hypersensitivity, and who can be 
monitored weekly for 2 weeks OR

ALT 3xULN and <5xULN and bilirubin <2xULN without symptoms believed 
to be related to liver injury or hypersensitivity, and who can be monitored 
weekly for 4 weeks

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6.3.2.1.
Required Actions and Follow Up Assessments for Increased 
Monitoring with Continued Therapy

Notify the GSK medical monitor within 24 hours of learning of the abnormality 
to discuss subject safety. 

Subject can continue study treatment

Subject must return weekly for repeat liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) until they resolve, stabilise or return to within baseline 

If at any time subject meets the liver chemistry stopping criteria, proceed as 
described above for Required Actions and Follow up Assessments following 
ANY Liver Stopping Event

If ALT decreases from ALT 5xULN and <8xULN to ≥3xULN but <5xULN, 
continue to monitor liver chemistries weekly. 

If, after 4 weeks of monitoring, ALT <3xULN and bilirubin <2xULN, monitor 
subjects twice monthly until liver chemistries normalize or return to within 
baseline.
6.3.3.
Study Treatment Restart
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than drug induced liver injury [DILI]) of the liver event 
(e.g. biliary obstruction, pancreatic events, hypotension, acute viral hepatitis). 
Furthermore, there should be no evidence of alcoholic hepatitis or hypersensitivity, and 
the study treatment should not be associated with HLA markers of liver injury.
Note:   At investigator sites in the Russian Federation, restart of study treatment after 
liver event is not permitted.
Approval by GSK for study treatment restart can be considered where:

Investigator requests consideration for study treatment restart if liver chemistries 
have a clear underlying cause (e.g., biliary obstruction, hypotension and liver 
chemistries have improved to normal or are within 1.5 x baseline and ALT 
<3xULN).

Restart risk factors (e.g., fever, rash, eosinophilia, or hypersensitivity, alcoholic 
hepatitis, possible study treatment-induced liver injury or study treatment has an 
HLA genetic marker associated with liver injury (e.g., lapatinib, abacavir, 
amoxicillin/clavulanate) are reviewed and excluded

Ethics Committee or Institutional Review Board approval of study treatment restart 
must be obtained, as required.

If restart of study treatment is approved by GSK Medical Governance in writing, the 
subject must be provided with a clear description of the possible benefits and risks of 
study treatment administration, including the possibility of recurrent, more severe 
liver injury or death.  

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
The subject must also provide signed informed consent specifically for the study 
treatment restart.  Documentation of informed consent must be recorded in the study 
chart.  

Study treatment must be administered at the dose specified by GSK.

Subjects approved by GSK Medical Governance for restarting study treatment must 
return to the clinic once a week for liver chemistry tests until stable liver chemistries 
have been demonstrated and then laboratory monitoring may resume as per protocol. 

If after study treatment re-start, subject meets protocol-defined liver chemistry 
stopping criteria, follow usual stopping criteria instructions.

GSK Medical Monitor, and the Ethics Committee or Institutional Review Board as 
required, must be informed of the subject’s outcome following study treatment 
restart. 

GSK to be notified of any adverse events, as per Section 6.3.6.
6.3.4.
IgG Stopping Criteria
Any subject who has a Grade 4 IgG level, by the DMID table, will have dosing with 
study agent withheld, and the appropriateness to continue study treatment must be 
discussed with Medical Monitor before the next dose. Any subject who has a Grade 4 
IgG level associated with a severe or serious infection will have study agent discontinued 
and will be placed into Part C the safety follow up phase.
6.3.5.
Independent Data Monitoring Committee
An IDMC comprised of experts in paediatric rheumatology, paediatric pharmacology, 
paediatric ethics and a statistician, none of whom are affiliated with the sponsor will be 
organized to monitor the study as it progresses.  A charter will be developed to govern 
the activities of this committee. The IDMC will conduct its first safety and PK data 
review after the first cohort has been treated through the Week 8 (Day 56) visit, or within 
4 months of the treatment of the first subject enrolled in Cohort 1, whichever is earlier.  If 
the later time point of within 4 months of the first subject enrolled is met, the IDMC will 
review the available safety data only. The committee will continue to meet, at a 
minimum, approximately every 6 months from the first meeting until the last subject 
concludes Part A, the randomized treatment period of the study.  After each meeting, the 
IDMC will generate a report of data reviewed and if applicable, actions taken.   
Investigators will be notified of the outcome of each IDMC meeting.  Notification of 
local EC/IRB of the IDMC review outcomes will be at the discretion and requirements of 
local regulations.
If recruitment of subjects to Cohort 2 is slower than expected, the sponsor and the IDMC 
may decide to initiate an early PK analysis and safety review at 6 months from the first 
subject’s first dose in Cohort 2 being dosed based on the Safety and PK data accrued up 
to this point from Cohorts 1 and 2. If the PK data analyzed is deemed sufficient, the 
sponsor and IDMC may recommend a dose adjustment for Cohort 2 subjects from the 
early PK review. After any early PK review, the sponsor and IDMC may re-review PK 

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and safety and possibly recommend a dose adjustment when PK data for all Cohort 2 
subjects is available.  Additionally, the sponsor and IDMC may decide that no additional 
PK review and dose adjustment is necessary if the data from the early PK review is 
deemed sufficient to support a finalized PK review.
6.3.6.
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.
6.3.6.1.
Definition of an AE
Any untoward medical occurrence in a subject 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 study treatment 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 study 
agent or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent. This should be reported regardless of sequelae).
“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

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
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
6.3.6.2.
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-subject 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,
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.
Medical or scientific judgment 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.
g.
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 

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required and the threshold value stated will not apply to subjects receiving 
anticoagulants).
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. 
6.3.7.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 
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.
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.
6.3.8.
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 6.3.14 .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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6.3.9.
Suicidality Assessment
Some autoimmune diseases have an increased risk of suicidal behavior and/or ideation 
(Bachen, 2009, Timonen, 2003, Stenager, 1992).  In order to objectively assess 
suicidality in belimumab clinical programs the C-SSRS will be utilized to collect 
information on suicidal behavior and ideation.  
SLE subjects have an increased prevalence of mood and anxiety disorders compared with 
the general population and disease activity may contribute to this higher risk. The 
incidence of major depressive disorder (MDD) among SLE subjects has been reported to 
be as high as 47% [Bachen, 2009]. Since active SLE and MDD may increase the risk of 
suicidal ideation or behavior before or during clinical studies, subjects participating in 
this study will be assessed at every visit for suicidality.  Suicidality will be assessed using 
the Columbia Suicide-Severity Rating Scale (C-SSRS) in children 12 years of age and 
older in this pediatric SLE study.  Children less than 12 years of age will not be assessed 
with the C-SSRS as the C-SSRS has not been fully validated for use in children less than 
12 years of age. 
Subjects who answer “yes” to any suicidal behavior or “yes” to suicidal ideation 
questions 4 or 5 on the C-SSRS should be referred to appropriate psychiatric care and 
prompts the completion of an SAE worksheet.  The medical monitor should be notified 
when these events occur.  In addition, a “yes” to any suicidal behavior or “yes” to 
suicidal ideation questions 3, 4 or 5 on the C-SSRS prompts the completion of a Possible 
Suicidality Related Questionnaire (PSRQ) eCRF at all times this condition is met (see 
PSRQ Section 6.3.10 and PSRQ form in Appendix 13 Possible Suicidality-Related 
Questionnaire.
Baseline and during treatment assessment of suicidality will be performed in this study 
using C-SSRS. (Refer to Appendix 12 for C-SSRS).The C-SSRS is a brief measure 
which is designed to assess severity and change of suicidality by integrating both 
behavior and ideation [Posner, 2007]. The C-SSRS is administered by a qualified 
clinician and is designed to address the need for a summary measure to track change in 
the severity/density of suicidality across both clinical settings and treatment trials. It 
assesses intensity of ideation (a potentially important marker of severity) by specifically 
asking about frequency, duration, intrusiveness, controllability, and deterrents. In 
addition, it captures both the modal and most severe forms of ideation. The C-SSRS is to 
be completed by the investigator or his/her qualified designee at every visit during the 
double blind portion of the study.
Although assessment of suicidality using the C-SSRS will take place only during the 
double blinded portion of the study, investigators are reminded of the importance to 
clinically assess for suicidality at every visit given that SLE subjects are at increased risk 
of suicidal behavior and/or ideation.

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6.3.10.
Possible Suicidality Related Questionnaire (PSRQ)
The PSRQ eCRF form should be completed (Appendix 13 Possible Suicidality-Related 
Questionnaire) in addition to the AE or SAE pages, as appropriate) if a “yes” response is 
given to any suicidal behavior or a “yes” response to suicidal ideation questions 3, 4 or 5 
on the C-SSRS. If the adverse event meets the definition of an SAE, which includes a 
“yes” answer to any suicidal behavior or a “yes” to suicidal ideation questions 4 or 5 on 
the C-SSRS, the site must ensure that there are no significant discrepancies between the 
PSRQ and SAE.
6.3.11.
Investigator Evaluation of Adverse Events
The investigator will evaluate all adverse events with respect to seriousness (criteria for 
serious are listed in Section 6.3.6.2) severity (intensity) and causality (relationship to 
study agent).  The severity of an AE is to be evaluated according to the Adverse Event 
Severity Grade Tables in Appendix 5 Clinical Laboratory Tests.  If an AE does not have 
Adverse Event Severity Grade in Appendix 5 Clinical Laboratory Tests, the following 
severity classifications will be used:
SEVERITY:
Grade 1- Mild - causing no limitation of usual activities (Grade 1 DMID).
Grade 2- Moderate - causing some limitation of usual activities (Grade 2 DMID)
Grade 3- Severe - causing inability to carry out usual 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.
6.3.12.
Pregnancy
Any pregnancy that occurs during study participation and up to 16 weeks after 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 termination) 
and status of mother and child.  Pregnancy complications and elective terminations for 
medical reasons must be reported as an AE or SAE.  Spontaneous miscarriage 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.

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6.3.13.
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 and until the follow up contact at 8 weeks after the last dose of study 
agent in subjects not entering the open-label (Part B) or safety follow-up phase (Part C), 
or every 4 weeks (± 7 days) for the first 3 months after entering the safety follow-up 
phase (Part C).  AEs of special interest (AESI, as defined in Section 8.3.5.3.2) will be 
reported every 6 months for subjects in Part B and annually in subjects entering Part C.    
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, and all AEs of special interest (including serious and non-serious events, as 
defined in Section 8.3.5.3.2) 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 6.3.14. 
6.3.14.
Prompt Reporting of Serious Adverse Events and Other Events 
to GSK
SAEs and pregnancies 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.
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:
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

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Initial Reports
Follow-up Information on a 
Previous Report
Type of Event
Time Frame
Documents
Time Frame
Documents
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
1.
*GSK to be notified at onset of liver chemistry elevations to discuss subject safety.
2.
** Liver event documents should be completed as soon as possible.
3.
*** INR measurement is not required; if measured, the threshold value stated will not apply to subjects 
receiving anticoagulants
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.
6.3.14.1.
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 

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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.
6.3.15.
Laboratory Evaluations
Clinical laboratory tests will consist of a complete blood count (CBC) with differential, 
Chem-20, magnesium, and urinalysis (see list in Appendix 4 Liver Safety Criteria). 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 11.5). Samples (blood and urine) for clinical laboratory tests will be 
collected as described in the Time and Events schedule (Table 2).
At screening, serum human immunodeficiency virus (HIV-1/2) antibody, Hepatitis B 
(Hepatitis B surface antigen (HBsAg), anti-HBc, anti-HBs), Hepatitis C antibody, 
prothrombin time (PT) and partial thromboplastin time (PTT) will be evaluated, as well 
as urine drug screens.  Hepatitis B will be assessed on Exit from the study.
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.  To maintain 
the treatment blind, the site will not be sent information on selected biomarkers from any 
visits post-randomisation either from the central laboratory or from GSK.
Blood sample collection
The largest volume of blood drawn from a subject occurs at the screening visit and the 
randomization visit (Day 0).  The amount of blood collected at the screening visit and 
randomization visit (Day 0) may exceed the acceptable volume per country or institution 
specific guidelines for the pediatric population in this study.  Therefore, the volume of 
blood to be collected should be monitored and blood samples may be drawn in separate 
visits within 1 week but prior to the scheduled study drug infusion.  Alternatively, the 
blood draw for CRP and other biomarkers may be omitted at the baseline visit.  It will be 
permissible to use the values for these laboratory parameters from the screening visit 
samples. 
6.3.16.
Infusion-related Reactions and Hypersensitivity Reactions
In the controlled clinical trials, adverse events associated with the infusion (occurring on 
the same day of the infusion) were reported in 17% (253/1,458) of subjects receiving 

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belimumab and 15% (99/675) of subjects receiving placebo.  Hypersensitivity reactions, 
including anaphylaxis and death, have been reported in association with 
belimumab. Delay in the onset of acute hypersensitivity reactions has been observed. 
Limited data suggest that subjects with a history of multiple drug allergies or significant 
hypersensitivity may be at increased risk. Investigators are instructed to assume a 
heightened awareness when screening subjects with a history of adverse reactions to IV 
contrast agents, other IV foreign proteins or other monoclonal antibodies; subjects with 
anaphylaxis to this family of agents should be excluded from enrolment in the study. 
Subjects will be monitored during all infusions and should remain under clinical 
supervision for 3 hours after completion of the first 3 infusions in Part A and for 3 hours 
after completion of the first 3 infusions in Part B the open label portion of the study 
according to study sites’ guidelines or standard operating procedure for IV infusions.  If 
symptoms of acute hypersensitivity occur, an extended period of monitoring may be 
appropriate, based on clinical judgment.
Subjects and parents/legal guardian should be made aware of the potential risk, the signs 
and symptoms of such reactions, and the importance of immediately seeking medical 
attention.
Premedication with an oral antihistamine, with or without an antipyretic, may be 
administered before the infusion of belimumab. There is insufficient evidence to 
determine whether premedication diminishes the frequency or severity of infusion 
reactions. In the over 15,000 belimumab infusions administered in the Phase III clinical 
studies, approximately 800 belimumab infusions were administered to subjects who had 
been premedicated with an antihistamine and antipyretic at the investigator’s discretion. 
In these trials, subjects with a history of allergies were more likely to have been 
premedicated than subjects without a history of allergies. Although the proportion of 
infusions with infusion reactions was greater for premedicated infusions than non-
premedicated infusions (3% vs <2%, respectively), the incidence of serious and/or severe 
infusion reactions was 0.1% for non-premedicated infusions while none occurred with 
premedicated infusions.  
Infusion related reactions and/or hypersensitivity reactions will be reported if they fulfill 
the definition of an AE or SAE.  
Delayed-type allergic reactions:  
Delayed-type, non-acute hypersensitivity reactions have also been observed and included 
symptoms such as rash, nausea, fatigue, myalgia, headache, and facial edema.
6.3.17.
Immunosuppression, Infections, and Malignancies
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.  
Therefore, the protocol will exclude subjects who may be at increased risk of infection or 
malignancy based on medical/medication history and screening physical examination or 
laboratory findings.  During the trial, subjects will be questioned at all study visits about 

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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. 
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) resulting in neurological deficits, 
including fatal cases, has been reported in SLE subjects 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.
6.3.18.
Vital Signs, Height and Weight
Systolic and diastolic blood pressure (sitting), heart rate, and body temperature will be 
measured.  Measurements of vital signs, height and weight will be taken for Part A, at 
screening and prior to dosing on Day 0 and at Weeks 2, 4, every 4 weeks up to week 
52/or Exit; and at follow-up visit Week 8 (vital signs only) for subjects who withdraw 
prior to completion of the 52-week treatment period.  At the discretion of the 
Investigator, vital signs may be assessed at unscheduled visits. 
Vital signs, height and weight will be collected at each visit prior to dosing for subject 
participating in the open label continuation portion of the study (Part B) and annually for 
those participating in the 10 year post infusion portion of the study (Part C).
6.3.19.
Physical Examination
Full physical examinations will be performed at screening.  Abbreviated, symptom-
driven examinations will be performed for Part A at Day 0 (predose), at every 4 weeks up 
to Week 52/or Exit; and at follow-up visit Week 8 for subjects who withdraw prior to 
completion of the 52-week treatment period.  At the discretion of the Investigator, 
physical and neurological examinations may be performed at unscheduled visits.
For subjects participating in the open label continuation portion of the study (Part B), 
abbreviated, symptom-driven examinations will be performed at every 4 week visit and 
annually for those participating in the 10 year post infusion portion of the study (Part 
C).As a minimum complete physical examination will include assessment of the head, 
eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver 
and spleen), lymph nodes, joints, and extremities.  
As a minimum brief physical examination will include assessment of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen).

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6.3.20.
Other Safety Outcomes
6.3.20.1.
Immunogenicity
Sample Collection and Handling
Serum samples will be collected for belimumab immunogenicity assays prior to dosing 
at: Day 0, Weeks 8, 24, and 52/or Exit, and at the 8-week follow-up visit for subjects who 
withdraw prior to completion of the 52-week treatment period and for subjects who 
choose not to enter the continuation protocol. Processing, storage and shipping 
procedures are provided in the SRM.
At each collection time, 2 mL of blood will be collected in a 2 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 0.5 mL per sample) will be harvested and placed in 2-mL Sarstedt vials 
for storage.  Serum samples will be stored at -20°C at the sites before daily shipment to 
the central laboratory.  Samples will be stored at -70°C at the central laboratory until 
shipment to Alliance Pharma and stored at -80°C after they arrive at Alliance Pharma. 
Samples will be shipped on dry ice in both shipments.
The total amount of blood drawn for immunogenicity testing per participant is 
approximately 10 mL. 
Assay Methods
Sample analysis will be performed under the control of GlaxoSmithKline. In the 
immunogenicity assessment for anti-belimumab antibodies, a tiered analysis approach 
will use a validated binding ADA assays (screening, confirmation and titration assays) 
and a validated neutralization antibody assay.
6.4.
Health Outcomes
6.4.1.
Pediatric Quality of Life Inventory - Generic Core (PedsQL)
To understand the effect of belimumab on the quality of life in the pediatric lupus 
population the PedsQL Generic Core will be utilized. The PedsQL is a generic quality of 
life scale validated for the pediatric population which consists of 23 items, encompassing 
4 health domains: Physical Functioning (8 items), Emotional Functioning (5 items), 
Social Functioning (5 items), and School Functioning (5 items). From the raw scores of 
the 23 items, a total summary score and individual domain scores can be calculated. The 
total and domain scores are each transformed on a 0 to 100 score with higher scores 
indicating higher quality of life.
The PedsQL measurements will be assessed at screening and prior to dosing at Day 0, 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52/or Exit and every 6 month in the 
open label safety follow up (Part B) and every year in the safety follow up phase (Part C).  
[Brunner, 2009] (See Appendix 14 Pediatric Quality of Life Inventory - Generic Core 
Scale (PedsQL)).

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Subjects ≥ 8 years of age will complete the PedsQL directly. For subjects aged 5-7 years, 
a parent/guardian will complete the Parent Report version of the PedsQL on their child’s 
behalf.
The PedsQL will only be administered to those subjects for which a validated translation 
exists in their language.
6.4.2.
Pediatric Quality of Life Multidimensional Fatigue Scale
The recently developed 18-item PedsQL Multidimensional Fatigue Scale was designed to 
measure fatigue in pediatric subjects and comprises the General Fatigue Scale (6 items), 
Sleep/Rest Fatigue Scale (6 items), and Cognitive Fatigue Scale (6 items). [Varni, 2004], 
(See Section 11.5, Appendix 15 Pediatric Quality of Life  Multidimensional Fatigue 
Scale (PedsQL Fatigue)).
The PedsQL Fatigue measurements will be assessed at screening and prior to dosing 
at Day 0, Weeks 4, 8, 12, 20, 24, 36, and 52/or Exit and every 6 month in the open-label 
safety (Part B) and every year in the safety follow up phase (Part C).
Subjects ≥ 8 years of age will complete the PedsQL-Fatigue directly. For subjects aged 
5-7 years, a parent/guardian will complete the Parent Report version of the PedsQL-
Fatigue on their child’s behalf. The PedsQL-Fatigue will only be administered to those 
subjects for which a validated translation exists in their language.
6.5.
Pharmacokinetics
Blood samples of 0.5 mL will be collected for measurement of serum belimumab 
concentrations according to schedules which depend on the pediatric cohort.
For Cohort 1 (first 12 children in the study [12-17 years of age]) and Cohort 2 (at least 
the first 10 children ages 5 to 11 years), samples will be drawn according to the enriched 
time schedule in Table 3. For all other children in the study (Cohort 3), samples will be 
drawn according to the standard time schedule in Table 4. 

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Table 3
PK visit days and sample times for Cohort 1 and Cohort 2
Day (Week)
Time (Related to Dosing of Study agent)
0, 14 (Week 2), 28 (Week 4), and 56 (Week 8)
Before the start of infusion, 5 minutes and 2 hours 
after the end of the infusion
2±1, 7±1, 16±1, 21±1
Any time during visit 
168 (Week 24)
0 - 4 hours after the end of infusion
364/Exit (Week 52)
(4 weeks after last dose)
Any time during visit
(or before start of infusion if going into the open-
label continuation phase of the study)
8-week follow-up
(8 weeks after last dose)
Any time during visit
(if not going into the open-label continuation phase 
of the study)
Table 4
PK visit days and sample times for Cohort 3
Day (Week)
Time (Related to Dosing of Study agent)
0
Before the start of infusion and 0-4 hours after the 
end of infusion
14 (Week 2)
Before the start of infusion and 0 - 4 hours after the 
end of infusion
28 (Week 4)
Before the start of infusion and 0-4 hours after the 
end of infusion
56 (Week 8)
Before the start of infusion
168 (Week 24)
0 - 4 hours after the end of infusion
364/Exit (Week 52)
(4 weeks after last dose)
Any time during visit
(or before start of infusion if going into the open-
label continuation phase of the study)
8-week follow-up
(8 weeks after last dose)
Any time during visit
(if not going into the open-label continuation phase 
of the study)
On days belimumab is administered and blood samples for pharmacokinetic analysis are 
obtained, subjects may have an intravenous cannula inserted in the contralateral arm to 
the arm in which belimumab is administered for laboratory safety assessments and serial 
pharmacokinetic sampling.  Blood samples for pharmacokinetic analysis should not be 
taken from the same arm as that used for the administration of belimumab.  Samples may 
be obtained by venipuncture.  
The total, maximum, amount of blood drawn for PK during this study is approximately 
9.5 mL for children in Cohorts 1 and 2 and 5 mL for all other children. 

