Conditions: Systemic Lupus Erythematosus
Keywords: Pediatric Belimumab Pharmacokinetics Active Systemic Lupus Erythematosus Safety Efficacy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 67
Healthy volunteers: no

Brief summary:
This study will be conducted to evaluate the safety, efficacy and pharmacokinetics of belimumab administered in combination with background standard therapy in pediatric participants with active SLE.

Detailed description:

Arms:
arm 1: None

Interventions: intervention 1: Belimumab intervention 2: Standard therapy
Intervention descriptions: intervention 1: Belimumab will be administered. intervention 2: Standard therapy will be continued.

Protocol document:
Prot_000.pdf: 
TMF-17745556 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
213560 
 
 
Protocol amendment 04 
22 Jan 2024 
1 
 
TITLE PAGE 
Protocol Title: A Multi-Center, Open-Label Study to Evaluate Safety, Efficacy and 
Pharmacokinetics of Belimumab Plus Standard Therapy in Chinese Paediatric Patients 
with Active Systemic Lupus Erythematosus (SLE)  
Protocol Number: 213560/Amendment 04 
Compound 
Number: 
GSK1550188  
Study Phase: Phase 4  
Short Title: Open label study of Belimumab plus standard therapy in Chinese Paediatric 
patients with active SLE   
Sponsor Name and Legal Registered Address:  
 
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Manufacturer: Not Applicable  
Medical Monitor Name and Contact Information: The details will be found in the 
Study Reference Manual 
Regulatory Agency Identifying Number(s): Not applicable. 
Sponsor Signatory: 
Deepak Assudani, MD 
Senior Clinical Development Director 
Clinical Science (Immunology)  
GSK 
 
Approval Date: 22 Jan 2024  
 
Copyright 2024 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited. 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 04 
22 Jan 2024 
Amendment 03 
02 January 2023 
Amendment 02 
03 June 2022 
Amendment 01 
29 January 2021 
Original protocol 
27 October 2020 
 
Amendment 04 22 Jan 2024 
This amendment is considered non-substantial based on the criteria defined in EU 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union because it neither significantly impacts the safety of participants nor the 
scientific value of the study. 
Overall Rationale for the amendment: 
The purpose of this amendment is to add definitions for several terms to comply with an 
update to the internal GSK protocol process and template. 
 
 
 
 
 
 
 
 
 
 
 
 


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List of main changes in the protocol and their rationale: 
 
 
 
 
Section # and Name Description of Change 
Brief Rationale 
LIST OF 
ABBREVIATIONS 
AND DEFINITIONS 
OF TERMS 
Addition or update of 
definitions for 
several terms, including 
Investigational Product, 
Standard of Care, Background 
treatment, Adverse Drug 
Reaction, SUSAR 
 
Move the section from 10.12 of 
previous version (amend 03) to 
the beginning of the protocol  
 
Delete Trademark Information 
 
 
To comply with an update 
to the internal GSK 
protocol process and template. 
10.5. 
Appendix 5: 
Liver Safety: 
Required Actions and 
Follow-up 
Assessments 
 
 
 
Delele “ References 
Le Gal F, Gordien E, Affolabi 
D, Hanslik T, Alloui C, Dény P, 
et al. Quantification of 
Hepatitis Delta Virus RNA in 
Serum by Consensus Real-
Time PCR Indicates Different 
Patterns of Virological 
Response to Interferon 
Therapy in Chronically Infected 
Participants. J Clin Microbiol. 
2005;43(5):2363–2369.” 
Per new protocol template references 
should be added in Section 11. And 
the reference is not used in the 
document. 
10.12. Appendix 12: 
Protocol Amendment 
History 
 
Update section number from 
10.13 to 10.12 
 
  
Previous 10.12 have been moved to 
the beginning of protocol, adapted to 
update. 
11. REFERENCES 
Add belimumab IV injection 
prescribing information  
To comply with an update 
to the internal GSK protocol process 
and template. 
 


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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY ........................................................................................ 11 
1.1. 
Synopsis ..................................................................................................... 11 
1.1.1. 
Schema ....................................................................................... 13 
1.2. 
Schedule of Activities (SoA) ........................................................................ 14 
2. 
INTRODUCTION .................................................................................................... 17 
2.1. 
Study Rationale .......................................................................................... 17 
2.2. 
Background ................................................................................................ 17 
2.2.1. 
Safety of Belimumab .................................................................... 18 
2.2.2. 
Efficacy of Belimumab ................................................................. 18 
2.2.3. 
Pharmacokinetics of Belimumab .................................................. 19 
2.2.4. 
Pharmacodynamics of IV Belimumab .......................................... 19 
2.3. 
Benefit/Risk Assessment ............................................................................ 19 
2.3.1. 
Risk Assessment ......................................................................... 20 
2.3.2. 
Benefit Assessment ..................................................................... 23 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 23 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 23 
4. 
STUDY DESIGN .................................................................................................... 24 
4.1. 
Overall Design ............................................................................................ 24 
4.2. 
Scientific Rationale for Study Design .......................................................... 25 
4.2.1. 
Participant Input into Design ........................................................ 26 
4.3. 
Justification for Dose .................................................................................. 26 
4.4. 
End of Study Definition ............................................................................... 26 
5. 
STUDY POPULATION ........................................................................................... 27 
5.1. 
Inclusion Criteria ......................................................................................... 27 
5.2. 
Exclusion Criteria ........................................................................................ 29 
5.3. 
Lifestyle Considerations .............................................................................. 31 
5.4. 
Screen Failures........................................................................................... 31 
5.5. 
Repeat Assessments during the 35 Day Screening Period ......................... 32 
6. 
STUDY INTERVENTION ........................................................................................ 32 
6.1. 
Study Intervention(s) Administered ............................................................. 32 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 34 
6.3. 
Measures to Minimise Bias: Randomisation and Blinding ........................... 34 
6.4. 
Study Intervention Compliance ................................................................... 34 
6.5. 
Concomitant Therapy.................................................................................. 34 
6.5.1. 
Permitted medications and non-drug therapies ............................ 35 
6.5.2. 
Prohibited Medications and Non-Drug Therapies ......................... 36 
6.6. 
Dose Modification ....................................................................................... 37 
6.7. 
Intervention after the End of the Study ........................................................ 37 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 37 
7.1. 
Discontinuation of Study Intervention .......................................................... 37 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 38 
7.1.2. 
IgG Stopping Criteria ................................................................... 40 


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C O N FI D E N TI A L  
 
 
 
2 1 3 5 6 0  
 
 
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2 2 J a n 2 0 2 4   
5  
 
7. 1. 3.  
R e c h all e n g e  ................................................................................. 4 1  
7. 1. 4.  
T e m p or ar y Di s c o nti n u ati o n  .......................................................... 4 1  
7. 2.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  ............................... 4 1  
7. 3.  
L o st t o F oll o w -U p  ........................................................................................ 4 1  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ..................................................... 4 2  
8. 1.  
S cr e e ni n g A s s e s s m e nt s  ............................................................................. 4 2  
8. 2.  
Effi c a c y A s s e s s m e nt s  ................................................................................. 4 5  
8. 3.  
S af et y A s s e s s m e nt s  ................................................................................... 4 5  
8. 3. 1.  
Cli ni c al S af et y L a b or at or y A s s e s s m e nt s  ...................................... 4 6  
8. 4.  
A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  ............................................. 4 6  
8. 4. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n ................................................................................... 4 7  
8. 4. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ............................................. 4 7  
8. 4. 3.  
F oll o w -u p of A E s a n d S A E s  ......................................................... 4 7  
8. 4. 4.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  ............................. 4 8  
8. 4. 5.  
Pr e g n a n c y  ................................................................................... 4 8  
8. 5.  
Tr e at m e nt of O v er d o s e  ............................................................................... 4 8  
8. 6.  
P h ar m a c o ki n eti c s  ....................................................................................... 4 9  
8. 7.  
 5 0  
8. 8.  
G e n eti c s  ..................................................................................................... 5 0  
8. 9.  
I m m u n o g e ni cit y A s s e s s m e nt s ..................................................................... 5 0  
8. 1 0.  H e alt h E c o n o mi c s  ....................................................................................... 5 0  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................ 5 0  
9. 1.  
St ati sti c al H y p ot h e s e s ................................................................................. 5 0  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  ........................................................................ 5 0  
9. 2. 1.  
P K S a m pl e Si z e D et er mi n ati o n  .................................................... 5 1  
9. 3.  
P o p ul ati o n s f or A n al y s e s  ............................................................................ 5 2  
9. 4.  
St ati sti c al A n al y s e s  ..................................................................................... 5 3  
9. 4. 1.  
G e n er al C o n si d er ati o n s  ............................................................... 5 3  
9. 4. 2.  
Pri m ar y E n d p oi nt( s)  ..................................................................... 5 3  
9. 4. 3.  
S e c o n d ar y E n d p oi nt( s)  ................................................................ 5 4  
9. 4. 4.  
Ot h er A n al y s e( s)  .......................................................................... 5 5  
9. 5.  
I nt eri m A n al y s e s ......................................................................................... 5 5  
9. 6.  
G S K s af et y r e vi e w t e a m ( S R T)  ................................................................... 5 5  
1 0.  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  ............................................................................................... 5 6  
1 0. 1.  A p p e n di x 1: R e g ul at or y, Et hi c al, a n d St u d y O v er si g ht 
C o n si d er ati o n s  ............................................................................................ 5 6  
1 0. 1. 1.  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  ........................................ 5 6  
1 0. 1. 2.  
Fi n a n ci al Di s cl o s ur e  ..................................................................... 5 6  
1 0. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s  .......................................................... 5 7  
1 0. 1. 4.  
D at a Pr ot e cti o n  ............................................................................ 5 7  
1 0. 1. 5.  
Di s s e mi n ati o n of Cli ni c al St u d y D at a  ........................................... 5 7  
1 0. 1. 6.  
D at a Q u alit y A s s ur a n c e  ............................................................... 5 8  
1 0. 1. 7.  
S o ur c e D o c u m e nt s  ...................................................................... 5 9  
1 0. 1. 8.  
St u d y a n d Sit e St art a n d Cl o s ur e  ................................................. 5 9  
1 0. 1. 9.  
P u bli c ati o n P oli c y  ......................................................................... 5 9  
1 0 . 2. A p p e n di x 2: Cli ni c al L a b or at or y T e st s  ......................................................... 6 1  
C CI


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10.2.1. 
Adverse Event and Laboratory Value Severity Grade 
Table ........................................................................................... 64 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 70 
10.3.1. 
Definition of AE ............................................................................ 70 
10.3.2. 
Definition of SAE .......................................................................... 71 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 72 
10.3.4. 
Reporting of SAE to GSK ............................................................. 74 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 75 
10.4.1. 
Definitions: ................................................................................... 75 
10.4.2. 
Contraception Guidance: ............................................................. 76 
10.4.3. 
Collection of Pregnancy Information: ........................................... 77 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 78 
10.6. 
Appendix 6: Country-specific requirements ................................................. 81 
10.7. 
Appendix 7: American College of Rheumatology (ACR) Criteria for 
SLE ............................................................................................................. 82 
10.8. 
Appendix 8: SELENA SLEDAI Disease Assessment Scales ....................... 83 
10.9. 
Appendix 9: SLE Flare Index ...................................................................... 84 
10.10. Appendix 10: Physician’s Global Disease Assessment ............................... 85 
10.11. Appendix 11: Parent’s Global Disease Assessment .................................... 86 
10.12. Appendix 12: Protocol Amendment History ................................................. 87 
11. REFERENCES ....................................................................................................... 96 
 
 
 


T M F -1 7 7 4 5 5 5 6  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
7  
 
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F T E R M S  
Li st of A b br e vi ati o n s  
A C R  
A m eric a n C oll e ge of R h e u m at ol o gy  
A D A  
A nti -dr u g a ntib o dies  
A E  
A dv ers e ev e nt  
A E SI  
A dv ers e ev e nt of s p ecial i nter est  
A L T  
Al a ni n e a mi n otra nsfer as e  
A N A  
A nti -n ucl ear a nti b ody  
A S T  
As p art at e a mi n otr a nsf er as e  
A U C  
Ar e a u n der t h e c urv e  
B Ly S  
B ly m p h ocyte Sti m ul at or  
C av g  
Av er a ge pl as m a c o nce ntr ati o n  
C B C  
C o m pl et e bl o o d c o u nt  
C D E  
C e nt er for Dru g Eval u ati o n  
Ci C  
C hil d i n c ar e  
C mi n  
T h e mi ni mu m bl o o d plas m a c o nc entr ati on r e ach ed by a dr u g 
pri or t o a d mi nistr ati o n of a sec o nd d os e  
C N S  
C e ntr al nerv o us syste m  
C O N S O R T  
C o ns oli d at e d St a n dar ds of R e p orti n g Tri als  
Cr Cl  
Cr e ati ni n e cle ar a nce  
C R D  
C o ntr oll e d Re p eat D ose  
C R P  
C -r e activ e pr otei n 
C R F  
C as e r e port f or m  
C T C A E  
C o m m o n T er mi n ol o gy Crit eria f or A dvers e Eve nts  
d L  
D ecilitr e  
ds D N A  
D o u bl e str a n de d d eoxyrib on ucl eic aci d  
e C R F  
El ectr o nic c ase r ep ort for m  
E C G  
El ectr oc ar di ogr a m  
E U  
E ur o pe a n U ni o n  
G C P  
G o o d Cli nic al Pr actic e  
G F R  
Gl o m er ul ar filtr ati o n r at e  
G S K  
Gl ax o S mit h Kli ne  
H B  
H e p atitis B  
H Bs A g  
H e p atitis B s urf ace a nti g en 
H Bc  
H e p atitis B c or e  
H G S  
H u m a n G en o m e Sci e nces, I nc  
HI V  
H u m a n i m m u n od efici ency virus  
H S R  
Hy p ers e nsitivity r e acti o n  
I A 
I ntr a artic ul ar 
I B 
I nv esti gat or’s Br och ur e 
I M 
I ntr a m usc ul ar 
I E C 
I n d ep en d ent et hics c o m mitte e 
C CI
C CI


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C O N FI D E N TI A L  
 
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
8  
 
I M 
I ntr a m usc ul ar 
I N R 
I nt er nati o nal N or m alis e d Rati o 
I R B 
I nstit utio n al R evie w B oar d 
I T T 
I nt e nti o n t o Tr eat 
I U D 
I ntr a uterin e d evic e 
I V 
I ntr av en o us 
I VI G 
I ntr av en o us i m m u n o gl ob ulin 
I W R S 
I nt er active w e b r es p ons e syst e m 
K g  
Kil o gr a m  
L D H  
L act at e d e hydr o ge n ase  
M g  
Milli gr a m  
m L  
Millilitr e  
M CI D  
Mi ni m ally cli nic ally i m p ort a nt diff er enc e  
M M F  
Myc o p h en ol ate m ofetil  
M RI  
M a g n etic Res o na nce I m a gery  
M S D S  
M at erials S afety D at a Sh eet  
N S AI Ds  
N o n -st er oi dal a nti-i nfla m m at ory dr u gs 
P ar e nt G A  
P ar e nt Gl o b al Ass ess m ent  
P C R  
P oly mer as e ch ai n r eacti on  
P G A  
P hysici a n Glo b al Ass ess m ent  
P D  
P h ar mac ody n a mic  
P Gx  
P h ar mac og e netics  
P K  
P h ar mac oki netic  
P O  
By m o uth ( p er os)  
P T  
Pr ot hr o m bi n ti me  
P T T  
P arti al t hr o mb o pl asti n ti me  
R A  
R h e u m atoi d arthritis  
R A P  
R e p orti n g a nd An alysis Pl an  
R B C  
R e d bl oo d cell  
R N A  
Ri b o n ucl eic aci d  
S A E  
S eri o us Adv ers e Ev ent  
S C  
S u bc ut a ne ous  
S E L E N A  
S af ety of Estr o ge n in L u p us N ati o nal Ass ess m ent  
S FI  
S L E Fl ar e I nd ex  
S L E  
Syst e mic L up us Eryt h e m atos us  
S L E D AI  
Syst e mic L up us Eryt h e m atos us Dis e as e Activity I nd ex  
S O C  
Syst e m Or g an Cl ass es  
S RI  
S L E R esp on d er In dex  
T A CI Fc  
Tr a ns m e m br a n e activ at or att ac he d to t he Fc p orti o n of a n 
i m m u n o gl o b uli n 
T N F  
T u m o ur N ecr osis F actor  
U L N  
U p p er li mit of nor mal  
U S  
T h e U nit ed stat es  
C CI


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WOCBP 
Woman of childbearing potential 
 
TABLE OF DEFINITIONS 
Term 
Definition 
Investigational 
Product 
A pharmaceutical form of an active substance or placebo being 
tested or used as a reference in a clinical trial, including products 
already with a marketing authorization but used or assembled 
(formulated or packaged) in a way different from the authorized 
form, or when used for an unauthorized indication, or when used to 
gain further information about the authorized form. 
Standard of 
Care 
Medicine(s) for a specific indication, or a component of the standard 
care for a particular medical indication, based on national and/or 
international consensus; there is no regulatory significance to this 
term.  
1. Products/regimens considered standard of care may differ country 
to country, depending on consensus in individual countries 
Background 
treatment 
Type of medicinal product administered to each of the clinical trial 
participant, regardless of randomization group, to treat the indication 
that is the object of the study. Background treatment is generally 
considered to be the current standard care for the particular 
indication. In these trials, the IMP is given in addition to the 
background treatment and safety efficacy are assessed. The protocol 
may require that the IMP plus the background treatment is compared 
with an active comparator or with placebo plus background 
treatment.  
Adverse Drug 
Reaction 
An adverse event where a causal relationship between a medicinal 
product and the adverse event is at least a reasonable possibility, i.e., 
the relationship cannot be ruled out.  
a. In the context of a clinical trial, an ADR can be serious or non-
serious. Serious ADRs may be subject to expedited reporting if they 
are considered unexpected (see SUSAR definition). 
b. For marketed products, ADRs are subject to expedited reporting 
within the country where they are authorized. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in a clinical trial, 
a serious adverse reaction that is considered unexpected, i.e., the 
nature or severity of which is not consistent with the reference safety 
information (e.g., Investigator's Brochure for an unapproved 
investigational medicinal product). All adverse drug reactions 


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(ADRs) that are both serious and unexpected are subject to 
expedited reporting. 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Multi-Center, Open-Label Study to Evaluate Safety, Efficacy and 
Pharmacokinetics of Belimumab Plus Standard Therapy in Chinese Paediatric Patients 
with Active Systemic Lupus Erythematosus (SLE)  
Short Title: Open label study of belimumab plus standard therapy in Chinese paediatric 
patients with active SLE  
Rationale: The purpose of this study is to evaluate the safety, efficacy and 
pharmacokinetics of belimumab (10 mg/kg) intravenous (IV) with standard therapy in 
Chinese paediatric patients aged 5 to 17 years with active SLE. This study is conducted to 
support the registration of IV belimumab in treating paediatric SLE indication in China.  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Primary 
➢ To evaluate the safety and efficacy of 
belimumab IV in Chinese paediatric patients 
with SLE. 
Safety 
➢ Incidence of adverse events of special interest 
(AESIs) through 52 weeks: 
• 
All Infections of special interest, including 
serious infections of special interest and 
opportunistic infections 
• 
Infusion related systemic reactions and 
anaphylactic reactions  
• 
Depression, suicidality 
• 
Malignancies 
Efficacy 
➢ Incidence of patients with 4 points reduction 
from Baseline to Week 52 in SELENA SLEDAI 
Secondary 
Secondary 
➢ To evaluate safety and tolerability of 
belimumab IV in Chinese paediatric patients 
with SLE 
➢ Incidence of AEs through 52 Weeks 
➢ Incidence of SAEs through 52 Weeks 
➢ To evaluate the efficacy of belimumab IV in 
Chinese paediatric patients with SLE 
➢ Incidence of patients with 4 points reduction 
from Baseline in SELENA SLEDAI by visit 
➢ Change from Baseline to Week 52 in Physician 
Global Assessment (PGA) 


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Objectives 
Endpoints 
➢ Change from Baseline to Week 52 in Parent 
Global Assessment (ParentGA) 
➢ Change from Baseline in daily prednisone 
equivalent dose at Week 52 
➢ Time to first flare/ first severe flare over 52 
weeks 
➢ To evaluate the pharmacokinetics (PK) of 
belimumab (10 mg/kg) IV in Chinese paediatric 
patients with SLE 
➢ Median belimumab concentration levels at Day 
0, 7 and 14 days post first dose, and pre-
infusion and post-infusion at Day 84 
➢ The PK will be evaluated with respect to 
clearance, volume of distribution and half-life, 
and individual steady state exposures Cmin, 
Cavg, Cmax and AUC. 
AESI- adverse events of special interest, AUC- Area under the concentration curve, Cavg- average plasma 
concentration, IV- Intravenous, Cmin- the minimum blood plasma concentration reached by a drug prior to 
administration of a second dose, ParentGA - Parent Global Assessment, PGA- Physician Global Assessment, 
SELENA SLEDAI- Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease 
Activity Index 
 
Overall Design: This is a multicentre, open label, single arm, prospective, 52-week study 
to assess the safety and efficacy of belimumab IV administered in combination with 
background standard therapy. The pharmacokinetics of belimumab will be assessed in a 
subset of participants. 
Disclosure Statement: This is a single arm treatment study with no masking.  
Number of Participants: 
The sample size is justified by safety aim to capture the serious infection events as well 
by the purpose of evaluating efficacy in Chinese paediatric patients with active SLE. 
Focusing on adverse events (AEs) of serious infection, the incidence rate of the serious 
AEs of “Infections and Infestations” system organ class (SOC) was 7.5% in the 
10 mg/kg-IV group of the phase II international joint study. Furthermore, for efficacy, the 
estimated percentage of subjects with ≥4-point reduction from Baseline in SELENA 
SLEDAI at Week 52 is 54.7%. Based on incidence rate of serious infections and efficacy 
endpoints in a previous study, approximately 65 participants are required to be enrolled in 
this study.  
Note: "Screened" means that a participant, or their legally acceptable representative, 
agreed to participate in a clinical study following completion of the informed consent 
process. Participants who are assigned to treatment will be considered as Enrolled 
participants.  
Intervention Groups and Duration: All the enrolled participants will be administered 
Belimumab (10 mg/kg) intravenously over a minimum of 1 hour on Days 0, 14, 28 and 
then every 28 days through the Week 48 (Day 336) visit. 