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For subjects enrolled in Japan only, additional PK samples (before the start of infusion 
and 0-4 hours after the end of infusion) will be taken at the 12 week / 3 month and first 6 
month visits only in Part B.
Please refer to the Study Procedures Manual for PK sample collection, processing, and 
shipping instructions.
6.6.
Pharmacodynamics
6.6.1.
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 for biomarker evaluations will be collected at the visits specified in the 
Time and Events schedule (Table 2), to enable the following endpoints to be assessed:

Baseline values:

ANA

aCL (IgG, IgM and IgA)

BLyS protein

Percent change from baseline:

Total serum immunoglobulin (IgG, IgM and IgA).

Autoantibodies (anti-dsDNA) and complement (C3, C4).
Samples will be collected pre-dose where taken at dosing visits. All biomarker samples 
will be analysed centrally.
Due to the potential for unblinding, the following lab results will not be provided to study 
sites after Day 0: serum immunoglobulin isotypes IgM/IgA, and B-cells.

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6.6.2.
Test for Functional Antibodies
Prior history of receiving influenza, diphtheria/tetanus, or pneumococcal vaccines will be 
obtained from each subject during screening as part of the subject’s medical history.  A 
blood sample will be drawn on all subjects for functional antibodies at the Week 0, Week 
24 and Week 52 visits.  Antibody titer tests will be completed on subjects that plan to 
receive a vaccine during the treatment period of this study.  A blood sample to measure 
the prevaccination titer will be obtained during a study visit closest to the time prior to 
the planned vaccination. A post-vaccine titer will be drawn on the next study visit at 
which other blood is drawn, provided it has been at least 21 days post-immunization.  If 
the immunization was administered less than 21 days prior to a study visit, the post-
vaccination titer should be obtained at the following visit.
6.6.3.
Vaccine Response
Because of the uncertainty of vaccine response in any immunosuppressed population, it is 
recommended that all vaccinations be up to date as per country specific guidelines prior 
to entry into this study.  Live vaccinations are not to be administered less than 30 days 
before first dose or while subjects are receiving study agent. 
In addition, consideration should be given to administration of certain vaccines, 
pneumococcus and meningococcus, prior to entry if the country specific vaccine schedule 
would require them soon after study start. 
Subjects’ immune responses to vaccines received during their participation in the study 
will be tested.  Subjects receiving a primary or a booster dose of influenza, tetanus, or 
pneumococcal vaccine at anytime during the study may be tested for pre- and post-
vaccination antibody titer.  Subjects will be asked to inform the investigator if a vaccine 
is planned.  A blood sample to measure the pre-vaccination titer will be obtained 
preferably prior to the planned immunization.  In cases where blood may not be drawn 
immediately before vaccination, the baseline (Day 0) blood sample will be used as a 
reference for pre-vaccination titer.  A post-vaccination antibody titer will be drawn on the 
next study visit provided it has been 21 to 60 days from the time the vaccine was given.
6.7.
Pharmacogenetics
Information regarding pharmacogenetic research is included in Appendix 1
Pharmacogenetic Research. Participation in this aspect of the study is voluntary.  The 
IEC/IRB and, where required, the applicable regulatory agency must approve the PGx 
assessments before these can be conducted at the site.  The approval(s) must be in writing 
and will clearly specify approval of the PGx assessments (i.e., approval of Appendix 1
Pharmacogenetic Research).  In some cases, approval of the PGx assessments can occur 
after approval is obtained for the rest of the study.  If so, then the written approval will 
clearly indicate approval of the PGx assessments is being deferred and the study, except 
for PGx assessments, can be initiated.  When PGx assessments will not be approved, then 
the approval for the rest of the study will clearly indicate this and therefore, PGx 
assessments will not be conducted.

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7.
DATA MANAGEMENT
For this study subject data will be entered into GSK defined electronic case report forms 
(eCRFs), transmitted electronically to GSK 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, 
GSKDrug.  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.
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
8.1.
Hypotheses
The study is designed to descriptively evaluate the efficacy and safety of belimumab, and 
as such no formal statistical hypothesis testing is planned.
8.2.
Study Design Considerations
8.2.1.
Sample Size Considerations
As juvenile SLE is a rare disease, recruitment of subjects will be challenging.  The
original decision to enrol 100 subjects was based on feasibility estimations.  The 
following is a description of what statistical information these 100 subjects would have 
provided.  Combining the subject cohorts, a total of 100 subjects would have been
randomized.  In the first two cohorts, at least 24 subjects would have been randomized in 
a 5:1 ratio (belimumab:placebo), and the remaining 76 subjects would have been
randomized in a 1:1 allocation ratio.  Therefore, 58 subjects would have been randomized 
to belimumab and 42 to placebo.  Using the methods of PASS 2005 [Hintze, 2006] for 
the precision of a confidence interval around a single proportion; a sample size of 42 
would have produced a 95% confidence interval around the sample proportion ± 0.15191 
when the estimated proportion of subjects attaining the primary efficacy response at 
Week 52 is 0.39 (for placebo), and a sample size of 58 would have produced a 95% 
confidence interval around the sample proportion ± 0.12793 when the estimated 
proportion is 0.51 (for belimumab).  
8.2.2.
Sample Size Sensitivity
The estimated proportions cited above are the Week 52 results for placebo and 
belimumab 10mg/kg from the combined Phase 3 studies in adults with SLE.  The 
estimated proportions of subjects attaining the primary efficacy response at Week 52 
from the 76 week Phase 3 studies in adults with SLE were 34% and 43% for placebo and 
belimumab 10mg/kg, respectively, and for the Week 52 study in adults with SLE were 
43% and 57%.

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Sample size sensitivity calculations were performed considering these results.  In this 
study, for estimated proportions ranging from 0.31 to 0.69, the precision for the 95% 
confidence interval ranges from approximately 0.12 to 0.13 when the sample size is 58, 
and from approximately 0.14 to 0.15 when the sample size is 42.
8.2.3.
Sample Size Re-estimation
As a consequence of continuing enrolment challenges, despite an increase in the number 
of participating clinical sites worldwide and concentrated outreach efforts, a sample size 
reduction based on the extrapolation of current recruitment performance to January 2017
has been agreed to with EMA/PDCO and FDA.
A reduction in subjects from 100 to ‘at least 70’, although affecting the sample size 
calculations, will not alter the fact that this study was designed to descriptively evaluate 
the efficacy and safety of belimumab in paediatric SLE. 
In the first two cohorts, at least 22 subjects will be randomized in a 5:1 ratio 
(belimumab:placebo), and the remaining subjects (at least 48) will be randomized in a 1:1 
allocation ratio.  Therefore, approximately 42 subjects will be randomized to belimumab 
and 28 to placebo.  Using the methods of PASS 2005 [Hintze, 2006] for the precision of a 
confidence interval around a single proportion; a sample size of 28 will produce a 95% 
confidence interval around the sample proportion ±0.18143 when the estimated 
proportion of subjects attaining the primary efficacy response at Week 52 is 0.39 (for 
placebo), and a sample size of 42 will produce a 95% confidence interval around the 
sample proportion±0.15286 when the estimated proportion is 0.51 (for belimumab).
Sample size sensitivity calculations were performed considering the primary efficacy 
response at Week 52 in the Phase 3 studies in adults with SLE. In this study, for 
estimated proportions ranging from 0.31 to 0.69, the precision for the 95% confidence 
interval ranges from approximately 0.14 to 0.15 when the sample size is 42 (Belimumab), 
and from approximately 0.17 to 0.20 when the sample size is 28 (Placebo).
8.3.
Data Analysis Considerations
8.3.1.
Analysis Populations
The analysis of the double-blind treatment phase will be performed on the intention-to-
treat (ITT) population, defined as all subjects who are randomized and treated with at 
least 1 dose of study agent. The ITT analysis will be performed according to the 
treatment that a subject was randomized to receive, regardless of the actual treatment 
received. 
The analysis populations for Parts B and C will include all subjects who enter the phase 
and have at least one assessment.

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8.3.2.
Analysis Data Sets
The double-blind treatment phase is the primary phase of the study for evaluating the 
efficacy and safety of the treatments.  Data from Part B and Part C will be analyzed 
separately.
Treatment Failure = Nonresponder (TF=NR)
The TF=NR dataset (treatment failure is described in Section 8.3.5) will be used for the 
primary response endpoint and each of the 3 components of the primary response.   The 
basic premise of the TF=NR is that a subject who drops out prior to the Week 52 
(Section 8.3.5 describes handling of missing data) visit and/or uses a prohibited 
medication or a non-allowed dose of a restricted medication will be considered a 
treatment failure and thus counted as a nonresponder in the analysis. 
LOCF
The last observation carried forward (LOCF) principle is applied whereby missing values 
will be replaced with the last previous non-missing value in Part A, B or C.  If the first 
assessment of the treatment phase is missing, then the missing data will be imputed with 
the baseline value.  
Observed
Observed data are the data collected for the subject with no imputation for missing data
8.3.3.
Analysis strategy and timing
Following completion of the double-blind treatment phase of the study, this portion of the 
study database will be locked and the final analysis will be performed.  This will not be 
considered an interim analysis.  
Part B and Part C of the study will be summarized separately, and the final analysis 
performed after completion of each of the phases.  Periodic analyses of these two phases 
may be performed before their completion, but following final analysis of the double-
blind phase.
8.3.4.
Interim Analysis
IDMC Safety Data Reviews
The IDMC will conduct its first safety and PK data review after Cohort 1 has been treated 
through the Week 8 (Day 56) visit, or within 4 months of the treatment of the first subject 
enrolled, whichever is earlier. If the first review occurs at the 4 month time point, then 
the IDMC will only review safety data. The IDMC will also conduct such a review for 
Cohort 2.  After the initial review, the committee will review the data approximately 
every 6 months.  After each meeting, the IDMC will generate a report of data reviewed 
and if applicable, recommendations made.  Investigators will be notified of the outcome 
of each IDMC meeting.

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The safety data analyses for the IDMC reviews will be performed by an independent 
statistical analysis data center (SDAC).  The PK data analyses will be performed as 
described below.  In addition, GSK GCSP staff may perform unblinding as described in 
Section 5.4.  Otherwise, all personnel having direct responsibility for the conduct of the 
study, or involved in the belimumab program, will remain blinded to treatment groups for 
all data until such time that the study is completed by protocol design or the IDMC 
recommends the termination of the entire study.
PK Interim Data Reviews
Two separate dose assessments will be made by the GSK Safety Review Team based on 
safety, tolerability and preliminary PK data obtained from Cohorts 1 and Cohorts 2, 
respectively. The study dose may be revised based upon this review. The Study Team 
will remain blinded to treatment during these dose assessment meetings, through the use 
of a PK dataset with scrambled subject identifiers (which may include subject 
demographics and other PK relevant covariates) prepared by a GSK statistician/ 
programmer independent to the study team and analyzed by a GSK pharmacokineticist 
independent to the study team.  Decisions regarding dose confirmation/adjustment will be 
summarized and distributed to study team members, investigators, the IDMC, and IRBs 
and/or regulatory authorities according to local regulations.
8.3.5.
Key Elements of Analysis Plan
This section provides definitions for the primary time point, Week 52.
Treatment Failures
A treatment failure is defined as any subject who 

withdraws from the study prior to Day 364 (Week 52) and has no visit within 
28 days of Day 364, and/or

receives a protocol-prohibited medication or a dose of permitted (but protocol-
restricted) medication that results in treatment failure designation 
(see Section 5.6.1 prior to Day 364 (Week 52).
Missing Data Rules
Any subject not otherwise classified as a failure who misses the Day 364 (Week 52) 
assessments will be handled as follows:
If the subject does not have a visit within 28 days of Day 364, the subject will be 
considered a treatment failure for the Week 52 analysis.
If a subject has at least 1 visit within 28 days of Day 364, the data from the visit closest 
to Day 364 will be used for the Week 52 analysis.
If a subject has 2 visits with equal distance within 28 days of Day 364, the data from 
the visit prior to Day 364 will be used for the Week 52 analysis.

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If a subject has a visit within the required window, but partial data of the primary 
endpoint are missing (including individual items of any component of the primary 
endpoint), LOCF will be used for the missing item or component. This will be modified 
for items in which scoring is dependent on both the actual score and the change from the 
previous visit (BILAG dipstick, BILAG 24 hour urinary protein, BILAG creatinine, and 
BILAG creatinine clearance). For these items, both the actual value from the last visit and 
the change observed at that visit will be carried forward.
8.3.5.1.
Laboratory Data for Disease Activity Scales
The BILAG and SELENA SLEDAI disease activity scales require laboratory data results 
for evaluation; therefore, the following procedure will be followed when there are no 
laboratory data with a sample date that matches the BILAG or SELENA SLEDAI 
assessment date:
An analysis window will be defined for laboratory data to map values to the BILAG and 
SELENA SLEDAI assessments.  

For BILAG, the analysis window is -28 days to + 7 days from the BILAG 
assessment date, excluding the sample that was used in the previous visit 
assessment.

For SELENA SLEDAI, the analysis window is -10 days to + 7 days from the 
SELENA SLEDAI assessment date, excluding the sample that was used in the 
previous visit assessment.
If there are 2 or more laboratory tests performed within the window, the test with a 
sample date closest to the disease activity assessment that is prior to the date of 
assessment will be used.  If all tests within the window are after the assessment date, then 
sample date closest to the assessment date will be used. 
If no laboratory data was collected in the window then the last lab test prior to the 
assessment date will be carried forward.  
8.3.5.2.
Efficacy Analyses
Since the study is not sized based on statistical power considerations, no p-values will be 
presented.  The data will be summarized using descriptive statistics and confidence 
intervals.  Exact methods may be employed for modelling and confidence intervals, if 
appropriate for the response rates and sample size. In the event that the overall or within-
strata sample sizes are too small to allow for adjustment for randomization stratification 
factors or other covariates, unadjusted analyses may be performed.  The analyses of the 
primary and major secondary endpoints are described below.  Details of analyses for 
other endpoints including exploratory and sensitivity analyses, will be described in the 
reporting and analysis plan (RAP). 
The primary time point for efficacy analyses will be Week 52.  Analysis of the disease 
activity data collected during Parts B and C of the study will be presented separately and 
analyzed using descriptive statistics and confidence intervals, using methods similar to 
the treatment phase.

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8.3.5.2.1.
Primary Efficacy Endpoint
The primary efficacy endpoint is SLE Responder Index (SRI) response rate at Week 52.
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
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).
The proportion and 95% confidence interval of subjects achieving a response at Week 52 
will be presented by treatment group as will the estimated treatment difference and 95% 
confidence interval.  A logistic regression model with main effects for treatment group 
(belimumab vs. placebo), baseline age group (5-11 vs. 12-17 years), and baseline 
SLEDAI score group (6-12 vs. ≥ 13) will be run to estimate the odds ratio and 95% 
confidence interval for belimumab vs. placebo. 
Treatment failures and handling of missing data will be managed as described in Section 
8.3.5.  
As supportive of the primary endpoint, the percentage of subjects meeting each of the 
three components of the primary endpoint at Week 52 will be presented.  To evaluate the 
response over time, the percentage of subjects achieving a response on the primary 
endpoint and each of the components of the primary endpoint will be presented by visit.
As a sensitivity analysis or in the event that the overall or within-strata sample sizes are 
too small to allow for adjustment, a logistic regression model without adjustment for any 
covariates, and a model with adjustment for baseline SELENA SLEDAI scores ≤ 7 vs. 
≥8, will be used to analyze the response at Week 52. To examine the robustness of the 
study results, a LOCF analysis and a completer analysis (i.e., those subjects who 
complete through Week 52 of the protocol) will also be performed. More details will be 
described in the statistical analysis plan.
Subgroup Analyses
For the primary endpoint results will be displayed by the randomization stratification 
subgroups and by complement/anti-dsDNA status at baseline (has low complement [low 
C3 and/or low C4] AND is anti-dsDNA positive). Other subgroups may be considered if 
sample size permits.

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8.3.5.2.2.
Major Secondary Efficacy Endpoints
Proportion of subjects meeting PRINTO/ACR Juvenile SLE Response Evaluation 
criteria for improvement in SLE at Week 52 using two definitions
The five endpoints considered in the PRINTO/ACR Juvenile SLE Response Evaluation 
definition are percent change in ParentGA, PGA, SELENA SLEDAI score, 24-hour 
proteinuria and change in PedsQL GC physical functioning domain score at Week 52. 
The two definitions of PRINTO/ACR Juvenile SLE Response Evaluation responders are:

PRINTO/ACR Juvenile SLE Response Evaluation 1: At least 50% improvement 
in 2 of 5 endpoints, with no more than 1 of the remaining worsening by more 
than 30%

PRINTO/ACR Juvenile SLE Response Evaluation 2: At least 30% improvement 
in 3 of 5 endpoints above, with no more than 1 of the remaining worsening by 
more than 30%
The proportions of subjects (with 95% confidence intervals) meeting PRINTO/ACR 
Juvenile SLE Response Evaluation criteria (by these two different definitions) at Week 
52 will be assessed using a logistic regression model with main effects for treatment 
group, baseline age group, and baseline SELENA-SLEDAI score group.
Percent change in Parent’s Global Assessment (ParentGA) at Week 52
An analysis of covariance (ANCOVA) model will be used to evaluate each treatment 
group on the percent changes from baseline in ParentGA at Week 52, adjusted for 
baseline ParentGA score, baseline SELENA SLEDAI score group and age group. The 
last observation carried forward (LOCF) method will be employed for subjects with 
missing data on ParentGA score at Week 52. Specifically, if a subject misses the Week 
52 visit (± 28 day window allowed), the missing data will be handled by using the last 
observation available. If a subject takes a protocol-prohibited medication or a dose of 
allowable medication that results in treatment failure designation prior to Week 52, the 
data on change from baseline on ParentGA will be handled by using the score from the 
last visit on or prior to the date that the medication was started.
Percent change in Physician’s Global Assessment (PGA) at Week 52
The percent change from baseline to Week 52 in PGA will be analyzed in the same 
manner as the ParentGA.
Percent change in SELENA-SLEDAI score at Week 52
The percent change from baseline to Week 52 in SELENA SLEDAI score will be 
analyzed in the same manner as the ParentGA.
Change in PedsQL Physical Functioning Domain Score at Week 52
The changes from baseline in the PedsQL GC physical functioning domain score at Week 
52 will be assessed using an analysis of covariance (ANCOVA) model, adjusted for 
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age group. The calculation of the PedsQL physical functioning domain score will be 
based on the developer instructions [Varni, 2002].  The last observation carried forward 
(LOCF) method will be employed for subjects with missing data at Week 52. 
Specifically, if a subject misses the Week 52 visit (± 28 day window allowed), the 
missing data will be handled by using the last observation available. If a subject takes a 
protocol-prohibited medication or a dose of allowable (but protocol-restricted) 
medication that results in treatment failure designation prior to Week 52, the data on 
change from baseline will be handled by using the score from the last visit on or prior to 
the date that the medication was started.
Percent change in 24 hour proteinuria at Week 52 (g/24hour equivalent by spot 
urine protein to creatinine ratio)
The percent change from baseline to Week 52 in 24 hour proteinuria will be analyzed 
using summary statistics and 95% confidence intervals, without any adjustment for 
covariates.
Proportion of subjects with a sustained SRI response (defined as having a 
response on the primary efficacy endpoint at Weeks 44, 48, and 52)
The proportion of subjects with a sustained SRI response will be evaluated by treatment 
group using a logistic regression model, adjusted for baseline SELENA SLEDAI score 
group, and age group.
Handling of missing data, including concomitant medication changes resulting in 
treatment failure designation, will be the same as described for the primary efficacy 
analysis (Section 8.3.5.2.1). 
Proportion of subjects with a sustained ParentGA response (defined as having 
>0.7 improvement at Weeks 44, 48, and 52 compared at baseline)
The proportion of subjects with a sustained ParentGA response will be analyzed in the 
same manner as the proportion of subjects with a sustained SRI response.  An 
improvement of 0.7 corresponds to the minimally clinically important difference (MCID) 
for the instrument using the physician external rating. [Filocamo, 2010]  
8.3.5.3.
Safety Analyses
Descriptive statistics will be used to summarize adverse events (AEs), changes in 
laboratory parameters, vital signs and immunogenicity.  Unless otherwise specified, 
safety data will be summarized separately for each study phase (Parts A, B and C).
8.3.5.3.1.
Extent of Exposure
Exposure to study agent will be summarized by the number of infusions received and the 
duration of exposure in days.  The total subject-years of exposure will be calculated by 
treatment group.

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8.3.5.3.2.
Adverse Events and Disease Related Events
Adverse events and Disease Related Events (DRE) will be coded using MedDRA and 
summarized by System Organ Classes (SOCs) and Preferred Term.  Additionally, AEs 
will be graded for severity by the investigator using Adverse Event Severity Grading 
Tables (Appendix 5 Clinical Laboratory Tests).  A summary of the number and 
percentage of subjects with AEs occurring on or after the treatment start date will be 
displayed by treatment group.  Additionally, adverse events will be presented for baseline 
age stratification subgroups.
The frequency of subjects experiencing an AE will be summarized by:

All AEs

Serious AEs

Severe AEs 

Study Agent Related AEs

AEs leading to permanent discontinuation of study agent
DRE’s will be summarized separately, by SOC, Preferred Term, and treatment group.
Adverse events occurring prior to treatment start date will also be summarized.
The hierarchical relationship between MedDRA, SOCs and Preferred Terms and 
verbatim text will be displayed for relevant AEs.
Adverse events of special interest are death, malignancies, infusion and hypersensitivity 
reactions, infections, and suicidality.  Separate analyses of these events will be performed 
as described above for adverse events.
8.3.5.3.3.
Laboratory Parameters
The frequency and percent of subjects experiencing a laboratory abnormality will be 
tabulated by treatment group.  Laboratory values will be assessed for significant changes 
from baseline.  For analysis, laboratory toxicity will be graded using Adverse Event 
Severity Grading tables (Appendix 5 Clinical Laboratory Tests) when possible.  
Lymphopenia will be graded using Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0 (U.S. Department of Health and Human Services, 2010).  Shift 
tables will be used to determine if subjects move from normal to abnormal (high or low) 
during the course of the study.  Shifts of ≥ 2 grades and Grade 3 or 4 laboratory 
abnormalities will be summarized.
8.3.5.3.4.
Vital Signs
Summary statistics for absolute values and changes from baseline to each visit for each of 
the vital signs will be presented by treatment group.  The number of subjects in each 
treatment group with vital sign values outside the normal ranges will be tabulated by 
visit.

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8.3.5.3.5.
Immunogenicity
Immunogenicity (anti-belimumab antibodies) will be summarized at baseline and 
following the start of treatment.
8.3.5.4.
Pharmacokinetic Analyses
All randomized subjects will be sampled for serum belimumab levels. A pharmacokinetic 
(PK) sample will be drawn on Days 0, 14 (Week 2), 28 (Week 4), 56 (Week 8), 168 
(Week 24), 364 (Week 52), and at the 8-week follow-up visit (if applicable).  For subjects
enrolled in Japan only, PK samples will also be taken at the 12 week / 3 month and the 
first 6 month visits only in Part B. Additional pharmacokinetic samples will be obtained 
from Cohorts 1 (12 subjects) and 2 (at least the first 10 subjects) for interim 
pharmacokinetic assessment as specified in the Time and Events Table (Table 2). The PK 
data for the 10 subjects receiving active treatment that are a part of the first 12 subjects 
randomized in the 12 and over age group will be reviewed, and dose adjustment may be 
made based on this review.  The same analysis will be performed on the PK data for the 
subjects on active treatment that are part of the subjects randomized in the 5-11 age group
(at least 10 subjects).  Population pharmacokinetic analysis is planned, possibly also 
utilizing adult data. 
PK analysis of subjects in Japan will be used to determine the pharmacokinetics of 
belimumab in pediatric subjects of Japanese descent.
8.3.5.5.
Pharmacogenetic Analyses
Any pharmacogenetic analyses will be described in a separate pharmacogenetic analysis 
plan and will be reported separately from the main clinical study report.  All endpoints of 
interest, all comparisons, will be descriptively and/or graphically summarized as 
appropriate to the data.  Analyses of pharmacogenetic data are described in Appendix 1
Pharmacogenetic Research
8.3.5.6.
Biological Markers
Changes from baseline (absolute and percent) and shifts relative to the reference range in 
collected biomarkers will be evaluated, and the analysis details will be included in the 
RAP.  Pre- and post- vaccination titres will be summarized using descriptive statistics.

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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/HGS 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/assent.

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’s parent(s) or legal 
guardian prior to the subject’s participation in the study.  The subject’s parent(s) or legal 
guardian will be re-consented whenever new information becomes available that may 
affect their willingness for their child to continue to participate in the trial.  Assent will be 
obtained from each pediatric subject in accordance with applicable country or IRB/Ethics 
Committee regulations.  Written informed consent will be obtained from subjects turning 
18 years of age to continue participation in the study.  
9.3.
Quality Control (Study Monitoring)
In accordance with applicable regulations, GCP, and GSK procedures, GSK monitors or 
those acting on behalf of GSK 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.

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
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.
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
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, 
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, 

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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 investigators with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis.
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. 
9.8.
Independent Data Monitoring Committee (IDMC)
An IDMC, previously described in Section 3.1, will be utilized in this study to ensure 
external objective medical and/or statistical review of safety and/or efficacy issues in 
order to protect the ethical and safety interests of subjects and to protect the scientific 
validity of the study.  The schedule of any planned interim analysis and the analysis plan 
for IDMC review is described in the charter, which is available upon request.

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10.
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relationship with disease activity. Lupus. 1997;6:425-35.
Wallace DJ. Management of lupus erythematosus: recent insights. Current Opinions in 
Rheumatology 2002;14:212-9.
Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and 
pharmacodynamics. Clin Pharmacol Ther 2008;84(5):548-58.
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.

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11.
APPENDICES
11.1.
Appendix 1: Pharmacogenetic Research
Pharmacogenetics – Background
Pharmacogenetics (PGx) is the study of variability in drug response due to hereditary 
factors in different populations.  There is increasing evidence that an individual's genetic 
composition (i.e., genotype) may impact the pharmacokinetics (absorption, distribution, 
metabolism, elimination), pharmacodynamics (relationship between concentrations and 
pharmacologic effects or the time course of pharmacologic effects) and/or clinical 
outcome (in terms of efficacy and/or safety and tolerability). Some reported examples of 
PGx analysis include:
Drug
Disease
Gene
Outcome
Abacavir
HIV 
[Hetherington, 
2002; Mallal, 
2002]
HLA –B*5701
Individuals with HLA-B*5701 variant may be 
at increased risk for experiencing 
hypersensitivity to abacavir. Clinical assays 
are available for HLA-B*5701 but none has 
been validated. HLA-B*5701 screening would 
supplement but never replace abacavir 
clinical risk management strategies aimed at 
minimising rare but serious outcomes 
associated with abacavir hypersensitivity.
Warfarin
Cardiovascular 
[Neergard, 2006; 
Wilke, 2005]
CYP2C9
Serious adverse events (SAEs) experienced 
by some subjects on warfarin may be 
explained by variations in the CYP2C9 gene 
that influences the degree of anticoagulation 
achieved. 
Irinotecan
Cancer [FDA
News Release, 
2005]
UGT1A1
Variations in the UGT1A1 gene can influence 
a subject’s ability to break down irinotecan, 
which can lead to increased blood levels of 
the drug and a higher risk of side effects. A 
dose of irinotecan that is safe for one subject
with a particular UGT1A1 gene variation, 
might be too high for another subject without 
this variation, raising the risk of certain side-
effects. 
A genetic blood test (Invader UGT1A1 
molecular assay) is available that can detect 
variations in the gene.    
A key component to successful PGx research is the collection of samples during the 
conduct of clinical studies.
Collection of whole blood samples, even when no a priori hypothesis has been identified, 
may enable PGx analysis to be conducted if at any time it appears that there is a potential 
unexpected or unexplained variation in handling or response to belimumab.

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Pharmacogenetic Research Objectives
The objective of the PGx research (if there is a potential unexpected or unexplained 
variation) is to investigate a possible genetic relationship to handling or response to 
belimumab.  If it appears there is potential variability in response in this clinical study or 
in a series of clinical studies with belimumab that may be attributable to genetic 
variations of subjects, the following objectives may be investigated: 

Relationship between genetic variants and the pharmacokinetics and/or 
pharmacodynamics of study treatment

Relationship between genetic variants and safety and/or tolerability of  study 
treatment

Relationship between genetic variants and efficacy of study treatment
Study Population
Any subject who has given informed consent to participate in the clinical study, has met 
all the entry criteria for the clinical study, and receives study treatment may take part in 
the PGx research.  Any subject who has received an allogeneic bone marrow transplant 
must be excluded from the PGx research.
Subject participation in the PGx research is voluntary and refusal to participate will not 
indicate withdrawal from the clinical study.  Refusal to participate will involve no penalty 
or loss of benefits to which the subject would otherwise be entitled.
Study Assessments and Procedures
As saliva is being collected for analysis, no additional whole blood samples will be 
necessary for the PGx analysis. Deoxyribonucleic acid (DNA) will be extracted from 
cells obtained from the subject’s saliva. Saliva (2mL) is spit into the DNA self-collection 
kit. A single sample will be taken but can be duplicated if the first sample is unusable. It 
is recommended that the saliva sample be collected at Day 0/Baseline visit.  
The PGx sample is labelled (or “coded”) with a study specific number that can be traced 
or linked back to the subject by the investigator or site staff.  Coded samples do not carry 
personal identifiers (such as name or social security number).  The saliva sample is taken 
on a single occasion unless a duplicate sample is required due to inability to utilize the 
original sample.  
The DNA extracted from the saliva sample may be subjected to sample quality control 
analysis.  This analysis will involve the genotyping of several genetic markers to confirm 
the integrity of individual samples.  If inconsistencies are noted in the analysis, then those 
samples may be destroyed.
The need to conduct PGx analysis may be identified after a study (or a set of studies) of 
belimumab has been completed and the study data reviewed.
In some cases, the samples may not be studied. e.g., no questions are raised about how 
people respond to belimumab.

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Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will use samples collected from the study for 
the purpose stated in this protocol and in the informed consent form.  
Subjects can request their sample to be destroyed at any time.
Subject Withdrawal from Study
If a subject who has consented to participate in PGx research and has a sample taken for 
PGx research withdraws from the clinical study for any reason other than lost to follow-
up, the subject will be given the following options:

The sample is retained for PGx research

Any PGx sample is destroyed.
If a subject withdraws consent from the PGx research or requests sample destruction for 
any reason, the investigator must complete the appropriate documentation to request 
sample destruction within the timeframe specified by GSK and maintain the 
documentation in the site study records.  If the sample has already been processed, it will 
be destroyed after all steps are complete. GSK will ensure that any data related to the 
sample will not be analysed. The sample will be destroyed after processing is complete. 
Screen and Baseline Failures
If a saliva sample for PGx research has been collected and it is determined that the 
subject does not meet the entry criteria for participation in the clinical study, then the 
investigator must complete the appropriate documentation to request sample destruction 
within 5 days. The sample will be destroyed and documentation sent to the site within 30 
working days of receipt of the request for destruction. All documents pertaining to 
sample destruction must be maintained in the site study records. 
Pharmacogenetics Analyses
1.
Specific sections of DNA may be selected from areas of the genome (e.g., candidate 
genes) known to encode the drug target, drug metabolizing enzymes, areas 
associated with mechanisms underlying adverse events, and those linked to study 
disease and, thus, linked to drug response. 
The candidate genes that may be investigated in this study include genes that code for 
enzymes, transporters, proteins or receptors that may be involved in response to 
belimumab. 
2.
By evaluating large numbers of polymorphic markers (e.g., single nucleotide 
polymorphisms or SNPs) throughout the genome, sets of markers may be identified 
that correspond to differential drug response. 
The results of PGx investigations will be reported either as part of the main clinical study 
report or as a separate report. All endpoints of interest from all comparisons will be 
descriptively and/or graphically summarised as appropriate to the data. In all cases, 

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appropriate statistical methods will be used to analyse the genetic markers in the context 
of other clinical data. Statistical methods may include, but are not limited to Hardy-
Weinberg Equilibrium testing, Comparison of Demographic and Baseline Characteristics 
by Genotype, Evaluation of Genotypic Effects, Evaluation of Treatment by Genotype and 
Gene-Gene Interaction, Linkage Disequilibrium, Multiple Comparison and Multiplicity 
and/or Power and Sample Size Considerations. Detailed description of the analyses to be 
conducted will be documented in the Pharmacogenetics Reporting and Analysis Plan.  
3.
Genome-wide scans involving a large number of polymorphic markers (e.g., single 
nucleotide polymorphisms) located throughout the genome. This approach is often 
employed when potential genetic effects are not well understood.
Informed Consent/Assent
Subjects who do not wish to participate in the PGx research may still participate in the 
clinical study.  PGx informed consent must be obtained prior to any saliva being taken for 
PGx research.
Provision of Study Results and Confidentiality of Subject’s PGx Data
GSK may summarize the cumulative PGx research results in the clinical study report.
In general, GSK does not inform the investigator, subject, or anyone else (e.g., family 
members, study investigators, primary care physicians, insurers, or employers) of the 
PGx research results that are not known to be relevant to the subject’s medical care at the 
time of the study, because the information generated from PGx studies is preliminary in 
nature, and the significance and scientific validity of the results are undetermined at such 
an early stage of research, under any circumstances unless required by law.
References
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, 
Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses 
AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. 
Lancet. 2002; 359:1121-2.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte 
C, Maxwell D, James I.  Association between presence of HLA-B*5701, HLA-DR7, and 
HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir.  
Lancet. 2002; 359:727-32.
Neergard. Reducing the risk of blood thinners. Associated press, September 2006. 
U.S. Food and Drug Administration, FDA Clears Genetic Test That Advances 
Personalized Medicine Test Helps Determine Safety of Drug Therapy 22 August 2005, 
http://www.fda.gov/bbs/topics/NEWS/2005/NEW01220.html.   
Wilke RA, Musana AK, Weber WW. Cytochrome P450 gene-based drug prescribing, 
and factors impacting translation into routine clinical practice. Personalized Med 2005; 2: 
213-224.  

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11.2.
Appendix 2: Country Specific Requirements
Information pending determination of country participation.
Study Inclusion Criterion – age of subjects
At sites in the Russian Federation, only subjects 12 years of age will be eligible to 
participate.
Study Inclusion Criterion specific for sites in the Russian Federation:
Subjects eligible for enrolment in the study must be 12 years of age to participate.
Study Treatment Restart per Section 6.3.3
At sites in the Russian Federation, restart of study treatment after liver event is not 
permitted.

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11.3.
Appendix 3: American College of Rheumatology (ACR) 
Criteria for SLE
The ACR Criteria for the Classification of Systemic Lupus Erythematosus* 
[Tan, 1982; Hochberg, 1997]
Criterion
Definition
1. Malar "butterfly" rash 
Fixed erythema, flat or raised, over the malar eminences, tending to spare the 
nasolabial folds.
2. Discoid rash 
Erythematosus raised patches with adherent keratotic scaling and follicular 
plugging; atrophic scarring may occur in older lesions.
3. Photosensitivity 
Skin rash as a result of unusual reaction to sunlight, by subject history or 
physician observation.
4. Oral ulcers 
Oral or nasopharyngeal ulceration usually painless.
5. Arthritis 
Nonerosive arthritis involving 2 or more peripheral joints characterized by 
tenderness.
6. Serositis 
a.
Pleuritis (convincing history or pleuritic pain or rub heard by physician or 
evidence of pleural effusion), OR
b.
Pericarditis (documented by ECG, rub, or evidence or pericardial 
effusion).
7. Renal disorder 
a.
Persistent proteinuria (0.5 grams/day or 3 + if quantitation not 
performed) OR
b.
Cellular casts (may be red cell, hemoglobin, granular, tubular, or mixed).
8. Neurologic disorder 
a.
Seizures (in the absence of offending drugs or known metabolic 
derangements; ie, uremia, ketoacidosis, or electrolyte imbalance) OR
b.
Psychosis (in the absence of offending drugs or known metabolic 
derangements; ie, uremia, ketoacidosis, or electrolyte imbalance.
9. Hematologic disorder 
a.
Hemolytic anemia (with reticulocytosis)
OR
b.
Leukopenia (4000/mL total on 2 or more occasions), OR
c.
Lymphopenia (1500/mL on 2 or more occasions), OR
d.
Thrombocytopenia (100,000/mL in the absence of offending drugs).
10. Immunologic disorder 
a.
Anti-DNA (antibody to native DNA in abnormal titer), OR
b.
Anti-Sm (presence of antibody to Sm nuclear antigen), OR
c.
Positive-finding of antiphospholipid antibodies based on 1) an abnormal 
serum level of IgG or IgM anticardiolipin antibodies, 2) a positive test 
result for lupus anticoagulant using a standard method, or 3) a false-
positive serologic test for syphilis known to be positive for at least 6 
months and confirmed by Treponema pallidum immobilization (TPI) or 
fluorescent treponemal antibody (FTA) absorption test.
11. Antinuclear antibody (ANA)
Abnormal titer of ANA by immunofluorescence or an equivalent assay at any 
point in time and in the absence of drugs known to be associated with "drug-
induced lupus" syndrome.
1.
*
The proposed classification is based on 11 criteria.  For the purpose of identifying subjects in clinical 
studies, a person shall be said to have systemic lupus erythematosus if any 4 or more of the 11 criteria are 
present, serially or simultaneously, during any interval or observation.

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11.4.
Appendix 4: Liver Safety Criteria
11.4.1.
Liver Stopping Event Algorithm
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Section 6.3.1.1 and Section 6.3.2.1. 
Continue Study Treatment 
Discontinue Study Treatment 
Plus 
Bilirubin≥2x
ULN (>35% 
direct) or plus
INR>1.5, if 
measured*
Possible  
Hy’s Law
ALT≥3xULN
ALT
≥8xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
*INR value not applicable to subjects on anticoagulants 
ALT 
≥3xULN 
but 
<8xULN
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*

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11.4.2.
Liver Monitoring Event Algorithm with Continued Therapy for 
ALT≥3xULN but <8xULN
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Section 6.3.1.1 and Section 6.3.2.1
References
Andrade RJ, Robles M, Lucena MI.  Rechallenge in drug-induced liver injury: the 
attractive hazard.  Expert Opin Drug Saf. 2009;8:709-714.
Hunt, CM.  Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review.  Hepatol. 2010;52:2216-
2222.
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, Hunt CM.  Drug-induced liver 
injury following positive drug rechallenge.  Regul Tox Pharm. 2009;54:84-90. 
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
*INR value not applicable to subjects on anticoagulants 
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*

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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)
Serum Pregnancy 
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)
Urine Pregnancy
Alcohol and Drug Screen 
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
HIV-1/2 antibody
Hepatitis C antibody
Hepatitis B surface antigen
Estimated Creatinine Clearance/ GFR 
(Cockroft-Gault)
Biological Markers
BLyS protein 
Serum complement (C3 and C4) 
C-Reactive Protein (CRP)
B-cell subtypes (CD20+, CD20+/27+ memory, CD20+/27– naïve, 
CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells).
Immunoglobulins
Serum immunoglobulin isotypes:  IgG, IgM, IgA
PK and Immunogenicity
Autoantibodies
ANA titer and OD
Anti-dsDNA
aCL

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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)
1.
*ULN = Upper Limit of Normal. 
2.
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 
subject 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)
1.
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
1.
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)
1.
*[Eibl, 1995; Goldfarb, 2001; Yamini, 2001].
2.
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
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
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
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
1.
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

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11.6.
Appendix 6: SELENA SLEDAI Disease Assessment Scales
SELENA SLEDAI Score (adapted from [Petri, 2005; Bombardier, 1992]) Score if 
descriptor is present at time of visit or in the preceding 10 days.
Wgt.
Descriptor
Definition
8
Seizure
Recent onset (last 10 days). Exclude metabolic, infectious drug cause, or seizure 
due to past irreversible CNS damage.
8
Psychosis
Altered ability to function in normal activity due to severe disturbance in the 
perception of reality. Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked illogical thinking, bizarre, 
disorganized, or catatonic behavior.   Exclude uremia and drug causes.
8
Organic Brain 
Syndrome
Altered mental function with impaired orientation, memory or other intellectual 
function with rapid onset and fluctuating clinical features. Include clouding of 
consciousness with reduced capacity to focus and inability to sustain attention to 
environment, plus at least 2 of the following: perceptual disturbance, incoherent 
speech, insomnia or daytime drowsiness, or increased or decreased psychomotor 
activity.   Exclude metabolic, infectious, or drug causes.
8
Visual Disturbance
Retinal and eye changes of SLE. Include cytoid bodies, retinal hemorrhages, 
serious exudate of hemorrhage in the choroid, optic neuritis, scleritis or episcleritis.   
Exclude hypertension, infection, or drug causes.
8
Cranial Nerve 
Disorder
New onset sensory or motor neuropathy involving cranial nerves. 
Include vertigo due to lupus.
8
Lupus Headache
Severe persistent headache: may be migrainous, but must be 
non-responsive to narcotic analgesia.
8
CVA
New onset of CVA(s).  Exclude arteriosclerosis or hypertensive causes.
8
Vasculitis
Ulceration, gangrene, tender finger nodules, periungual infarction, splinter 
hemorrhages, or biopsy or angiogram proof of vasculitis.
4
Arthritis
More than 2 joints with pain & signs of inflammation (ie, tenderness, swelling or 
effusion).
4
Myositis
Proximal muscle aching/weakness associated with elevated creatine 
phosphokinase/aldolase or electromyogram changes or a biopsy showing myositis.
4
Urinary Casts
Heme-granular or red blood cell casts.
4
Hematuria
5 red blood cells/high power field. Exclude stone, infection, or other causes.
4
Proteinuria
New onset or recent increase of more than 0.5 g/24 hours.
4
Pyuria
5 white blood cells/high power field. Exclude infection.
2
Rash
New or ongoing inflammatory lupus rash.
2
Alopecia
New or ongoing abnormal, patchy or diffuse loss of hair due to active lupus.
2
Mucosal Ulcers
New or ongoing oral or nasal ulcerations due to active lupus.
2
Pleurisy
Classic and severe pleuritic chest pain or pleural rub or effusion or new pleural 
thickening due to lupus.
2
Pericarditis
Classic and severe pericardial pain or rub or effusion, or electrocardiogram 
confirmation.
2
Low Complement
Decrease in CH50, C3, or C4 below the lower limit of normal for testing laboratory.
2
Increased DNA 
Binding
25% binding by Farr assay or above normal range for testing laboratory.
1
Fever
38°C. Exclude infectious cause.
1
Thrombocytopenia
100,000 platelets/mm3
1
Leukopenia
3,000 white blood cells/mm3.  Exclude drug causes.
TOTAL SCORE
(Sum of weights next to descriptors marked present)

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11.7.
Appendix 7: SLE Flare Index
(Adapted from [Buyon, 2005; Petri, 2005; Neergard, 2006. Petri, 1999])
Mild-moderate flare
Severe flare
Change in SELENA SLEDAI instrument 
score of 3 points or more (but not to more 
than 12), or
Change in SELENA SLEDAI instrument 
score to greater than 12a,  or
New/worse:
   Discoid, photosensitive, profundus,
       cutaneous vasculitis, bullous lupus
   Nasopharyngeal ulcers
   Pleuritis
   Pericarditis
   Arthritis
   Fever (SLE)
Or
New/worse:
   CNS-SLE
   Vasculitis
   Nephritis
   Myositis
   Plt<60,000
   Hemolytic anemia with Hb<70g/L or 
decrease in Hb>3g/L 
Requiring:  double prednisone , or 
prednisone increase to >0.5mg/kg/day, or 
hospitalization, or
Increase in prednisone, but not to 
>0.5mg/kg/day, or
Increase in prednisone to >0.5mg/kg/day, 
or
Added NSAID or hydroxychloroquine for 
SLE activity, or
New cyclophosphamide, azathioprine, 
methotrexate, or mycophenolate for SLE 
activity, or
1.0 Increase in PGA score, but not to 
more than 2.5
Hospitalization for SLE activity, or
Increase in a PGA score to 2.5
a.
Severe flares that are triggered only by an increase is SLEDAI Score to greater than 12 will not be categorised 
as severe in the analysis.