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Safety Review Team (SRT): An internal GSK Safety Review Team will monitor and 
perform in-stream review of safety data throughout the study. 
1.1.1. 
Schema 
 
 
 
 


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1.2. 
Schedule of Activities (SoA) 
Procedure 
Screening  
Observational Period (52 Weeks) 
 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
Study Day 
up to -35 
days 
Day 
0 
Day 
7  
±1 
day 
Day 
14 
±3 
days 
Day 
28 
±3 
days 
Day 
56 
±7 
days 
Day 
84 
±7 
days 
Day 
112 
±7 
days 
Day 
140 
±7 
days 
Day 
168 
±7 
days 
Day 
196 
±7 
days 
Day 
224 
±7 
days 
Day 
252 
±7 
days 
Day 
280 
±7 
days 
Day 
308 
±7 
days 
Day 
336 
±7 
days 
Day 364 
or Exit (4 
weeks 
post last 
dose)1 ±7 
days 
16 Week 
post last 
dose 
Follow-
Up9 
±7 days 
Study Week 
 
Wk 
0 
Wk 
1 
Wk 
2 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
16 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52 / 
EW 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Assessments 
Concomitant 
Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Symptom Driven 
Physical Exam 
X7 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signs 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Daily Prednisone 
Dose 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight +Height 2 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray 
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 
Haematology 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


T M F -1 7 7 4 5 5 5 6  
C O N FI D E N TI A L  
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
1 5  
 
Pr o c e d ur e  
S cr e e ni n g  
O b s er v ati o n al Peri o d ( 5 2 W e e k s)  
 
Vi sit  
V 1  
V 2  
V 3  
V4  
V5  
V6  
V7  
V8  
V9  
V1 0  
V1 1  
V1 2  
V 1 3  
V 1 4  
V 1 5  
V 1 6  
V 1 7  
V 1 8  
St u d y D a y  
u p t o  -3 5  
d a y s  
D ay  
0  
D ay  
7  
± 1 
d ay  
D ay  
1 4 
± 3 
d ays  
D ay  
2 8 
± 3 
d ays  
D ay  
5 6 
± 7 
d ays  
D ay  
8 4 
± 7 
d ays  
D ay  
1 1 2 
± 7 
d ays  
D ay  
1 4 0 
± 7 
d ays  
D ay  
1 6 8 
± 7 
d ays  
D ay  
1 9 6 
± 7 
d ays  
D ay  
2 2 4 
± 7 
d ays  
D ay  
2 5 2 
± 7 
d ays  
D ay  
2 8 0 
± 7 
d ays  
D ay  
3 0 8 
± 7 
d ays  
D ay  
3 3 6 
± 7 
d ays  
D ay 3 6 4 
or E xit  ( 4 
w e eks 
p ost l ast 
d os e) 1 ± 7 
d ays  
1 6 W e ek  
p ost l ast 
d os e  
F oll o w -
U p 9 
± 7 d ays  
St u d y W e e k  
 
W k  
0  
W k  
1  
W k  
2  
W k  
4  
W k 
8  
W k  
1 2  
W k 
1 6  
W k 
2 0  
W k  
2 4  
W k 
2 8  
W k 
3 2  
W k  
3 6  
W k 
4 0  
W k 
4 4  
W k  
4 8  
W k 5 2  / 
E W  
 
Uri n alysis 3 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
S p ot Uri n e ( pr ot ei n 
t o cr e ati ni n e r ati o) 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
Pr e g n a ncy T est 4 , 8 
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
A N A  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HI V, H e p atitis B 
a n d C scr e e ni n g  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Q u a nti F E R O N -T B 
G ol d Pl us   
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
P T, P T T  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Effi c a c y  A s s e s s m e nt  
S E L E N A S L E D AI  
X  
X  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
S L E Fl ar e I n d ex  
X  
X  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
P G A  
X  
X  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
P ar e nt G A  
X  
X  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
St u d y Tr e at m e nt  
B eli m u m a b 
a d mi nistr ati o n  
 
X 6 
 
X 6 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
P K S a m pli n g 5 
 
X  
X 1 0 
X 1 1 
 
 
X 1 2 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI
C CI


T M F -1 7 7 4 5 5 5 6  
C O N FI D E N TI A L  
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
1 6  
 
A N A - A nti -n ucl e ar a nti b o dy, 
, E C G- el ectr oc ar di o gr a m, E W - E arly wit h dr a w al, 
 P T- Pr ot hr o m bi n ti m e, P T T - Parti al t hr o m b o pl asti n ti m e, S EL E N A S L E D AI - Saf ety of Estr o g e n i n L u p us N ati o n al Ass ess m e n t - Syst e mic 
L u p us Eryt h e m at os us Dis e as e Activity I n d ex, Wk - W e ek  
1.  
T h e Exit visit ( D ay 3 6 4) will occ ur a p pr oxi m at ely 4 w e eks aft er t h e l ast d os e of b eli m u m a b. F or p artici p a nts w h o wit h dr a w fr o m tr e at m e nt pri or t o W e ek 4 8, i n a d diti o n t o t h e 1 6 -
w e ek f oll o w-u p visit a n d ass ess m e nts, a n E W visit s h o ul d b e c o m pl et e d. T h e E W visit r e q uir es i d e ntic al ass ess m e nts a n d pr oc e d ur es t o t h e W e ek 5 2 visit.  
2.  
T h e p artici p a nt’s w ei g ht at t h e c urr e nt visit s h o ul d b e us e d f or c alc ul ati n g t h e d os e t o b e a d mi nist er e d.  
3.  
Ur i n alysis i ncl u d es r o uti n e a n alysis a n d uri n ary s e di m e nts.  At scr e e ni n g, it will als o i ncl u d e a n alysis of dr u g a n d alc o h ol pres e nc e.  
4.  
S er u m pr e g n a ncy t est r e q uir e d at scr e e ni n g f or all f e m al es of c hil d b e ari n g p ot e nti al. Uri n e pr e g n a ncy t est is s uffici e nt f or all s u bs e q u e nt visits. A h o m e uri n e pr e g n a ncy t est will 
b e pr ovi d e d t o all f e m al e p artici p a nts of c hil d b e ari n g p ot e nti al.  
5.  
O nly f or p artici p a nts ( a p pr oxi m at ely 2 5) fr o m w h o m P K s a m pl es will b e c oll ect e d at D ay 0 ( 0 -4 h o urs aft er t h e e n d of i nf usi o n), D ay 7 a n d D ay 1 4 ( pr e -i nf usi o n) a n d D ay 8 4 
( b ef or e t h e st art of i nf usi o n a n d 0-4 h o urs aft er t h e e n d of i nf usi o n) . 
6.  
P artici p a nts will r e m ai n u n d er cli nic al s u p ervisi o n f or 3 h o urs aft er c o m pl eti o n of b eli m u m a b i nf usi o n  
7.  
C o m pl et e p hysic al ex a mi n ati o n will b e d o n e  d uri n g t h e visit.  
8.  
F or f e m al e p artici p a nts w h o ar e n ot w o m e n of c hil d b e ari n g p ot e nti al ( W O C B P) at t h e scr e e ni n g b ut b ec o m e W O C B P d uri n g t h e st u d y, t h e i nv esti g at or will c o nfir m t h e W O C B P 
st at us of f e m al e p artici p a nts d uri n g e ac h visit a n d st art wit h pr e g n a ncy t esti n g fr o m t h at visit o n w ar ds.  
9.  
T h e 1 6 -w e ek f oll o w -u p r e q uir es a p h o n e c all t o c oll ect A Es a n d t h e r es ults of h o m e uri n e pr e g n a ncy t est (if a p plic a bl e) f or f e m al e p artici p a nts.  T h e 1 6 -w e ek f oll o w -u p m ay b e 
p erf or m e d at a cli nic visit p er l oc al r e q uir e m e nt.  If t h e p artici p a nt tr a nsf ers i nt o st u dy 2 1 7 0 9 1, 1 6-w e ek f oll o w -u p visit will n ot b e c o n d uct e d.  
1 0.  If miss t h e s a m pl e c oll ecti o n o n visit 3, t h e P K s a m pli n g s h o ul d b e r esc h e d ul e d t o a ny f e asi bl e visit at 7 d ays aft er d osi n g wit h ± 3 d ays wi n d o w.  
1 1.  If miss t h e s a m pl e c oll ecti o n o n visit 4, t h e P K s a m pli n g s h o ul d b e r esc h e d ul e d t o a ny f e asi bl e visit at 1 4 d ays aft er d osi n g wi t h ± 7 d ays wi n d o w. 
1 2.  If miss t h e s a m pl e c oll ecti o n o n visit 7, t h e P K s a m pli n g s h o ul d b e r esc h e d ul e d t o w h e n p ati e nts t ak e t h e n ext dos e.  
 
 
 
C CI
C CI


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2. 
INTRODUCTION 
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterised by 
autoantibody production and abnormal B lymphocyte function. This disorder shares the 
same aetiology, pathogenesis and diagnosis criteria in paediatric and adult patients 
[Stichweh, 2004; Thakral, 2016]. 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 (BENLYSTA™) for intravenous (IV) use was approved in the USA in 2011 
as an add-on treatment for adult patients with autoantibody positive SLE despite standard 
therapy. Belimumab IV was approved by the China National Medical Products 
Administration to treat adult patients with active SLE on 12 July 2019. Results from a 
phase 2 study (BEL110455) with belimumab in paediatric SLE patients have supported 
approval of an SLE paediatric indication in children 5-17 years of age in the USA 
(approval in 26 April 2019), the European Union (approval 21 October 2019) and Japan 
(20 September 2019). 
2.1. 
Study Rationale 
The treatment strategy and medications for SLE are similar between adults (including 
Chinese) and paediatric patients [Stichweh, 2004; Thakral, 2016]. The existing data of 
belimumab in Western children (age 5-17 years), adults from Western and northeast Asia 
allow extrapolation of efficacy to Chinese paediatric patients at the approved dose of 10 
mg/kg IV, leading to waiver of phase 3 clinical trial in Chinese paediatric population.  
However, there is an absence of information on the safety and efficacy profile of 
Belimumab in Chinese paediatric SLE patients. The differences between China and 
Western countries in population density, environment and endemic pathogens may 
influence the infection rate and safety profile of belimumab in Chinese paediatric 
population. In addition, the pharmacokinetic profile of belimumab should be further 
investigated to demonstrate if exposure in Chinese paediatric SLE patients is similar to 
SLE paediatric patients in Western countries. 
Based on a requirement from China’s Centre for Drug Evaluation (CDE), 
GlaxoSmithKline intends to conduct a post approval commitment (PAC) study in 
Chinese paediatric patients. The objective of this study is to evaluate safety and efficacy 
of belimumab IV plus background standard therapy in Chinese paediatric patients with 
active SLE aged 5 to 17 years, and to characterise the pharmacokinetic profile in a subset 
of the study population. 
2.2. 
Background 
The safety profile of belimumab is consistent between the Western adult studies 
(HGS1006-C1056, HGS1006-C1057, LBSL02; also referred to as the IV Controlled 
Repeat Dose [CRD] studies) and the North East Asian adult studies (BEL113750). BEL 
113750 was a Phase 3, multi-centre, randomised, double-blind, placebo-controlled study, 
consisting of a 52-week blinded period in Northeast Asia, followed by an open-label 


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extension period in China to evaluate the efficacy and safety. Also, consistency was also 
demonstrated between paediatric and adult studies safety results.  
2.2.1. 
Safety of Belimumab 
The safety of belimumab in paediatric subjects has been evaluated in one placebo-
controlled study, BEL114055. 
In the double-blind phase of study BEL114055, 82.5% of subjects experienced at least 1 
AE in placebo group and 79.2% in the belimumab 10 mg/kg group. 35.0% of subjects 
experienced at least 1 SAE in placebo group and 17.0% in the belimumab group. The 
SOC with the highest incidence of SAEs was infections and infestations (12.5%, placebo; 
7.5%, belimumab). Adverse events of special interest in this protocol were death, 
malignancies, infusion and hypersensitivity reactions, infections, and suicidality. The 
overall incidence of all infections of special interest was 7.5% in the placebo group and 
13.2% in the belimumab group. The incidences of all serious infections of special interest 
(2.5% placebo, 1.9% belimumab) and all serious opportunistic infections per GSK 
adjudication (0% placebo, 1.9% belimumab) were similar between treatment groups. No 
subjects in either treatment group experienced a malignancy AESI. The incidence of 
depression/suicide/self-injury AESI was 10.0% in the placebo group and 1.9% in the 
belimumab 10 mg/kg group. One (2.5%) subject in the placebo group experienced a fatal 
SAE (pancreatitis acute), while no death occurred in the belimumab group. 
The safety results in adult study in Northeast Asia including patients from China 
(BEL113750) and the Western pivotal studies population (1C056 and C1057) are 
comparable with the paediatric study (BEL114055) presented above. Therefore, it may be 
estimated that a comparable safety profile would be expected in paediatric patients from 
China. 
2.2.2. 
Efficacy of Belimumab 
There were comparable efficacy results found in the adult study in Northeast Asia 
including patients from China (BEL113750), the pivotal studies in Western population 
(C1056 and C1057), and the paediatric study (BEL114055). Therefore, a comparable 
efficacy would be expected in paediatric patients from China. 
The SLE Responder Index (SRI) Response rate at Week 52 for belimumab versus 
placebo was analysed post-hoc for the subgroup of race. The SRI response rates and 
observed differences between belimumab versus placebo were generally consistent 
within the racial groups, although the small number of subjects in the subgroups limits 
interpretation of these results. The odds of being an SRI responder at Week 52 versus 
placebo favoured belimumab in all cases, with a range of odds ratio (OR) 1.32 in White 
subjects (95% CI: 0.42, 4.18) to OR 1.67 in Asian subjects (95% CI: 0.11, 24.25). These 
results in the Asian subgroup are also consistent with the observed differences in overall 
study population that had a percentage of SRI responders of 52.8% for the belimumab 
group compared with 43.6% for the placebo group, an observed difference of 9.24% and 
OR of 1.49. 


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2.2.3. 
Pharmacokinetics of Belimumab 
The Pharmacokinetics of IV belimumab (dose ranging from 1 to 20 mg/kg) has been 
extensively studied in adults with SLE studies (Phase 1, Phase 2, and Phase 3). The PK 
has been studied in a smaller paediatric population (study BEL114055) and in Chinese 
adults (study BEL113750). Population PK analyses have been conducted in both adults 
(Report No. HGS1006-POPPK) and paediatrics (BEL114055 POPPK). Steady-state 
geometric mean Cmax, Cmin, Cavg, and AUC values were, respectively, 315 g/mL, 
50 g/mL, 108 g/mL, and 3012 day.g/mL in the overall paediatric population; 
305 g/mL, 42 g/mL, 92 g/mL, and 2569 day.g/mL in the 5-11-year-old group, and 
317 g/mL, 52 g/mL, 112 g/mL, and 3126 day.g/mL in the 12-17-year-old group 
compared to 311 g/mL, 46 g/mL, 100 g/mL, and 2811 day.g/mL in adults. The 
results showed belimumab PK to be dependent on body weight, dose-proportional and 
time-invariant after IV administration, similar to many monoclonal antibodies targeting 
soluble ligands. Because of body weight difference between Asian and Caucasian 
subjects, there is small difference in exposure of belimumab when the same dosing 
regimens are given. However, no clinically relevant difference in efficacy has been 
observed. 
2.2.4. 
Pharmacodynamics of IV Belimumab 
Similar to results of adult IV [Stohl, 2012] studies, reductions in overall B cells, naive B 
cells, other B cell subsets, and immunoglobulins were observed following IV belimumab 
administration in paediatric participants in the double blind phase of BEL114055 [GSK 
document number 2017N34326_00]. 
2.3. 
Benefit/Risk Assessment 
Overall, the positive benefit/risk profile of IV belimumab in the BEL114055 paediatric 
SLE cohort appears consistent with that of adult IV and subcutaneous (SC) study 
populations. More detailed information about the known and expected benefits and risks 
and reasonably expected adverse events of belimumab may be found in the current 
Investigator brochure (IB) [IB, GSK document number 2011N128591_06, 2020] and IB 
supplement(s) (if applicable) and product label. 


T M F -1 7 7 4 5 5 5 6  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
2 0  
 
2. 3. 1.  
Ri s k A s s e s s m e nt  
P ot e nti al Ri s k of Cli ni c al Si g nifi c a n c e  
S u m m ar y of D at a/ R ati o n al e f or Ri s k  
Miti g ati o n Str at e g y  
I n v e sti g ati o n al Pr o d u ct - G S K 1 5 5 0 1 8 8/ b eli m u m a b  
I nf e cti o n s 
As wit h ot h er i m m u n o m o d ul at ors, t h e m ec h a nis m of 
acti o n of b eli m u m a b, w hic h r es ults i n a r e d ucti o n i n B -
c ells a n d I g G, m ay i ncr e as e risk f or t h e d ev el o p m e nt 
of i nf ecti o ns i ncl u di n g s ev er e i nf ecti o ns, o p p ort u nistic 
i nf ecti o ns a n d Pr o gr essiv e m ultif oc al 
l e uko e nc e p h al o p at hy ( P M L ). F at al i nf ecti o ns h av e 
b e e n r e p ort e d i n S L E p ati e nts r ec eivi n g 
i m m u n os u p pr ess a nt t h er a py, i ncl u di n g b eli m u m a b. 
T h e r at e of s eri o us i nf ecti o ns f or S L E is 
5 % of p artici p a nts r ec eivi n g eit h er 
b eli m u m a b or pl ac e b o.  
Excl usi o ns (s e e S ecti o n 5. 2 ) b as e d o n hist ory of pri m ary i m m u n o d efici e ncy, 
 d efici e ncy  
l ev el < 1 0 m g/ d L), ac ut e or c hr o nic i nf ecti o ns r e q uiri n g 
m a n a g e m e nt, s er ol o gic  evi d e nc e of H e p atitis B, H e p atitis C or HI V i nf ecti o n, 
a n d gr a d e 3 ( or gr e at er) hy p o g a m m a gl o b uli n e mi a or (if u nr el at e d t o S L E) 
gr a d e 3 ( or gr e at er) n e utr o p e ni a, ly m p h o p e ni a, l e uk o p e ni a will b e a p pli e d.  
Partici p a nts w h os e I g G l ev el f alls b el o w 2 5 0  m g/ d L w ill h av e b eli m u m a b 
tr e at m e nt wit h h el d ( S e e S ecti o n 8. 3. 1  Cli nic al L a b or at ory Ass ess m e nts), a n d 
t h e a p pr o pri at e n ess t o c o nti n u e d osi n g m ust b e disc usse d a n d a gr e e d wit h 
t h e M e dic al M o nit or b ef or e t h e n ext d os e. A ny p artici p a nt w h os e I g G l ev el 
f alls b el o w 2 5 0 m g/ d L a n d is ass oci at e d wit h a s ev er e or s eri o us i nf ecti o n 
will h av e st u dy a g e nt p er m a n e ntly disc o nti n u e d.  
A di a g n osis of P M L s h o ul d b e c o nsi d er e d i n a ny p artici p a nt pr es e nti n g wit h 
n e w -o ns et or d et eri or ati n g n e ur ol o gic al si g ns a n d sy m pt o ms. T h e p artici p a nt 
s h o ul d b e r ef err e d t o a n e ur ol o gist or ot h er a p pr o pri at e s p eci alist f or 
ev al u ati o n. If P M L is c o nfir m e d, disc o nti n u ati o n of b eli m u m a b s h o ul d b e 
co nsi d er e d. If P M L is s us p ect e d, t his s h o ul d b e r e p ort e d t o t h e M e dic al 
M o nit or wit hi n 2 4 h o urs.  T h e a p pr o pri at e n ess of c o nti n ui n g b eli m u m a b 
d osi n g w hil e t h e c as e is b ei n g ass ess e d, s h o ul d b e disc uss e d.  
I nf u si o n-R el at e d r e a cti o n s, H y p er s e n siti vit y R e a cti o n s a n d I m m u n o g e ni cit y  
A d mi nistr ati o n of b eli m u m a b m ay r es ult i n i nf usi o n -
r el at e d syst e mic r e acti o ns a n d all er gic/ hy p ers e nsitivity 
r e acti o ns. 
Ad mi nistr ati o n of b eli m u m a b m ay r es ult i n 
i nf usi o n a n d hy p ers e nsitivity r e acti o ns, 
w hic h c a n b e s ev er e a n d c a n b e f at al. 
D el ay i n t h e o ns et of s eri o us 
hy p ers e nsitivity r e acti o ns c a n occ ur. 
Beli m u m a b h as b e e n ass oci at e d wit h 
d el ay e d ty p e n o n -ac ut e hy p ers e nsitivity 
r e acti o n ( H S R)/s er u m sick n ess, alt h o u g h 
Partici p a nts wit h a hist ory of a n a n a p hyl actic r e acti o n t o p ar e nt er al 
a d m i nistr ati o n of c o ntr ast a g e nts, h u m a n or m uri n e pr ot ei ns, or m on ocl o n al 
a nti b o di es will b e excl u d e d fr o m t his st u dy.  
Partici p a nts will r e m ai n u n d er cli nic al s u p ervisi o n f or 3 h o urs aft er c o m pl eti o n 
of t h e first 2 b eli m u m a b i nf usi o ns. 
Partici p a nts will b e m a d e a w ar e of t h e p ot e nti al risk, t h e si g ns a n d sy m pt o ms 
of s uc h r e acti o ns, a n d t h e i m p ort a nc e of i m m e di at ely s e eki n g m e dic al 
C C
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
no relationship to anti-drug antibody 
(ADA) has been established. 
Infusion-related systemic reactions and 
hypersensitivity reactions occur more 
frequently with the first two doses and 
tend to decrease with subsequent doses.  
attention. Patients will be given an alert card for hypersensitivity/allergic 
reactions. 
Malignancy 
As with other immunomodulating agents, the 
mechanism of action of belimumab may increase the 
potential risk for the development of malignancies.  
Immunomodulatory drugs like belimumab 
may increase the risk of malignancy. To 
date, no causal relationship between 
belimumab and malignancy, including B 
cell lymphoma, has been detected. 
Participants with a history of malignancy in the 5 years prior to screening will 
be excluded. 
Monitor patients for signs and symptoms of malignancy, monitor laboratory 
values, request that patients report signs and symptoms. Treat appropriately. 
Interactions with Vaccinations 
Because of its mechanism of action, belimumab may 
interfere with the response to immunisations. 
The efficacy of concurrent vaccination in 
patients receiving belimumab is not 
known; however, in the belimumab 
vaccination trial, evaluation of the impact 
of belimumab treatment on response to 
on-treatment vaccination with 23-valent 
pneumococcal vaccine revealed that 
immune responses to the different 
serotypes were similar in SLE patients 
receiving belimumab compared with those 
not receiving treatment at the time of 
vaccination. 
Immunisation with live or live attenuated vaccines is prohibited from 30 days 
prior to Day 0 and during belimumab use. 
Participants’ vaccination status should be assessed and current 
immunisation guidelines followed; all necessary vaccinations should be 
administered no later than 30 days prior to Day 0. 
Psychiatric Events 
Psychiatric events including depression and 
suicidality. 
 In a recent one-year, randomised, 
double-blind, placebo-controlled post 
marketing study (BEL115467) of 4,003 
subjects with SLE (1:1 randomisation): 
Serious adverse events (SAE) of suicidal 
ideation or behaviour or self-injury were 
Participants who, in the investigator’s opinion, pose a significant suicide risk 
will be excluded. 
Monitor participants for psychiatric signs and symptoms, request that 
patients report psychiatric symptoms. Treat psychiatric symptoms 
immediately and appropriately. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
reported in 0.7% (n= 15) of subjects 
receiving belimumab intravenously 
10 mg/kg (IV) vs. 0.2% (n=5) of subjects 
taking placebo. No suicide-related deaths 
were reported. SAEs of depression were 
reported in 0.3% (n=7) of subjects 
receiving belimumab 10 mg/kg IV vs. 
<0.1% (n=1) taking placebo. On the 
Columbia-Suicide Severity Rating Scale 
(C-SSRS), 2.4% (n=48) subjects on 
belimumab 10 mg/kg IV reported suicidal 
ideation or behaviour and 2.0% (n=39) 
subjects on placebo reported suicidal 
ideation or behaviour. 
Hypotension 
Risk of hypotension associated with hypersensitivity 
reaction. 
Hypotension may accompany 
infusion/post-injection systemic reactions 
with belimumab. This has rarely been 
observed in clinical studies with 
belimumab. 
Consider withholding anti-hypertensive medications 12 hours prior to 
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2.3.2. 
Benefit Assessment 
The primary data supporting efficacy of IV belimumab in adults are the Phase 3 trials 
(C1056 and C1057) in which 1684 participants were treated for up to 52 weeks (C1057) 
or 76 weeks (C1056) [Furie, 2011; Navarra, 2011]. Belimumab produced significant 
improvements in the SRI as well as in the individual component SELENA-SLEDAI score 
in both studies. Pooled analyses demonstrated steroid sparing and decreased risk of 
severe flares over 52 weeks. Data from completed belimumab clinical studies provided in 
the current IB and IB supplement(s) (if applicable) since approval continue to show 
efficacy in the treatment of SLE through decreased SLE flares and decreased disease 
activity across multiple organ systems. Similar results in adults were observed in the 
pivotal Phase 3 trial of belimumab SC 200 mg/week [Stohl, 2017], with significant 
improvements in the SRI and time to first severe flare endpoints. Overall efficacy of IV 
belimumab in a randomised placebo-controlled clinical trial in paediatric patients with 
SLE (BEL114055) was consistent with that seen in adult patients. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures that will be implemented to minimise risk to patients 
participating in this study, the potential risks associated with administration of 
belimumab are justified by the anticipated benefits that may be afforded to paediatric 
patients with SLE who choose to participate in this trial. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
Primary 
➢ To evaluate the safety and efficacy of 
belimumab IV in Chinese paediatric patients 
with SLE. 
Safety 
➢ Incidence of adverse events of special interest 
(AESIs) through 52 weeks: 
• 
All infections of special interest, including 
serious infections of special interest and 
opportunistic infections 
• 
Infusion-related systemic reactions and 
anaphylactic reactions  
• 
Depression, suicidality 
• 
Malignancies 
Efficacy 
➢ Incidence of patients with ≥4-point reduction 
from Baseline to Week 52 in SELENA SLEDAI 
 