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11.8.
Appendix 8: Physician’s Global Disease Assessment
(Adapted from [Petri, 2005]) 

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11.9.
Appendix 9: Parent’s Global Disease Assessment
Considering all the ways the illness affects your child, please evaluate how he/she feels at 
the moment

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11.10.
Appendix 10: BILAG Index Assessment
All features must be attributable to SLE and refer to the last 4 weeks compared with prior 
disease activity.
Answer      0) Not present
1) Improving 2) Same
3) Worse
4) New
GENERAL
MUSCULOSKELETAL
1.
Pyrexia (documented)
(   )
39.
Definite myositis (Bohan & Peter)
(   )
2.
Weight Loss – unintentional >5%
(   )
40.
Severe polyarthritis – with loss of 
function
(   )
3.
Lymphadenopathy/splenomegaly
(   )
4.
Fatigue/malaise/lethargy
(   )
41.
Arthritis
(   )
5.
Anorexia/nausea/vomiting
(   )
42.
Tendonitis
(   )
MUCOCUTANEOUS
43.
Mild chronic myositis
(   )
6.
Maculopapular eruption – severe, active 
(bulbous)
(   )
44.
Arthralgia
(   )
45.
Myalgia
(   )
7.
Maculopapular eruption – mild
(   )
46.
Tendon contractures and fixed 
deformity
Y/N
8.
Active discoid lesions –
generalized/extensiive
(   )
47.
Aseptic necrosis
Y/N
9.
Active discoid lesions – localized include 
lupus profundus
(   )
CARDIOVASCULAR & RESPIRATORY
48.
Pleuroopericardial pain
(   )
10.
Alopecia (severe, active)
(   )
49.
Dyspnea
(   )
11.
Alopecia (mild)
(   ) 
50.
Cardiac failure
(   )
12.
Panniculitis (severe)
(   )
51.
Friction Rub
(   )
13.
Angioedema
(   )
52.
Effusion (pericardial or pleural)
(   )
14.
Extensive mucosal ulceration
(   )
53.
Mild or intermittent chest pain
(   )
15.
Small mucosal ulceration
(   )
54.
Progressive chest X-ray changes –
lung fields
Y/N
16.
Malar erytheme
(   )
17.
Subcutaneous nodules
(   )
55.
Progressive chest X-ray changes –
heart size
Y/N
18.
Perniotic skin lesions
(   )
19.
Periungual erythema
(   )
56.
ECG evidence of pericarditis or 
myocarditis
Y/N
20.
Swollen fingers
Y/N
21.
Sclerodactyly
Y/N
57.
Cardiac arrhythmias including 
Y/N
22.
Calcinosis
Y/N
tachycardia >100 in absence of fever
23.
Telangiectasia
Y/N
58.
Pulmonary function fall by >20%
Y/N
NEUROLOGICAL
59
Cytohistological evidence of
Y/N
24.
Deteriorating level of consciousness
(   )
. 
inflammatory lung disease
25.
Psychosis or confusional state
(   )
. VASCULITIS
26.
Seizures
(   )
60.
Major cutaneous vasculitis inc. 
ulcers
(   )
27.
Stroke or stroke syndrome
(   )
61.
Major abdominal crisis due to 
Vasculitis
(   )
28.
Aseptic meningitis
(   )
29.
Mononeuritis multiplex
(   )
62.
Recurrent thromboembolism
(excluding strokes)
(   )
30.
Ascending or transverse myelitis
(   )
31.
Peripheral or cranial neuropathy
(   )
63.
Raynaudis
(   )
32.
Disc swelling/cytoid bodies
(   )
64.
Livido reticularis
(   )
33.
Chorea
(   )
65.
Superficial phlebitis
(   )
34.
Cerebellar ataxia
(   )
66.
h.
Minor cutaneous vasculitis
i.
(nailfold vasculitis, digital 
vasculitis pupura, urticaria)
(   )
35.
Headache severe, unremitting
(   )
36.
Organic depressive illness
(  )
37.
Organic brain syndrome incl. 
pseudotumor cerebri
(   )
67.
Thromboembolism (excl. stroke)
1st episode
Y/N
38.
Episodic migranous headaches
(   )

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RENAL
HAEMATOLOGY
68.
Systolic blood pressure
(         ) 
mm/Hg
79.
Hemoglobin
(           ) g/dL
69.
Diastolic blood pressure
(5th phase)
(         ) 
mm/Hg
80.
Total white cell count
(           ) x109/L
81.
Neutrophils
(           ) x109/L
70.
Accelerated hypertension
Y/N
82.
Lymphocytes
(           ) x109/L
71. 
Dipstick (-=0, +=1, ++=2
  +++=3)
(         )
83. 
Platelets
(           ) x109/L
84. 
Evidence of active
hemolysis
Y/N
72. 
Urinary protein (record a or b)
a. 24 hour urinary protein
b. Urine protein-creatinine ratio
(         ) g
85. 
Coombs test positive
Y/N
(     ) mg/mmol
86. 
Evidence of circulating
anticoagulant
Y/N
73.
Proteinuria (record a or b)
a. Newly documented
proteinuria of >1g/24hrs
b. Newly documented
protein-creatinine ratio
of >100mg/mmol
Y/N
Y/N
74.
Nephrotic syndrome
Y/N
75.
Creatinine (plasma/serum)
(        ) mg/dL
76. 
Creatinine clearance/GFR
(        ) mL/min
77.
Active urinary sediment
Y/N
78.
Histological evidence of active
Nephritis – within 3 months
Y/N
Adapted from [Hay, 1993; Isenberg, 2000] 

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11.11.
Appendix 11: Pediatric SLICC/ACR Damage Index
The Pediatric Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index* 
(from Ginsberg, 1983; Gladman, 1996, Gutiérrez, 2006) 
Item 
Possible score 
Ocular (either eye, by clinical assessment) 
Any cataract ever 
0or1 
Retinal change or optic atrophy 
0or1 
Neuropsychiatric 
Cognitive impairment (e.g., memory deficit, difficulty with 
calculation, poor concentration, difficulty in spoken or 
0or1 
written language, impaired performance level) or major 
psychosis 
Seizures requiring therapy for 6 months 
0or1 
Cerebrovascular accident ever (score 2 if >1), resection not 
for malignancy 
0, 1, or 2 
Cranial or peripheral neuropathy (excluding optic) 
0or1 
Transverse myelitis 
0or1 
Renal 
Estimated or measured glomerular filtration rate <50%
0or1 
Proteinuria >3.5 gm/24 hours 
0or1 
or 
End-stage renal disease (regardless of dialysis or 
transplantation) 
3 
Pulmonary 
Pulmonary hypertension (right ventricular prominence or loud 
P2) 
0 or 1 

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Item 
Possible score 
Pulmonary fibrosis (by physical and radiographic 
examination) 
0 or 1 
Shrinking lung (by radiographic examination) 
0or1 
Pleural fibrosis (by radiographic examination) 
0or1 
Pulmonary infarction (by radiographic examination) or 
resection not for malignancy 
0 or 1 
Cardiovascular 
Angina or coronary artery bypass 
0or1 
Myocardial infarction ever (score 2 if >1) 
0, 1, or 2 
Cardiomyopathy (ventricular dysfunction) 
0or1 
Valvular disease (diastolic murmur, or systolic murmur >3/6) 
0 or 1 
Pericarditis for >6 months or pericardiectomy 
0or1 
Peripheral vascular 
Claudication for >6 months 
0or1 
Minor tissue loss ever (pulp space) 
0or1 
Significant tissue loss ever (e.g., loss of digit or limb, 
resection) (score 2 if >1) 
0, 1, or 2 
Venous thrombosis with swelling ulceration, or venous stasis 
0 or 1 
Gastrointestinal 
Infarction or resection of bowel (below duodenum), spleen, 
liver, or gall bladder ever (score 2 if >1) 
0, 1, or 2 
Mesenteric insufficiency 
0or1 
Chronic peritonitis 
0or1 
Stricture or upper gastrointestinal tract surgery ever 
0or1 

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Item 
Possible score 
Pancreatic insufficiency requiring enzyme replacement or 
with pseudocyst 
0 or 1 
Musculoskeletal 
Muscle atrophy or weakness 
0or1 
Deforming or erosive arthritis (including reducible 
deformities, excluding avascular necrosis) 
0 or 1 
Osteoporosis with fracture or vertebral collapse (excluding 
avascular necrosis) 
0 or 1 
Avascular necrosis (score 2 if >1) 
0, 1, or 2 
Osteomyelitis 
0or1 
Ruptured tendons 
0or1 
Skin 
Scarring chronic alopecia 
0or1 
Extensive scarring or panniculum other than scalp and pulp 
space 
0 or 1 
Skin ulceration (excluding thrombosis) for >6 months 
0or1 
Diabetes (regardless of treatment) 
0or1 
Malignancy (exclude dysplasia) (score 2 if >1 site) 
0, 1, or 2 
Premature gonadal failure 
0or1 
Growth failure 
0or1 
Delayed puberty 
0or1 
*Damage occurring since diagnosis of systemic lupus erythematosus is ascertained by 
clinical assessment and defined as persistent changes in anatomy, physiology, pathology, 
or function, which may be the result of prior active disease, complications of therapy, or 
comorbid conditions, are not due to currently active disease, and have been present for at 
least 6 months. The same lesion cannot be scored twice. Damage is often irreversible and 
cumulative, and thus, damage scores are most frequently expected to increase or remain 
stable over time. However, because some forms of damage may improve or even resolve 

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in pediatric subjects, it is anticipated that in some cases scores may decline (i.e., a 
manifestation that was previously present and has resolved would be scored as “0” at the 
time of the present assessment). All items are defined according to the glossary of terms 
included with the original Systemic Lupus International Collaborating Clinics/American 
College of Rheumatology Damage Index. However, it is recommended that proteinuria 
be adjusted for height and weight in younger children. Growth failure is defined as the 
presence of at least 2 of the following 3 features: 1) height below the third percentile for 
age; 2) growth velocity over 6 months below the third percentile for age; 3) crossing at 
least 2 percentiles (5%, 10%, 25%, 50%, 75%, 95%) on growth chart. In each subject, 
final height assessment is always needed to verify whether growth failure results in a 
permanently short height. Delayed puberty is defined as a delay in development of 
secondary sexual characteristics more than 2 SD below the mean for age by Tanner 
staging. For assessment of growth failure and delayed puberty, national standards or 
standards appropriate for the subject’s racial or ethnic background should be used 
whenever available, instead of international standards. 

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11.12.
Appendix 12: Columbia Suicide Severity Rating Scale C-
SSRS

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Baseline/Screening

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Since Last Visit

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11.13.
Appendix 13: Possible Suicidality-Related Questionnaire
POSSIBLE SUICIDALITY-RELATED QUESTIONAIRE
Has the subject had any SLE-related neuropsychiatric events in the past? 
Yes 
No
If yes, specify by entering the most recent date of occurrence for all that apply 
a.
Acute Confusional State
DAY-MON-YEAR
b.
Acute Inflammatory Demyelinating Polyradiculoneuropathy
(Guillain-Barré Syndrome)
DAY-MON-YEAR
c.
Anxiety Disorder
DAY-MON-YEAR
d.
Aseptic Meningitis
DAY-MON-YEAR
e.
Autonomic Disorder
DAY-MON-YEAR
f.
Cerebrovascular Disease
DAY-MON-YEAR
g.
Cognitive Dysfunction
DAY-MON-YEAR
h.
Demyelinating Syndrome
DAY-MON-YEAR
i.
Headache
DAY-MON-YEAR
j.
Mononeuropathy single
DAY-MON-YEAR
k.
Mononeuropathy multiplex
DAY-MON-YEAR
l.
Mood Disorders
DAY-MON-YEAR
m. Movement Disorder (Chorea)
DAY-MON-
YEAR
n.
Myasthenia Gravis
DAY-MON-YEAR
o.
Myelopathy
DAY-MON-YEAR
p.
Neuropathy, Cranial
DAY-MON-YEAR
q.
Plexopathy
DAY-MON-YEAR
r.
Polyneuropathy
DAY-MON-YEAR
s.
Psychosis
DAY-MON-YEAR
t.
Seizures and Seizure Disorders
DAY-MON-YEAR
u.
Other (___free text field___)
DAY-MON-YEAR
Is the subject currently using illicit drugs? 
Yes 
No
If yes, check all that apply:
a.
Amphetamines
b.
Benzodiazepines
c.
Cannabinoids
d.
Cocaine
e.
Opiates
f.
Other – Please specify (___free text field___)
Is the subject currently using alcohol? 
Yes 
No
If yes – indicate units:

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a.
Units (investigator will be referred to separate eCRF which will 
calculate)
Any family history of suicidality? 
Yes 
No
If yes check ideation and/or behavior next to all that apply:
a.
Father
Ideation 
Behavior
b.
Mother
Ideation 
Behavior
c.
Sibling
Ideation 
Behavior
d.
Other
Ideation 
Behavior
Any family history of psychiatric disorders? 
Yes 
No
If yes specify disorder next to all that apply:
a.
Father 
(___free text field___)
b.
Mother
(___free text field___)
c.
Sibling
(___free text field___)
d.
Other
(___free text field___)
Has the subject experienced any recent stress? 
Yes 
No
If yes, check all that apply:
a.
Family problems
b.
Relationships
c.
Worker unemployment
d.
Finances
e.
Other factors
(___free text field___)
Reference:
American College of Rheumatology (ACR) Ad Hoc Committee on Neuropsychiatric 
Lupus Nomenclature. The American College of Rheumatology Nomenclature and Case 
Definitions for Neuropsychiatric Lupus Syndromes.  Arthritis & Rheumatism. Vol. 42, 
No. 4, April 1999, pp 599–608. 

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11.14.
Appendix 14: Pediatric Quality of Life Inventory - Generic
Core Scale (PedsQL)

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11.15.
Appendix 15: Pediatric Quality of Life Multidimensional 
Fatigue Scale (PedsQL Fatigue)

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11.16.
Appendix 16: Protocol Amendment 01 Changes
Protocol Amendment 01 applies to all countries and sites.
Summary of Changes and Rationale
A detailed description of substantive changes to the protocol are listed below.  
Additional administrative and minor editorial changes have also been made.  
Changes to assessment frequencies described in the text have also been updated in 
the time and events table.
Section
Previous Wording
New Wording
Rationale
Page 1, 
Protocol Title 
Page
Author:  Revision of 
author list and addition 
of each author’s 
department name.
Update to 
authors for 
amended 
protocol 
including 
author’s 
department 
name
Page 2, 
Protocol Title 
Page
No Previous Text
Added “Revision 
Chronology” table 
outlining the protocol 
version and listing of 
major changes for this 
protocol amendment 01.
GSK 
defined 
protocol 
amendment 
template
Page 3, 
Sponsor 
Signatory
David Gordon, MD ChB
Vice President, Medicines 
Development Leader
GlaxoSmithKline
GSK SPONSOR 
SIGNATORY 
David A. Roth, MD
Director, Immuno-
Inflammation
Physician Project Lead
GlaxoSmithKline
Change of 
GSK 
sponsor 
signatory
PPD

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Previous Wording
New Wording
Rationale
Page 4, 
Sponsor 
Information 
Page
Sponsor Medical Monitor 
Contact Information:  
, DO
GlaxoSmithKline
2301 Renaissance Blvd
King of Prussia, PA 19406
United States
Telephone: 
Fax: 
Mobile : 
Email: 
Sponsor Medical Monitor 
Contact Information:  
 MD
GlaxoSmithKline
B9 2nd Floor Stockley 
Park
United Kingdom
Telephone: 
 
Fax: 
Mobile: 
 
Email: 
Back-up Sponsor 
Medical Monitor 
Contact Information
, DO
GlaxoSmithKline
2301 Renaissance Blvd
King of Prussia, PA 
19406
United States
Telephone: 
Fax: 
Mobile : 
Email: 
Change of 
Primary 
Medical 
Monitor.  
Previous 
Primary 
Medical 
Monitor 
will now 
serve as 
“Backup 
Medical 
Monitor” 
for the 
study.
Page 5, 
Investigator 
Agreement
I confirm agreement to 
conduct the study in 
compliance with the 
protocol.
For protocol BEL114055 
I confirm agreement to 
conduct the study in 
compliance with the 
protocol, as amended by 
this protocol 
amendment.
Update 
investigator 
agreement 
page for the 
protocol 
amendment
Page 13, 
Rationale 
Additionally, subjects who 
withdraw from treatment at 
any time during the study 
will be assessed in a long 
term follow-up period 
where annual safety 
Additionally, subjects 
who withdraw from 
treatment at any time 
during the study will be 
assessed in a long term 
follow-up period where 
Modificatio
n of 
language in 
study design 
sections to 
clarify 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Section
Previous Wording
New Wording
Rationale
evaluations and limited 
disease activity 
assessments will be 
performed for a minimum 
of 10 years from the first 
administration of 
belimumab.
safety evaluations and 
limited disease activity 
assessments will be 
performed for up to 10 
years.
safety 
follow up 
for subjects 
who 
withdraw 
and modify 
language 
pertaining 
to duration 
of long term 
follow-up 
for up to 10 
years.
Pages 15, 26 
Study Design
A target enrolment of 100 
subjects will be 
randomized.  
A target enrolment of 100 
subjects (at least 20 
subjects less than 13 
years of age) will be 
randomized.  
Clarify 
requirement 
of 20 
subjects less 
than 13 
years. 
Page 15, 26 
Study Design
Enrolment of subjects in 
the 12 to 17 years of age 
group may be terminated 
when enrolment reaches 
approximately 80 subjects 
in this age group to allow 
the enrolment of at least 20 
younger subjects less than 
13 years of age.
Enrolment of subjects in 
the 12 to 17 years of age 
group may be terminated 
when enrolment reaches
approximately 80 
subjects to allow the 
enrolment of at least 20 
younger subjects less than 
13 years of age.
Clarify that 
enrolment 
of older age 
subjects 
may stop 
when total 
enrolment 
reaches 80 
to allow 
randomizati
on of 20 
subjects <13 
years of 
age.
Page 15, 26 
Study Design
All subjects withdrawing 
from the study will return 
for a safety assessment at 4 
weeks after their last dose 
of study agent and then 
continue in the safety 
follow-up period (Part C) 
where annual safety 
evaluations and limited 
All subjects withdrawing 
from Part A of the study 
will return for an exit 
visit at 4 weeks after their 
last dose of study agent, 
and then continue in the 
safety follow-up period 
(Part C) where safety 
evaluations and limited 
Clarify 
safety 
follow up 
for subjects 
who 
withdraw 
and modify 
language 
pertaining 

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Section
Previous Wording
New Wording
Rationale
disease activity 
assessments will be 
performed for a minimum 
of 10 years from the first 
administration of 
belimumab. Subjects 
choosing not to continue in 
Part A or participate in 
Part B and do not wish to 
be monitored in the safety 
follow-up period (Part C),
will return for safety 
follow-up visit 
approximately 8 weeks 
following their last 
scheduled/exit visit.  
disease activity 
assessments will be 
performed for up to 10 
years from the first 
administration of study 
agent or open label 
belimumab. Subjects 
choosing not to continue 
in Part A or participate in 
Part B and do not wish to 
be monitored in the safety 
follow-up period (Part C), 
will return for a safety 
follow-up visit 
approximately 8 weeks 
following their last dose 
of study agent.
to study 
duration of 
up to 10 
years.
Page 15,16, 
Protocol 
Summary 
Study Design
Part B: Open 
Label 
Belimumab 
Safety 
Follow up 
And 
Page 27, 
Section 3.1 
Study 
Design, Part 
B: Open 
Label 
Belimumab 
Safety 
Follow up 
Part B: Open Label 
Belimumab Safety Follow 
up
Subjects may continue in 
Part B of the study up to 
10 years from the first 
administration of 
belimumab.  Any subject 
who withdraws during the 
continuation phase will 
return for a safety follow 
up visit at 4 weeks after 
their last dose and proceed 
to Part C, safety follow-up 
– non-belimumab phase.  
Part B: Open Label 
Belimumab Continuation
Subjects will continue in 
Part B of the study for up 
to 10 years from the first 
administration of 
belimumab. However, 
the study will conclude 
earlier if all subjects 
continuing belimumab 
treatment have received 
at least 5 years of 
treatment with 
belimumab (Part B or a 
combination of Part A 
and Part B) and if there 
are 15 or fewer subjects 
continuing to receive 
belimumab in the study
(See Section 5.7.1 Study 
Conclusion). Any subject 
who withdraws during the 
continuation phase will 
return for an exit visit at 4 
Modificatio
n of 
language for 
Part B of 
the study to 
correct title 
and to 
describe the 
potential 
earlier end 
of study 
should the 
number of 
subjects 
treated with 
belimumab 
for at least 5 
years drop 
to 15 or 
less.