 


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O bj e cti ve s  
E n d p oi nt s  
S e c o n d ar y  
S e c o n d ar y  
➢ T o ev alu at e s af ety a n d tol er a bility of 
b eli mu m a b I V i n C hi nes e p a edi atric  p atie nts 
wit h S L E  
➢ I nci d enc e of A Es t hr ou g h 5 2 W e ek s 
➢ I nci d enc e of S A Es t hr o ug h 5 2 w e eks 
➢ T o ev alu at e th e effic acy  of b eli m u m a b I V i n 
Chi n es e p a e diatric  p ati ents with S L E  
➢ I nci d enc e of p atie nts wit h 4 -p oi nt r e ductio n 
fr o m B as eli n e  i n S E L E N A S L E D AI by visit 
➢ C h a n g e fr o m B as eli n e  to W e ek  5 2 i n P hysicia n 
Gl o b al Assess m e nt ( P G A)  
➢ C h a n g e fr o m B as eli n e  to W e ek  5 2 i n P ar e nt 
Gl o b al Assess m e nt ( P are nt G A)  
➢ C h a n g e fr o m B as eli n e  i n d aily pr e d niso n e 
e q uiv al e nt d os e at W e ek  5 2 
➢ Ti m e t o first fl ar e/ first s ev ere fl ar e over 5 2 
w e eks  
➢ T o ev alu at e th e p h ar m acoki netics of  
b eli mu m a b (1 0  m g/k g) I V i n  Chi n es e p a e di atric  
p ati e nts wit h S L E  
➢ M e di a n b eli m u ma b co nc entr ati o n l ev els at D ay 
0 , 7 a n d 1 4 d ays p ost first d ose, a n d pr e-
i nf usio n a nd p ost -i nf usi o n at Day 8 4  
➢ T h e P K will be ev al u at ed wit h r es p ect t o 
cl e ar a nc e, v ol u m e of distri b utio n a n d half-lif e, 
a n d i n divid u al st e a dy stat e exp os ur es C mi n, 
C av g, C m ax a n d A U C.  
Ot h er  
Ot h er  
A E SI - a dv ers e ev e nts of s p eci al i nt er est, A U C - Ar e a u n d er t h e c o nc e ntr ati o n c urv e, C mi n - t h e mi ni m u m bl o o d pl as m a 
c o nc e ntr ati o n r e ac h e d by a dr u g pri or t o a d mi nistr ati o n of a s ec o n d d os e, C av g - av er a g e pl as m a c o nc e ntr ati o n, I V - 
I ntr av e n o us, P ar e nt G A - P ar e nt Gl o b al Ass ess m e nt, P G A - Physici a n Gl o b al Ass ess m e nt, S EL E N A S L E D AI - Saf ety of 
Estr o g e n i n L u p us N ati o n al Ass ess m e nt - Syst e mic L u p us Eryt h e m at os us Dis e as e A ctivity I n d ex 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
T his is a m ultice ntre, si n gle ar m, pr os pecti ve, 5 2 -wee k st u d y t o c ollect a n d assess t he 
safet y a n d effic ac y  of beli m u ma b I V a d mi nistere d i n c o m bi nati o n wit h bac k gr o u n d 
sta n dar d t hera p y i n 6 5 pae diatric  partici pa nt s a ge d 5  t o 1 7 years wit h acti ve S L E. T he 
p har mac o ki netic pr ofile of beli m u ma b will be i n vesti gate d i n a s u bset of p artici pa nts.  
Pae diatric  partici pa nt s wit h S L E as dia g n ose d wit h A merica n C olle ge of R he u mat ol o g y 
( A C R) classificati o n criteria w h o ha v e acti ve dise ase ( defi ne d as S E L E N A S L E D AI 
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score ≥8) at screening will be enrolled. Participants need to be on stable standard SLE 
therapy for at least 30 days prior to Baseline. 
Belimumab (10 mg/kg) will be administered intravenously over a minimum of 1 hour on 
Days 0, 14, 28, and then every 28 days through the Week 48 (Day 336) visit. All 
participants will continue to receive their standard SLE therapy with restrictions on the 
changes that are permitted throughout the 52-week observational period. Participants 
completed the last Benlysta IV administration at Week 48 and transfer to study 217091 
successfully will continue to complete the 52-week visit of 213560. However, 16-week 
follow-up visit will not be conducted. 
Participants may withdraw or discontinue from the study at any time for any reason. 
Participants withdrawing from belimumab treatment will return for an exit visit, i.e. 4 
weeks after their last dose of belimumab, and then continue safety monitoring at the 
scheduled visit (Section 1.2) until Day 364 if they are willing to stay in safety 
monitoring. Participants choosing to discontinue from the study and not willing to 
continue for safety monitoring will return for Exit visit following their last dose of 
belimumab for safety monitoring. 
Participants who complete this study and who are willing to continue belimumab IV 
treatment with commercially available BENLYSTA™ may participate in an ongoing 
Intensive Drug Monitoring study of belimumab (Study 213210). 
4.2. 
Scientific Rationale for Study Design 
Recent and past studies consistently show that adult and paediatric SLE patients have 
increased serum B-lymphocyte stimulator (BLyS) levels [Cheema, 2001; Hong, 2009; 
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 prone 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 4 pivotal adult lupus studies. In general, 
paediatric SLE patients have more severe disease and thus higher disease activity index 
on an average than adults. Adult SLE patients who presented with disease that is more 
active performed better with belimumab. Based on this information, it is hypothesised, 
that belimumab will have a beneficial effect in the paediatric SLE population. 
Results of phase 2 study (BEL110455) of belimumab in 93 paediatric SLE patients 
demonstrated similar efficacy and safety profile in paediatric and adult Western 
population. Belimumab was granted approval in the United states (US)/Japan/European 
Union (EU) in 2019 to extend the indication to paediatric patients aged 5 to 17 years with 
active SLE despite standard therapy.  
The existing data thus allow extrapolation from Western paediatrics to Chinese paediatric 
patients at the approved dose of 10 mg/kg IV and a waiver of phase 3 clinical trial in 
Chinese paediatric population. However, there is an absence of safety and efficacy profile 
in Chinese paediatric SLE patients. Overall consistent steady-state average concentrations 
(Cavg_ss) were predicted in Chinese paediatric patients and Western/Chinese adults 


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base d o n a p o p ulati o n P K a nal ysis ( G S K d oc u me nt n u m ber 2 0 2 0 N 4 2 7 5 1 7 _ 0 0 ). 
H o we ver, t he P K e x p os ure of beli m u ma b is t o be f urt her c o nfir me d i n C hi nese pae di atric  
S L E patie nts. T o s u p p ort t he re gistrati o n of pae diatric  S L E i n dicati o n i n C hi na, P A C will 
be  c o n d ucte d t o d e m o nstrate t hat beli m u ma b e x p os ure, efficac y a n d safet y o bser ve d i n 
Wester n p ae diatric  p o p ul ati o n is si milar t o t hat o bser ve d i n C hi nese a n d Wester n a d ults.  
T he pri mar y o bje cti ve of t his st u d y is t o e val uate t he safet y  a n d efficac y  of beli m u ma b i n 
C hi nese pae diatric  p atie nts a ge d 5  t o 1 7 years wit h acti ve S L E des pite sta n d ar d t hera p y. 
Pri mar y safet y e n d p oi nt is t he o cc urre nce of A E SI . Pri mar y efficac y  e n d p oi nt defi ne d as  
i nci de nce of patie nts wit h 4 -p oi nt re d ucti o n fr o m Baseli ne  t o Wee k  5 2 i n S E L E N A 
S L E D AI sc ore. Sec o n dar y safet y e n d p oi nt is occ urre nce of A Es a n d S A Es. Sec o n dar y 
effic ac y  e n d p oi nts i ncl u d e i nci de nce of patie nts wit h 4 -p oi nt re d ucti o n i n S E L E N A 
S L E D AI sc ore fr o m Bas eli ne  t o Wee k  5 2 b y visit, P h ysicia n gl o bal assess me nt ( P G A), 
pare nt gl o bal assess me nt ( Pare nt G A), c ha n g e i n dail y pre d nis o ne d ose a n d S L E flare 
i n de x. 
 
  
T his st u d y will c ollect t he p har mac o ki netic sa m pl es of beli m u ma b t o de m o nstrate if 
e x p os ure i n a s u bset ( ap pr o xi matel y  2 5 ) of C hi nes e pae diatri c  patie nts  wit h S L E  is 
si milar t o Wester n pae diatric  patie nts  wit h S L E . S u m mar y statistics i ncl u di n g m e dia n 
beli m u ma b c o nce ntr ati o n le vels at D a y 0 , D a y 7 , D a y 1 4 a n d Da y 8 4 ( Wee k 1 2 ) will be 
calc ulate d. T h e feasi bilit y of t his will lar gel y de pe n d o n data a v aila bilit y, alt h o u g h eff orts 
will be ma de t o c olle ct as m uc h i nf or mati o n as p ossi ble. T he s u bse q ue nt dat a a nal ysis 
ra n ges fr o m s u m mar y statistics at sa m pli n g ti mes t o a m o delli n g a n d si m ulati o n a nal ysis 
after data p o oli n g wit h ot her st u d y data. If nee d e d, res ults of t he a nal ysis a n d c o m paris o n 
wit h ot her st u dies (e. g., B E L 1 1 0 4 5 5 ) will be re p orte d i n a se parate d oc u me nt. 
4. 2. 1.  
P arti ci p a nt I n p ut i nt o D e si g n  
N ot A p plica ble  
4. 3.  
J u stifi c ati o n f or D o s e  
I ntr a ve n o us a d mi nistrati o n  of beli m u ma b 1 0 m g/ k g at 2 -wee k i nter vals f or t he first 3 
d oses a n d at 4 -w ee k i nter vals t hereafter h as bee n a p pr o ve d i n Wester n a n d C hi nese a d ults 
a n d i n pae diatric  p atie nts  i n t he U S, t he E U a n d Ja pa n. F ro m t he pre dicti o n base d o n 
p o p ulati o n P K m o del, i n C hi nese pe diatric patie nts wit h S L E, beli m u ma b 1 0 m g/ k g I V 
Q 4 W is e x pect e d t o ha ve e x p os ure si milar t o t hat i n C hi nese a d ults a n d n o n -C hi nese 
pe diatric patie nts wit h S L E, s u p p orti n g t he use of t his re gi me n i n C hi nese pe diatric 
patie nts wit h S L E ( G S K d oc u me nt n u m ber 2 0 2 0 N 4 2 7 5 1 7 _ 0 0 ). T he st u d y will t heref ore 
a d o pt t he sa me d osi n g re gi me n.  
4. 4.  
E n d of St u d y D efi niti o n  
A partici pa nt is c o nsi dere d t o ha ve c o m plet e d t he st u d y if he/s he has c o m plete d all 
p hases of t he st u d y u p t o a n d i ncl u di n g t he Wee k 5 2 visit.  
C CI


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T he e n d of t he st u d y is d efi ne d as t he d ate of t he l ast assess me nt ( 1 6 -wee k p ost -treat me nt 
f oll o w-u p) of t he last partici pa nt i n t he st u d y.  F or partici pa nts s witc h t o st u d y 2 1 7 0 9 1 , t he 
e n d of t he st u d y defi ne d as c o m plete d Wee k 5 2 visit.  
5.  
S T U D Y P O P U L A TI O N  
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr ol me nt criteria, als o 
k n o w n as pr ot oc ol wai v ers or e xe m pti o ns, is n ot per mitte d.  
5. 1.  
I n cl u si o n Crit eri a 
T y pe of P artici p a nt a n d Dise ase C h ar acteristi cs  
1.  Partici pa nts ha ve or ha ve ha d i n series, 4 or m ore of t he A merica n C olle ge of 
R he u mat ol o g y ( A C R) 1 1 criteria f or t he classifi cati o n of S L E ( Secti o n 1 0. 7 : 
A p pe n di x 7 ). 
2.  Partici pa nt’s a ge is 5 t o 1 7 years at t he ti me of i nf or me d c o nse nt . 
3.  Ha ve acti ve S L E disease defi ne d as a S E L E N A S L E D AI sc ore 8 at scree ni n g 
( S E L E N A S L E D AI sc ori n g see Secti o n 1 0. 8 : A p pe n di x 8 ). 
4.  Ha ve u ne q ui v o call y p ositi ve a ut oa nti b o d y test res ults defi ne d as a n A N A titre 1: 8 0 
a n d/ or a p ositi ve 
 ser u m a nti b o d y test.  
5.  Are o n a sta bl e S L E t hera p y at Baseli ne .  
T he sta ble treat me nt at Baseli ne  c o nsists of c ortic oster oi ds, a nti -malarials, 
i m m u n os u p pressi ve/i m m u n o m o d ulat or y a ge nts a n d N S AI Ds, al o ne or i n 
c o m bi nati o n, at a fi xe d d ose f or a p eri o d of at least 3 0 da ys pri or t o Da y 0.  
a)  C ortic oster oi ds ( pre d nis o ne or pre d nis o n e e q ui val e nt u p t o 0. 5 m g/ k g/ da y):  
i. 
F or t h ose partici pa nt s o n alter nati n g da y d oses of ster oi ds, use t he 
a vera g e of 2 d ail y d oses t o calc ulate t he a vera ge d ail y ster oi d d ose.  
b)  Ot her i m m u n os u p pressi ve or i m m u n o m o d ulat or y a ge nts i ncl u di n g met h otre xate, 
azat hi o pri ne, lefl u n o mi de, m yc o p he n olate (i ncl u di n g m yc o p he n olate m ofetil, 
m yc o p he n olate m ofetil h y dr oc hl ori de, a n d m y c o p he n olate s o di u m), cal ci ne uri n 
i n hi bit ors (e. g. tacr oli m us, c ycl os p ori ne), sir oli m us, oral c ycl o p h os p ha mi de, 6-
merca pt o p uri n e or t hali d o m i de. 
c)  A nti -malarials (e. g. h y dr o x yc hl or o q ui ne, c hl or o q ui ne, q ui nacri ne)  
d)  N o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds)  
e)  Ne w S L E t hera p y m ust n ot be a d de d wit hi n 3 0 da ys of Da y 0.  
Se x  
6.  
Male a n d/ or fe male  
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Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
 
Male Participants 
No contraceptive measures are required for male participants. 
Female participants: 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
• 
Is not a WOCBP (See Section 10.4, Appendix 4) 
OR 
• 
Is a WOCBP and is using a contraceptive method that is highly effective, with a 
failure rate of <1%, as described in Section 10.4 (Appendix 4) during the 
belimumab treatment period and for at least 16 weeks, corresponding to the time 
needed to eliminate any study intervention(s) (e.g., 5 terminal half-lives), after 
the last dose of study intervention. The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of 
study intervention. 
A WOCBP must undergo a negative highly sensitive [Section 10.2, Appendix 2] 
pregnancy test (serum or as required by local regulations) within 35 days before the first 
dose of belimumab. 
7. The investigator is responsible for review of medical history, menstrual history and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Informed Consent 
8. The investigator, or a person designated by the investigator, will obtain written 
informed assent from each study participant or the participant's legally acceptable 
representative, parent(s), or legal guardian and the participant’s assent, when 
applicable, before any study-specific activity is performed. The investigator will 
retain the original copy of each participant's signed assent document. 
 


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5. 2.  
E x cl u si o n Crit eri a  
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
Me dic al C o n diti o ns  
1.  Ha ve a n esti mate d gl o mer ular filtrati o n rat e (e G F R) as calc ulat e d b y Sc h wartz 
F or m ula of less t ha n 3 0 m L / mi n. 
2.  Ha ve ac ute se v ere n e p hritis defi ne d as a si g nifica nt w orse ni n g of re n al disease (e. g., 
t he prese n ce of uri nar y s e di me nts a n d ot her la b a b n or malities) t hat, i n t he o pi ni o n of 
t he st u d y i n vesti gat or, ma y lea d t o t he partici pa nt  re q uiri n g i n d ucti o n t hera p y wit h I V 
c ycl o p h os p ha mi de, M M F or hi g h d ose c ortic oster oi ds d uri n g t he first 6 m o nt hs of t he 
st u d y. 
N ote: Cli nicall y sta ble l u p us ne p hritis t hat ca n be ma na ge d wit h me dicati o ns all o we d i n 
t he st u d y will n ot e xcl u de partici pa nts fr o m partici pati n g i n t he trial ( n or will a n y 
ma xi m u m le vel of pr otei n uria e xcl u de partici pa nts). Cli nical assess me nt a n d me dical 
ma na ge me nt of n e p hritis will be at t he disc reti o n of t he st u d y i n vesti gat or. 
3.  Ha ve a hist or y of a maj or or ga n tra ns pla nt ( e. g., heart, l u n g, ki d ne y, li ver) or 
he mat o p oietic  ste m cell/ marr o w tra ns pl a nt. 
4.  Ha ve cli nic al e vi de nce of si g nifica nt, u nsta ble or u nc o ntr olle d, ac ute or c hr o nic 
diseases n ot d ue  t o S L E (i.e., car di o vas c ular, p ul m o nar y, hae m at ol o gic, 
gastr oi ntesti nal, he patic, re nal, ne ur ol o gical, mali g na nc y or i nfecti o us diseases) 
w hic h, i n t he o pi ni o n of t he i n vesti gat or, c o ul d c o nf o u n d t he res ults of t he st u d y or 
p ut t he partici pa nt  at u n d ue ris k.  
5.  Ha ve a pl a n ne d s ur gical pr oce d ure or a hist or y of a n y ot her me dical diseas e (e. g., 
car di o p ul m o nar y), l a b orat or y a b n or malit y, or c o n diti o n (e. g., p o or ve n o us access) 
t hat, i n t he o pi ni o n of t he i n vesti gat or, ma kes t he partici pa nt  u ns uita ble f or t he st u d y. 
6.  Ha ve a hist or y of mali g na nt ne o plas m wit hi n t he last 5 years.  
7.  Ha ve a hist or y of a pri mar y i m m u n o deficie nc y . 
8.  Ha ve a n  
 deficie nc y ( 
 le vel < 1 0 m g/ d L).  
9.  Ha ve ac ute or c hr o nic i nf ecti o ns re q uiri n g ma na g e me nt, as f oll o ws:  
a)  C urre ntl y o n a n y s u p pressi ve t hera p y f or a c hr o nic i nfecti o n (s uc h as 
t u berc ul osis, p ne u m oc ystis, c yt o me gal o vir us, her pes si m ple x vir us, her pes 
z oster a n d at y pical m yc o bacteria).  
b)  H os pitali sati o n f or treat me nt of i nfecti o n wit hi n 6 0 da ys of Da y 0.  
1 0.  Ha ve rece nt i nfecti o ns t hat, i n t he o pi ni o ns of t he i n vesti gat or, ma kes t he p artici pa nt  
u ns uita ble f or t he st u d y or c o ul d p ut t he partici pa nt  at u n d ue ris k.  
1 1.  Ha ve c urre nt dr u g or alc o h ol a b use or de p e n de nce, or a hist or y of dr u g or alc o h ol 
a b use or de p e n de n ce wit hi n 3 6 4 da ys pri or t o Da y 0.  
1 2.  Ha ve a Gra d e 3 or greater la b orat or y a b n or malit y base d o n t he pr ot oc ol t o xicit y scale 
( Secti o n 1 0. 2. 1 ) e xce pt  f or t he f oll o wi n g t hat are all owe d:  
C CI
C CI


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a) Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. 
b) Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant 
and not related to liver disease or anti-coagulant therapy. 
c) Stable Grade 3 hypoalbuminemia due to lupus nephritis and not related to 
liver disease or malnutrition. 
d) Any grade proteinuria 
e) 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. 
f) Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 
leukopenia, due to SLE 
13. Have a history of an anaphylactic reaction to parenteral administration of contrast 
agents, human or murine proteins or monoclonal antibodies. 
14. Have evidence of serious suicide risk including any history of suicidal behaviour in 
the last 6 months or who in the investigator's judgment, poses a significant suicide 
risk. 
Prior/Concomitant Therapy 
15. Have received treatment with belimumab at any time. 
16. Have received any of the following within 364 days of Day 0: 
a) 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) Abatacept 
c) A biologic investigational agent 
17. Have required 3 or more courses of systemic corticosteroids for concomitant 
conditions (e.g., asthma, atopic dermatitis) within 90 days of Day 0 (Topical or 
inhaled steroids are permitted). 
18. Have received any of the following within 90 days of Day 0: 
a) Anti-Tumour Necrosis Factor (TNF) or anti-IL-6 therapy (e.g., adalimumab, 
etanercept, infliximab, tocilizumab certolizumab, golimumab) 
b) Interleukin-1 receptor antagonist (anakinra) 
c) Intravenous immunoglobulin (IVIG) 
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19. Have received any of the following within 30 days of Day 0: 
a) Intravenous (IV) cyclophosphamide 
b) A non-biologic investigational agent (30 days window OR 5 half-lives, 
whichever is longer) 
c) Any new immunosuppressive/immunomodulatory agent, anti-malarial, 
NSAID (See Inclusion Criteria #5) 
d) High dose prednisone or equivalent (>1.5 mg/kg/day) or any intramuscular or 
intravenous steroid injection 
e) Note: New inhaled steroids, intraarticular steroids, and new topical 
immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any 
NSAID use for <1 week is allowed. 
20. Have received a live or live-attenuated vaccine within 30 days of Day 0. 
21. 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. 
22. Have required renal replacement therapy (e.g. haemodialysis, peritoneal dialysis) 
within 90 days of Day 0 or be currently on renal replacement therapy 
Prior/Concurrent Clinical Study Experience 
23. Participation in an interventional clinical study either concurrently or within 6 months 
of screening. Participation in an observational study may be permitted. 
Diagnostic assessments 
24. Have a historically positive test or test positive at screening for HIV antibody. 
25. Evidence of active or latent tuberculosis (TB) as documented by medical history and 
examination, chest X-rays (posteroanterior) and a positive (not indeterminate) 
QuantiFERON-TB Gold Plus test. 
26. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B 
surface antigen positive (HBsAg+) OR Hepatitis B core antibody positive (HBcAb+). 
27. Hepatitis C: Positive test for Hepatitis C antibody at screening. 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required during the course of this study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 


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respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations and any 
serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once at the investigator’s discretion following discussion with the 
medical monitor. Such participants will be assigned a new participant number and all 
screening assessments will be repeated. 
5.5. 
Repeat Assessments during the 35 Day Screening Period 
Laboratory assessments may be repeated if determined necessary by the investigator, for 
example: (a) in cases of technical malfunction (e.g., loss of laboratory specimen), (b) in 
the event of a value close enough to the exclusionary threshold that it may reasonably lie 
within the degree of variability of the assay; (c) if there is reason to believe the result may 
be false (e.g. contradicts recent result for the same parameter). 
These are repeat assessments and not rescreening events. If the original result was 
exclusionary and is confirmed by a repeat test, the participant will be excluded. 
6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
ARM Name 
Belimumab 10 mg/kg IV 
Intervention Name 
Belimumab 
Type  
Biologic 
Dose Formulation  
Lyophilised cake for reconstitution and dilution in 
normal saline 
Unit Dose Strength(s)  
5 mL vial containing 120 mg lyophilised belimumab 
(80 mg/mL after reconstitution). 
Dosage Level(s) 
10 mg/kg body weight by IV infusion on Days 0, 14, 
28 and then every 28 days through Week 48. 
Route of Administration 
IV Infusion 
Use 
Investigational 
IMP and NIMP 
IMP 


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Sourcing 
 
Provided by the Sponsor 
Packaging and Labelling 
 
Study Intervention will be provided in vial. Each vial 
will be labelled as required per country 
requirement. 
Current name 
The trade name of the investigational product is 
BENLYSTA™. The generic (USAN/INN) name is 
belimumab. Another trademarked name 
LymphoStat-B. The company code numbers for 
belimumab are HGS1006 and GSK1550188. 
 