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Section
Previous Wording
New Wording
Rationale
weeks after their last dose 
and proceed to Part C, 
safety follow-up – non-
belimumab phase. 
Subjects choosing to 
discontinue from the 
study and not be 
monitored in the safety 
follow-up period (Part 
C), will return for a 
follow-up visit 
approximately 8 weeks 
following their last dose 
of open label 
belimumab.
Page 16, 
Protocol 
Summary 
Study Design 
Part C: Safety 
Follow-up –
Non-
belimumab 
Phase
And
Page 27, 
Section 3.1 
Study 
Design,  Part 
C: Safety 
Follow-up 
Non-
belimumab 
phase
Part C will include any 
subject who discontinues 
study agent from Part A or 
open label belimumab 
from Part B.  
These subjects will return 
for a follow-up visit 
approximately 4 weeks 
after their last dose of 
study agent or open label 
belimumab and then 
continue in Part C where 
annual safety evaluations 
and limited disease activity 
assessments will be 
performed for a minimum 
of 10 years from the first 
administration of 
belimumab.  
Part C will include any 
subject who discontinues 
study agent from Part A or 
open label belimumab 
from Part B.  These 
subjects will return for 
safety follow up visits in 
Part C monthly for 3 
months and then 
annually after their last 
dose of study agent or 
open label belimumab.  In 
Part C safety evaluations 
and limited disease 
activity assessments will 
be performed for up to 10 
years from the first 
administration of study 
agent or open label 
belimumab.  However, 
the study will conclude 
earlier if all subjects 
continuing belimumab 
treatment have received 
at least 5 years of 
treatment with 
belimumab (Part B or a 
combination of Part A 
and Part B) and if there 
Modificatio
n of 
language for 
Part C of 
the study to 
clarify visit 
schedule 
and 
assessments 
and to 
describe the 
potential 
earlier end 
of study 
should the 
number of 
subjects 
treated with 
belimumab 
for at least 5 
years drop 
to 15 or 
less.

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Section
Previous Wording
New Wording
Rationale
are 15 or fewer subjects 
continuing to receive 
belimumab in the study 
(See Section 5.7.1 Study 
Conclusion).
Page 17, 
Protocol 
Summary, 
Study Design
Major Secondary Efficacy 
Endpoints
1.Proportion of subjects 
meeting PRINTO/ACR 
Juvenile SLE Response 
Evaluation criteria for 
improvement in juvenile 
SLE using two different 
PRINTO/ACR Juvenile 
SLE Response Evaluation 
definitions of improvement
A  At least 50% 
improvement in any 2 
of 5 endpoints below 
and no more than 1 of 
the remaining 
worsening by more than 
30% 
B  At least 30% 
improvement in 3 of 
5endpoints below and 
no more than 1 of the 
remaining worsening 
more than 30%. 
I.Percent change in
Parent’s Global 
Assessment 
(ParentGA) at Week 
52.
II.Percent change in 
Physician’s Global 
Assessment (PGA) at 
Week 52.
III. Percent change in 
SELENA SLEDAI 
score at Week 52.
Major Secondary 
endpoints
1. Proportion of subjects 
meeting PRINTO/ACR 
Juvenile SLE Response 
Evaluation criteria for 
improvement in juvenile 
SLE using two different 
PRINTO/ACR Juvenile 
SLE Response Evaluation 
definitions of 
improvement
A At least 50% 
improvement in any 2 
of 5 endpoints below 
and no more than 1 of 
the remaining 
worsening by more 
than 30% 
B At least 30% 
improvement in 3 of 
5endpoints below and 
no more than 1 of the 
remaining worsening 
more than 30%. 
I  Percent change 
in Parent’s Global 
Assessment 
(ParentGA) at 
Week 52.
II  Percent change 
in Physician’s 
Global Assessment 
(PGA) at Week 
52.
Deletion of 
“efficacy” 
in header 
and deletion 
of sub-
heading 
“Other 
endpoints” 
to clarify 
the major 
secondary 
endpoints as 
described in 
the Pediatric 
Investigatio
nal Plan 
(PIP) for 
belimumab.

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Section
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New Wording
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IV. Change in PedsQL 
physical functioning 
domain at Week 52
V.Percent change in 
24 hour proteinuria at 
Week 52 (g/24hour 
equivalent by spot 
urine protein to 
creatinine ratio).
2.  Proportion of subjects 
with a sustained SRI 
response 
3.  Proportion of subjects 
with a sustained ParentGA 
response
Other endpoints
1. Safety of 
belimumab
2.  PK comparison 
with Adult PK
3. PedsQL 
Multidimensional 
Fatigue Scale
III  Percent change 
in SELENA 
SLEDAI score at 
Week 52.
IV  Change in 
PedsQL physical 
functioning 
domain at Week 
52
V  Percent change 
in 24 hour 
proteinuria at 
Week 52 
(g/24hour 
equivalent by spot 
urine protein to 
creatinine ratio).
2.  Proportion of subjects 
with a sustained SRI 
response 
3.  Proportion of subjects 
with a sustained ParentGA 
response
4. Safety of belimumab
5.  PK comparison with 
Adult PK
6. PedsQL 
Multidimensional Fatigue 
Scale
Page 28, 
Figure 1 
BEL114055 
Study 
Schematic
No description of earlier 
study conclusion criteria 
***May conclude if the 
last subject has 
completed at least 5 
years of treatment with 
belimumab and the 
number of subjects 
continuing with 
belimumab treatment is 
15 or less.
Clarify 
criteria for 
potential 
earlier study 
conclusion 

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Section
Previous Wording
New Wording
Rationale
Page 30, 
Section 4.2 
Inclusion 
Criteria #6
•  Implants of 
levonorgestrel; 
Implants of levonorgestrel 
or etonogestrel; 
Ethinyl 
estradiol/Etonogestrel 
vaginal ring;
Addition of 
other 
acceptable 
birth control
Page 31, 
Section 4.2 
Inclusion 
Criteria #6
No previous wording
Note: Mycophenolate 
mofetil (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 (eg, barrier 
method). 
MMF can 
affect the 
metabolism 
and 
effectivenes
s of oral 
contraceptiv
es. Based on 
this, it is 
recommend
ed that 
women 
receiving 
MMF who 
rely on oral 
contraceptiv
es for birth 
control 
should be 
required to 
use an 
additional 
method to 
minimize 
the risk of 
pregnancy.  
Page 31, 
Section 4.2, 
Inclusion 
Criteria #7
7. Subject signs and dates 
a written assent form (age 
appropriate) and the legal 
guardian (or emancipated 
minor) that has the ability 
to understand the 
requirements of the study, 
provides written informed 
consent (including consent 
for the use and disclosure 
of research-related health 
information) that the 
Subject signs and dates a 
written (age appropriate 
assent form (in 
accordance with 
applicable regulations) 
and the parent or legal 
guardian (or emancipated 
minor) that has the ability 
to understand the 
requirements of the study, 
provides written informed 
consent (including 
Rephrasing 
of 
consent/asse
nt inclusion 
criterion

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Section
Previous Wording
New Wording
Rationale
subject will comply with 
the study protocol 
procedures (including 
required study visits). 
consent for the use and 
disclosure of research-
related health 
information) that the 
subject will comply with 
the study protocol 
procedures (including 
required study visits).
Page 31 
Section 4.3 
Exclusion 
Criteria #2
A biologic investigational 
agent other than B-cell 
targeted therapy (e.g., 
abetimus sodium, anti 
CD40L antibody 
[BG9588/ IDEC 131]). 
(Investigational agent 
applies to any drug not 
approved for sale in the 
country in which it is being 
used.)
A biologic 
investigational agent
Text not 
considered 
necessary
Page 37 
Section 5.1 
Study Agent 
and Other 
Study 
Treatment
Subjects will be monitored 
during and after each 
infusion according to study 
sites’ guidelines or 
standard operating 
procedure for IV infusions.  
Subjects will be 
monitored during all 
infusions.  Subjects will 
remain under clinical 
supervision for 3 hours
after completion of the 
first 3 infusions
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. If  
symptoms of acute 
hypersensitivity occur, 
an extended period of 
monitoring may be 
appropriate, based on 
clinical judgment.
Trained personnel and 
rescue 
medications/equipment 
should be available during 
To help 
ensure that 
potential 
hypersensiti
vity 
reactions 
are 
promptly 
detected and 
treated, a
defined 
observation 
period has 
been added 
for all 
subjects 
after their 
first three 
infusions. In 
the studies 
of 
belimumab 
in adult 
subjects 
with SLE, 

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Section
Previous Wording
New Wording
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infusion visits. Sites are 
encouraged to follow their 
standard practices to 
manage any untoward 
infusion reactions noted 
during the infusion 
period. Subjects should 
be made aware of the 
potential risk, the signs 
and symptoms of such 
reactions, and the 
importance of 
immediately seeking 
medical attention.
hypersensiti
vity 
reactions 
were most 
likely to 
occur with 
the initial 
infusions.  
Page 45,  
Section 5.7.1 
Study 
Conclusion
No previous wording
The long term follow up 
portion of the study 
(Part B and Part C) is 
planned for a total of up 
to 10 years.  However, 
the study may conclude 
earlier if all subjects 
continuing belimumab 
treatment have received 
at least 5 years of 
treatment with 
belimumab and if there 
are 15 or fewer subjects 
continuing to receive 
belimumab in the study. 
Provide for 
earlier 
termination 
of the study 
if defined 
study 
criteria are 
met.
Pg 46, 
Section 6.0 
Study 
Assessments 
and 
Procedures; 
Pg 55,Critical 
Baseline and 
Screening 
Assessments; 
Pg 107, 
Appendix 5 
Clinical 
B cells
B-cell subsets: (CD20+, 
CD20+/27+ memory, 
CD20+/27– naïve, 
CD20+/69+ activated,  
CD20+/138+ 
plasmacytoid, 
CD19+/27BRIGHT/38B
RIGHT SLE subset and 
CD20-/138+ plasma 
cells).
The specific 
B cell
subsets to 
be 
investigated 
were 
previously 
omitted. 

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New Wording
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Laboratory 
Tests

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New Wording
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Page 47, 
Section 6.0  
Study 
Assessments 
and 
Procedures 
and Page 56 
Section 6.1 
Critical 
Screening 
and Baseline 
Assessments

Disease activity scales:

SELENA SLEDAI 
(See ‘Guidelines for 
Scoring Proteinuria’)

Confirm SLE disease 
is active, defined as 
SELENA SLEDAI 
score ≥ 8 at 
screening

Physician’s Global 
Assessment (PGA)

Parent Global 
Assessment 
(ParentGA)

SLE Flare Index

BILAG

Pediatric 
SLICC/ACR 
Damage Index

PRINTO/ACR 
Juvenile SLE 
Response 
EvaluationQuality of 
Life

PedsQL

PedsQL-Fatigue 

Disease activity 
scales:

SELENA SLEDAI 
(See ‘Guidelines for 
Scoring 
Proteinuria’)

Confirm SLE 
disease is active, 
defined as SELENA 
SLEDAI score ≥ 8 
at screening

Physician’s Global 
Assessment (PGA)

Parent Global 
Assessment 
(ParentGA)

SLE Flare Index

BILAG

Pediatric 
SLICC/ACR 
Damage Index

PRINTO/ACR 
Juvenile SLE 
Response 
Evaluation

Pediatric Quality 
of Life Inventory 
(PedsQL)

PedsQL-
Multidimensional 
Fatigue Scale  
Correction 
of typo to 
provide full 
name of 
assessments
.  

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New Wording
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Page 50 and 
54 , Section 
6.0 Table 2 
Study 
Assessments 
and 
Procedures 
Part A and 
Footnote 19
No previous wording
Functional antibodies at 
Day 0, Week 24 and 
Week 52.
Vaccine Antibody titer 
assessment
Previously 
omitted 
from Time 
and Event 
(T&E) table
Page 51, 
Table 2, 
Time and 
Events Table, 
Part B Open 
–Label 
Continuation, 
column 
header
8-Week Post Treatment
Follow up
+ 7 days 2
Exit Visit2 and 8-Week
Post Treatment 
Follow up 
+ 7 days 2
Previously 
omitted 
from T&E 
table
Page 52 , 
Section 6.0 
Table 2 Study 
Assessments 
and 
Procedures 
Part B
No mention of 
immunogenicity testing in 
Part B of the Time and 
Events table
Addition of 
immunogenicity testing
to the Time and Events 
table at every 6 months in 
Part B of the study
Previously 
omitted 
from T&E 
table
Page 53 , 
Section 6.0 
Table 2 Study 
Assessments 
and 
Procedures 
Footnotes 1, 
2, 3, and 10 
1.    The Exit (Day 364) 
visit will occur 
approximately 4 weeks 
after the last dose of study 
agent. For subjects 
completing all 48 weeks of 
treatment and continuing 
into the safety follow-up 
with belimumab  portion 
of the protocol (Part B) or 
safety follow up non-
belimumab (Part C) , this 
visit will also serve as their 
1st (i.e., Day 0) visit of the 
open label safety follow up 
of the study.
1. The Exit (Day 364) 
visit will occur 
approximately 4 weeks 
after the last dose of study 
agent. For subjects 
completing all 48 weeks 
of treatment and 
continuing into the safety 
follow-up with 
belimumab  portion of the 
protocol (Part B) or safety 
follow up non-belimumab 
(Part C) , this visit will 
also serve as their 1st (i.e., 
Day 0) visit of the open 
label safety follow up of 
the study. Only subjects 
who will continue in 
Update to 
existing text 
to clarify 
activities 
that are
footnoted

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2.    The 8-week follow-up 
visit is to occur 
approximately 8 weeks 
after last dose of study 
agent (belimumab in the 
case of the open label 
period).
3.    Unscheduled Visits: 
Other assessments as 
clinically indicated.
10.   Pharmacokinetic 
sampling: Before the start 
of infusion on Days 0, 
56/Week 8 and 364/Week 
52; 0-4 hours after the end 
of infusion on Days 
14/Week 2and 168/Week 
24; at any time during the 
visit during the 8 week 
follow-up visit. Details of 
the sampling schedule are 
included in Section 6.5, 
Table 4 of the protocol.  
Part B will have study 
drug administered at the 
Day 364/Week 52 visit 
after the completion of 
all Day 364/Week 52 
assessments.
2. Subjects stopping 
treatment in Part A or 
Part B will return in 4 
weeks from last dose for 
an Exit visit.  For 
subjects withdrawn 
from Part A or Part B of 
the study and who are 
not continuing into Part 
C, a follow-up visit will 
occur approximately 8 
weeks after last dose of 
study agent (belimumab in 
the case of the open label 
period).
3. Other assessments 
may be performed as 
clinically indicated.
10. Pharmacokinetic 
sampling: Before the start 
of infusion and 0-4 hours 
after the end of infusion 
on Days 0, 14/Week2, 
28/Week4, before the 
start of infusion on Days 
56/Week 8 and 364/Week 
52 (or at any time during 
visit if Day 364 visit is 
Exit visit); 0-4 hours after 
the end of infusion on Day 
168/Week 24; at any time 
during the visit during the 
8-week follow-up visit. 
Details of the sampling 
schedule are included 
Section 6.5, Table 4 of the 
protocol.  

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Page 54, 
Section 6.0 
Table 2 Study 
Assessments 
and 
Procedures 
Footnote 15, 
16, 17, 18, 19
15.  Serum immunoglobulin 
isotypes: IgG, IgM,     IgA.Must be 
completed prior to any study-related 
discussion with the investigator or 
study coordinator.
16.  Subjects ≥ 8 years of age will 
complete the PedsQL and PedsQL 
Fatigue directly. For subjects aged 
5-7 years, a parent/guardian will 
complete the Parent Report version 
of the PedsQL and PedsQL Fatigue 
on their child’s behalf.  Must be 
completed prior to any study-related 
discussion with the investigator or 
study coordinator.
17. Refer to Section 6.2.1.3 for 
guidelines for scoring proteinuria for 
SELENA SLEDAI and BILAG 
evaluation.
18. Study agent is to be 
administered to all randomized 
subjects for 48 weeks.  Subjects 
completing the double-blind period 
will continue in the open-label, long 
term continuation portion of the 
protocol for 10 years (dose on week 
52/Day 364 and this dose will be the 
1st dose in Part B.  Dosing 
information will be recorded in the 
continuation page of the e CRF
15. Serum immunoglobulin 
isotypes: IgG, IgM, IgA.
16.  Refer to Section 6.2.1.3 for 
guidelines for scoring 
proteinuria for SELENA SLEDAI 
and BILAG evaluation.
17. Subjects ≥ 8 years of age will 
complete the PedsQL and 
PedsQL Fatigue directly. For 
subjects aged 5-7 years, a 
parent/guardian will complete 
the Parent Report version of the 
PedsQL and PedsQL Fatigue on 
their child’s behalf.  Must be 
completed prior to any study-
related discussion with the 
investigator or study 
coordinator.
18.  Study agent is to be 
administered to all randomized 
subjects for 48 weeks in Part A.  
Subjects completing the double-
blind period (Part A) will 
continue in the open-label, long 
term continuation portion of the 
protocol for up to 10 years.  The 
Day 364/Week 52 visit of Part A 
will serve as the 1st visit of Part 
B. Only subjects who will 
continue in Part B will have 
study drug administered at the 
Day 364/Week 52 visit after the 
completion of all Day 364/Week 
52 assessments.
19. Blood sample for functional 
antibodies on all subjects.
Vaccine antibody titer test will 
be completed on subjects who 
receive a vaccine during the 
treatment period of this study. A 
blood sample to measure the 
pre-vaccination titer will be 
obtained during a study visit 
closest to the time prior to the 
planned vaccination. In cases 
where blood may not be drawn 
immediately before vaccination, 
the baseline (Day 0) blood 
sample will be used as a 
reference for pre-vaccination 
titer. A post-vaccine titer will be 
drawn on the next study visit if it 
Addition of 
footnotes 
and edits to 
detail 
information 
regarding  
procedures 
and allowed 
sequential 
numbering. 

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New Wording
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has been at least 21 to 60 days 
post-immunization.
Page 54, 
Section 6.1 
Critical 
Screening 
and Baseline 
Assessments 
6.1  Critical Baseline 
Assessments
Screening and 
Randomization 
assessments at Visit 1 
(Week -5/Day -35) or Visit 
2 (Week 0/Day 0) will 
comprise the following:
6.1  Critical Screening 
and Baseline Assessments
Screening assessments at 
Visit 1 (Week -5/Day -
35) or Randomization 
assessments at Visit 2 
(Week 0/Day 0) as 
detailed in Table 2 will 
comprise the following:
Provide 
additional 
detail and 
listing of 
assessments 
performed 
at Screening 
and 
Baseline 
Randomizat
ion visits
Page 56, 
Section 
6.2.1.2 
Laboratory 
Tests for 
SALENA 
SLEDAI and 
BILAG 
Therefore, GFR estimated 
by the Schwartz formula 
will be used in the BILAG 
disease activity index.  
Schwartz Formula 
[Schwartz, 2009]
GFR(ml/min per 1.73 
m2) = 39.1[height (m)/Scr 
(mg/dl)] 0.516
X 
[1.8/cystatin C 
(mg/L)]0.294[30/BUN 
(mg/dl)]0.169[1.099]male[height(m
)/1.4]0.188
Therefore, GFR estimated 
by the Schwartz formula 
or Cockroft-Gault 
formula will be used in 
the BILAG disease 
activity index.  The 
procedure for 
calculation of GFR using 
the Schwartz formula or 
Cockroft-Gault formula 
will be provided in the 
Study Procedure 
Manual.  The age 
appropriate formula 
should be used. 
Cystatin C 
used in the 
Schwartz 
formula 
may not be 
available at 
all sites.  
After 
puberty the 
Cockroft-
Gault 
formula is 
the age 
appropriate 
formula to 
use. Details 
for 
calculation 
of GFR will 
be provided 
in the study 
procedures 
manual.
Page 72, 
Section 
6.3.14 
Infusion-
related 
Reactions 
and 
Infusion-related reactions 
(selected events, including 
hypersensitivity reactions 
occurring during or on the 
same day as an infusion) 
occurred in approximately 
17% of subjects treated 
In the controlled clinical 
trials, adverse events 
associated with the 
infusion (occurring on 
the same day of the 
infusion) were reported 
in 17% (253/1,458) of 
Update 
safety 
information 
per current 
Investigator 
Brochure 
pertaining 

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Hypersensitiv
ity Reactions
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 subjects). These events 
have included reports of 
rash, urticaria, 
angioedema, hypotension, 
bradycardia, dyspnea, and 
anaphylactic reaction. 
Infusion reactions occurred 
more frequently on the 
first two infusion days and 
tended to decrease with 
subsequent 
infusions. Investigators 
are instructed to assume a 
heightened awareness 
when screening subjects 
with a history of adverse 
reactions to IV contrast 
agents, other IV foreign 
proteins or other 
monoclonal antibodies; 
subjects with anaphylaxis 
to this family of agents 
should be excluded from 
enrolment in the study. 
subjects receiving 
belimumab and 15% 
(99/675) of subjects 
receiving placebo.  
Hypersensitivity 
reactions, including 
anaphylaxis and death, 
have been reported in 
association with 
belimumab. Delay in the 
onset of acute 
hypersensitivity 
reactions has been 
observed. Limited data 
suggest that subjects 
with a history of 
multiple drug allergies 
or significant 
hypersensitivity may be 
at increased 
risk. Investigators are 
instructed to assume a 
heightened awareness 
when screening subjects 
with a history of adverse 
reactions to IV contrast 
agents, other IV foreign 
proteins or other 
monoclonal antibodies; 
subjects with anaphylaxis 
to this family of agents 
should be excluded from 
enrolment in the study. 
Subjects will remain 
under clinical 
supervision for 3 hours 
after completion of the 
first 3 infusions.  If 
symptoms of acute 
hypersensitivity occur, 
an extended period of 
monitoring may be 
to 
hypersensiti
vity reaction 
and to 
update 
existing 
language 
regarding 
site 
monitoring 
for potential 
infusion 
related 
hypersensiti
vity 
reactions.