Belimumab is a recombinant, human, IgG1λ 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.  
Belimumab IV will be supplied in sterile, single-use 5 mL vials as a lyophilised 
formulation for IV use.  
Belimumab IV will be administrated at 10 mg/kg body weight by IV infusion on Days 0, 
14, 28 and then every 28 days through Week 48. The calculated dose of belimumab to be 
administered is determined by participant’s body weight at each visit. The calculated 
dose of study intervention to be administered to the participant is determined in 
milligrams (mg) by the participant's body weight in kilograms (kg) at each visit. The 
study intervention should be delivered to all participants 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 intervention is administered at a dose of 10 mg/kg, to maintain a 
belimumab concentration of 4 mg/mL or less, use of the 100 mL bag may only be 
considered for the participants whose body weight is ≤40 kg. 
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 intervention should be infused over 1 hour. 
The dose of study intervention administered may not be altered. The rate of infusion may 
be slowed or interrupted if the participant appears to develop signs of adverse reaction or 
infusion-associated symptoms. Rate of infusion should not be increased above 
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Participants should be monitored during all infusions. Participants should remain under 
clinical supervision for 3 hours after completion of the first 2 infusions. 
6.2. 
Preparation/Handling/Storage/Accountability 
1. The investigator or designee must confirm that appropriate temperature conditions 
have been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. The excipients used in the paediatric formulation are safe for administration in the 
paediatric population participating in the study. Only participants enrolled in the 
study may receive study intervention and only authorised site staff may supply or 
administer study intervention. All study interventions must be stored in a secure, 
environmentally controlled and monitored (manual or automated) area in accordance 
with the labelled storage conditions with access limited to the investigator and 
authorised site staff. 
3. The investigator, institution or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation and record 
maintenance (i.e., receipt, reconciliation and final disposition records). 
4. Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Reference Manual.  
Under normal conditions of handling and administration, study intervention 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. In the case of 
unintentional occupational exposure, notify the monitor, Medical Monitor and/or GSK 
study contact. 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from GSK. 
6.3. 
Measures to Minimise Bias: Randomisation and Blinding 
This is an open-label study without randomisation and blinding. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents. The dose of study 
intervention and study participant identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study 
intervention. 
6.5. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements or other specific categories of interest) that the 


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participant is receiving at the time of enrolment or receives during the study must be 
recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.5.1. 
Permitted medications and non-drug therapies 
Participants must be on a stable SLE therapy for at least 30 days prior to Day 0. 
Corticosteroids may be added as new medication or their doses adjusted only up to 30 
days prior to Day 0. 
Once the participant receives the first dose of belimumab 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 
participants being withdrawn from the study. 
6.5.1.1. 
Anti-malarials 
A new anti-malarial (e.g., hydroxychloroquine, chloroquine, quinacrine) may be started 
between Day 0 and the 16-week post-treatment follow-up assessment. 
The dose of an anti-malarial may be reduced or increased as clinically required, between 
Day 0 and the 16-week post-treatment follow-up assessment. 
An anti-malarial may be replaced by another anti-malarial due to documented toxicity or 
lack of availability at any time during the study. 
6.5.1.2. 
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. 
Systemic Steroids for SLE-related Disease Activity 
The total dose of systemic steroids may be increased or decreased as clinically indicated 
from Day 0 through the 16-week post-treatment follow-up assessment. Treatment of SLE 
Flares with Steroids: If a participant has an SLE flare requiring an increase in steroid 
dose the investigator should consider the guidelines prepared for the ACR, for steroid 
dose/duration of induction therapy [Liang, 2004]. 


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Intra-articular Injections 
Participants may receive intraarticular (IA) corticosteroid injections at any time between 
Day 0 and the 16-week post-treatment follow-up assessment. 
Steroids for Reasons Other Than SLE Disease Activity 
Inhaled and topical steroids are allowed throughout the course of the study.   
Steroids may be given for reasons other than SLE disease activity (such as asthma, 
contact dermatitis) as clinically indicated.  
6.5.1.3. 
Other Immunosuppressive/Immunomodulatory Agents 
Starting any new allowable immunosuppressive/immunomodulatory agent is permitted 
from Day 0 through the 16-week post-treatment follow-up assessment. 
The dose of existing immunosuppressive/immunomodulatory agents may be increased or 
decreased, as clinically required, from Day 0 through the 16-week post-treatment follow-
up assessment. 
An immunosuppressive/immunomodulatory agent may be replaced with one of the agents 
above due to documented toxicity or lack of availability. New topical immunosuppressive 
agents (e.g., eye drops, topical creams) are allowed from Day 0 through the 16-week 
post-treatment follow-up visit.  
6.5.1.4. 
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) 
NSAIDs may be given within 30 days prior to Day 0 only if given for <1 week. From 
Day 0 through the 16-week post-treatment follow-up visit, NSAIDs may be given as 
clinically indicated (even if >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. 
6.5.2. 
Prohibited Medications and Non-Drug Therapies 
Participants who start prohibited medications or therapies at any time during the study 
will be considered protocol violation. Belimumab will be discontinued and participants 
will be withdrawn from the study.  
The following medications and therapies are prohibited at any time during the study: 
• Other investigational agents (biologic or non-biologic). Investigational applies to 
any drug not approved for sale in the country in which it is being used. 


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• Participation in a study using an investigational agent or non-drug therapy that 
may interfere with the conduct of this protocol, except study 217091. 
• Anti-TNF or anti-IL-6 therapy (e.g., adalimumab, etanercept, infliximab, 
certolizumab, tocilizumab, golimumab). 
• All biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist). 
• Intravenous immunoglobulin (IVIG). 
• IV cyclophosphamide (oral cyclophosphamide is permitted). 
• Plasmapheresis, leukapheresis. 
• Any live or live attenuated vaccines. (Participants who require a live or live 
attenuated vaccine during the study should have belimumab discontinued prior to 
receiving the vaccine). 
6.6. 
Dose Modification 
No dose modifications of belimumab are allowed. 
6.7. 
Intervention after the End of the Study 
Following the end of treatment at Week 48 or early withdrawal from the study, the 
participant will return to standard of care for SLE as determined by the investigator. 
Participants completed the last Benlysta IV administration at Week 48 and transfer to 
study 217091 successfully will continue to complete the 52-week visit of 213560. 
However, 16-week follow-up visit will not be conducted.Participants who complete this 
study and who are willing to continue belimumab IV treatment with commercially 
available BENLYSTA™ may participate in an ongoing Intensive Drug Monitoring study 
of belimumab (Study 213210). 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue 
(definitive discontinuation) study intervention. If study intervention is definitively 
discontinued, the participant will not remain in the study to be evaluated for Safety and 
efficacy. See the SoA (Section 1.2) for data to be collected at the time of discontinuation 
of study intervention and follow-up and for any further evaluations that need to be 
completed. 
Participants may be withdrawn from belimumab treatment or from this study if at any 
time: 


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• Withdrawal of consent by the participant (or their legally acceptable 
representative) for any reason. 
• The investigator judges it necessary due to medical reasons. 
Furthermore, participants will be withdrawn from belimumab treatment, if at any time: 
• Participant becomes pregnant 
• Receives prohibited therapy (Definition see Section 6.5.2) 
• Participates in another interventional trial, except study 217091 
• Misses 3 or more consecutive belimumab infusions   
• Experiences unacceptable toxicity 
7.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event aetiology. 
Discontinuation of study intervention for abnormal liver tests is required when: 
• a participant meets one of the conditions outlined Algorithm A or Algorithm B  
OR 
• when in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the investigator believes study intervention discontinuation is in 
the best interest of the participant.  


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Algorithm A: Phase 3/4 Liver Chemistry Stopping and Increased Monitoring 
Algorithm 
 
Abbreviations: ALT = alanine transaminase; bili = bilirubin; INR = international normalised ratio; SAE = 
serious adverse event; ULN = upper limit of normal. 
Refer to Section 10.5 (Appendix 5) for required Liver Safety Actions and Follow-up 
Assessments  


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Algorithm B: Phase 3/4 Liver Chemistry Increased Monitoring Algorithm with 
Continued Therapy for ALT 3xULN but <8xULN 
 
 
 
Abbreviations: ALT = alanine transaminase; bili = bilirubin; INR = international normalised ratio; SAE = 
serious adverse event; ULN = upper limit of normal. 
Refer to Section 10.5 (Appendix 5) for required Liver Safety Actions and Follow-up 
Assessments  
7.1.2. 
IgG Stopping Criteria 
Any participant who has a Grade 4 IgG level, by the protocol-defined Adverse Event and 
Laboratory Value Severity Grade Scale (see Appendix 2, Section 10.2.1), will have 
dosing with study agent withheld, and the appropriateness to continue study treatment 
must be discussed with the Medical Monitor before the next dose. Any participant who 
has a Grade 4 IgG level associated with a severe or serious infection will have study 
agent discontinued and should complete the follow-up assessments as described in the 
SoA (Section 1.2). 


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7.1.3. 
Rechallenge 
7.1.3.1. 
Study Intervention Restart or Rechallenge after liver stopping criteria 
met 
Study intervention restart or rechallenge after liver chemistry stopping criteria are met by 
any participant in this study is not allowed. 
7.1.4. 
Temporary Discontinuation 
In the event of a participant experiencing an AE or SAE, the investigator may at their 
discretion choose to instruct the participant/caregiver to skip one or more scheduled 
administrations of belimumab. If a participant misses 3 or more consecutive belimumab 
infusions, participant will be withdrawn from belimumab treatment. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural, compliance or administrative reasons. This is expected to be 
uncommon. 
• 
At the time of discontinuing from the study, if possible, an early discontinuation 
or exit visit should be conducted, as shown in the SoA (Section 1.2) for data to 
be collected at the time of study discontinuation and follow-up and for any 
further evaluations that need to be completed. 
• 
The participant will be permanently discontinued both from the study 
intervention and from the study at that time. 
• 
If the participant’s parent/caregiver withdraws consent for disclosure of future 
information, the sponsor may retain and continue to use any data collected 
before such a withdrawal of consent. 
• 
If a participant withdraws from the study, her/his parent/caregiver may request 
destruction of any samples taken and not tested, and the investigator must 
document this in the site study records. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 


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• 
Before a participant is deemed lost to follow-up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of Section 
10.1 (Appendix 1). 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarised in the SoA.  
Protocol waivers or exemptions are not allowed.  
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, will not exceed local 
guidelines. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples 
8.1. 
Screening Assessments 
Information collected during the screening phase assessments represent key data that 
identify and define participant Baseline status. This information is critical for evaluation 
of subsequent safety assessments. 
Informed Consent 
Informed consent will be obtained from the participant’s parent/legally appointed 
representative (LAR) prior to the initiation of any study procedures or study-specific data 
collection. The participant will provide their assent to participate in the study at the same 
time.  
After obtaining written informed consent from participant’s parent/LAR and assent from 
participants, the participant will be screened (up to 35 days) for eligibility. A participant 


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may have treatment assigned when all screening procedures have been completed and 
eligibility criteria confirmed.  
Screening Assessments 
During the screening period, the following assessments will be performed: 
Demographic parameters will be captured: Date and year of birth, sex, race and ethnicity. 
Medical history/medication will be assessed as related to the exclusion criteria listed in 
Section 5.2. A complete medical history will be taken at the Screening Visit. Information 
from the medical history is important to establish the Baseline condition of the participant 
and will impact the safety monitoring assessments during the study. Any significant 
medical conditions affecting the participant in the past 5 years should be recorded on the 
Medical conditions page of the eCRF. The history should include the following: 
• 
Confirm classification of SLE disease (based on ACR criteria) by reviewing 
previously documented clinical records. 
• 
Past or current conditions 
• 
Prior surgical procedures 
• 
Pharmacotherapy and chronic or current use of any medication or herbal 
preparation 
• 
Allergies and significant allergic reactions 
• 
Significant infections, or history of recurrent infection, including urinary and 
respiratory tract infections  
• 
Smoking history (current or previous smoker, number of cigarettes smoked per 
day) 
Pregnancy Test 
A serum pregnancy test will be performed for females of childbearing potential at the 
Screening Visit, and a urine pregnancy test will be performed during each subsequent 
clinic visit. Refer to the pregnancy section (Section 8.4.5). 
Investigator will confirm the WOCBP status of female participants during each visit. For 
females who are not WOCBP at the screening visit, but become WOCBP during the 
study, pregnancy test will be performed according SoA from that onwards.  
Full Physical Examination, Height, Weight and Vital Signs 
The full physical examination will include complete assessment of all organ systems 
including assessments of the head and neck (including eyes, ears, nose, throat, and 
thyroid gland), skin, musculoskeletal (including evaluation of both small and large 
joints), neurological, respiratory, and cardiovascular systems, gastrointestinal system, and 
abdomen (including liver and spleen), lymph nodes and extremities. 


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2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
4 4  
 
Hei g ht a n d wei g ht, a n d vital si g ns (s yst olic a n d diast olic bl o o d press ure [sitti n g], heart 
rate, a n d b o d y te m p erat ure) will be meas ure d a n d rec or de d. 
El e ctr o c ar di o gr a m  
A si n gle 1 2 -lea d E C G will be o btai ne d f or scree ni n g p ur p oses o nl y as o utli ne d i n t he 
S o A (see Secti o n 1. 2 ) usi n g a n E C G mac hi ne t hat a ut o maticall y calc ulat es t he heart rate 
a n d meas ur es P R, Q R S a n d Q T i nter vals. If t he s cree ni n g E C G is a b n or mal, t he 
I n v esti gat or ma y at t heir discreti o n e xcl u de t h e partici pa nt fr o m t he st u d y a n d/ or c o ntact 
t he Me dical M o nit or t o disc uss t he a p pr o priate ness of i ncl u di n g t he partici pa nt. 
C h e st X - r a y 
A c hest X -ra y ( p oster oa nteri or) will  be ta ke n f or s cree ni n g p ur p ose as o utli ne d i n t he 
S o A (see Secti o n 1. 2 ). 
L a b or at or y T e st s  
T he f oll o wi n g la b orat or y tests will be perf or me d b y t he ce ntral la b orat or y at scree ni n g, as 
relate d t o t he eli gi bilit y criteria descri be d i n Secti o n 5 . 
Bl o o d t e st s  
•  
Hae mat ol o g y  
•  
M o difie d C he m 2 0 ( n o n -fasti n g) ( C P K M U S T be d o ne f or partici pa nt s wit h 
m y ositis i n or der t o sc ore S E L E N A S L E D AI)  
•  
HI V a nti b o d y, He p atitis B s urface a nti ge n, a nti -H Bc, a nti -H Bs a n d He p atitis C 
a nti b o d y testi n g.  
•  
Pr ot hr o m bi n ti me ( P T), partial t hr o m b o plasti n t i me ( P T T) 
•  
 
•  
 
•  
A N A a n d 
 
•  
Q ua nti F E R O N -T B G ol d Pl us  
•  
N O T E: T o mai ntai n t he v ol u me of bl o o d c ollecti o n wit h l ocal g ui deli nes, t he 
scree ni n g assess me nts f or participa nts < 3 0  k g will be s plit acr oss 2 visits 
se parat e d b y a mi ni m u m of 2 wee ks. T h ere m ust als o be a mi ni m u m of 2 wee ks 
bet wee n t he s ec o n d scree ni n g a n d t he Da y 0  bl o o d dra ws (see S R M f or details). 
T his ma y als o a p pl y t o partic ipa nts 3 0 k g acc or di n g t o l ocal g ui deli nes.  
Uri n e s a m pl e : 
•  
R o uti ne uri nal ysis  
•  
S p ot uri ne f or macr os c o pic/ micr osc o pic/ pr otei n uri a assess me nts  
•  
Uri ne pr otei n:creati ni ne rati o  
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Disease activity scales: 
• 
SELENA SLEDAI 
• 
At Screening, confirm SLE disease is active, defined as SELENA SLEDAI 
score 8 
• 
Physician’s Global Assessment (PGA) (Section 10.10: Appendix 10) 
• 
Parent Global Assessment (ParentGA) (Section 10.11: Appendix 11) 
• 
SLE Flare Index (Section 10.9 Appendix 9) 
Suicidality Assessment 
Possible suicidal behaviour or ideation will be assessed at screening (See Section 5.2, 
exclusion #14). 
Baseline Assessment 
Procedures at the Baseline Visit are listed in the SoA (Section 1.2). They include clinical 
assessments including efficacy, laboratory tests and biomarkers. The interim medical 
history, including concomitant medications should be reviewed to ensure the participant’s 
eligibility for the study has not changed. 
8.2. 
Efficacy Assessments 
Planned efficacy assessments will be conducted with the following 4 disease activity 
scales as mentioned in SoA table (Section 1.2): SELENA SLEDAI, PGA, ParentGA and 
SLE Flare index 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.2). 
• 
A complete physical examination will be included at screening and symptoms 
driven physical examination at the time points mentioned in the SoA table 
(Section 1.2). 
• 
Adverse event (including infusion-related and hypersensitivity reactions, 
infections and malignancies) reported throughout the 52-week treatment period. 
• 
Haematological and clinical chemistry parameters (including urinalysis) 
throughout the 52-week treatment period. 
• 
Vital signs (i.e., heart rate and systolic and diastolic blood pressure) throughout 
the 52-week treatment period. 
• 
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 
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• 
The possible suicidality related event (PSRAE) form must be completed in the 
eCRF, if evidence of suicidal behaviour or ideation by a participant is detected 
at any visit.  
8.3.1. 
Clinical Safety Laboratory Assessments 
• 
Refer to Section 10.2 (Appendix 2) for the list of clinical laboratory tests to be 
performed and to the SoA (Section 1.2) for the timing and frequency.  
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 60 days after the last dose of study 
intervention should be repeated until the values return to normal or Baseline or 
are no longer considered significantly abnormal by the investigator or medical 
monitor.  
• 
If such values do not return to normal/Baseline within a period of time judged 
reasonable by the investigator, the aetiology should be identified and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Section 10.2 
(Appendix 2), must be conducted in accordance with the laboratory manual and 
the SoA. 
• 
Laboratory toxicity will be graded using the Adverse Event and Laboratory 
Value Severity Grading Table (Section 10.2.1). The Table is based upon 
publicly available Tables from the National Institute of Allergy and Infectious 
Disease Division of Microbiology and Infectious Diseases (www.niaid.nih.gov). 
Lymphopenia will be graded according to Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.0 (U.S. Department of Health and Human 
Services, 2010). 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.3 (Appendix 3). 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorised representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the belimumab treatment (see Section 
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8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of treatment until the follow-up visit at 
the time points specified in the SoA (Section 1.2). However, any SAEs assessed 
as related to study participation (e.g., study intervention, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a participant consents to participate in 
the study. 
• 
All AEs will be collected from the start of treatment until the follow-up visit at 
the time points specified in the SoA (Section 1.2). 
• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the case report form (CRF) not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in Section 
10.3 (Appendix 3). The investigator will submit any updated SAE data to the 
sponsor within 24 hours of it being available. Non-serious related AEs should be 
reported using ADR CRF to the sponsor pharmacovigilance team 
(qwy11935@gsk.com) via email within 5 calendar days.  
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Section 10.3 (Appendix 3). 
• 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence.  
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and related AE and non-serious and 
serious AEs of special interest (AESI) (i.e., post-injection systemic reactions and 
hypersensitivity reactions, infections, malignancies, and depression/suicidality/self-
injury) will be followed until the event is resolved, stabilised, otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-
up procedures is given in Section 10.3 (Appendix 3). 


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8.4.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators. 
• 
For all studies except those utilizing medical devices, investigator safety reports 
must be prepared for suspected unexpected serious adverse reactions (SUSAR) 
according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAEs) from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements. 
8.4.5. 
Pregnancy 
If a pregnancy in a female participant is reported, the investigator should inform GSK 
within 24 hours of learning of the pregnancy and should follow the procedures outlined in 
Section 10.4 (Appendix 4). 
A pregnancy is not considered to be an SAE, although abnormal pregnancy outcomes or 
complications (e.g., spontaneous abortion, foetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) are considered to be SAEs. 
There is no requirement to collect pregnancy information from female partners of male 
participants. 
8.5. 
Treatment of Overdose 
There is limited experience with overdosage of belimumab. Adverse reactions reported in 
association with cases of overdosage have been consistent with those expected for 
belimumab. 
Two doses up to 20 mg/kg administered 21 days apart by IV infusion have been given to 
humans with no increase in incidence or severity of adverse reactions compared with 
doses of 1, 4 or 10 mg/kg. 
GSK does not recommend specific treatment for an overdose of belimumab. 
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1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for AEs/SAEs. 
3. Document the quantity of the excess dose as well as the duration of the overdosing. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
8.6. 
Pharmacokinetics 
Blood samples will be collected for measurement of serum belimumab concentrations 
according to schedules that depend on the paediatric cohort. 
Table 1 
PK visit days and sample times study participants 
Day (Week) 
Time (Related to Dosing of Study agent) 
0 
0-4 hours after the end of infusion 
7 (Week 1) 
Day 7 ± 1 day 
14 (Week 2) 
Day 14 ± 3 days (Before the start of infusion)  
84 (Week 12) 
Day 84 ± 7 days (Before the start of infusion and 0-4 
hours after the end of infusion) 
On days belimumab is administered and blood samples for pharmacokinetic analysis are 
obtained, participants 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 venepuncture. The actual date and time (24-hour clock time) of each 
sample will be recorded.   
If sampling for PK is missed, the impact will be minimized by attempting to reschedule 
the missing PK sampling to ensure sufficient precision of PK characterization in Chinese 
paediatric patients: 
• For the scenario that patients will miss the sample collection on visit 3 (Day 7±1 
day), the PK sampling should be rescheduled to any feasible visit at 7 days after 
dosing with ±3 days window. 
• For the scenario that patients will miss the sample collection on visit 4 (Day 14±3 
days), the PK sampling should be rescheduled to any feasible visit at 14 days after 
dosing with ±7 days window. 
• For the scenario that patients will miss the sample collection on visit 7 (Day84±7 
days), the PK sampling should be rescheduled to when patients take the next dose. 
 


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2 2 J a n 2 0 2 4   
5 0  
 
Please refer t o t he St u d y Refere n ce  M a n ual f or P K sa m ple c ollecti o n, pr o cessi n g a n d 
s hi p pi n g i nstr ucti o ns. 
8. 8.  
G e n eti c s  
Ge netic a n al ysis will n ot be  e val uat e d i n t his st u d y.  
8. 9.  
I m m u n o g e ni cit y A s s e s s m e nt s 
T he prese n ce of a nti b o dies t o beli m u ma b will n ot be e val uat e d i n t his st u d y. 
8. 1 0.  
H e alt h E c o n o mi c s  
Healt h Ec o n o mics/ Me dic al Res o urce Utili sati o n a n d Healt h Ec o n o mics  para meters are 
n ot e val uate d i n t his st u d y.  
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
T his is an  o pe n -la bel st u d y. A  descri pti ve a p pr oac h  will be use d, a n d n o f or mal i nfere n ce 
is pla n ne d i n t his st u d y. F or pri mar y efficac y e val uati o n,  u si n g t he perce nt a ge of 
partici pa nts wit h ≥4 -p oi nt re d ucti o n fr o m bas eli ne i n S E L E N A S L E D AI at Wee k 5 2 i n 
t he place b o gr o u p i n a P hase 2 pae di atric st u d y ( St u d y B E L 1 1 4 0 5 5)  as tar g et val ue t o 
g ui de t he a nal ysis pla n ne d f or C hi nese P A C st u d y.  T he tar get ca n be d escri be d as  the 
o bser ve d pr o p orti o n of p atie nts wit h cli nical be nefit > 4 3. 6 % (t he mea n place b o gr o u p 
res p o nse rate esti mate i n st u d y B E L 1 1 4 0 5 5 ). 
9. 2.  
S a m pl e Si z e D et er mi n ati o n  
F oc usi n g o n seri o us i nf ecti o ns, t he i nci de nce rate of t he seri o us A E “I nfecti o ns a n d 
I nfestati o ns” ( S O C) was 7. 5 % ( 4/ 5 3 part ici pa nts) i n t he 1 0 m g/ k g-I V gr o u p of t he gl o bal 
pae diatric  st u d y ( St u d y B E L 1 1 4 0 5 5).  
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Under the assumption that the incidence rate of the serious infections is 7.5%, it is 
calculated that a study with 65 participants will have more than 99.0% probability to 
observe at least one serious infection. Under this sample size, for any other adverse 
events, there are more than 90% probability to observe at least one event once the 
incidence rate is larger than 4%. Additionally, using the Exact method in PASS 2019 for 
the confidence interval (CI) around a single proportion: a sample size of 65 would have 
produced a 95% CI of [2.4%, 16.8%] when the incidence rate of the serious infections is 
7.5%. 
For the efficacy purpose, as one of the key efficacy endpoints, the estimated percentage 
of participants with ≥4-point reduction from Baseline in SELENA SLEDAI at Week 52 
is 54.7% in BEL114055. Using the Exact method in PASS 2019 for the confidence 
interval (CI) around a single proportion: a sample size of 65 would produce a 95% CI of 
[41.9%, 67.1%] when the estimate is 54.7%. Under the assumption that the percentage of 
participants with ≥4 points reduction from baseline in SELENA SLEDAI at week 52 is 
54.7%, it is calculated by simulation that a study with 65 participants will have more than 
95.0% probability to observe a percentage lager than 43.6%. 
9.2.1. 
PK Sample Size Determination 
The FDA recommends that for paediatric studies, the 95% confidence interval of the 
average CL and V estimates are within 60% to 140% of the geometric mean, with at least 
80% power [Wang, 2012]. The same principles are applied here, but for this study a more 
stringent criterion will be applied requiring the precision of the CL and V to be 
determined within 80% to 120% of the geometric mean with at least 80% power. It is 
recommended to collect PK blood samples from 25 Chinese paediatric patients, which is 
considered the minimum number to meet this more stringent condition and therefore 
enable a quantitative comparison with the PK in a Western paediatric population. 
The sampling of the PK from each subject will be sparse, but when the data is integrated 
with the population PK model previously developed for paediatrics, the belimumab 
clearance (CL) and volume of distribution (V) may be estimated for each subject as if the 
PK had been frequently sampled in these subjects. To show that PK samples from N=25 
evaluable Chinese paediatric patients should be sufficient to accurately determine the PK 
in a Chinese paediatric population, one needs to consider the precision of the average CL 
and V estimates derived from the N=25 individual values. 
The power to estimate the CL is calculated by integrating over all possible values of the 
estimated standard deviation s, weighted by the probability density and for each value 
assigning one to the integrand if the 95% confidence interval is within the 80% to 120% 
range or zero otherwise: 
 
where   
 


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The results from this power calculation show N=25 paediatric subjects with evaluable PK 
results in at least 80% power to estimate the CL and V with 95% confidence intervals 
within 80% to 120% of their geometric mean values (blue line, Figure 1). In this regard 
the precision of the CL and V estimates in a Chinese paediatric population can be 
considered sufficient for this study design to compare against the corresponding 
parameters derived in a Western paediatric population. Additionally, there is 100% power 
the same sample size will estimate CL and V with 95% confidence intervals within the 
wider window of 60%-140% of their geometric means (red line, Figure 1). 
Figure 1 
The power to estimate CL and V versus sample size 
 
The power to estimate the 95% confidence interval within 80% to 120% of the 
geometric mean is shown (blue solid line). The power calculation was also repeated 
for the less stringent criteria requiring the 95% confidence interval to be within 
60% to 140% of the geometric mean (red solid line). 
9.3. 
Populations for Analyses 
Table 2 
Definitions of analyses population 
Population 
Description 
Screened 
All participants whose parent/caregiver sign the ICF 
Enrolled 
All participants assigned treatment.  
Intent to Treat (ITT) 
All participants assigned treatment who received at least one dose 
of study treatment. 


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Population 
Description 
PK 
All participants assigned treatment who received at least one dose 
of study treatment and for whom at least one post belimumab 
treatment PK sample was obtained and analysed. 
 
9.4. 
Statistical Analyses 
9.4.1. 
General Considerations 
No formal hypothesis testing is planned in the study; all analyses are descriptive. 
9.4.1.1. 
Safety Analysis 
All safety analyses will be performed on the ITT Population.  
Endpoint 
Statistical Analysis Methods 
Primary 
(Safety) 
Endpoints:  
Incidence of adverse events of special interest (AESIs) through 52 weeks: 
o 
All infections of special interest, including serious 
infections of special interest and opportunistic infections 
o 
Infusion-related systemic reactions and anaphylactic 
reactions  
o 
Depression, suicidality 
o 
Malignancies 
Analysis:  
Descriptive statistics will be used to summarise AEs, SAEs and AESIs. The 
frequency of AEs will be tabulated by MedDRA system organ class (SOC) and 
preferred term. 
 
9.4.2. 
Primary Endpoint(s) 
9.4.2.1. 
Efficacy Analysis 
All efficacy analyses will be performed on the ITT Population.  
Endpoint 
Statistical Analysis Methods 
Primary 
(Efficacy) 
Endpoint:  
Incidence of participants with ≥4-point reduction from Baseline to Week 52 in SELENA 
SLEDAI 


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Endpoint 
Statistical Analysis Methods 
Analysis:  
Descriptive statistics with frequency, percentage and 95% CI will be used to 
summarise incidence of participants with ≥4-point reduction from Baseline to Week 
52 in SELENA SLEDAI. Further, the corresponding results of the previous study 
(BEL114055) will be used to guide the evaluation of consistency for this 
efficacy endpoint collected on Chinese subjects. 
 
9.4.3. 
Secondary Endpoint(s) 
Endpoint 
Statistical Analysis Methods 
Secondary 
Endpoints:  
• Incidence of participants with ≥4-point reduction from Baseline in 
SELENA SLEDAI by visit 
• Change from Baseline to Week 52 in Physician Global Assessment 
(PGA) 
• Change from Baseline to Week 52 in Parent Global Assessment 
(ParentGA) 
• Change from Baseline to Week 52 in daily prednisone equivalent dose 
• Time to first flare/ first severe flare over 52 weeks 
 
Analysis:  
Descriptive statistics with frequency, percentage and 95% CI will be used to 
summarise the incidence of participants with ≥4-point reduction from Baseline in 
SELENA SLEDAI by week. Other endpoints will be summarised by descriptive 
statistics with mean, median, SD and 95% CI.  
 
All pharmacokinetic (PK) analyses will be performed on the PK Population.  
Endpoint 
Statistical Analysis Methods 
Secondary 
Endpoints:  
Median belimumab concentration levels at Day 0, 7 and 14 days post first dose, and 
pre-infusion and post-infusion at Day 84 
Analysis:  
Descriptive statistics will be used to summarise the observed belimumab 
concentrations. Pharmacokinetic parameters with respect to clearance, volume 


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2 2 J a n 2 0 2 4   
5 5  
 
E n d p oi nt  
St ati sti c al A n al ysi s M et h o d s  
of distri b uti o n a nd h alf -lif e, a n d in divi d ual st e a dy stat e ex p osur es C mi n, C av g, 
C m ax a n d A U C will b e eval u at e d.  
9. 5.  
I nt eri m A n al y s e s 
N o f or mal i nteri m a nal ys es are pl a n ne d.  
9. 6.  
G S K s af et y r e vi e w t e a m ( S R T)  
T he st u d y Me dical M o nit or a n d me m bers of t he G S K S R T will perf or m i n -strea m re vie w 
of all safet y dat a f or t he d urati o n of t he st u d y a n d ma ke a n d c o m m u nicate 
rec o m me n dati o ns as a p pr o priate. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organisations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
• Reporting cases of suspected child abuse and/or neglect according to local 
medical association (e.g., AAP) or health department guidelines. 
 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 


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10.1.3. 
Informed Consent Process 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorised representative will be required to provide a statement of 
informed consent/assent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study centre.  
• The medical record must include a statement that legally authorised representative 
(parent/guardian) consent and child/adolescent assent (if deemed appropriate by local 
ethics review) was obtained before the participant was enrolled in the study and the 
date the written consent was obtained. The medical record should also describe how 
the clinical investigator determined that the person signing the ICF was the 
participant’s legally authorised representative (parent/guardian). The authorised 
person obtaining the informed consent must also sign the ICF. 
• Participants and their legally authorised representative (parent/guardian) must be 
re-consented and re-assented to the most current version of the ICF(s) during their 
participation in the study.  
• Minor participants must be re-consented if they reach the age of majority during the 
course of the study, in order to continue participating. 
• A copy of the ICF(s) must be provided to the participant or the participant’s 
parent/guardian. 
10.1.4. 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent.  
• 
The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorised personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
10.1.5. 
Dissemination of Clinical Study Data 
• 
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. 


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• 
GSK will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• 
GSK intends to make anonymised participant-level data from this trial available 
to external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve participant care. This helps ensure 
the data provided by trial participants are used to maximum effect in the creation 
of knowledge and understanding. 
10.1.6. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organisations). 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorised site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 


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sponsor. No records may be transferred to another location or party without 
written notification to the sponsor.  
10.1.7. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
• 
Definition of what constitutes source data can be found in the Monitoring Plan. 
10.1.8. 
Study and Site Start and Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
Inadequate recruitment of participants by the investigator 
Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform 
the Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organisation(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up. 
10.1.9. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 


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support publication of multicentre studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 3 will be performed by the central laboratory.  
 
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• 
Pregnancy Testing  
• 
Refer to Section 5.1 Inclusion Criteria for screening pregnancy criteria. 
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at monthly intervals on WOCBP during intervention. 
• 
The investigator will confirm the WOCBP status of female participants during 
each visit. For females who are not WOCBP at the screening visit, but become 
WOCBP during the study, pregnancy test will be performed according to the 
SoA from that visit onwards.  
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at the end of relevant systemic exposure plus an additional 30 days 
and correspond with the time frame for female participant contraception in 
Section 5.1, Inclusion Criteria 
• 
Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant's participation in the 
study. 
Table 3 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Haemoglobin 
Haematocrit 
 
 
Clinical 
Chemistry1 
Calcium 
Potassium 
Aspartate 
Aminotransferase 
(AST)/ Serum 
Glutamic-Oxaloacetic 
Transaminase (SGOT) 
Total bilirubin 


T M F -1 7 7 4 5 5 5 6  
C O N FI D E N TI A L  
 
 
 
2 1 3 5 6 0  
 
 
Pr ot o c ol a m e n d m e nt  4  
2 2 J a n 2 0 2 4   
6 2  
 
L a b or at or y 
A s s e ss m e nt s  
P ar a met er s  
 
C alci u m 
c orrect e d f or 
Al b u mi n 
I n or g a nic 
P h os ph ate  
S o di u m  
Al a ni n e 
A mi n otr a nsfer as e  
( A L T)/ S er u m 
Gl ut a mic -Pyr uvic 
Tr a ns a mi n as e  ( S G P T) 
T ot al Pr otei n  
 
C ar b o n 
di oxi d e  
M a g n esi u m  
Alk ali n e ph osp h at as e  
Al b u mi n  
 
Gl uc os e 
( n o nf asti n g) 
Cre ati n e 
p h osp h oki nas e 
( C P K) 
G a m m a gl uta myl 
tr a ns p epti das e ( G G T) 
Cre ati ni n e  
 
Uric aci d  
Bl o o d ur e a 
nitr o g en ( B U N)  
B U N/cr e ati ni ne r ati o  
Esti m at e d 
Cre ati ni n e 
Cl e ar a nc e/ G F R  
( Sc h w artz3) 
R o uti n e 
Uri n alysis  
•  p H, gl ucos e, pr ot ein, blo o d, k et o nes, occ ult blo o d by di pstick  
•  Micr osc o pic ex a mi n atio n  
Uri n e 
Pr e g na ncy 2 
•  Uri n e pr e g n a ncy if a pplic a ble 
P K  
•  Bl o o d coll ecti on  
 
•  A N A titr e, 
 
Ot h er Scr ee ni ng 
T ests  
•  Uri n e alc o h ol a nd dr ug scr ee n (t o incl u d e at mi ni mu m: a m p h eta mi n es, 
b ar bit ur at es, coc ai ne, opi ates, c an n abi n oi ds a nd b e nzodi az e pin es)  
•  Hi g hly s e nsitiv e h u m an c h orio nic g o na dotr o pi n ( h C G) pr e g n ancy t est ( as 
n e ed e d f or w o m en of c hil d be arin g p ote nti al) 3 
•  S er ol o gy ( HI V anti b ody, hep atitis B surf ac e a nti g en [ H Bs A g], a nti -H Bs 
A nti b ody, a nti -H Bc anti bo dy a n d h ep atitis C vir us a nti body)  
•  Pr ot hr o m bi n ti me ( P T), P artial t hr o m bo pl asti n ti me ( P T T)  
 
C CI
C CI
C CI
C CI


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NOTES : 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.2 and Appendix 5. All events of ALT 3 × upper limit of normal 
(ULN) and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalised ratio (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). 
2. 
A home kit will be provided to perform urine pregnancy test.   
3. 
Schwartz, 2009 


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10.2.1. 
Adverse Event and Laboratory Value Severity Grade Table 
 
 
HEMATOLOGY 
 
 
GRADE 1 
 
GRADE 2 
 
GRADE 3 
 
GRADE 4 
MILD 
MODERATE 
SEVERE 
POTENTIALLY LIFE-
THREATENING 
Haemoglobin 
> 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 
Methaemoglobin 
5.0-10.0 % 
10.1-15.0 % 
15.1-20.0 % 
> 20% 
 
Lymphocyte count** 
<LLN - 
800/mm3; <LLN 
- 0.8 
x 10e9 /L 
<800 - 500/mm3; 
<0.8 - 0.5 x 
10e9 /L 
<500 - 200/mm3; 
<0.5 - 0.2 x 
10e9 /L 
<200/mm3; <0.2 x 10e9 /L 
 
 
 
 
(continued) 
*ULN = Upper Limit of Normal 
**Lymphopenia calculated from CTCAE table 
Adverse Event and Laboratory Value Severity Grade Table (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 
hospitalisation 
and treatment required 
Hypotension 
Transient 
orthostatic 
hypotension, no 
treatment 
Symptoms correctable  
with oral fluid treatment 
IV fluid req, 
no hospitalisation 
req 
 
Hospitalisation req 
Hypertension 
Transient, 
increase 
> 20 mm/Hg; no 
treatment 
Recurrent; chronic 
increase 
> 20 mm/Hg, treatment 
req 
Acute treatment 
req; out subject 
hospitalisation 
possible 
 
Hospitalisation req 
Pericarditis 
Minimal effusion Mild/moderate 
asymptomatic effusion, 
no treatment 
Symptomatic 
effusion, 
pain, ECG changes 
 
Tamponade OR 
pericardiocentesis  
OR surgery req 
Haemorrhage, Blood 
Loss 
- 
Mildly symptomatic;  
no treatment required 
Gross blood loss 
OR 
1-2 units transfused 
Massive blood loss OR 
> 2 units transfused 
 
 
 
 
 
(continued) 


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Adverse Event and Laboratory Value Severity Grade Table (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 
   Hypokalaemia 
3.0-3.4 meq/L 
2.5-2.9 meq/L 
2.0-2.4 meq/L 
< 2.0 meq/L 
   Hyperkalaemia 
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) 
   Hypocalcaemia 
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 
   Hypoglycaemia 
55-64 mg/dL 
40-54 mg/dL 
30-39 mg/dL 
< 30 mg/dL 
   Hyperglycaemia  
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 
 
Adverse Event and Laboratory Value Severity Grade Table (continued) 
 
 
CHEMISTRIES 
(continued) 
 
GRADE 1 
 
GRADE 2 
 
GRADE 3 
 
GRADE 4 
MILD 
 
MODERATE 
SEVERE 
POTENTIALLY LIFE-
THREATENING 
Uric Acid 
   Hyperuricemia 
7.5-10.0 mg/dL 10.1-12.0 mg/dL 
12.1-15.0 mg/dL 
> 15.0 mg/dL 
Liver Transferases  
(AST, ALT, and GGT) 
1.25-2.5 x ULN > 2.5-5.0 x ULN 
> 5.0-10.0 x ULN 
> 10.0 x ULN 
Alkaline Phosphatase 
1.25-2.5 x ULN > 2.5-5.0 x ULN 
> 5.0-10.0 x ULN 
> 10.0 x ULN 
Pancreatic Enzymes 
Amylase 
> 1.0-1.5 x ULN > 1.5-2.0 x ULN 
> 2.0-5.0 x ULN 
> 5.0 x ULN 
Pancreatic amylase 
> 1.0-1.5 x ULN > 1.5-2.0 x ULN 
> 2.0-5.0 x ULN 
> 5.0 x ULN 
Lipase 
> 1.0-1.5 x ULN > 1.5-2.0 x ULN 
> 2.0-5.0 x ULN 
> 5.0 x ULN 
Hypoglobulinemia 
(IgG)* 
550-700 mg/dL 400-549 mg/dL 
250-399 mg/dL 
< 250 mg/dL 
 
 
 
 
 
(continued) 
 
*[Eibl, 1995; Goldfarb, 2001; Yamani, 2001]. 
 


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Adverse Event and Laboratory Value Severity Grade Table (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 
Hospitalisation 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 
hospitalisation  
required for IV treatment req 
Diarrhoea 
Mild or transient;  
3-4 loose stools 
per day  
OR mild 
diarrhoea lasting  
< 1 week 
Mod OR 
persistent;  
5-7 loose stools 
per day  
or diarrhoea 
lasting  
1 week 
Bloody diarrhoea;  
OR orthostatic 
hypotension  
OR > 7 loose 
stools/day  
OR IV treatment req 
Hypotensive shock  
OR hospitalisation 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 
 
 
 
 


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Adverse Event and Laboratory Value Severity Grade Table (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; 
normalises with 
bronchodilator;  
FEV1 50% to < 70%  
(or peak flow) 
 
No Normalisation  
with bronchodilator;  
FEV 25% to < 50%  
(or peak flow), 
retractions 
Cyanosis; FEV1 < 25%  
(or peak flow) OR intubated 
Dyspnoea 
Dyspnoea on 
exertion 
Dyspnoea with  
normal activity 
Dyspnoea at rest 
Dyspnoea requiring O2 therapy 
 
 
 
URINALYSIS 
 
GRADE 1 
GRADE 2 
GRADE 3 
GRADE 4 
MILD 
MODERATE 
SEVERE 
POTENTIALLY LIFE-
THREATENING 
Proteinuria 
 
Dipstick 
 
 
 
 
Protein 
 
1 + 
2-3 + 
4 + 
Nephrotic syndrome 
Spot Urine:    
Protein:Creatinine  
Ratio mg/mg 
0.2-1.0 
> 1.0-2.0 
> 2.0-3.5 
> 3.5 
24 Hour Urine: 
Protein 
200 mg - 1g 
loss/day 
 
> 1-2 g loss/day 
 
> 2-3.5 g loss/day 
 
Nephrotic syndrome 
OR > 3.5 g loss/day 
 
Haematuria 
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. 
 
 


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Adverse Event and Laboratory Value Severity Grade Table (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 
Localised urticaria 
Generalised 
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 
 
 
 


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Adverse Event and Laboratory Value Severity Grade Table (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  
Hospitalisation 
Paraesthesia  
(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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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study intervention, whether or not considered related to the 
study intervention. 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from Baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
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 intervention administration even 
though it may have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfil the definition of an AE or SAE. Also, "lack of 
efficacy" or "failure of expected pharmacological action" constitutes an AE or SAE. 
 
Events NOT Meeting the AE Definition  
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
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Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
Situations in which 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. 
 
10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalisation for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant 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. 
Requires inpatient hospitalisation or prolongation of existing hospitalisation 
• In general, hospitalisation signifies that the participant 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 outpatient setting. Complications that occur during 
hospitalisation are AE. If a complication prolongs hospitalisation or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalisation” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalisation for elective treatment of a pre-existing condition that did not 
worsen from Baseline is not considered an AE. 
Results in persistent or significant disability/incapacity 
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, diarrhoea, influenza, 
and accidental trauma (e.g. sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 


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Is a congenital anomaly/birth defect 
Other situations: 
Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life threatening or result in death or hospitalisation but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
Examples of such events include 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 hospitalisation, or development of drug dependency or 
drug abuse. 
 
10.3.3. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) related 
to the event. 
The investigator will then record all relevant AE/SAE information in the CRF. 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
There may be instances when copies of medical records for certain cases are requested 
by GSK. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to 
GSK. 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities. 
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 


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Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilised for rating the 
intensity of an event; and both AE and SAE can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to GSK. 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
If a participant dies during participation in the study or during a recognised follow-up 
period, the investigator will provide GSK with a copy of any post-mortem findings 
including histopathology. 
New or updated information will be recorded in the originally completed CRF. 
The investigator will submit any updated SAE data to GSK within 24 hours of receipt 
of the information. 