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New Wording
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appropriate, based on 
clinical judgment.
Subjects and 
parents/legal guardian 
should be made aware of 
the potential risk, the 
signs and symptoms of 
such reactions, and the 
importance of 
immediately seeking 
medical attention.
Page 73, 
Section 
6.3.16 Vital 
Signs, Height 
and Weight
Vital signs, height and 
weight will be collected 
every 4 weeks for subject 
participating in the open 
label continuation portion 
of the study (Part B) and 
annually for those 
participating in the 10 year 
post infusion portion of the 
study (Part C).
Vital signs, height and 
weight will be collected at 
each visit prior to dosing
for subject participating in 
the open label 
continuation portion of the 
study (Part B) and 
annually for those 
participating in the 10 
year post infusion portion 
of the study (Part C).
Clarify that 
assessments 
listed 
should be 
performed 
prior to 
dosing
Page 75, 
Section 6.4.2 
Pediatric 
Quality of 
Life 
Multidimensi
onal Fatigue 
Scale
The PedsQL Fatigue 
measurements will be 
assessed at screening and 
prior to dosing at Day 0, 
Weeks 12, 24, 36, and 
48/or Exit and every 6 
month in the open-label 
safety (Part B) and every 
year in the safety follow up 
non-belimumab phase
(Part C).
The PedsQL Fatigue 
measurements will be 
assessed at screening and 
prior to dosing at Day 0, 
Weeks 4, 8, 12, 24, 36, 
and 52/or Exit and every 6 
month in the open-label 
safety (Part B) and every 
year in the safety follow 
up non-belimumab phase
(Part C).
Addition of 
fatigue 
assessments 
at earlier 
timepoints.  
Change 
assessment 
to Week 52 
to align 
with 
timeframe 
of the 
primary 
endpoint.
Page 76,  
Section 6.5 
Pharmacokin
etics Table 4 
Day 0 
Before the start of infusion
Day 14 (Week 2)
0 - 4 hours after the end of 
Day 0 - Before the start of 
infusion and 0-4 hours 
after the end of infusion
Additional 
PK samples 
to be drawn 
as indicated.

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New Wording
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PK visit days 
and sample 
times for 
children not 
among the 
first 12 of the 
two age 
groups 
infusion
No previous wording for 
Day 28
Day 14 (Week 2) -  
Before the start of 
infusion and 0 - 4 hours 
after the end of infusion
Day 28 (Week 4) -
Before the start of 
infusion and 0-4 hours 
after the end of infusion
Page 77, 
Section 6.5 
Pharmacokin
etics
The total, maximum, 
amount of blood drawn for 
PK during this study is 
approximately 9.5 mL for 
children in the open label 
PK and 3 mL for all other 
children. 
The total, maximum, 
amount of blood drawn 
for PK during this study is 
approximately 9.5 mL for 
children in Cohorts 1 and 
2 and 5 mL for all other 
children. 
Correction 
to 
description 
of  cohort 
and volume 
of blood to 
be collected 
for PK 
analysis
Page 86, 
Section 
8.3.5.2.2 ; 
Proportion of 
Subjects with 
a Sustained 
ParentGA 
Response
Proportion of subjects with 
a sustained ParentGA 
response (defined as 
having >0.7 improvement 
at Weeks 44, 48, and 52 
compared at baseline)   
The proportion of subjects 
with a sustained ParentGA 
response will be analyzed 
in the same manner as the 
proportion of subjects with 
a sustained SRI response.  
An improvement of 0.7 
corresponds to the 
minimally clinically 
important difference 
(MCID) for the instrument 
using the physician 
external rating. [Filocamo , 
2010]  The LOCF method 
will be used for handling 
missing data.
Proportion of subjects 
with a sustained ParentGA 
response (defined as 
having >0.7 improvement 
at Weeks 44, 48, and 52 
compared at baseline)   
The proportion of subjects 
with a sustained ParentGA 
response will be analyzed 
in the same manner as the 
proportion of subjects 
with a sustained SRI 
response.  An 
improvement of 0.7 
corresponds to the 
minimally clinically
important difference 
(MCID) for the instrument 
using the physician 
external rating. [Filocamo, 
2010]  
Deletion of 
last 
sentence 
regarding 
LOCF 
method to 
avoid 
confusion 
with other 
sections 
explaining 
methodolog
y.
Page 88, 
Section 
8.3.5.4  
A pharmacokinetic (PK) 
sample will be drawn on 
Days 0, 14 (Week 2), 56 
(Week 8), 168 (Week 24), 
A pharmacokinetic (PK) 
sample will be drawn on 
Days 0, 14 (Week 2), 28 
(Week 4), 56 (Week 8), 
Additional 
PK sample 
to be drawn.

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Pharmacokin
etics
364 (Week 52), and at the 
8-week follow-up visit (if 
applicable).  
168 (Week 24), 364 
(Week 52), and at the 8-
week follow-up visit (if 
applicable).  
Page 89, 
Section 9.2  
Regulatory 
and Ethical 
Consideration
s, Including 
the Informed 
Consent 
Process
Written informed consent 
must be obtained from 
each subject prior to 
participation in the study.  
Subjects will be re-
consented whenever new 
information becomes 
available that may affect 
their willingness to 
participate in the trial.
Written informed consent 
must be obtained from 
each subject’s parent(s) 
or legal guardian prior to
the subject’s participation 
in the study.  The 
subject’s parent(s) or 
legal guardian will be re-
consented whenever new 
information becomes 
available that may affect 
their willingness for their 
child to continue to 
participate in the trial.  
Assent will be obtained 
from each pediatric 
subject in accordance 
with applicable country 
or IRB/Ethics 
Committee regulations.  
Written informed 
consent will be obtained 
from subjects turning 18 
years of age to continue 
participation in the 
study.  
Additional 
language to 
clarify the 
person(s) 
providing  
consent and 
that 
informed 
consent will 
be obtained 
for pediatric 
subjects 
turning 18 
years of age
Page 90, 
Section 9.5 
Study and 
Site Closure
Completion of study will 
be defined as all subjects 
either completed the safety 
follow-up visits after their 
initial dose and have been 
entered into the pediatric 
registry.
No new wording
Sentence 
deleted as it 
contradicts 
study 
conclusion 
section. 

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11.17.
Appendix 17: Country Specific Protocol Amendment 02 
Changes
Country specific changes in Protocol Amendment 02 apply to Investigator sites in 
the Russian Federation.
Summary of Country Specific Changes and Rationale
Section
Previous Wording
New Wording
Rationale
Page 107; 
Appendix 2: 
Country 
Specific 
Requirements
Appendix 2:  No 
previous wording
4.
At sites in the 
Russian Federation, only 
subjects 12 years of age 
will be eligible to 
participate. 
5.
Appendix 2: 
Country Specific 
Requirements:  
Study Inclusion Criterion 
specific for sites in the 
Russian Federation:
Subjects eligible for 
enrolment in the study must 
be 12 years of age to 
participate.
Country specific 
protocol 
amendment. The 
Ministry of Health 
Care of the Russian 
Federation will 
permit only subjects 
12 years of age to 
participate in the 
study. 

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11.18.
Appendix 18: Protocol Amendment 02 Changes
Protocol Amendment 02 changes apply to all countries and all sites.
Summary of Changes and Rationale
A detailed description of substantive changes to the protocol are listed below.  
Additional administrative and minor editorial changes have also been made.  
Changes to assessment frequencies described in the text have also been updated in 
the time and events table.
Section
Previous Wording
New Wording
Rationale
Page 16, 27 
Study 
Design; 
Part C and 
Page 53, 
Time & 
Event 
footnote 
No previous wording 
regarding exit visit for 
subjects who withdraw 
from the study 
completely in Part C.
An Exit Visit may be 
conducted by phone for 
any subject who 
withdraws completely 
from the study while in 
Part C.
Clarify procedure 
for Exit Visit if 
subject withdraws 
completely from 
study while in 
Part C.
Pg 31, 
Exclusion 
Criteria #1 
and 2
6.
1. Have 
received treatment with 
any B-cell targeted 
therapy (e.g., 
rituximab, other anti-
CD20 agents, anti-
CD22 [epratuzumab], 
anti-CD52 
[alemtuzumab], BLyS-
receptor fusion protein 
[BR3], TACI-Fc, or 
belimumab) at any 
time.
7.
2. Have received 
any of the 
following within 
364 days of Day 0:

Abatacept.

A biologic 
investigational 
agent 
8.
1.Have received 
treatment with
belimumab
(BENLYSTA) at any 
time
9.
2.  Have received 
any of the following 
within 364 days of 
Day 0:

Treatment with 
any B-cell 
targeted therapy 
(e.g., rituximab, 
other anti-CD20 
agents, anti-
CD22 
[epratuzumab],
anti-CD52 
[alemtuzumab], 
BLyS-receptor 
fusion protein 
[BR3], 
TACI-Fc)
B cell targeted 
therapy within 1 
year of study is 
permitted in adult 
belimumab trials 
as there is no 
residual effect on 
B cell after one 
year of targeted 
therapy.  This 
change may allow 
more subjects to 
be considered for 
enrolment.    

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
Abatacept.
A biologic investigational 
agent 
Pg 34, 
Exclusion 
criterion 
#23
23. Hepatitis C: 
Positive test for 
Hepatitis C antibody 
confirmed on the same 
sample with a Hepatitis 
C RIBA  immunoblot 
assay. Subjects who 
are positive for 
Hepatitis C antibody 
and negative when the 
Hepatitis C RIBA 
immunoblot assay is 
performed on the same 
sample will be eligible 
to participate.  Subjects 
who are positive for 
Hepatitis C antibody 
and have a positive or 
indeterminate result 
when the Hepatitis C 
RIBA immunoblot 
assay is performed on 
the same sample will 
not be eligible to 
participate.
10.
23. Hepatitis C: 
Positive test for Hepatitis
C antibody confirmed on 
an additional blood 
sample by RNA PCR 
assay.  Subjects who are 
positive for Hepatitis C 
antibody and negative 
when the Hepatitis C 
RNA-PCR assay is 
performed on an
additional sample will be 
eligible to participate. 
Subjects who are positive 
for Hepatitis C antibody 
and have a positive result 
for the HCV when the 
Hepatitis C RNA PCR 
assay is performed on the 
additional sample will 
not be eligible to 
participate. (Institution or 
country specific 
guidelines for blood 
sample volume limits 
must be followed in 
collection of the 
additional blood sample.)
Quest Diagnostic 
Laboratories have 
informed us that 
the reagent to 
perform the 
confirmatory 
RIBA 
immunoblot assay 
is no longer 
available.  A 
confirmatory 
PCR-RNA assay 
is available but 
will require 
collection of an 
additional 10ml of 
serum which may 
be a restrictive 
amount to add at 
the screening visit 
for this pediatric 
population.  
Page 36, 
Section 5.1. 
Study 
Agent and 
Other Study 
Treatment
The calculated dose of 
study agent to be 
administered to the 
subject is determined 
in milligrams (mg) by 
the assigned treatment 
group and the subject's 
body weight in 
kilograms (kg) at each 
visit to calculate the 
The calculated dose of 
study agent to be 
administered to the 
subject is determined in 
milligrams (mg) by the 
assigned treatment group 
and the subject's body 
weight in kilograms (kg) 
at each visit.  The study 
agent should be delivered 
to all subjects in 250 mL 
of saline solution. 
To allow study 
agent to be 
administered in 
less volume for 
subjects who 
weigh ≤40 kg of 
weight.

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New Wording
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dose of study agent 
administered.
Alternatively, infusion 
bags with 100 mL saline 
solution may be 
considered providing that 
the resulting belimumab 
concentration in the 
infusion bag does not 
exceed 4 mg/mL. When 
the study agent is 
administered at a dose of 
10 mg/kg, to maintain a 
belimumab concentration 
of 4mg/mL or less, use of 
the 100 mL bag may only 
be considered for the 
subjects whose body 
weight is <=40 kg. This 
weight threshold may 
change as a result of any 
changes in the dose level 
of the study agent 
determined by the 
evaluation of PK data.
The reconstituted 
belimumab will be 
diluted in 250 mL or 100 
mL normal saline for IV 
infusion.  An amount of 
normal saline, equal to 
the calculated amount of 
product to be added, 
should be removed from 
the 250 mL or 100 mL 
infusion bag prior to 
adding the product.  After 
adding the reconstituted 
product, gently invert the 
bag to mix the solution.  
The prepared study agent 
should be infused over 1 
hour. 

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New Wording
Rationale
Placebo will be 250 mL 
or 100 mL normal saline 
for IV infusion.  
Pg 37, 
Section 5.1 
and Pg 72, 
Section 
6.3.14 
Subjects will remain 
under clinical 
supervision for 3 hours 
after completion of the 
first 3 infusions 
according to study 
sites’ guidelines or 
standard operating 
procedure for IV 
infusions.  
Subjects will remain 
under clinical supervision 
for 3 hours after 
completion of the first 3 
infusions in Part A and 
for 3 hours after 
completion of the first 3 
infusions in Part B the 
open label portion of the 
study according to study 
sites’ guidelines or 
standard operating
procedure for IV 
infusions.  
Subjects entering 
Part B open label 
extension will still 
be blinded to 
previous treatment 
and for previous 
placebo subjects 
this would be the 
first 
administration of 
belimumab and 
thus should be 
observed post 
infusion for 
potential 
hypersensitivity.
Pg 63, 
Section 
6.3.3. 
Independent 
Data 
Monitoring 
Committee
No previous wording
If recruitment of subjects 
to Cohort 2 is slower than 
expected, the sponsor and 
the IDMC may decide to 
initiate an early PK 
analysis and safety 
review at 6 months from 
the first subject’s first 
dose in Cohort 2 based 
on the Safety and PK 
data accrued up to this 
point from Cohorts 1 and 
2. If the PK data analyzed 
is deemed sufficient, the 
sponsor and IDMC may 
recommend a dose 
adjustment for Cohort 2 
subjects from the early 
PK review. After any 
early PK review the 
sponsor and IDMC may 
re-review PK and safety 
and possibly recommend 
a dose adjustment when 
PK data for all 12 
To ensure 
continued safety 
monitoring and 
PK assessment of 
enrolled Cohort 2 
subjects if the full 
recruitment is 
delayed.

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Section
Previous Wording
New Wording
Rationale
subjects is available.  
Additionally, the sponsor 
and IDMC may decide 
that no additional PK 
review and dose 
adjustment is necessary if 
the data from the early 
PK review is deemed 
sufficient to support a 
finalized PK review.
Pg 72;  
Section 
6.3.13 
Laboratory 
Evaluations
No previous wording
Blood sample collection
The largest volume of 
blood drawn from a 
subject occurs at the 
screening visit and the 
randomization visit (Day 
0).  The amount of blood 
collected at the screening 
visit and randomization 
visit (Day 0) may exceed 
the acceptable volume 
per country or institution 
specific for the pediatric 
population in this study.  
Therefore, the volume of 
blood to be collected 
should be monitored and 
blood samples may be 
drawn in separate visits 
within 1 week but prior 
to the scheduled study 
drug infusion.  
Alternatively, the blood 
draw for CRP and other 
biomarkers may be 
omitted at the baseline 
visit.  It will be 
permissible to use the 
values for these 
laboratory parameters 
from the screening visit 
samples. 
To allow separate 
visits for blood 
collection 
procedure in order 
to comply with 
country specific or 
site specific 
guidance 
regarding blood 
volume collection.  

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Minor Edits for Protocol Amendment 2
P16, P27,Pg 
65 IDMC, 
… comprised of at 
least 4 physicians …
The IDMC comprises of 
5 members: 2 experts in 
paediatric rheumatology, 
1 in paediatric 
pharmacology, 1 in 
paediatric ethics and a 
statistician
The pharmacology 
expert and the 
statistician are not 
physicians. 
Pg 17, 
Study 
Endpoints / 
Assessments 
for Part A
The primary efficacy 
endpoint is response 
rate at Week 52 which 
is defined as: 
The primary efficacy 
endpoint is SLE 
Responder Index (SRI) 
response rate at Week 52 
which is defined as...
To provide clarity 
on the composite 
endpoint and 
make it consistent 
with the protocols 
and documents of 
other studies, and 
Benlysta 
publications 
Pg 43; Con 
meds
Sirolimus 2mg/kg/day
Sirolimus 2mg/day
Incorrect 
maximum dose
Pg 44; 
Prohibited 
medications
Finally, for Part C, the 
open label non-
belimumab portion of 
the study, there are no 
restrictions on 
prohibited medication 
use.
Finally, for Part C, the 
non-belimumab portion 
of the study, there are no 
restrictions on prohibited 
medication use.
Error in 
description of Part 
C. 
Pg 73; 
Section 
6.3.16 Vital 
Signs, 
Height and 
Weight
Systolic and diastolic 
blood pressure 
(sitting), heart rate, 
and oral temperature 
will be measured.
Systolic and diastolic 
blood pressure (sitting), 
heart rate, and body 
temperature will be 
measured.
Allow the method 
for the collection 
of temperature by 
either oral or ear 
thermometer as 
per site specific 
standard of care 
guidance. 
T&E table
Missing “X” to 
indicate assessment to 
be done
“X” added to the T&E 
table at the following 
assessment and visit:
Part A - PedsQL at 
Screening visit
Part B - Symptom Driven 
Physical Examination at 
Omitted in error

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the Exit Visit; IVRS in 
additional Assessments 
Every 6 Months 
Part C -
Immunoglobulins 
assessment Every Year
Time & 
Event table; 
Sect 6.1 
Screening 
and 
Baseline 
Assessments
No previous wording 
for CRP
CSSRS
Add CRP to T&E table.  
Add CSSRS assessment 
for  “≥12 years of age”
Omitted in error
Pg 53, Table 
2, Time & 
Event table; 
footnote #4
4. Vital signs include 
temperature, sitting 
blood pressure, 
respiratory rate and 
pulse.  
Remove “respiratory 
rate” from T&E footnote 
#4.
Vital signs include 
temperature, sitting blood 
pressure, and pulse.  
Respiratory rate 
was included in 
error
Appendix 
11- SLICC
Estimated or measured 
glomerular filtration 
rate >50%
Estimated or measured 
glomerular filtration rate 
less than 50% (<50%)
Correct typo

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11.19.
Appendix 19: Protocol Amendment 03 - Summary of 
Changes
Protocol Amendment 03 applies to all countries and sites.
A detailed description of substantive changes to the protocol are listed below.  Additional 
administrative and minor editorial changes have also been made.  
Section
Previous Wording
New Wording
Rationale
Page 37, Exclusion 
Criteria #5 
Exclusion Criteria:
5.  Have received 
any of the following 
within 90 days of 
Day 0:
•  Anti-TNF therapy 
(e.g., adalimumab, 
etanercept, 
infliximab).
•  Interleukin-1 
receptor antagonist 
(anakinra).
•  Intravenous 
immunoglobulin 
(IVIG).
•  High dose 
prednisone 
(> 1.5 mg/kg/day) 
or equivalent.
•  Plasmapheresis.
Exclusion criterion 
#5 includes:
Have received any 
of the following 
within 90 days of 
Day 0:
•  Anti-TNF therapy 
(e.g., adalimumab, 
etanercept, 
infliximab).
•  Interleukin-1 
receptor antagonist 
(anakinra).
•  Intravenous 
immunoglobulin 
(IVIG).
•  Plasmapheresis.
To increase 
enrolment 
eligibility.  The 
change to the 
exclusion of high 
dose IV 
corticosteroid 
within 90 days of 
baseline (Day0) 
to within 60 days 
of baseline (see 
below exclusion 
#6) may allow 
increased 
enrolment and 
subject 
eligibility. 
Page 37, Exclusion 
Criteria #6 
6.  Have received 
any of the following 
within 60 days of 
Day 0:
•  A non-biologic 
investigational 
agent. 
•  Any new 
immunosuppressive 
immunomodulatory 
agent, anti-malarial, 
NSAID, (See 
Inclusion Criteria 
#5)
Note: New inhaled 
steroids and new 
topical 
6.  Have received 
any of the following 
within 60 days of 
Day 0:
•  A non-biologic 
investigational agent. 
•  Any new 
immunosuppressive 
immunomodulatory 
agent, anti-malarial, 
NSAID, (See 
Inclusion Criteria #5)
Note: New inhaled 
steroids and new 
topical 
immunosuppressive 
agents (e.g., eye 
The change to 
the exclusion of 
high dose IV 
corticosteroid 
within 90 days of 
baseline (Day0) 
to within 60 days 
of baseline may 
allow increased 
enrolment and 
subject eligibility 

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Section
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New Wording
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immunosuppressive 
agents (e.g., eye 
drops, topical 
creams) are 
allowed. Any 
NSAID use for 1 
week is allowed.
•  Any steroid 
injection 
(intramuscular, 
intraarticular or 
intravenous).
drops, topical creams) 
are allowed. Any 
NSAID use for 1 
week is allowed.
•  High dose 
prednisone (> 1.5 
mg/kg/day) or 
equivalent or any 
steroid injection 
(IM, IA, IV)
Page 35-36, 
Section 4.4
Withdrawal Criteria
4.4.
Withdrawal 
Criteria
Subjects may be 
withdrawn from 
study agent or from 
the study if at any 
time (i.e., during the 
double-blind):
•   It is the wish of 
the subject (or their 
legally acceptable 
representative) for 
any reason.
•   The investigator 
judges it necessary 
due to medical 
reasons
Furthermore, 
subjects will be 
withdrawn from 
study agent and 
transitioned to Part 
C, the long term 
safety follow-up, if 
at any time:
•   Subject becomes 
pregnant.
•   Receives 
4.4.   Withdrawal 
Criteria
Subjects may be 
withdrawn from 
study agent or from 
the study if at any 
time:
•   It is the wish of the 
subject (or their 
legally acceptable 
representative) for 
any reason.
•   The investigator 
judges it necessary 
due to medical 
reasons
Furthermore, subjects 
will be withdrawn 
from study agent and 
transitioned to Part C, 
the long term safety 
follow-up, if at any 
time:
•   Subject becomes 
pregnant.
•   In Part A or Part 
B, receives 
prohibited therapy 
(See Section 5.6.2) 
•   In Part A are 
Clarify the 
withdrawal 
criteria 
specifically for 
Part A and Part 
B of the 
protocol.  
Additionally, to 
provide 
clarification of a 
protocol 
violation 
rendering a 
subject as a 
treatment failure, 
subsequent 
withdrawal of 
investigational 
product and 
transfer to Part C 
of the study.  