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10.3.4. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
The investigator or medically-qualified sub-investigator must show evidence within the 
eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of SAE 
entry into the eCRF. 
After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to the SAE coordinator by telephone. 
Contacts for SAE reporting can be found in SRM. 
 
SAE Reporting to GSK via Paper CRF 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the SAE coordinator. 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service. 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
Contacts for SAE reporting can be found in SRM. 
 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
• 
A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). 
However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-oestrogen hormonal highly effective contraception 
methods if they wish to continue their HRT during the study. Otherwise, they 
must discontinue HRT to allow confirmation of postmenopausal status before 
study enrolment. 
 


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10.4.2. 
Contraception Guidance: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency  
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
Intrauterine device (IUD) 
Intrauterine hormone-releasing system (IUS)c 
Bilateral tubal occlusion 
Vasectomised partner 
Note: Vasectomised partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 
Combined (oestrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
oral 
intravaginal 
transdermal 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
oral 
injectable 
Sexual abstinence 
Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c. 
If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those that inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction) 
 
 


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10.4.3. 
Collection of Pregnancy Information: 
Female Participants who become pregnant 
• Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study.  
• The initial information will be recorded on the appropriate form and submitted to 
GSK within 24 hours of learning of a participant's pregnancy.  
• Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which 
will be forwarded to GSK Generally, follow-up will not be required for longer 
than 6 to 8 weeks beyond the estimated delivery date.   
• Any termination of pregnancy will be reported, regardless of foetal status 
(presence or absence of anomalies) or indication for procedure.  
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
• A spontaneous abortion (occurring at <22 weeks gestational age) or stillbirth 
(occurring at > 22 weeks gestational age) is always considered to be an SAE and 
will be reported as such.  
• Any SAE occurring as a result of a post-study pregnancy that is considered 
reasonably related to the study intervention by the investigator, will be reported to 
GSK as described in Appendix 3. While the investigator is not obligated to 
actively seek this information in former study participants, he or she may learn of 
an SAE through spontaneous reporting.  
• 
Any female participant who becomes pregnant while participating will 
discontinue study intervention and withdrawn from the study. 


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10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase 3-4 liver chemistry stopping, and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event aetiology  
Phase 3/4 liver chemistry stopping criteria and required follow up assessments  
Liver Chemistry Stopping Criteria  
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 
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 
Required Actions and Follow up Assessments  
Actions 
Follow Up Assessments 
• Immediately discontinue study intervention  
• Report the event to GSK within 24 hours 
• Complete the liver event CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• Perform liver event follow up assessments  
• Monitor the participant until liver chemistries 
resolve, stabilise, or return to within 
Baseline (see MONITORING below) 
• Do not restart/rechallenge participant with 
study intervention. Permanently discontinue 
study intervention and continue participant 
in the study for any protocol specified follow 
up assessments. 
 
• Viral hepatitis serology4 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend 
• Obtain blood sample for pharmacokinetic 
(PK) analysis, within 6 weeks after last 
dose5 
 
• Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH). 
• Fractionate bilirubin, if total 
bilirubin2xULN 
• Obtain complete blood count with 
differential to assess eosinophilia 


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Liver Chemistry Stopping Criteria  
MONITORING: 
For bilirubin or INR criteria:  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24 hours 
• Monitor participant twice weekly until liver 
chemistries resolve, stabilise 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 INR) 
and perform liver event follow up 
assessments within 24-72 hours  
• Monitor participant weekly until liver 
chemistries resolve, stabilise or return to 
within Baseline 
• 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 (CRF) 
page 
 
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. 
• 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. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant 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 which may 
indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants 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)    
4. 
Includes: Hepatitis A Immunoglobulin M (IgM) antibody; HBsAg and HBcAb (conduct quantitative Hepatitis B DNA 
test if positivity for HBsAg and/or HBcAb); hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral 
capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot testing); and hepatitis E IgM 
antibody. 
5. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’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 SRM. 
 


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Phase 3/4 liver chemistry increased monitoring criteria with continued therapy 
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event 
Criteria 
Actions 
 
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. 
 
• Notify the GSK medical monitor within 24 hours 
of learning of the abnormality to discuss 
participant safety.  
• Participant can continue study intervention 
• Participant 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 participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 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 participants twice 
monthly until liver chemistries normalise or return 
to within Baseline. 


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10.6. 
Appendix 6: Country-specific requirements 
Not applicable. 


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10.7. 
Appendix 7: 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 patient history or 
physician observation. 
4. Oral ulcers  
Oral or nasopharyngeal ulceration usually painless. 
5. Arthritis  
Nonerosive arthritis involving 2 or more peripheral joints characterised 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. 
Haemolytic anemia (with reticulocytosis) 
 
OR 
b. 
Leukopenia ( 4000/mm3 total on 2 or more occasions), OR 
c. 
Lymphopenia ( 1500/mm3 on 2 or more occasions), OR 
d. 
Thrombocytopenia ( 100,000/mm3 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 immobilisation (TPI) or 
fluorescent treponemal antibody (FTA) absorption test. 
11. Antinuclear antibody (ANA) 
Abnormal titre 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. 
* 
The proposed classification is based on 11 criteria. For the purpose of identifying patients 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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8  
S eiz ur e  
R ec e nt o ns et (l ast 1 0 d ays). Excl u d e m et a b olic, i nf ecti o us dr u g c a us e, or s eiz ur e 
d u e t o p ast irr ev ersi bl e C N S d a m a g e.  
8  
P syc h osis 
Alt er e d a bility t o f u ncti o n i n n or m al activity d u e t o s ev er e dist ur b a nc e i n t h e 
p erc e pti o n of r e ality. I ncl u d e h all uci n ati o ns, i nc o h er e nc e, m ark e d l o os e 
ass oci ati o ns, i m p ov eris h e d t h o u g ht c o nt e nt, m ark e d ill o gic al t hi nki n g, biz arr e, 
dis or g a ni se d, or c at at o nic b e h avi o ur . Excl u d e ur a e mi a  a n d dr u g c a us es.  
8  
Or g a nic Br ai n 
Sy n dr o m e  
Alt er e d m e nt al f u ncti o n wit h i m p air e d ori e nt ati o n, m e m ory or ot h er int ell ect u al 
f u ncti o n wit h r a pi d o ns et a n d fl uct u ati n g cli nic al f e at ur es. I ncl u d e cl o u di n g of 
c o nsci o us n ess wit h r e d uc e d c a p acity t o f oc us a n d i n a bility t o s ust ai n att e nti o n t o 
e nvir o n m e nt, pl us at l e ast 2 of t h e f oll o wi n g: p erc e pt u al dist ur b a nc e, i nc o h er e nt 
s p e ec h, i ns o m ni a or d ayti m e dr o wsi n ess, or i ncr e as e d or d ecr e as e d psyc h o m ot or 
activity. Exc l u d e m et a b olic, i nf ecti o us or dr u g c a us es. 
8  
Vis u al Dist ur b a nc e  
R eti n al a n d ey e c h a n g es of SL E. I ncl u d e cyt oi d b o di es, r eti n al h a e m orr h a g es , 
s eri o us ex u d at e of h a e m orr h a g e  i n t h e c h or oi d, o ptic n e uritis, scl eritis or e piscl eritis. 
Excl u d e hy p ert e nsi o n, i n f ecti o n, or dr u g c a us es. 
8  
Cr a ni al N erv e 
Dis or d er  
N e w o ns et s e ns ory or m ot or n e ur o p at hy i nv olvi n g cr a ni al n erv es.  
I ncl u d e v erti g o d u e t o l u p us. 
8  
L u p us H e a d ac h e  
S ev er e p ersist e nt h e a d ac h e: m ay b e mi gr ai n o us, b ut m ust b e  
n o n -r es p o nsiv e t o n arc otic a n al gesi a.  
8  
C V A  
N e w o ns et of C V A(s). Excl u d e art eri oscl er osis or hy p ert e nsiv e c a us es.  
8  
V asc ulitis  
Ulc er ati o n, g a n gr e n e, t e n d er fi n g er n o d ul es, p eri u n g u al i nf arcti o n, s pli nt er 
h a e m orr h a g es , or bi o psy or a n gi o gr a m pr o of of v asc ulitis. 
4  
Art hritis  
M or e t h a n 2 j oi nts wit h p ai n & si g ns of i nfl a m m ati o n (i e, t e n d er n ess, s w elli n g or 
eff usi o n).  
4  
My ositis  
Pr oxi m al m uscl e ac hi n g/ w e ak n ess ass oci at e d wit h el ev at e d cr e ati n e 
p h os p h oki n as e/ al d ol as e or el ectr o my o gr a m c h a n g es or a bi o psy s h o wi n g my ositis.  
4  
Uri n ary C asts  
H e m e -gr a n ul ar or r e d bl o o d c ell c asts.  
4  
H a e m at uri a  
 5 r e d bl o o d c ells/ hi g h p o w er fi el d. Excl u d e st o n e, i nf ecti o n, or ot h er c a us es.  
4  
Pr ot ei n uri a  
N e w o ns et or r ec e nt i ncr e as e of m or e t h a n 0. 5 g/ 2 4 h o urs.  
4  
Py uri a  
 5 w hit e bl o o d c ells/ hi g h p o w er fi el d. Excl u d e i nf ecti o n.  
2  
R as h  
N e w or o n g oi n g i nfl a m m at ory l u p us r as h.  
2  
Al o p eci a  
N e w or o n g oi n g a b n or m al, p atc hy or diff us e l oss of h air d u e t o activ e l u p us.  
2  
M uc os al Ulc ers  
N e w or o n g oi n g or al or n as al ulc er ati o ns d u e t o activ e l u p us.  
2  
Pl e urisy  
Cl assic a n d s ev er e pl e uritic c h est p ai n or pl e ur al r u b or eff usi o n or n e w pl e ur al 
t hick e ni n g d u e t o l u p us. 
2  
P eric ar ditis  
Cl assic a n d s ev er e p eric ar di al p ai n or r u b or eff usi o n, or el ectr oc ar di o gr a m 
c o nfir m ati on.  
2  
L o w C o m pl e m e nt  
D ecr e as e i n C H 5 0,  
 or  
b el o w t h e l o w er li mit of n or m al f or t esti n g l a b or at ory.  
2  
I ncr e as e d D N A 
Bi n di n g  
 2 5 % bi n di n g by F arr ass ay or a b ov e n or m al r a n g e f or t esti n g l a b or at ory.  
1  
F ev er  
 3 8° C. Excl u d e i nf ecti o us c a us e.  
1  
T hr o m b ocyt o p e ni a  
 1 0 0, 0 0 0 pl at el ets/ m m 3 
1  
L e uk o p e ni a  
 3, 0 0 0 w hit e bl o o d c ells/ m m 3. Excl u d e dr u g c a us es. 
 
T O T A L S C O R E  
( S u m of w ei g ht s n e xt t o d e s cri pt or s m ar k e d pr e s e nt)  
 
C C
I
C C
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10.9. 
Appendix 9: SLE Flare Index 
(Adapted from [Buyon, 2005; Petri, 2005; Neergaard, 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 vasulitis, bullous lupus 
   Nasopharyngeal ulcers 
   Pleuritis 
   Pericarditis 
   Arthritis 
   Fever (SLE) 
Or 
 New/worse: 
   CNS-SLE 
   Vasculitis 
   Nephritis 
   Myositis 
   Plt<60,000 
   Haemolytic anaemia with Hb<70g/L or 
decrease in Hb>3 g/L  
 
Requiring: double prednisone, or prednisone 
increase to >0.5mg/kg/day, or hospitalization, 
or 
 Increase in prednisone, but not to >0.5 
mg/kg/day, or 
 Increase in prednisone to >0.5 
mg/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 
 Hospitalisation 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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10.10. 
Appendix 10: Physician’s Global Disease Assessment 
 
 
(Adapted from [Petri, 2005])  
 
 


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10.11. 
Appendix 11: 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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10.12. 
Appendix 12: Protocol Amendment History 
Amendment 01 （29 January 2021） 
Overall Rationale for the Amendment:  
This amendment specifies the criteria for primary efficacy evaluation and sample size 
consideration and for this criteria, adjusts the screening laboratory test for latent 
tuberculosis, removes the volume of blood samples for PK analysis, defines the tests 
conducted before informed consent would not be utilized for screening or baseline 
purpose, clarifies dose strength of the study intervention; specifies non-serious related AE 
reporting method. Additionally the following changes have been added: addition of 
wording to allow a repeat laboratory test for screening; requirement on recording the 
actual date and time of PK sample; addition of “CPK” in clinical chemistry test, 
clarification that PK sample will be collected when liver event happens, and addition of 
the missing items to the SoA according to the exclusion criteria and screening 
assessments. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
1.2 SOA: Safety 
Assessments 
Addition of chest X-ray 
examination at screening visit.  
Chest X-ray as an examination to rule 
out latent tuberculosis infection has not 
been defined in the SoA. 
1.2 SOA: 
Laboratory 
Assessments  
Replacement of “TSPOT” test 
by “QuantiFERON-TB Gold 
Plus” test. 
The central lab only provides 
“QuantiFERON-TB Gold Plus” test, 
which has similar efficacy as “TSPOT” 
test in ruling out latent tuberculosis 
infection. 
5.2 Exclusion 
Criteria 
Replacement of “TSPOT” test 
by “QuantiFERON-TB Gold 
Plus” in exclusion criterion #25 
To accommodate the availability of 
“QuantiFERON-TB Gold Plus” test in 
central lab.  
5.5 Repeat 
Assessments 
during the 35 Day 
Screening Period 
Addition of the wording to allow 
repeat laboratory test for 
screening purpose.  
To reduce the probability of rescreening 
in cases of technical malfunction; or a 
value close enough to the exclusionary 
threshold that it may reasonably lie 
within the degree of variability of the 
assay; or if there is reason to believe the 
result may be false by investigator. 
6.1 Study 
Intervention(s) 
Administered 
Removal of the dose strength of 
“20 mL vial containing 400 mg 
lyophilised belimumab” from the 
table and the main content. 
To clarify the dose strength used in this 
study.  
8. Study 
Assessments and 
Procedures 
Removal of the wording 
“Procedures conducted as part 
of the participant’s routine 
clinical management (e.g., 
blood count) and obtained 
before signing of ICF may be 
utilised for screening or 
Baseline purposes provided the 
procedure met the protocol-
specified criteria and was 
performed within the time frame 
defined in the SoA”. 
To ensure the screening tests are 
conducted in same central lab and to 
maintain the consistency. 
8.1 Screening 
Assessments 
Addition of “chest X-ray” and 
“QuantiFERON-TB Gold Plus 
test” in screening assessments.  
To keep it consistent with the 
requirement in exclusion criterion #25 
and items in the SoA. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
8.4.1 Time Period 
and Frequency 
for Collecting AE 
and SAE 
Information 
Specifies non-serious related 
AEs should be reported using 
ADR CRF to the sponsor 
pharmacovigilance team 
(qwy11935@gsk.com) via email 
within 5 calendar days. 
Reporting form and email box has not 
been defined. 
8.6 
Pharmacokinetics 
Removal of “0.5 mL” for the 
volume of blood samples. 
Addition of wording on recording 
the actual date and time (24-
hour clock time) of each 
sample.   
Removal of the maximum 
amount of blood drawn for PK 
during this study is 
approximately 5 mL for each 
participant. 
Replacement of “Study 
Procedures Manual” with “Study 
Reference Manual”. 
The volume of blood samples will be 
provided in Study Reference Manual. 
The requirement on recording the time of 
PK blood sampling has not been 
defined. 
 
The overall volume of blood samples will 
be provided in Study Reference Manual. 
 
 
To keep consistent on the document 
name. 
9.1 Statistical 
Hypotheses 
Addition of the target value of 
the primary efficacy endpoint. 
For compliance with authority’s 
requirement. 
9.2 Sample Size 
Determination 
Addition of sample size 
consideration for the target 
value. 
For compliance with authority’s 
requirement. 
10.2 Appendix 2: 
Clinical 
Laboratory Tests 
Addition of “Creatine 
phosphokinase (CPK)” test in 
Clinical Chemistry of Table 3. 
The CPK test required for patients with 
myositis has not been defined in the 
Appendix. 
10.5 Appendix 5: 
Liver Safety: 
Required Actions 
and Follow-up 
Assessments 
In Note #4, addition of 
quantitative Hepatitis B DNA 
test if positivity for HBsAg 
and/or HBcAb. 
Quantitative Hepatitis B DNA test is 
required when evidences indicative of 
Hepatitis B infection exist. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
10.5 Appendix 5: 
Liver Safety: 
Required Actions 
and Follow-up 
Assessments 
In the column of Follow Up 
Assessments, remove “Only in 
those with underlying chronic 
Hepatitis B at study entry 
(identified by positive Hepatitis 
B surface antigen) and 
quantitative Hepatitis B DNA”. 
In Note #5, removal of “PK 
sample may not be required for 
participants known to be 
receiving placebo or non-
comparator interventions”. 
This language is not applicable because 
patients with underlying chronic HBV will 
be excluded at screening. 
 
 
Clarification of the wording that PK 
sample will be collected when liver event 
happens. 
 
Amendment 02 （03 June 2022） 
Overall Rationale for the amendment: 
One purpose of this amendment is to provide further clarity on the anti-dsDNA assay, 
including removal of a specific positive cut-off value as this can vary depending on the 
type of assay used. In addition, and to reflect current clinical practice, the requirement for 
a positive anti-dsDNA test, from two independent time points within the study screening 
period, as an Inclusion Criterion has been removed. 
The other purpose is to reschedule the missing PK sampling to ensure sufficient precision 
of PK characterization especially during COVID pandemic period. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
5.1 Inclusion 
Criteria 
Delete "(≥30IU/ml)"   
 
 
 
 
 
 
 
 
 
 
Delete “from 2 independent time 
points as follows: 
a) 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 
b) One positive historical test 
result and 1 positive test 
result during the screening 
period.” 
The anti-dsDNA positive cut-off value is 
dependent on the type of assay used 
and is established by each laboratory. 
See the Laboratory Specifications 
Document for further details. 
 
 
 
 
 
 
To align with current clinical practice in 
minimizing the assessment burden on 
patients and to ensure consistency with 
the ongoing global belimumab SC 
paediatric study (200908). 
 
 
 
1.2 Schedule of 
Activities (SoA) 
Add footnote to SoA referencing 
for PK sampling and new 
wording as below, 
10. If miss the sample collection 
on visit 3, the PK sampling 
should be rescheduled to any 
feasible visit at 7 days after 
dosing with ±3 days window. 
11. If miss the sample collection 
on visit 4, the PK sampling 
should be rescheduled to any 
feasible visit at 14 days after 
dosing with ±7 days window. 
12. If miss the sample collection 
on visit 7, the PK sampling 
should be rescheduled to when 
patients take the next dose. 
To help investigator further understand 
rescheduling the missing PK sampling. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
8.6 
Pharmacokinetics 
Add new wording as below:  
If sampling for PK is missed, 
the impact will be minimized 
by attempting to reschedule 
the missing PK sampling to 
ensure sufficient precision of 
PK characterization in 
Chinese paediatric patients: 
• For the scenario that 
patients will miss the 
sample collection on 
visit 3 (Day 7±1 day), 
the PK sampling 
should be 
rescheduled to any 
feasible visit at 7 
days after dosing 
with ±3 days 
window. 
• For the scenario that 
patients will miss the 
sample collection on 
visit 4 (Day 14±3 
days), the PK 
sampling should be 
rescheduled to any 
feasible visit at 14 
days after dosing 
with ±7 days 
window. 
• For the scenario that 
patients will miss the 
sample collection on 
visit 7 (Day84±7 
days), the PK 
sampling should be 
rescheduled to when 
patients take the next 
dose. 
To reschedule the missing PK sampling 
to ensure sufficient precision of PK 
characterization especially during 
COVID pandemic period. 
 


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Amendment 03 (02 January 2023) 
Overall Rationale for the amendment: 
The key purpose of this amendment is to add wording to clarify and reflect the 
connection with study 217091. Study 217091 is for participants who have completed IV 
treatment for 48 weeks in study 213560, and who, in the opinion of the investigator, may 
benefit from SC treatment with GSK1550188. 
Other minor amendments are included to provide additional clarity and to reflect local 
GCP requirements in China.  
 


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Section # and Name Description of Change 
Brief Rationale 
1.2 SOA 
Update wording” N=25” to 
“approximately 25” in note 5, 
 
Add new wording in note 9, 
“If the participant transfers into 
study 217091, 16-week follow-
up visit will not be conducted.” 
  
Add wording to ensure some 
operational feasibility. 
 
Add wording to reflect the connection 
with study 217091. To clarify that 
participants who transfer into study 
217091 will not conduct 16-week 
follow-up visit.  
 
4.1. Overall Design 
Add new wording as below, 
“Participants completed the 
last Benlysta IV administration 
at Week 48 and transfer to 
study 217091 successfully will 
continue to complete the 52-
week visit of 213560. 
However, 16-week follow-up 
visit will not be conducted.” 
 
To reflect the connection with study 
217091 and clarify that participants 
who transfer into study 217091 will not 
conduct 16-week follow-up visit of 
study 213560. 
4.2.Scientific 
Rationale for Study 
Design 
 
Update wording in the 5th 
paragraph, 
“target N=25” update to 
“approximately 25” 
 
Add wording to ensure some 
operational feasibility. 
4.4. End of Study 
Definition 
Add new wording as below: 
“For participants switch to 
study 217091, the end of the 
study defined as completed 
Week 52 visit.” 
Add wording to reflect the connection 
with study 217091. To clarify that 
participants who transfer into study 
217091 will not conduct 16-week 
follow-up visit and the end of study 
213560 defined as completed Week 
52 visit. 
 
6.5.2. Prohibited 
Medications and 
Non-Drug Therapies 
 
Add new wording,  
“except study 217091” 
Allow participants to transfer to study 
217091. 
6.7. Intervention after 
the End of the Study 
Add new wording as below, 
“Participants completed the 
last Benlysta IV administration 
at Week 48 and transfer to 
study 217091 successfully will 
continue to complete the 52-
week visit of 213560. 
However, 16-week follow-up 
visit will not be conducted.” 
 
Add wording to reflect the connection 
with study 217091. To clarify that 
participants who transfer into study 
217091 will not conduct 16-week 
follow-up visit of study 213560. 


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7.1 Discontinuation 
of Study Intervention 
Add new wording  
“except study 217091.” 
 
Allow participants to transfer to study 
217091. 
10.2. Appendix 2: 
Clinical Laboratory 
Tests 
Delete wording, 
“or by the local laboratory” 
“In the event that the central 
laboratory results are not 
available in time for either 
study intervention 
administration and/or response 
evaluation, local laboratory 
results could be considered. If 
a local sample is required, it is 
important that the sample for 
central analysis is obtained at 
the same time.“ 
 
Double sampling does not comply with 
local EC policy. The study operation 
execution will follow local clinical 
practice. Delete the wording to avoid 
misunderstanding.  
 
 
 
 
 
 
 
 
 
 
 


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11. 
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BENLYSTA™ (belimumab) injection, for intravenous use. Package Insert. 02 December 
2020 (Chinese). 


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SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  213560
Official Title of Study: A Multi-Center, Open-Label Study to 
Evaluate Safety, Efficacy and Pharmacokinetics of Belimumab Plus 
Standard Therapy in Chinese Paediatric Patients with Active Systemic 
Lupus Erythematosus (SLE)
Date of Document: 30-Aug-2024


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
213560 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 1 of 49 
Information Type: 
Statistical Analysis Plan (SAP) 
TITLE PAGE 
Protocol Title: 
A Multi-Center, Open-Label Study to Evaluate Safety, 
Efficacy and Pharmacokinetics of Belimumab Plus Standard 
Therapy in Chinese Paediatric Patients with Active 
Systemic Lupus Erythematosus (SLE). 
Study Number: 
 213560 
Compound Number: 
GSK1550188 
Sponsor Name: GlaxoSmithKline Research & Development Limited  
Regulatory Agency Identifier Number(s)  
Registry 
ID 
Not Applicable 
Not Applicable 
Copyright 2024 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 


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TABLE OF CONTENTS 
PAGE 
VERSION HISTORY ....................................................................................................... 5 
1. 
INTRODUCTION ...................................................................................................... 7 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 7 
1.2. 
Study Design .............................................................................................. 10 
2. 
STATISTICAL HYPOTHESES ............................................................................... 10 
2.1. 
Multiplicity Adjustment ................................................................................ 10 
3. 
ANALYSIS SETS ................................................................................................... 11 
4. 
STATISTICAL ANALYSES ..................................................................................... 11 
4.1. 
General Considerations .............................................................................. 11 
4.1.1. 
General Methodology .................................................................. 11 
4.1.2. 
Baseline Definition ....................................................................... 11 
4.2. 
Primary Efficacy Endpoint(s) Analyses ....................................................... 12 
4.2.1. 
Definition of estimands ................................................................. 12 
4.2.2. 
Handling of Missing Data ............................................................. 13 
4.2.3. 
Main analytical approach ............................................................. 14 
4.2.4. 
Supplementary Analyses ............................................................. 14 
4.2.4.1. 
Supplemental Estimand .............................................. 14 
4.2.5. 
Additional analyses ...................................................................... 15 
4.2.5.1. 
Additional analyses 1 .................................................. 15 
4.2.5.2. 
Additional analyses 2 .................................................. 15 
4.3. 
Secondary Efficacy Endpoint(s) Analyses ................................................... 15 
4.3.1. 
Secondary efficacy endpoint(s) .................................................... 15 
4.3.1.1. 
Definition of estimands ............................................... 15 
4.3.1.2. 
Handling of Missing Data ............................................ 18 
4.3.1.3. 
Main analytical approach ............................................ 18 
4.4. 
Safety Analyses .......................................................................................... 22 
4.4.1. 
Extent of Exposure ...................................................................... 23 
4.4.2. 
Adverse Events............................................................................ 24 
4.4.2.1. 
Adverse Events of Special Interest ............................. 25 
4.4.3. 
Additional Safety Assessments .................................................... 28 
4.4.3.1. 
Laboratory Data .......................................................... 28 
4.4.3.2. 
Vital Signs .................................................................. 29 
4.5. 
Pharmacokinetic Analyses .......................................................................... 29 
4.5.1. 
Pharmacokinetic endpoint(s) ........................................................ 29 
4.5.2. 
Main analytical approach ............................................................. 29 
4.5.2.1. 
Drug Concentration Measures .................................... 29 
4.5.2.2. 
Population Pharmacokinetic (PopPK) Analyses .......... 29 
4.6. 
Other Endpoint(s) Analyses ........................................................................ 29 
4.7. 
Other Analyses ........................................................................................... 31 
4.8. 
Interim Analyses ......................................................................................... 31 
4.9. 
Changes to Protocol Defined Analyses ....................................................... 31 
CCI
CCI


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5. 
SAMPLE SIZE DETERMINATION ......................................................................... 31 
5.1. 
PK Sample Size Determination ................................................................... 32 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 34 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 34 
6.1.1. 
Participant Disposition ................................................................. 34 
6.1.2. 
Demographic and Baseline Characteristics .................................. 34 
6.1.3. 
Protocol Deviations ...................................................................... 36 
6.1.4. 
Prior and Concomitant Medications ............................................. 36 
6.1.5. 
Study Intervention Compliance .................................................... 37 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 37 
6.2.1. 
Analysis age ................................................................................ 37 
6.2.2. 
Study Period ................................................................................ 38 
6.2.3. 
Study Day and Reference Dates .................................................. 38 
6.2.4. 
Assessment Window ................................................................... 38 
6.2.5. 
Multiple measurements at One Analysis Time Point .................... 39 
6.2.6. 
Handling of Partial Dates ............................................................. 40 
6.2.7. 
Average Daily Prednisone Equivalent .......................................... 42 
6.2.7.1. 
Baseline Prednisone Dose ......................................... 45 
6.2.7.2. 
Average Daily Prednisone Dose Between 
Visits .......................................................................... 45 
6.2.7.3. 
Average Daily Prednisone Dose at the Visit ............... 45 
6.2.8. 
SLE Allowable Medication Categories ......................................... 46 
6.2.9. 
Prohibited Medications and Non-Drug Therapies ......................... 47 
6.2.10. 
SLE Flare Index ........................................................................... 47 
6.3. 
Appendix 3 Missing Data Imputation ........................................................... 48 
6.3.1. 
Multiple imputation under MAR assumption ................................. 48 
6.3.2. 
LOCF ........................................................................................... 48 
TRADEMARKS ............................................................................................................. 48 
7. 
REFERENCES ....................................................................................................... 49 
 


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LIST OF TABLES 
PAGE 
Table 1 
Prednisone Conversion Factors (mg) ..................................................... 43 
Table 2 
Frequency Factors ................................................................................. 44 
 
 
 
LIST OF FIGURES 
PAGE 
Figure 1 
The power to estimate CL and V versus sample size ............................. 33 
 
 


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VERSION HISTORY 
SAP 
Version 
Approval Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
SAP 
14 July 2021 
Amendment 
01 (Date: 29 
January 
2021) 
Not Applicable 
Original version 
SAP 
Amendment 
1 
30 Aug 2024 
Amendment 
04 (Date: 22 
January 
2024) 
• 
Addition of 
supplementary 
estimand and 
additional 
analysis for 
primary 
efficacy 
endpoints. 
• 
Additional 
analysis to 
further 
explore the 
efficacy in 
supplementa
ry estimand 
and 
additional 
analysis 
with 
different 
method of 
missing data 
imputation. 
• 
Change in 
handling of 
missing data 
imputation- 
and add 
technical 
details for 
missing data 
imputation. 
• 
Change to 
handle 
missing data 
imputation 
by using 
multiple 
imputation 
(MI) instead 
of last 
observation 
carried 
forward 
(LOCF) and 
provide 
further 
details for 
missing data 
imputation. 


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SAP 
Version 
Approval Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
 
 
 
• 
Addition of 
estimand for 
Safety 
endpoint and 
additional 
analysis based 
on all safety 
data including 
52-week on-
treatment 
period and 16-
week post-
treatment 
follow-up 
period.  
• 
Addition 
estimand for 
Safety 
endpoint to 
describe the 
clinical 
interest in 
Safety 
endpoint. 
 
 
 
• 
Addition of 
Population 
Pharmacokinet
ic (PopPK) 
Analyses for 
Pharmacokinet
ic endpoints 
• 
Added to 
clarify the 
Pharmacoki
netic   
analysis for 
Pharmacoki
netic 
endpoints 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR for 
Study 213560. Details of the planned analyses are provided. 
1.1. 
Objectives, Estimands and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the safety and efficacy of 
belimumab IV in Chinese paediatric 
patients with SLE. 
Safety 
➢ Incidence of adverse events of special 
interest (AESIs) through 52 weeks: 
• 
All Infections of special interest, 
including serious infections of 
special interest and opportunistic 
infections 
• 
Infusion related systemic reactions 
and anaphylactic reactions  
• 
Depression, suicidality 
• 
Malignancies 
Efficacy 
➢ Incidence of patients with ≥ 4 points 
reduction from baseline to Week 52 in 
SELENA SLEDAI 
Secondary 
 
• 
To evaluate safety and tolerability of 
belimumab IV in Chinese paediatric 
patients with SLE 
• 
Incidence of AEs through 52 Weeks 
• 
Incidence of SAEs through 52 
Weeks 
• 
To evaluate the efficacy of belimumab 
IV in Chinese paediatric patients with 
SLE 
• 
Incidence of patients with ≥ 4 points 
reduction from baseline in SELENA 
SLEDAI by visit 
• 
Change from baseline to Week 52 in 
Physician Global Assessment (PGA) 
• 
Change from baseline to Week 52 in 
Parent Global Assessment 
(ParentGA) 


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Objectives 
Endpoints 
• 
Change from baseline in daily 
prednisone equivalent dose at Week 
52 
• 
Time to first flare/ first severe flare 
over 52 weeks 
• 
To evaluate the pharmacokinetics 
(PK) of belimumab (10 mg/kg) IV in 
Chinese paediatric patients with SLE 
• 
Median belimumab concentration 
levels at Day 0, 7 and 14 days post 
first dose, and pre-infusion and post-
infusion at Day 84 
• 
The PK will be evaluated with 
respect to clearance, volume of 
distribution and half-life, and 
individual steady state exposures 
Cmin, Cavg, Cmax and AUC. 
Other 
Other 
 
 
AESI- adverse events of special interest, AUC- Area under the concentration curve, Cavg- average plasma 
concentration, IV- Intravenous, Cmin- the minimum blood plasma concentration reached by a drug prior to 
administration of a second dose, ParentGA - Parent Global Assessment, PGA- Physician Global Assessment, 
SELENA SLEDAI- Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease 
Activity Index 
Primary estimand for efficacy 
The primary clinical question of interest is: What is the treatment effect on SELENA 
SLEDAI after 52 weeks of treatment with GSK1550188 in Chinese paediatric patients 
with SLE while considering initiation of prohibited medications and treatment 
discontinuation for any reason to be unfavorable outcomes. For primary efficacy 
evaluation, using the percentage of participants with ≥4-point reduction from baseline in 
SELENA SLEDAI at Week 52 in the placebo group in a Phase 2 paediatric study (Study 
BEL114055) as target value to guide the primary analysis planned for this study. The 
target can be described as the observed proportion of patients with clinical benefit 
>43.6% (the mean placebo group response rate estimate in study BEL114055). 
CCI


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The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight by 
IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be found 
in protocol Section 6. 
• 
Variable / endpoint: response status at Week-52 assessment, where response is 
defined as: 
 
with ≥ 4 points reduction from baseline at Week 52 in SELENA SLEDAI, and 
 
Not using prohibited medications, and 
 
Not discontinuing study intervention for any reason   
• 
Summary measure: The percentage of participants with ≥4-point reduction from 
baseline in SELENA SLEDAI at Week 52. 
• 
Intercurrent event:  
 
Initiation of prohibited medications– composite strategy (Non-responder) 
 
Study intervention discontinuation for any reason - composite strategy (Non-
responder) 
Rationale for estimand: Interest lies in the treatment effect on SELENA SLEDAI after 52 
weeks of treatment with GSK1550188 in Chinese paediatric patients with SLE while 
considering initiation of prohibited medications and treatment discontinuation for any 
reason to be unfavorable outcomes.  Participants who receive a protocol-prohibited 
medication at any time during the study will be considered protocol violation. 
Belimumab will be discontinued and participants will be withdrawn from the study. The 
composite strategy is used for this intercurrent event (ICE) where response is imputed as 
a non-responder from the date of the earliest ICE and all timepoints thereafter through 
Week 52. For participants who discontinue study intervention for any reason, the 
participants will not remain in the study to be evaluated for efficacy. The composite 
strategy is used for this ICEs where response is imputed as a non-responder at all 
timepoints thereafter through Week 52.  


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1.2. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
A multicentre, open label, single arm, prospective, 52-week study to 
assess the safety and efficacy of belimumab IV administered in 
combination with background standard therapy in Chinese Paediatric 
Patients with Active Systemic Lupus Erythematosus (SLE). 
Study 
intervention 
All the enrolled participants will be administered Belimumab (10 
mg/kg) intravenously over a minimum of 1 hour on Days 0, 14, 28 
and then every 28 days through the Week 48 (Day 336) visit. 
Study 
intervention 
Assignment 
This is a single arm and open-label study without randomisation and 
blinding. 
Interim 
Analysis 
No formal interim analyses are planned. 
2. 
STATISTICAL HYPOTHESES  
This is an open-label study. A descriptive approach will be used, and no formal inference 
is planned in this study. For primary efficacy evaluation, using the percentage of 
participants with ≥ 4-point reduction from baseline in SELENA SLEDAI at Week 52 in 
the placebo group in a Phase 2 paediatric study (Study BEL114055) as target value to 
guide the analysis planned for this post approval commitment (PAC) study. The target 
can be described as the observed proportion of patients with clinical benefit >43.6% (the 
mean placebo group response rate estimate in study BEL114055). 
2.1. 
Multiplicity Adjustment 
This is a single arm study. No formal statistical hypothesis testing is planned. Hence no 
adjustment for multiple comparisons is required. 


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3. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
All participants whose 
parent/caregiver sign the ICF 
• 
Study Population 
Enrolled 
• 
All participants assigned treatment. 
• 
Study Population 
Intent to Treat 
(ITT) 
• 
All participants assigned treatment 
who received at least one dose of 
study treatment. 
• 
Efficacy and 
safety 
Pharmacokinetic 
(PK) 
• 
All participants assigned treatment 
who received at least one dose of 
study treatment and for whom at least 
one post belimumab treatment PK 
sample was obtained and analysed. 
• 
PK 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
Confidence intervals will use 95% confidence levels unless otherwise specified.  
Unless otherwise specified, the following will apply: 
• 
Continuous data will be summarized using descriptive statistics: n, mean, standard 
deviation (std), median, minimum, 25th percentile, 75th percentile and maximum.  
• 
Categorical data will be summarized as the number and percentage of participants in 
each category.  
• 
Where means or medians are displayed graphically, standard error bars or 
interquartile ranges (IQRs) will be presented, respectively. 
• 
The minimum and maximum will be reported to the same number of decimal places 
as the raw data recorded in the database. The mean, median, 25th percentile, and 
75th percentile will be reported to one more decimal place than the raw data 
recorded in the database. The SD will be reported to two more decimal places than 
the raw data recorded in the database. A maximum of four decimal places will be 
used. Percentages will be presented to one decimal place. A count of zero will have 
no corresponding percentage.  
4.1.2. 
Baseline Definition 
The protocol specifies “Day 0” as First Treatment, but due to CDISC standard 
implementation first treatment date will appear as “Day 1” in the analyses and throughout 
this document. 


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For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits. If time is not collected, Day 1 
assessments are assumed to be taken prior to first dose and used as baseline. 
If a subject has the day 1 visit but partial data of the endpoint are missing (including 
individual items of any component of the primary endpoint), the last available answer(s) 
to the corresponding question(s) from the most recent pre-dose visit will be used for the 
missing item or component.  For example, if the data on one or more items of the 24 
SELENA SLEDAI questions are missing, the last available answer(s) to the 
corresponding question(s) from the most recent pre-dose visit where the corresponding 
item(s) are non-missing will be assigned to the missing item(s) in order to obtain a total 
score as beseline. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
Concomitant medications and adverse events recorded on Day 1 will be assumed to be 
on-treatment. 
4.2. 
Primary Efficacy Endpoint(s) Analyses 
4.2.1. 
Definition of estimands 
The primary clinical question of interest is: What is the treatment effect on SELENA 
SLEDAI after 52 weeks of treatment with GSK1550188 in Chinese paediatric patients 
with SLE while considering initiation of prohibited medications and treatment 
discontinuation for any reason to be unfavorable outcomes. For primary efficacy 
evaluation, using the percentage of participants with ≥4-point reduction from baseline in 
SELENA SLEDAI at Week 52 in the placebo group in a Phase 2 paediatric study (Study 
BEL114055) as target value to guide the primary analysis planned for this study. The 
target can be described as the observed proportion of patients with clinical benefit 
>43.6% (the mean placebo group response rate estimate in study BEL114055). 
The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight by 
IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be found 
in protocol Section 6. 
• 
Variable / endpoint: response status at Week-52 assessment, where response is 
defined as: 
 
with ≥ 4 points reduction from baseline at Week 52 in SELENA SLEDAI, and 
 
Not using prohibited medications, and 
 
Not discontinuing study intervention for any reason  


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• 
Summary measure: The percentage of participants with ≥4-point reduction from 
baseline in SELENA SLEDAI at Week 52. 
• 
Intercurrent events:  
 
Initiation of prohibited medications– composite strategy (Non-responder) 
 
Study intervention discontinuation for any reason - composite strategy (Non-
responder) 
Rationale for estimand: Interest lies in the treatment effect on SELENA SLEDAI after 52 
weeks of treatment with GSK1550188 in Chinese paediatric patients with SLE while 
considering initiation of prohibited medications and treatment discontinuation for any 
reason to be unfavorable outcomes.  Participants who receive a protocol-prohibited 
medication at any time during the study will be considered protocol violation. 
Belimumab will be discontinued and participants will be withdrawn from the study. The 
composite strategy is used for this ICE where response is imputed as a non-responder 
from the date of the earliest ICE and all timepoints thereafter through Week 52. For 
participants who discontinue study intervention for any reason, the participants will not 
remain in the study to be evaluated for efficacy. The composite strategy is used for this 
ICEs where response is imputed as a non-responder at all timepoints thereafter through 
Week 52.  
4.2.2. 
Handling of Missing Data 
Missing data will be imputed differently depending on the handling strategy for the 
specific intercurrent event.  
• 
Missing data due to initiation of prohibited medications or study intervention 
discontinuation for any reason. For participants who receive a protocol-prohibited 
medication or discontinue study intervention for any reason at any time during the 
study, participants will be withdrawn from the study. Study withdrawal before the 
completion of the study will create missing outcome data. This may occur 
concurrently or after the ICE. The NRI (non-response imputation) is used where 
response is imputed as a non-responder at all timepoints thereafter through Week 52. 
• 
Any subject not otherwise classified as a non-responder who misses the Week 52 
visit will be handled as follows: the missing data will be imputed under a missing at 
random (MAR) assumption. Missing data will be imputed using multiple imputation 
(MI) model. The imputation models will include terms for baseline age group (5-11 
years vs.12-17 years), baseline SELENA SLEDAI score (≤12 vs. ≥13 ) and all 
previous visit values. Further details of MI approach for missing data are provided in 
Section 6.3 Appendix 3 Missing Data Imputation Strategies. 


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4.2.3. 
Main analytical approach 
Endpoint / Variables 
• Incidence of patients with ≥ 4 points reduction from baseline to Week 52 in SELENA 
SLEDAI 
Approach Specification 
• The efficacy analyses will be based in the “Intent-to-Treat” population, subjects with baseline 
SELENA SLEDAI score less than 4 are excluded from the analysis. Unless otherwise 
specified, endpoints/variables defined in Section 4.2.1 will be summarized using descriptive 
statistics, graphically presented (where appropriate) and listed. 
• 
If there is any subject not classified as a non-responder but misses the Week 52 visit, the MI 
approach will be used to impute the missing data. In this scenario, each estimate will be 
generated for each imputed dataset produced by the MI procedure described in Section 
4.2.2 and the corresponding results will be combined using Rubin’s rules. 
Results Presentation 
• 
Results will be summarized using number and percentage of subjects achieving a response, 
standard error (SE) and 95% CI(Wald). In the event that the MI approach is used to impute 
missing data, the percentage of subjects (after MI) achieving a response, SE and 95% CI 
will be summarized. 95% CI will be constructed using their asymptotic standard errors 
(asymptotic Wald confidence limits).  
• For the primary endpoint, the disposition of factors contributing to response or non-response 
will be presented as the number and percentage of subjects in each of the following 
categories at Week 52: 
• Responder 
• Non responder (if subjects have multiple ICEs, only the earliest ICE will be counted in 
this summary): 
 <4-point reduction in SELENA SLEDAI 
 Using prohibited medications or therapies 
 Study intervention discontinuation for any reason 
• Missing 
Subgroup Analyses 
• See Section 4.7.1 for details on subgroup analyses. The primary estimand will be used for 
subgroup analyses.  
4.2.4. 
Supplementary Analyses 
4.2.4.1. 
Supplemental Estimand  
As a supplemental estimand for the primary objective, a hypothetical strategy will be 
considered for the handling of the ICE of discontinuation of study intervention for any 
reason. Specifically, the effects estimated will be under the hypothetical scenario where 
the ICE of discontinuation of study intervention for any reason did not occur. All data for 
the treatment response after the occurrence of this ICE or missing data will be imputed 
conditional on the participant’s observed outcomes by MI approach. The use of this MI 
model assumes that missing outcomes would behave in a similar way to other 
participants who had data collected in the study. 


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All other ICE(initiation of prohibited medications) will be handled using the same 
strategy(composite strategy) as for the Primary Estimand Strategy. 
4.2.5. 
Additional analyses 
4.2.5.1. 
Additional analyses 1 
In the event that there is any subject not classified as a non-responder but misses the 
Week 52 visit in the primary estimand, the LOCF method (See Section 6.3.2 for details)  
will be used as additional analyse to impute the missing data instead of MI approach in 
the main analyse. The primary estimand will be used in this additional analysis. 
4.2.5.2. 
Additional analyses 2 
In supplemental estimand, the missing data and all data for the treatment response after 
the occurrence of discontinuation from study intervention for any reason will be imputed 
based on MI approach. In additional analyses 2, the LOCF method (See Section 6.3.2 for 
details)  will be used to impute the missing data and all data for treatment response after 
the occurrence of discontinuation from study intervention for any reason.  
4.3. 
Secondary Efficacy Endpoint(s) Analyses 
4.3.1. 
Secondary efficacy endpoint(s) 
• 
Incidence of patients with ≥ 4 points reduction from baseline in SELENA SLEDAI 
by visit 
• 
Change from baseline to Week 52 in Physician Global Assessment (PGA) 
• 
Change from baseline to Week 52 in Parent Global Assessment (ParentGA) 
• 
Change from baseline in daily prednisone equivalent dose at Week 52 
• 
Time to first flare/ first severe flare over 52 weeks 
4.3.1.1. 
Definition of estimands 
Endpoint(s) 
• 
Incidence of patients with ≥ 4 points reduction from baseline in SELENA 
SLEDAI by visit 
Estimand 
Similar estimand as the primary efficacy analysis (see Section 4.2.1 for details) will be 
used. 
Endpoint(s) 
• 
Change from baseline to Week 52 in Physician Global Assessment (PGA) 


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Estimand 
The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight 
by IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be 
found in protocol Section 6. 
• 
Variable: Change from baseline at Week 52 in Physician Global Assessment 
(PGA).  
• 
Summary measure: Mean change from baseline at Week 52 in Physician Global 
Assessment (PGA). 
• 
Intercurrent events: 
 
Initiation of prohibited medications - hypothetical strategy 
 
Study treatment discontinuation for any reason- hypothetical strategy  
The handling strategy for the ICEs will be based on a hypothetical approach; 
specifically, the effects estimated will be under the hypothetical scenario where the 
ICE did not occur. 
Endpoint(s) 
• 
Change from baseline to Week 52 in Parent Global Assessment (ParentGA) 
Estimand 
The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight 
by IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be 
found in protocol Section 6. 
• 
Variable: Change from baseline at Week 52 in Parent Global Assessment 
(ParentGA). 
• 
Summary measure: Mean change from baseline at Week 52 in Parent Global 
Assessment (ParentGA). 
• 
Intercurrent events: 
 
Initiation of prohibited medications or therapies- hypothetical strategy 
 
Study treatment discontinuation for any reason- hypothetical strategy  
The handling strategy for the ICEs will be based on a hypothetical approach; 
specifically, the effects estimated will be under the hypothetical scenario where the 
ICE did not occur. 
Endpoint(s) 
• 
Change from baseline in daily prednisone equivalent dose at Week 52 


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Estimand 
The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight 
by IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be 
found in protocol Section 6. 
• 
Variable: Change from baseline at Week 52 in daily prednisone equivalent dose. 
• 
Summary measure: Mean change from baseline at Week 52 in in daily prednisone 
equivalent dose. 
• 
Intercurrent events: 
 
Initiation of prohibited medications or therapies– only the observed data 
before initiation of prohibited medications or therapies will be used for daily 
prednisone equivalent dose at each visit and no imputation will be done for 
missing data. 
 