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Section
Previous Wording
New Wording
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prohibited therapy 
(See Section 5.6.2) 
or are deemed a 
treatment failure.
•   Experiences 
unacceptable 
toxicity
•   Misses 3 or more 
consecutive study 
agent infusions
•   Participates in 
another 
interventional trial.
deemed a treatment 
failure (see Section 
5.6.1) 
•   Experiences 
unacceptable toxicity
•   Misses 3 or more 
consecutive study 
agent infusions
•   Participates in 
another interventional 
trial.
Page 40, Section 
5.6.1
Permitted 
Medication and 
Non-drug Therapies
Once the subject is 
randomized and 
receives the first 
dose of study agent 
on Day 0, the 
investigator may 
adjust concurrent 
medications (add, 
eliminate, change 
dose 
level/frequency) as 
clinically required; 
however, changes 
in certain 
medications (as 
outlined below) 
may result in the 
subject being 
defined as a 
treatment failure 
and will require 
withdrawal from 
Part A of the study 
and transition to 
Part C.
Once the subject is 
randomized and 
receives the first dose 
of study agent on Day 
0, the investigator 
may adjust 
concurrent 
medications (add, 
eliminate, change 
dose level/frequency) 
as clinically required; 
however, in Part A
changes in certain
medications (as 
outlined below) may 
result in the subject 
being defined as a 
treatment failure and 
will require 
withdrawal from Part 
A of the study and 
transition to Part C.
To provide 
clarity

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Section
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New Wording
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Page 45, 
Section 5.6.2. 
Prohibited 
Medications and 
Non-Drug Therapies
5.6.2. Prohibited 
Medications and 
Non-Drug 
Therapies
Subjects who start 
prohibited 
medications or 
therapies at any 
time during Part A, 
the double blind 
placebo controlled 
portion of the study, 
or Part B the 
belimumab open 
label safety follow 
up will be 
considered 
nonresponders for 
primary efficacy 
analysis and must 
have study agent 
discontinued and 
placed into Part C 
the non-belimumab 
safety follow up.  
5.6.2. Prohibited 
Medications and 
Non-Drug Therapies
Subjects who start 
prohibited 
medications or 
therapies at any time 
during Part A, the 
double blind placebo 
controlled portion of 
the study will be 
considered treatment 
failure, 
nonresponders for 
primary efficacy 
analysis and must 
have study agent 
discontinued and 
placed into Part C the 
non-belimumab 
safety follow-up. 
In Part B the 
belimumab open 
label safety follow-
up, subjects who 
start prohibited 
medications or 
therapies will be 
considered a 
protocol violation 
and will have study 
treatment 
(belimumab) 
discontinued.  These 
subjects will be 
placed into Part C 
the non-belimumab 
safety follow-up 
period.
Clarify the 
prohibited 
medications and 
consequence 
during specific 
parts of the 
study, i.e. Part A
Page 80 
Section 6.3.15 
Progressive 
Multifocal 
Leukoencephalopat
y
Progressive 
multifocal 
leukoencephalopath
y (PML) resulting in 
neurological deficits, 
To provide 
update to safety 
information.

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Section
Previous Wording
New Wording
Rationale
There have been no 
reported cases of 
PML in subjects 
with SLE or RA 
treated with 
belimumab.  
However, subjects 
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 
judgment in further 
workup and clinical 
intervention as 
appropriate.  If 
PML is suspected, 
this should be 
promptly reported 
to the sponsor.
including fatal cases, 
has been reported in 
SLE subjects 
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
Page 80
Section 6.3.14
No previous 
wording
•Delayed-type 
allergic reactions:  
Delayed-type, non-
acute 
To provide 
update to safety 
information.

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Section
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New Wording
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hypersensitivity 
reactions have also 
been observed and 
included symptoms 
such as rash, 
nausea, fatigue, 
myalgia, headache, 
and facial edema.
Page 41, paragraph 
4: Section 5.1  
Study Agent and 
Other Study 
Treatment
All used product 
vials should be
destroyed according 
to site guidelines 
for the destruction 
of study agents, 
after the monitor 
has conducted a 
check of the 
product 
accountability log 
during the study.  
At the end of the 
study, unused 
product vials will 
be destroyed on site 
at the study 
closeout visit, after 
the monitor has 
conducted final 
product 
accountability and 
given the site 
approval to destroy 
all remaining 
supplies.
All used product vials 
should be destroyed 
locally according to 
local site regulations
for the destruction of 
study agents, after the 
monitor has 
conducted a check of 
the product 
accountability log 
during the study.  At 
the end of the study, 
unused product vials 
will be returned to 
GSK or destroyed on 
site according to 
local regulations at 
the study closeout 
visit, after the 
monitor has 
conducted final 
product 
accountability and 
given the site 
approval to destroy 
or return all 
remaining supplies.
Clarification of 
study close out 
procedure for 
destruction of 
investigational 
product
Page 53-60 Time 
and Events table  
and footnotes:
Pregnancy Testing
No previous column 
and wording for 16 
week follow-up 
visit phone call.
16 Week follow up 
visit 20
#20 A home 
pregnancy test will 
be provided to all 
female subjects of 
child bearing 
potential. These
Previously 
omitted.  Added 
to clarify 
procedure at 16 
week post dose 
follow up phone 
call to subject to 
verify pregnancy 
status post dose.  

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Section
Previous Wording
New Wording
Rationale
subjects will be 
contacted by phone 
approximately 16 
weeks after the last 
dose of belimumab 
to obtain the results 
of the test. 
AEs/SAEs will not 
be actively solicited, 
but SAE(s) reported 
by the subject 
during this call will 
be reported to the 
Drug Safety
designee on the SAE 
worksheet.
This addition 
provides 
compliance with 
GSK policy.
Page 53 Time and 
Events Table 2
Part B and Part C 
Part B
Assessment Every 4 
weeks ± 3 days
Part B: Assessment 
Every  4 weeks ±7 
days
Part C: Assessment 
Every 4 weeks ±7 
days for the First 3 
Months
Extended visit 
window in long 
term extension 
phases to ease 
subject visit 
schedule 
Time & Event table 
2; footnote #10; 
page 59.
10.Pharmacokinetic 
sampling: Before 
the start of infusion 
and 0-4 hours after 
the end of infusion 
on Days 0, 
14/Week2, 
28/Week4, before 
the start of infusion 
on Days 56/Week 8 
and 364/Week 52 
(or at any time 
during visit if Day 
364 visit is Exit 
visit); 0-4 hours 
after the end of 
infusion on Day 
168/Week 24; at 
any time during the 
visit during the 8 
week follow-up 
Pharmacokinetic 
sampling: 
Cohort 1 and Cohort 
2: Days 0, 14/Wk2, 
28/Wk4 - Before the 
start of infusion, 5 
minutes and 2 hours 
after the end of 
infusion on; Days 2, 
7, 16, 21 - Anytime 
during visit; Day 
168/wk24 - 0-4 hours 
after the end of 
infusion; Day 
364/Wk52 and 8 
week follow-up visit -
Any time during visit 
before start of 
infusion (if 
applicable). 
Correction of 
discrepancy 
between T&E 
table footnote 
and Section 6.5 
Table 3 and 
Table 4 
Pharmacokinetic
s sampling 
schedule.

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Section
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New Wording
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visit. Details of the 
sampling schedule 
are included in 
Section 6.5, Table 4 
of the protocol.
Cohort 3 PK sample 
schedule: Day 0, 14, 
28 – Before the start 
of infusion and 0-4 
hrs after the end of 
infusion; Day 56 –
Before the start of 
infusion; Day 
168/wk24 – 0-4 hrs 
after the end of 
infusion; Day 
364/wk52 and 8 week 
follow-up visit – any 
time during visit 
before start of 
infusion (if 
applicable).
Typos/CorrectionsP
g 82, Section 6.4.2 
PedsQL Fatigue
The PedsQL 
Fatigue 
measurements will 
be assessed at 
screening and prior 
to dosing at Day 0, 
Weeks 4, 8, 12, 24, 
36, and 52/or Exit 
and every 6 month 
in the open-label 
safety (Part B) and 
every year in the 
safety follow up 
non-belimumab 
phase (Part C).
The PedsQL Fatigue 
measurements will be 
assessed at screening 
and prior to dosing at 
Day 0, Weeks 4, 8, 
12, 20,24, 36, and 
52/or Exit and every 
6 month in the open-
label safety (Part B) 
and every year in the 
safety follow up non-
belimumab phase 
(Part C).
Week 20 
assessment 
omitted in error.
Typos/Correction
Page 78
Section 6.6 to 
Section 6.8
6.6  
Pharmacodynamics
6.7  Biomarkers
6.7.1  Test for 
Functional 
Antibodies
6.7.2  Vaccine 
Response
6.8  
Pharmacogenetics
6.6  
Pharmacodynamics
   6.6.1  Biomarkers
   6.6.2  Test for 
Functional 
Antibodies
   6.6.3  Vaccine 
Response
6.7  
Pharmacogenetics
Formatting error 
effecting 
paragraph 
numbering. 

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11.20.
Appendix 20: Protocol Amendment 04 - Summary of 
Changes
Protocol Amendment 04 applies to all countries and sites.
A detailed description of substantive changes to the protocol are listed below.  Additional 
administrative and minor editorial changes have also been made.  
Section
Previous Wording
New Wording
Rationale
Pg 14, 15: 
Protocol 
Summary, 
Study Design 
Pg 26 
Section 3.1 
Study Design 
Part A
Pg 30 
Section 4.2
Inclusion 
Crtieria
Page 50, 61 
Section 6.0 
Study 
Assessments 
and 
Procedures
Inclusion Criteria Section 
4.2
3. Have active SLE disease 
defined as a SELENA 
SLEDAI score ≥ 8 at 
screening.
Confirm SLE disease is 
active, defined as SELENA 
SLEDAI score ≥ 8 at 
screening
Inclusion Criteria Section 
4.2
3. Have active SLE disease 
defined as a SELENA 
SLEDAI score ≥ 6 at
screening
Confirm SLE disease is 
active, defined as SELENA 
SLEDAI score ≥ 6 at 
screening
There are several 
places 
throughout the 
protocol that 
reflect the change 
to SELENA 
SLEDAI score at 
screening visit.  
Lowering the 
SELENA 
SLEDAI (SS) 
disease activity 
score at 
screening was 
done in order to 
increase number 
of subjects to be 
considered for 
study 
participation.
Pg 14, 15: 
Protocol 
Summary  
Study Design
Pg 26, 27, 
Section 3.1 
Study Design 
Part A
In this study 100 subjects 
will be randomized in three 
cohorts with Cohort 3 
stratified by age (5-11 years 
vs. 12-17 years) and 
screening SELENA 
SLEDAI scores (8-12 vs. ≥ 
13).
In this study 100 subjects 
will be randomized in three 
cohorts with Cohort 3 
stratified by age (5-11 years 
vs. 12-17 years) and 
screening SELENA 
SLEDAI scores (6 -12 vs. ≥ 
13).  
With change in 
SS score 
screening 
criterion it was 
necessary to also 
change the 
Cohort 3 
stratification to 
include SS score 
6 – 12.
Pg 16; Study 
Design
Pg 27; 
Section 3.1 
Study Design
A target enrolment of 100 
subjects (at least 20 subjects 
less than 13 years of age)
will be randomized.  
…Enrolment of subjects in 
the 12 to 17 years of age 
group may be terminated 
when enrolment reaches 
approximately 80 subjects to 
A target enrolment of 100 
subjects will be randomized.  
…
Enrolment of subjects in the 
12 to 17 years of age group 
may be terminated when 
enrolment reaches 
approximately 80 subjects to 
allow the enrolment of at 
Removed 
redundant 
information.
To ensure that at 
least half of the 
subjects are 
enrolled with SS 
of at least 8 

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Section
Previous Wording
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allow the enrolment of at 
least 20 younger subjects 
less than 13 years of age.
least 20 younger subjects 
less than 13 years of age. In 
addition, enrolment will 
ensure that at least 50% of 
the randomised subjects 
will have presented with 
SELENA SLEDAI ≥ 8 at 
screening.
indicative of 
increased disease 
severity.
Pg 88;  
8.3.5.2.1 
Primary 
Efficacy 
Endpoint
A logistic regression model 
with main effects for 
treatment group (belimumab 
vs. placebo), baseline age 
group (5-11 vs. 12-17 years), 
and baseline SLEDAI score 
group (8-12 vs. ≥ 13) will 
be run to estimate the odds 
ratio and 95% confidence 
interval for belimumab vs. 
placebo.
A logistic regression model 
with main effects for 
treatment group (belimumab 
vs. placebo), baseline age 
group (5-11 vs. 12-17 years), 
and baseline SLEDAI 
score group (6-12 vs. ≥ 13) 
will be run to estimate the 
odds ratio and 95% 
confidence interval for 
belimumab vs. placebo.
Change in SS 
score at 
screening 
requires change 
in stratification 
of baseline SS 
score group.
Pg 32, 
Section 4.3 
Exclusion 
Criteria 
Exclusion Criterion  #4
Have received intravenous 
(IV) cyclophosphamide 
within 90 days of Day 0.
Exclusion Criterion #4
Have received intravenous 
(IV) cyclophosphamide 
within 60 days of Day 0.
Updated the 
exclusion to 
allow less of a 
time restriction 
as it may be more 
relevant to 
medical practice
Page 33, 
Exclusion 
Criteria #11
11.  Have severe nephritis 
defined as a significant 
worsening of renal disease 
manifested by the presence 
of urinary sediments and 
other lab abnormalities that, 
in the opinion of the study 
investigator, may lead to the 
subject requiring IV 
cyclophosphamide, MMF or 
high dose IV corticosteroids 
during the first 6 months of 
the trial.  
Note: Lupus nephritis which 
can be controlled or 
managed in the short term 
with medications allowed in 
the study will not exclude 
subjects from participating 
in the trial (nor will any 
11.  Have acute severe 
nephritis defined as a 
significant worsening of 
renal disease (eg. the 
presence of urinary 
sediments and other lab 
abnormalities) that, in the 
opinion of the study 
investigator, may lead to the 
subject requiring induction 
therapy with IV 
cyclophosphamide, MMF or 
high dose corticosteroids 
during the first 6 months of 
the trial.
Note: clinically stable lupus 
nephritis which can be 
managed with medications 
allowed in the study will not 
exclude subjects from 
participating in the trial (nor 
Clarification of 
the original 
exclusion 
wording.  
Clinically stable 
lupus nephritis 
managed with 
allowed 
medications will 
not exclude 
subject.

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Section
Previous Wording
New Wording
Rationale
maximum level of 
proteinuria exclude 
subjects).
will any maximum level of 
proteinuria exclude 
subjects).  
Page 34, 
Exclusion 
Criteria #19
19. Have required 
management of acute or 
chronic infections, as 
follows:
• Use of parenteral (IV or 
IM) antibiotics 
(antibacterials, antivirals, 
anti-fungals, or anti parasitic 
agents) within 60 days of 
Day 0
19. Have acute or chronic 
infections requiring 
management, as follows:
• Use of parenteral (IV or 
IM) antibiotics 
(antibacterials, antivirals, 
anti-fungals, or anti parasitic 
agents) for infection within 
60 days of Day 0
Clarification that 
the use of 
antibiotics for 
prophylaxis (ie 
no ongoing 
infection) does 
not exclude a 
subject
Pg 35; 
Section 4.3 
Exclusion 
Criteria
24. Have a Grade 3 or 
greater laboratory 
abnormality based on the 
protocol toxicity scale 
except for the following that 
are allowed: 
Stable Grade 3 neutropenia 
or stable Grade 3 white 
blood cell count 
24. Have a Grade 3 or 
greater laboratory 
abnormality based on the 
protocol toxicity scale 
except for the following that 
are allowed:
•Stable Grade 3 neutropenia; 
or stable Grade 3 
lymphopenia; or stable 
Grade 3  leukopenia, due 
to SLE
Clarification of 
exclusion 
criterion and 
allowable 
toxicities. 
Pg 42; Sec 
5.6.1.2.2 
Intra-
articular 
Injections
Subjects may receive 
intraarticular (IA) injections 
between baseline (Day 0) 
and the Day 336 (Week 48) 
visit.
A subject who receives any 
intraarticular injection(s) 
within 8 weeks before the 
Day 364 (Week 52) visit will 
be defined as a treatment 
failure
Subjects may receive 
intraarticular (IA) injections 
between baseline (Day 0) 
and the Day 308 (Week 44) 
visit.
Error in previous 
protocol 
corrected.
[8 weeks before 
Day 364 is Day 
308, not Day 
336.]
Page 42, 
Section 
5.6.1.2.4 
Tapering or 
Restoration 
/ Restart of 
Steroids
However, it is understood 
that an important goal of 
therapy is to reduce steroids, 
given their associated 
morbidity.  As such, subjects 
who have improving SLE 
disease activity for at least 4 
weeks may, at the 
investigator’s discretion, 
reduce the steroid dose 
targeting a reduction to 7.5 
However, it is understood 
that an important goal of 
therapy is to reduce steroids 
with clinical improvement 
maintained, given their 
associated morbidity.  As 
such, subjects who have 
clinically significant 
improvement of SLE
disease activity for at least 4 
weeks may, at the 
investigator’s discretion, 
Clarification that 
with clinical 
improvement 
maintained, 
reduction of 
steroid therapy is 
permitted.

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mg/day or lower after the 
Day 168 (Week 24) visit.  
reduce the steroid dose 
targeting a reduction to 7.5 
mg/day or lower. 

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Section
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New Wording
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Page 45; 
Section 
5.6.1.4. 
Nonsteroidal 
Anti-
inflammatory 
Drugs 
(NSAIDs)
Since NSAIDs may affect 
efficacy parameters (e.g., 
arthritis) and may affect 
renal function (NSAID 
nephropathy), the use of 
these agents should be 
initiated and stabilised prior 
to the screening visit. 
NSAIDs may be given as 
clinically indicated until the 
Day 308 (Week 44) visit
For subjects who never 
received an NSAID between 
the Day 0 and Day 308 
(Week 44) visit, starting a 
new NSAID after the Day 
308 (Week 44) visit will 
declare the subject a 
treatment failure unless the
NSAID is given for < 1 
week. 
Since NSAIDs may affect 
efficacy parameters (e.g., 
arthritis) and may affect 
renal function (NSAID 
nephropathy), the use of 
these agents should be 
initiated and stabilised prior 
to the screening visit. 
NSAIDs may be given as 
clinically indicated until the 
Day 308 (Week 44) visit. 
For subjects who have 
received an NSAID between 
Day 0 and Day 308, the 
existing NSAID can 
continue at a stable dose 
after Day 308.
For subjects who never 
received an NSAID between 
the Day 0 and Day 308 
(Week 44) visit, starting a 
new NSAID after the Day 
308 (Week 44) visit will 
declare the subject a 
treatment failure unless the 
NSAID is given for < 1 
week.
Clarification of 
NSAID use 
during the trial 

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Section
Previous Wording
New Wording
Rationale
Page 16, 27 
Study 
Design, Part 
A – Dose 
confirmation 
or 
adjustment
Page 86, PK 
Interim Data 
Reviews
The SRT will review the 
available blinded safety, key 
biomarker and PK data and a 
decision by consensus will 
be made regarding dose 
confirmation or adjustment 
and the initiation of the 
subsequent cohorts.  The PK 
analysis and decision
regarding dose confirmation 
or adjustment will be 
reviewed by the IDMC.  The 
Study Team will remain 
blinded to treatment during 
these dose assessment 
meetings, through the use of 
a PK dataset with scrambled 
subject identifiers prepared 
by GSK statistician/ 
programmer independent to 
the study ream and analyzed 
by a GSK 
pharmacokineticist 
independent to the study 
team.  Decisions regarding 
dose confirmation or 
adjustment will be 
summarized and distributed 
to study team members, 
investigators, IRBs, 
regulatory authorities and 
the IDMC.  Final decisions 
will be made by the sponsor 
considering the 
recommendation from the
IDMC and independent 
pharmacokineticist.
The SRT will review the 
available blinded safety, key 
biomarker and PK data and a 
recommendation by 
consensus will be made 
regarding dose confirmation 
or adjustment and the 
initiation of the subsequent 
cohorts.  The PK analysis 
and recommendation
regarding dose confirmation 
or adjustment will be 
reviewed by the IDMC.  
Final decisions will be 
made by the sponsor 
considering the 
recommendation from the 
IDMC and independent 
pharmacokineticist. The 
Study Team will remain 
blinded to treatment during 
these dose assessments.  
Decisions regarding dose 
confirmation or adjustment 
will be summarized and 
distributed to study team 
members, investigators, the 
IDMC and IRBs and/or 
regulatory authorities 
according to local 
regulations. 
Clarify the GSK 
Safety Review 
Team procedure 
for review and 
recommendations 
to IDMC 
regarding interim 
PK analysis for 
dose 
confirmation or 
adjustment. 

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Section
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New Wording
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Page 17, 
IDMC
Page28, 
Section 3.1; 
Study 
Design, 
IDMC
Page 68, 
Section 6.3.3  
Independent 
Data 
Monitoring 
Committee
An Independent Data 
Monitoring Committee 
(IDMC) comprised of 5
members: 2 experts in 
paediatric rheumatology, 1
in paediatric pharmacology,
1 in paediatric ethics and a 
statistician, none of whom 
are affiliated with the 
sponsor, will be organized to 
monitor the study as it 
progresses.
An IDMC comprised of 
experts in paediatric 
rheumatology, paediatric 
pharmacology, paediatric 
ethics and a statistician, none 
of whom are affiliated with 
the sponsor, will be 
organized to monitor the 
study as it progresses.
Notification of local 
EC/IRB of the IDMC 
review outcomes will be at 
the discretion and 
requirements of local 
regulations.
Decisions regarding dose 
confirmation or 
adjustment as a result of 
the planned Cohort 1 and 
Cohort 2 PK and safety 
analyses will be 
summarized and 
distributed to study team 
members, investigators, 
the IDMC, and IRBs 
and/or regulatory 
authorities according to 
local regulations.
Removed the 
exact number of 
paediatric 
‘experts’ to allow 
for any 
subsequent 
change in the 
overall IDMC 
membership over 
the long term 
course of the 
clinical trial.  
Added 
clarification for 
notification of 
review outcomes 
per local, country 
specific 
regulations.
Page 74, 
Section 6.3.4 
IgG Stopping 
Criteria
Any subject who has a 
Grade 4 IgG level, by the 
DMID table, will have study 
agent discontinued and will 
be placed into Part C the 
non-belimumab safety 
follow up.
Section 6.3.4
Any subject who has a 
Grade 4 IgG level, by the 
DMID table, will have 
dosing with study agent 
withheld, and the 
appropriateness to 
continue study treatment 
must be discussed with 
Medical Monitor before 
the next dose. Any subject 
who has a Grade 4 IgG 
level associated with a 
severe or serious infection
will have study agent 
discontinued and will be 
placed into Part C the non-
belimumab safety follow up.
Clarify IgG 
monitoring and 
potential 
stopping and/or 
continuation of 
study agent. 
Section 
numbering 
advanced with 
addition of 
revised Liver 
Chemistry 
Stopping and 
Restart Crtieria.

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Section
Previous Wording
New Wording
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Page 65, 
Section 6.3.1 
Liver 
Chemistry 
Stopping and 
Follow Up 
Criteria
Page 67, 
Section 6.3.4 
Liver 
Monitoring 
and Restart 
Criteria
Page 120, 
Appendix 4 –
Liver 
Chemistry 
Stopping 
Algorithm
Page 96 
Section 10: 
References
Section 6.3.1 Liver 
Chemistry Stopping and 
Follow Up Criteria are 
deleted. 
No previous wording for 
Study Agent Restart criteria
Appendix 4 Liver Chemistry 
Stopping Algorithm
Page 65 to 67 replaced in 
entirety with GSK revised 
standard text 
6.3.1  Liver Chemistry 
Stopping and Monitoring 
Criteria 
(see pg 65)
6.3.2.  Increased 
Monitoring Criteria with 
Continued Therapy
Page 67: Addition of Study 
Agent Restart Criteria 
6.3.3  Study Treatment 
Restart
Appendix 4:  Liver 
Chemistry Stopping 
Criterial algorithm.  
Added Liver Monitoring 
Event Algorithm with 
Continued Therapy
Added Study Agent Restart 
Algorithm, actions and 
follow up.
References:
Andrade, Hunt, James, Le 
Gal, Papay
Updated Liver 
Chemistry 
Stopping criteria 
text per 2014 
revised GSK 
required policy.
Added GSK 
standard text of 
criteria and 
procedure for 
restart of study 
agent after liver 
chemistry 
stopping event. 
Updated with 
GSK revised 
algorithms
Additional 
references with 
revisions to Liver 
Chemistry 
Stopping Criteria 
and Study Drug 
Restart section

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Section
Previous Wording
New Wording
Rationale
Minor corrections and changes have been made throughout the protocol to provide 
updated information and/or to clarify a previously described process or procedure in the 
study.
Page 25 
Section 1.2 
Rationale
Page 26 
Section 1.2.1 
Dose 
Rationale
Belimumab was also 
approved in Canada on 06 
July 2011
The 10 mg/kg dose is 
approved in the US, EU, and 
Canada for the treatment of 
adult subjects with active, 
autoantibody-positive SLE.
Belimumab is currently 
approved in the United 
States, all European Union 
Member States, as well as in 
over 20 countries.
The 10 mg/kg dose is 
approved in the United 
States, all European Union 
Member States, as well as in 
over 20 countries for the 
treatment of adult subjects 
with active, autoantibody-
positive SLE.
Updated 
information of 
additional 
country 
approvals since 
inception of 
original 
protocol.

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11.21.
Appendix 21: Country Specific Protocol Amendment 05
Changes
Country specific changes in Protocol Amendment 05 apply to Investigator sites in 
the Russian Federation only.
Summary of Country Specific Changes and Rationale
Section
Previous Wording
New Wording
Rationale
Page 109; 
Appendix 2: 
Country 
Specific 
Requirements
Appendix 2: Country 
Specific Requirements
Study Treatment 
Restart per Section 
6.3.3
11.
At sites in the 
Russian Federation, 
restart of study treatment 
after liver event is not 
permitted.
Country specific 
protocol 
amendment. The 
Ministry of Health 
Care of the Russian 
Federation will not 
permit the restart of 
study treatment 
after a liver 
chemistry stopping 
event for 
participating 
subjects in the 
Russian Federation. 
Page 66; 
Section 6.3.3 
Study 
Treatment 
Restart
Approval by GSK for 
study treatment restart 
can be considered 
where:
12.
Note:   At 
investigator sites in the 
Russian Federation, 
restart of study treatment 
after liver event is not 
permitted.
Approval by GSK for study 
treatment restart can be 
considered where:
Country specific 
protocol 
amendment.  

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11.22.
Appendix 22: Protocol Amendment 06 Changes
Protocol Amendment 06 applies to all countries and sites unless otherwise specified.
A detailed description of substantive changes to the protocol are listed below.  Additional 
administrative and minor editorial changes have also been made.  
Section
Previous Wording
New Wording
Rationale
Title page
Author list
Revision of author list.
Update to 
authors and 
authors’
department 
name for 
amended 
protocol
Sponsor 
Information 
Page
Sponsor 
Information 
Page
Sponsor Medical Monitor 
Contact Information:  
, MD
GlaxoSmithKline
Stockley Park West, 
1-3 Ironbridge Road, 
Uxbridge,
Middlesex, UB11 1BT, 
United Kingdom
Telephone: 
 
Fax: 
Mobile: 
Email: 
Sponsor Medical Monitor 
Contact Information:  
, MD
GlaxoSmithKline
Research & Development
1250 South Collegeville 
Road
UP 1230
Collegeville, PA 19426
USA
Mobile: 
Email:
Back-up Sponsor Medical 
Monitor Contact 
Information
, MD
GlaxoSmithKline
Stockley Park West, 
1-3 Ironbridge Road, 
Uxbridge,
Middlesex, UB11 1BT, 
United Kingdom
Telephone: 
 
Fax: 
Mobile: 
Email: 
Change of 
Primary 
Medical 
Monitor.  
Previous 
Primary 
Medical 
Monitor will 
now serve as 
“Backup 
Medical 
Monitor” for 
the study.
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Section
Previous Wording
New Wording
Rationale
Sponsor Information Page:
GlaxoSmithKline
2301 Renaissance 
Boulevard,  King of 
Prussia PA 19406-2722 
USA
Telephone 1-610-270-
4800
Sponsor Information Page:
GlaxoSmithKline
1250 South Collegeville 
Road
Collegeville, PA 19146-
0989
Telephone: +001 610 917 
7000
Protocol 
Summary,
Section 3.1 
Study Design 
Section 4.1 
(and 
throughout the 
protocol) 
Number of 
Subjects 
A target enrollment of 100 
subjects will be 
randomized
Cohort 2 will enrol at 
least 12 subjects 5-11 
years of age at the dose 
determined from the PK 
analysis of Cohort 1
Cohort 3: This cohort will 
consist of  76 subjects
Therefore, at least 48 
subjects will be 
randomized to belimumab 
and 42 to placebo 
N/A
A target enrollment of at 
least 70 subjects will be 
randomized
Cohort 2 will enroll at 
least 10 subjects 5-11 
years of age
Cohort 3: This cohort will 
consist of at least 48
subjects
Therefore, at least 42
subjects will be 
randomized to belimumab 
and 28 to placebo 
The study will also enrol at 
least 14 subjects who are 
younger than 13 years of 
age
Revision to 
total sample 
size in view of 
recruitment 
challenges and 
desire to 
generate 
expedient data 
for 
commitment 
Figure 1: Study 
Schematic
N=100
Cohort 2 N=12
N≥70 
Cohort 2: N= at least 10
Figure updated 
to reflect 
change to 
sample size
Time and 
Events Table
N/A
Part B column header: 
Additional Assessments 
Every 6 Months 7 days
Part C Column headed: 
Assessments Every Year 
PedsQL added to Day 0
Part B column header: 
Additional Assessments 
Every 6 Months/Yearly 7 
days
Corrected 
errors in 
previous 
version of 
protocol

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Previous Wording
New Wording
Rationale
28 days beginning after 3 
Month Period
N/A
Part C Column Header:
Assessments Every Year 
28 days after last infusion
Part B 6 month visit: 
added Anti-dsDNA; C3/C4
Part C: Clarification of 
AE and SAE reporting
Time and 
Events Table
(footnote 20)
Section 6.5 
Pharmacokineti
cs 
Section 8.3.5.4 
Pharmacokineti
c Analyses
N/A
Part B – week 12 / 3month 
and first 6 month visits: 
added PK Samples for 
subjects enrolled in Japan
For subjects enrolled in 
Japan only, additional PK 
samples (before the start 
of infusion and 0-4 hours 
after the end of infusion) 
will be taken at the 12 
week / 3 month and  first 6 
month visits only in Part 
B. 
PK analysis of subjects in 
Japan will be used to 
determine the 
pharmacokinetics of 
belimumab in pediatric 
subjects of Japanese 
descent.
Need to collect 
PK samples for 
subjects on 
active drug in 
Japan
Section 
6.3.20.1 
Immunogenicit
y 
Time and 
Events Table,  
(footnote page)
For subjects who have a 
positive anti-belimumab 
antibody response at the 
8-week follow-up (or 
last study visit at which 
immunogenicity was 
assessed), 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 
or upon completion 
N/A
(Note: footnote numbering 
subsequent to the deleted 
footnote was updated 
accordingly)
Deleted due to 
increased 
safety 
knowledge of 
asset since 
earlier versions 
of the protocol 
and it is no 
longer required 
to capture 
immunogenicit
y samples once 
the subject has 
left the study.

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Section
Previous Wording
New Wording
Rationale
and/or unblinding of the 
study, whichever is later.
Part C
(throughout the 
protocol)
“safety follow up non-
belimumab phase”  
Changed to “safety follow 
up phase”
Allow standard 
of care SLE 
medications, 
without 
restrictions, 
which may 
include 
commercial 
Benlysta in 
subjects who 
transition to 
adulthood 
during Part C
Section 6.3.13 
Time period 
and frequency 
of reporting 
AEs and SAEs
Clarification of time 
period for reporting AEs, 
SAEs, and AESIs in Parts 
B and C
Section 8.2.1 
Sample Size 
Considerations
Section 8.2.2 
Sample Size 
Sensitivity
Section 8.2.3 
Sample Size 
Re-estimation
Section 8.2.3 revised to 
incorporate changes in 
sample size from 100 to 70
Revision to 
total sample 
size in view of 
recruitment 
challenges and 
desire to 
generate 
expedient data 
for 
commitment 

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11.23.
Appendix 23: Protocol Amendment 07 Changes
Protocol Amendment 07 applies to all countries and sites unless otherwise specified.
A detailed description of substantive changes to the protocol are listed below.  Additional 
administrative and minor editorial changes have also been made.
Section
Previous Wording
New Wording
Rationale
Title page
Author list
Revision of author list.
Update to 
authors and
department 
names for 
amended 
protocol
Sponsor 
Information 
Page
Sponsor Medical 
Monitor Contact 
Information:
, MD
GlaxoSmithKline
1250 South Collegeville 
Road
UP 1230
Collegeville, PA 19426
USA
Mobile: 
Email: 
Replaced
GlaxoSmithKline
1250 South Collegeville 
Road
UP 1230
Collegeville, PA 19426
USA
Mobile: 
Email:
Back-up Sponsor 
Medical Monitor Contact 
Information
, MD
GlaxoSmithKline
Stockley Park West, 
Sponsor Medical Monitor 
Contact Information text 
removed
Change of 
Primary and 
Back-up 
Medical 
Monitors. 
Details now in 
SRM in line 
with current 
GSK process.
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Section
Previous Wording
New Wording
Rationale
1-3 Ironbridge Road, 
Uxbridge,
Middlesex, UB11 1BT, 
United Kingdom
Telephone: 
 
Fax: 
Mobile: 
Email: 
Sponsor 
Information 
GlaxoSmithKline
2301 Renaissance 
Boulevard, King of Prussia 
PA 19406-2722 USA
Telephone 1-610-270-
4800
GlaxoSmithKline Research 
& Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Telephone: +44 (0)208 047 
5000
Change to 
registered 
Sponsor 
location
Introduction
New text added
Results of double-blind 
phase
To include 
results from the 
completed 
double-blind 
phase of study
Section 4.4 
Withdrawal 
Criteria
Misses 3 or more 
consecutive study agent 
infusions.
New text added
Misses 3 or more 
consecutive study agent 
infusions (Note: This 
changes to 4 or more missed 
consecutive infusions if any 
of the doses are missed due 
to COVID-19 related 
reasons).
In the event a participant 
tests positive for COVID-
19, or if no testing is 
available and a participant 
exhibits symptoms 
consistent with COVD-19, 
dosing of belimumab should 
be withheld until symptoms 
resolve and contact the 
Medical Monitor to discuss 
To increase 
flexibility on 
missed doses to 
avoid 
continued 
access to study 
medication if 
one or more 
doses missed 
due to COVID-
19 reasons.
Guidance to 
investigators to 
suspend IP 
administration 
and to discuss 
with Medical 
Monitor before 
resuming IP 
administration 
in subjects with 
known or 
PPD
PPD
PPD
PPD

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Section
Previous Wording
New Wording
Rationale
reinitiating belimumab 
treatment.
suspected 
COVID-19.
Section 5.2 
Treatment 
Assignment
Subjects will be 
randomized centrally using 
the IVRS) system.  This is 
a telephone-based system 
which will be used by the 
Investigator or designee to 
register the subject, 
randomize the subject and 
receive medication 
assignment information
Details of how to use the 
IVRS to register and 
randomize subjects will 
be provided in the SPM.
Although study agent 
will be stored at the site, 
the Investigator (or 
designee) must register 
in the IVRS to obtain 
study agent assignments
Subjects will be randomized 
centrally using the 
IVRS/IWRS) system.  This 
is a telephone-based system 
which will be used by the 
Investigator or designee to 
register the subject, 
randomize the subject and 
receive medication 
assignment information
Details of how to use the 
IVRS/IWRS to register 
and randomize subjects 
will be provided in the 
SPM/SRM.
Although study agent will 
be stored at the site, the 
Investigator (or designee) 
must register in the 
IVRS/IWRS to obtain 
study agent assignments.
The original 
telephone 
based system is 
now used as a 
web-based 
system.
GSK has 
changed the 
naming of the 
Study 
Procedures 
Manual (SPM) 
to Study 
Reference 
Manual (SRM).
Section 5.6 
Treatment 
Compliance
A subject will be 
withdrawn if they have 
missed 3 or more 
consecutive study agent 
infusions.
A subject will be withdrawn 
if they have missed 3 or 
more consecutive study 
agent infusions (4 or more 
consecutive infusions if one 
or more of these are missed 
due to COVID-19).
To clarify the 
number of 
allowable 
consecutive 
missed 
infusions.
Table 2 Time 
& Events: 
Open Label and 
Follow Up 
Periods
New footnote added
† Note the first annual visit 
occurs 9 months after the 3rd
monthly visit in Part C and 
every 12 months thereafter.
To clarify 
when the 
annual visits in 
Part C 
commence.

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11.24.
Appendix 24: Protocol Amendment 08 Changes
Protocol Amendment 08 applies to all countries and sites unless otherwise specified.
A detailed description of substantive changes to the protocol are listed below.  Additional 
administrative and minor editorial changes have also been made.
Note: Protocol Amendment 07 had been distributed but not submitted to Health 
Authorities and IRB/ECs in all participating countries. Clarification was requested on the 
exact number of allowable consecutive missed study IP infusions. The wording was 
modified in Amendment 08 to avoid ambiguity.
Where not yet approved the changes in Protocol Amendment 07 should be reviewed 
together with Protocol Amendment 08.
Section
Previous Wording
New Wording
Rationale
Sponsor 
Signatory
Beulah Ji
David A Roth
Change in role
Sponsor 
Information 
Page
Sponsor Medical Monitor 
Contact Information:
Back-up Sponsor Medical 
Monitor Contact 
Information
Change of 
Back-up 
Medical 
Monitor.
Section 4.4 
Withdrawal 
Criteria
Misses 3 or more 
consecutive study agent 
infusions. (Note: This 
changes to 4 or more 
missed consecutive 
infusions if any of the 
doses are missed due to 
COVID-19 related 
reasons).
Misses 3 consecutive study 
agent infusions (Note: This 
changes to 4 missed 
consecutive infusions if any 
of the doses are missed due 
to COVID-19 related 
reasons).
To clarify the 
allowable 
number of 
consecutive 
infusions that 
can be missed 
without 
requirement for 
withdrawal if 
related to 
COVID-19 and 
to increase 
flexibility on 
missed doses to 
avoid 
continued 
access to study 
medication if 
any doses 
missed due to 
COVID-19 

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Section
Previous Wording
New Wording
Rationale
reasons and to 
clarify the 
number of 
allowable 
consecutive 
missed 
infusions.
Section 5.6 
Treatment 
Compliance
A subject will be 
withdrawn if they have 
missed 3 or more 
consecutive study agent 
infusions (4 or more 
consecutive infusions if 
any of these are missed 
due to COVID-19).
A subject will be 
withdrawn if they have 
missed 3 consecutive 
study agent infusions (4 
consecutive infusions if 
any of these are missed 
due to COVID-19).
To clarify the 
number of 
missed 
consecutive 
infusions that 
require 
withdrawal 
from study 
medication.
Section 6.3.20
Serum samples will be 
stored at -20°C at the 
sites before weekly 
batch shipment to the 
central laboratory.  
Samples will be stored 
at -70°C at the central 
laboratory until 
shipment to HGS and 
stored at -80°C after 
they arrive at HGS. 
Samples will be shipped 
on dry ice in both 
shipments.
The total amount of 
blood drawn for 
immunogenicity testing 
during this study is 
approximately 10 mL. 
Assay method
All immunogenicity 
testing will be carried 
out at HGS (Rockville, 
Maryland).  HGS has 
developed a 3-part 
(screening, 
confirmation/specificity 
.  Serum samples will be 
stored at -20°C at the sites 
before daily shipment to 
the central laboratory.  
Samples will be stored 
at -70°C at the central 
laboratory until shipment 
to Alliance Pharma and 
stored at -80°C after they 
arrive at Alliance Pharma. 
Samples will be shipped 
on dry ice in both 
shipments.
The total amount of blood 
drawn for 
immunogenicity testing 
per participant is 
approximately 10 mL. 
Assay methods
Sample analysis will be 
performed under the 
control of 
GlaxoSmithKline. In the 
immunogenicity 
assessment for anti-
The laboratory 
performing the 
immunogeni-
city testing has 
changed. The 
assay 
methodology is 
now included 
in the SRM.

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Section
Previous Wording
New Wording
Rationale
and neutralisation) 
belimumab 
immunogenicity assay 
paradigm.
In the screening assay, 
the presence of anti-
belimumab antibodies 
will be assessed using an 
electrochemiluminescen
ce (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. 
belimumab antibodies, a 
tiered analysis approach 
will use a validated 
binding ADA assays 
(screening, confirmation 
and titration assays) and a 
validated neutralization 
antibody assay.