Study treatment discontinuation for any reason- only the observed data before 
initiation of prohibited medications or therapies will be used for daily 
prednisone equivalent dose at each visit and no imputation will be done for 
missing data. 
Only the observed data before the ICEs will be used in the analysis. 
Endpoint(s) 
• 
Time to first flare/ first severe flare over 52 weeks 
Estimand 
The estimand is described by the following attributes: 
• 
Population: Chinese paediatric patients with active SLE. 
• 
Treatment condition: Belimumab will be administrated at 10 mg/kg body weight 
by IV infusion on Days 0, 14, 28 and then every 28 days through Week 48 in 
combination with standard therapy. Further details on standard therapy can be 
found in protocol Section 6. 
• 
Variable: Time to first flare/ first severe flare over 52 weeks which is defined as 
the number of days from first exposure until the subject meets an event (event date 
– first exposure date + 1). 
• 
Summary measure: Median of days to first flare/ first severe flare. 
• 
Intercurrent events: 
 
Initiation of prohibited medications–composite strategy (the event date is the 
earliest of the first flare/ first severe date and the date of initiation of 
prohibited medications or therapies). 


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 
Study treatment discontinuation for any reason- hypothetical strategy (the date 
will be censored at last flare assessment date). 
 
Subject dies during Week 52-composite strategy (the event date is the date of 
death). 
4.3.1.2. 
Handling of Missing Data 
• 
For incidence of patients with ≥ 4 points reduction from baseline in SELENA 
SLEDAI by visit, the same methodology for handling missing data as the primary 
efficacy endpoint in Section 4.2.2 will be used. 
• 
For change from baseline to Week 52 in Physician Global Assessment (PGA) and 
Parent Global Assessment (ParentGA), missing data will be imputed as below. 
 
Intermittent missing data (i.e. data between two non-missing assessments) will 
be imputed under a missing at random (MAR) assumption.  
 
Missing data due to hypothetical strategy for intercurrent event, assuming that 
missing data is missing at random (MAR). Missing data will be imputed using 
MI model. This MI model uses all available data collected and assumes missing 
outcomes would behave in a similar way to participants who had data collected 
in the study. Further details of MI approach for missing data are provided in 
Section 6.3 Appendix 3 Missing Data Imputation Strategies.   
 
Missing data without any intercurrent event. Assuming that missing data is 
missing at random (MAR). Missing data will be imputed using MI model. This 
MI model uses all available data collected and assumes missing outcomes would 
behave in a similar way to participants who had data collected in the study. 
Further details of MI approach for missing data are provided in Section 6.3 
Appendix 3 Missing Data Imputation Strategies.   
• 
For change from baseline in daily prednisone equivalent dose at Week 52, only the 
observed data will be used for analysis and no imputation will be done for missing 
data. 
• 
For time to first flare/ first severe flare over 52 weeks, the censoring rules can be 
found in Section 4.3.1.1. 
4.3.1.3. 
Main analytical approach 
Endpoint / Variables 
• 
Incidence of patients with ≥ 4 points reduction from baseline in SELENA 
SLEDAI by visit 
Approach Specification 
• 
This endpoint will be analyzed using the same methodology as the primary 
efficacy endpoint in Section 4.2.3.  


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 Results Presentation 
• 
Similar results as the primary efficacy analysis (see Section 4.2.3 for details) will 
be presented. The number and percentage of subjects with ≥ 4 points reduction 
from baseline in SELENA SLEDAI will be summarized by visit. Plots of the 
proportion of subjects (after MI) achieving a response and their corresponding 
errors will be generated by time. 
Additional Analysis 
• 
The LOCF method (See Section 6.3.2 for details) will be used as additional 
analyse to impute the missing data instead of MI approach in the main analyse. 
The primary estimand will be used in this additional analysis. 
• 
The observed SELENA SLEDAI response at each visit will be summarized. No 
imputation will be done for missing data. 
• 
The change from baseline and percent change from baseline in SELENA SLEDAI 
score will be summarized by visit. Similar primary estimand as PGA and 
ParentGA (see Section 4.3.1.1 for details) will be used. The mean change from 
baseline and mean percent change from baseline in SELENA SLEDAI score at 
each visit will be presented graphically using a line graph by visit. For missing 
data imputation and intercurrent events with hypothetical strategy, each estimate 
will be generated for each imputed dataset produced by the multiple imputation 
(MI) procedure described in Section 4.3.1.2 and the corresponding results will be 
combined using Rubin’s rules. 
Endpoint / Variables 
• 
Change from baseline to Week 52 in Physician Global Assessment (PGA) 
Approach Specification 
• 
The efficacy analyses will be based in the “Intent-to-Treat” population, unless 
otherwise specified. This endpoint will be summarized using descriptive statistics 
and graphically presented (where appropriate). 
• 
For missing data imputation and intercurrent events with hypothetical strategy, 
each estimate will be generated for each imputed dataset produced by the multiple 
imputation (MI) procedure described in Section 4.3.1.2 and the corresponding 
results will be combined using Rubin’s rules. 
 Results Presentation 
• 
The change from baseline at week 52 in PGA will be summarized. Descriptive 
statistics with N, Min, Median, Max, Mean, SE, SD, 95% CI, 25th and 75th 
percentiles will be presented. The change from baseline in PGA will also be 
summarized by visit. The mean change from baseline in PGA at each visit will be 
presented graphically using a line graph by visit. 
Additional Analysis 
• 
The LOCF method (See Section 6.3.2 for details) will be used as additional 
analyse to impute the missing data and all data after the occurrence of initiation of 
prohibited medications and study treatment discontinuation for any reason. 


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• 
The observed change from baseline in PGA at each visit will be summarized. No 
imputation will be done for missing data. 
• 
The percent change from baseline in PGA will be summarized by visit. Similar 
primary estimand as change from baseline in PGA will be used. The mean percent 
change from baseline in PGA at each visit will be presented graphically using a 
line graph by visit. For missing data imputation and intercurrent events with 
hypothetical strategy, each estimate will be generated for each imputed dataset 
produced by the multiple imputation (MI) procedure described in Section 4.3.1.2 
and the corresponding results will be combined using Rubin’s rules. 
• 
The number and percentage of subjects with no worsening (increase of <0.30 
points from baseline) in PGA will be summarized by visit. Similar estimand and 
methodology as the primary efficacy endpoint (see Section 4.2.1 for details) will 
be used. 
• 
To evaluate the response over time, the number and percentage of subjects with a 
• 
≥0.3 point improvement in PGA will be summarized by visit and presented 
graphically. Similar estimand and methodology as the primary efficacy endpoint 
(see Section 4.2.1 for details) will be used. 
Endpoint / Variables 
• 
Change from baseline to Week 52 in Parent Global Assessment (ParentGA) 
Approach Specification 
• 
The efficacy analyses will be based in the “Intent-to-Treat” population, unless 
otherwise specified. This endpoint will be summarized using descriptive statistics 
and graphically presented (where appropriate). 
• 
For missing data imputation and intercurrent events with hypothetical strategy, 
each estimate will be generated for each imputed dataset produced by the multiple 
imputation (MI) procedure described in Section 4.3.1.2 and the corresponding 
results will be combined using Rubin’s rules. 
 Results Presentation 
• 
The change from baseline at week 52 in ParentGA will be summarized. 
Descriptive statistics with N, Min, Median, Max, Mean, SE, SD, 95% CI, 25th and 
75th percentiles will be presented. The change from baseline in ParentGA will also 
be summarized by visit. The mean change from baseline in ParentGA at each visit 
will be presented graphically using a line graph by visit. 
Additional Analysis 
• 
The LOCF method (See Section 6.3.2 for details) will be used as additional 
analyse to impute the missing data and all data after the occurrence of initiation of 
prohibited medications and study treatment discontinuation for any reason. 
• 
The observed change from baseline in ParentGA at each visit will be summarized. 
No imputation will be done for missing data. 
• 
The percent change from baseline in ParentGA will be summarized by visit. The 
mean percent change from baseline in ParentGA at each visit will be presented 


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graphically using a line graph by visit. For missing data imputation and 
intercurrent events with hypothetical strategy, each estimate will be generated for 
each imputed dataset produced by the multiple imputation (MI) procedure 
described in Section 4.3.1.2 and the corresponding results will be combined using 
Rubin’s rules. 
Endpoint / Variables 
• 
Change from baseline in daily prednisone equivalent dose at Week 52 
Approach Specification 
• 
For analyses, all corticosteroids are converted to a prednisone equivalent average 
daily dose (mg/day), therefore analyses refer to average daily prednisone 
equivalent dose instead of average daily steroid dose. The definition and 
derivation of this can be found in Section 6.2.7. 
• 
The analyses will be based in the “Intent-to-Treat” population, unless otherwise 
specified. The absolute change from baseline in average daily prednisone 
equivalent dose (mg/day) at each post-baseline visit up to and including Week 52 
will be summarized. This summary will be based on the observed data only. No 
imputation will be done for missing data.  
 Results Presentation 
• 
The change from baseline at week 52 in daily prednisone equivalent dose will be 
summarized. Descriptive statistics with N, Min, Median, Max, Mean, SE, SD, 
95% CI, 25th and 75th percentiles will be presented. The change from baseline in 
daily prednisone equivalent dose will also be summarized by visit. The absolute 
change from baseline in daily prednisone dose at each visit will be presented 
graphically using a line graph. 
Additional Analysis 
• 
The number and percentage of subjects with any decrease in daily prednisone 
equivalent dose will be summarized by visit and presented graphically. A 
responder is defined as having any reduction in prednisone compared to baseline. 
Similar estimand and methodology as the primary efficacy analysis (see Section 
4.2.1 for details) will be used. 
• 
The number and percentage of subjects with any increase in daily prednisone 
equivalent dose will be summarized by visit. Hypothetical strategy will be used for 
study intervention discontinuation for any reason and initiation of prohibited 
medications or therapies. Each estimate will be generated for each imputed dataset 
produced by the multiple imputation (MI) procedure and the corresponding results 
will be combined using Rubin’s rules. 
Endpoint / Variables 
• 
Time to first flare/ first severe flare over 52 weeks 


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Approach Specification 
• 
Time to first flare(defined as mild, moderate, or severe) over 52 weeks and time to 
first severe flare over 52 weeks will be analysed separately. 
• 
The derivations rule of flares and severe flares can be found in Section 6.2.10. 
• 
The analyses will be based in the “Intent-to-Treat” population, unless otherwise 
specified. Descriptive statistics will be used to summarise time to first flare/ first 
severe flare over 52 weeks. For subjects who experience a flare/ severe flare, the 
study day of the flare/severe flare will be summarized. 
 Results Presentation 
• 
Descriptive statistics with the number and percentage of subjects with a flare 
/severe flare, the median and 25th and 75th percentiles of days to first severe flare 
to summarise time to first flare/ first severe flare over 52 weeks. Statistics will be 
missing when the number of events is too low to estimate the value. For subjects 
who experience a flare/ severe flare, the study day of the flare/severe flare will be 
summarized and the table will display the N, median, 25th and 75th percentiles , 
minimum, and maximum. A Kaplan-Meier plot for time to first flare/ first severe 
flare will also be produced. 
4.4. 
Safety Analyses 
The safety analyses will be based on the ITT Population, unless otherwise specified. 
Endpoint 
Statistical Analysis Methods 
Safety 
Endpoints:  
➢ Incidence of adverse events of special interest (AESIs) through 52 
weeks: 
 
All infections of special interest, including serious 
infections of special interest and opportunistic infections 
 
Infusion-related systemic reactions and anaphylactic 
reactions  
 
Depression, suicidality 
 
Malignancies 
➢ Incidence of AEs through 52 Weeks 
➢ Incidence of SAEs through 52 weeks 
Analysis:  
Descriptive statistics will be used to summarise AEs, SAEs and AESIs. 
The frequency of AEs will be tabulated by MedDRA system organ 
class (SOC) and preferred term. 


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For estimand strategy in safety. The estimand is described by the following attributes: 
Population 
Chinese paediatric patients with active SLE. 
Treatment 
• 
Belimumab will be administrated at 10 mg/kg body weight 
by IV infusion on Days 0, 14, 28 and then every 28 days 
through Week 48 in combination with standard therapy. 
Further details on standard therapy can be found in protocol 
Section 6. 
Endpoints 
• 
Incidence of adverse events, serious adverse events and 
adverse events of special interest through Week 52. 
Summary 
Measure 
• 
 Frequency and percentage 
Intercurrent 
events and 
strategies 
• 
Discontinuation of study medication, addressed with while-
on-treatment strategy. Safety data in the 52-week on-
treatment period will be used in analysis. The definition of 
on-treatment period can be found in Section 6.2.2. 
Rationale for Estimand: This attempts to estimate on-treatment safety effects likely to be 
attributable to the drug. 
In addition to the primary estimand strategy in safety, additional analysis will be 
performed in some key endpoints based on all safety data including 52-week on-
treatment period and 16-week post-treatment follow-up period. The definition of on-
treatment period and post-Treatment period can be found in Section 6.2.2. 
4.4.1. 
Extent of Exposure 
Summaries of extent of exposure will be presented for the ITT population. 
The extent of exposure to study treatment through Week 52 will be assessed by 
examining the duration of exposure to belimumab in days and the total number of 
infusions a subject receives. 
The duration of exposure, the total number of infusions (including partial and complete), 
and the percent compliance will be summarized using descriptive statistics. The total 
number of infusions will also be summarized using counts and percentages using the 
following categories: 1 – 5 doses, 6 – 10 doses and 11 – 14 doses. 
Duration of exposure in days for each subject will be calculated as: Last infusion date– 
first infusion date + 28. 
Study intervention Compliance (%) = (Number of infusions prescribed- Number of 
infusions missed / Number of infusions prescribed])*100. 
Exposure data will be listed for all subjects. 


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4.4.2. 
Adverse Events 
Primary analysis 
In primary analysis, AEs will be summarized for on-treatment period, unless otherwise 
specified.  
The definition of on-treatment period can be found in Section 6.2.2. 
AEs with partial or missing start and/or stop dates will be assumed to be on-treatment 
unless there is evidence through comparison of partial dates to suggest otherwise. 
The duration of the AE will be calculated as follows: 
Duration of AE (days) = Date of AE resolution – AE start date + 1. 
If the AE is ongoing the duration will be left blank and no imputation will be done. 
An overall summary of AEs will be presented showing the number and percent of 
subjects with at least one: AE, related AE, serious AE (SAE), severe AE, serious and/or 
severe AE, AE resulting in study agent discontinuation, and deaths: 
• 
Overview of all AEs 
The number and percentage of subjects experiencing an AE and the incidence of AEs will 
be summarized for each of the following AE categories: 
• 
All AEs (by SOC; by SOC and PT; by PT only) 
• 
Serious AEs (by SOC; by SOC and PT; by PT only) 
• 
Severe AEs (by SOC; by SOC and PT; by PT only) 
• 
Study Agent Related AEs (by SOC; by SOC and PT; by PT only) 
• 
AEs Resulting in Study Agent Discontinuation (by SOC; by SOC and PT; by PT 
only) 
• 
Common (≥ 5%) Adverse Events(by SOC and PT) 
• 
Non-Serious Adverse Events (by SOC and PT) 
• 
Common (>= 5%) Non-Serious Adverse Events (by SOC and PT) 
• 
Study Agent Related Serious Adverse Events (by SOC and PT) 
• 
Fatal Serious Adverse Events (by SOC and PT) 
• 
Non-Fatal Serious Adverse Events (by SOC and PT) 
• 
Study Agent Related Non-Fatal Serious Adverse Events (by SOC and PT) 
A summary of AEs by SOC and severity will also be provided. For this display, the 
number and percentage of subjects will be summarized as mild, moderate, or severe 
based on the maximum severity observed across all PTs within the 


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SOC during the specified study period for a given subject. 
A summary of AEs by SOC, PT and severity will also be provided. The number and 
percentage of subjects will be summarized as mild, moderate, or severe based on the 
maximum severity observed within each PT, and within each SOC, during 
the specified study period. 
A listing of all AEs will be presented, including duration and study day. 
A listing for all SAEs will be produced. 
Additional analysis 
All subjects (except for participant who transfers into study 217091) will be followed for 
safety at 16 weeks post last dose of belimumab. In addition to the primary analysis for 
on-treatment period, the following summary tables will be produced for all AEs including 
52-week on-treatment period and 16-week post-treatment follow-up period: 
• 
Overview of all AEs 
• 
All AEs (by SOC and PT) 
• 
Study Agent Related AEs (by SOC and PT) 
• 
Severe AEs (by SOC and PT) 
• 
Serious AEs (by SOC and PT) 
The following listings will be produced: 
• 
Listing of all Adverse Events in 16-week post-treatment follow-up period 
4.4.2.1. 
Adverse Events of Special Interest 
Primary analysis 
In primary analysis, AESIs will be summarized for on-treatment period, unless otherwise 
specified.  
To ensure consistency across belimumab studies, AESI will be defined per the version of 
the Program Safety Analysis Plan (PSAP) and MedDRA in effect at the time of data base 
release (DBR).  
The Benlysta PSAP has been developed to include an adverse event of special interest 
(AESI) analysis for consistent reporting across belimumab studies. Categorizations for 
the AESIs are defined in the PSAP.  
An overall summary of AESIs will be presented and each specific category of AESI will 
be presented separately by PT. The number and percentage of subjects with at least one 
occurrence and the number of events of the following AESIs will be provided.  
The following AESI will be identified and adjudicated as detailed in the PSAP. 


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Adverse Events 
Adverse Events of Special Interest (AESI) 
AESI will be defined per the version of the PSAP/MedDRA in effect at the time of 
DBR. 
Malignant Neoplasms 
• 
Malignancies Excluding non-melanoma skin cancer (NMSC) 
• 
Malignancies Including NMSC 
• 
Solid Tumour 
• 
Hematologic 
• 
Skin (All) 
 
NMSC 
 
Excluding NMSC 
• 
Tumours of unspecified malignancy adjudicated as malignant per GSK 
Post-Infusion Systemic Reactions (PISR) 
• 
PISR per Anaphylactic Reaction Customized MedDRA Query (CMQ) narrow 
search 
• 
Serious PISR per Anaphylactic Reaction Customized MedDRA Query (CMQ) 
narrow search 
• 
PISR per Anaphylactic Reaction CMQ broad search 
• 
Serious PISR per Anaphylactic Reaction CMQ broad search 
• 
PISR per Anaphylactic Reaction CMQ algorithmic search 
• 
Serious PISR per Anaphylactic Reaction CMQ algorithmic search 
All Infections of Special Interest (Opportunistic Infections (OI), Herpes Zoster (HZ), 
Tuberculosis (TB), And Sepsis; All and Serious, separately) 
• 
All opportunistic infections (OI) per GSK adjudication 
• 
OI per GSK adjudication excluding Tuberculosis and Herpes Zoster 
• 
Active Tuberculosis 
 
Non-Opportunistic  
 
Opportunistic 
• 
Herpes Zoster 
 
Non-Opportunistic  


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Adverse Events 
Adverse Events of Special Interest (AESI) 
 
Opportunistic 
 
Recurrent  
 
Disseminated 
• 
Sepsis 
Depression (including mood disorders and anxiety)/suicide/self-injury (All and 
Serious, separately)  
• 
Depression (including mood disorders and anxiety) (excluding suicide and self-
injury)  
• 
Suicide/self-injury 
• 
Serous suicide/self-injury per GSK adjudication  
 
Suicidal Behavior  
 
Completed Suicide  
 
Suicidal Ideation  
 
Self-injurious Behavior without Suicidal Intent   
Deaths 
Malignant neoplasm events identified as “tumours of unspecified malignancy” will be 
reviewed for classification as malignant per GSK adjudication and will be presented by 
category and PT. 
Post-infusion systemic reactions and serious post- infusion systemic reactions will be 
presented using different definitions as indicated above. These will be presented by 
category and PT. 
Infection AESIs will be presented by Category and PT for all infections and for infections 
leading to study treatment discontinuation. 
Depression, suicide and self-injury as defined in the PSAP will be presented by Category 
and PT. 
Summaries of post-infusion systemic reactions that occur on the day of an infusion or 
within 3 days after an infusion will be presented by the first six infusion and over all 
infusions, and PT for the following:   
• 
Post-Infusion Systemic Reactions per Anaphylactic Reaction CMQ broad search (on 
the day of the infusion or within 3 days after the Belimumabinfusion) by PT in the 
first six infusion. 


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• 
Serious Post-Infusion Systemic Reactions per Anaphylactic Reaction CMQ broad 
search (on the day of the infusion or within 3 days after the Belimumab infusion) by 
PT in the first six infusions. 
All AESI will be presented in a listing.  
Additional analysis 
All subjects (except for participant who transfers into study 217091) will be followed for 
safety at 16 weeks post last dose of belimumab. In addition to the primary analysis for 
on-treatment period, an overall summary of AESIs will be produced including 52-week 
on-treatment period and 16-week post-treatment follow-up period. 
4.4.3. 
Additional Safety Assessments  
4.4.3.1. 
Laboratory Data 
For laboratory analyses, only analytes with a numeric normal range will be analyzed. 
Summaries and analyses will be performed based on the observed data. No imputation 
will be done for missing data. 
Listings will be generated for all laboratory results. 
• 
Descriptive statistics for each analyte will be displayed for each visit. No statistical 
tests will be performed. Line graphs will be produced for each analyte which 
displays the mean value by visit. 
• 
Laboratory toxicity will be graded using Adverse Event Severity Grading Tables 
when possible. The worst laboratory toxicity grade during the study period, including 
unscheduled visits, for each laboratory parameter within each laboratory category 
(hematology, liver function, electrolytes, other chemistries and urinalysis) will be 
presented. 
• 
Toxicity grade shifts from baseline of ≥ 2 grades during the study period, including 
unscheduled visits, will be summarized for each laboratory parameter within each 
laboratory category (hematology, liver function, electrolytes, other chemistries, 
urinalysis, and immunoglobulins). The table will display the number and percentage 
of subjects with at least one ≥ 2 grade shift as well as the specific shift categories: 
Grade 0 to 2, Grade 0 to 3, Grade 0 to 4, Grade 1 to 3, Grade 1 to 4 and Grade 2 to 4. 
• 
For laboratory tests without toxicity grades within each laboratory category 
(hematology, liver function, electrolytes, other chemistries, urinalysis and 
immunoglobulin), shifts relative to the normal range will be summarized for each 
analyte as shifts ‘to low’ and shifts ‘to high’. For example, for the ‘to low’ category 
the percentage of subjects with at least one low post-baseline value relative to the 
baseline will be displayed using the categories:   remained low and normal/high to 
low. For the ‘to normal/high’ category the percentage of subjects with at least one 
high post-baseline value relative to baseline will be displayed using the categories:   
remained normal/high and low to normal/high. No statistical tests will be performed. 
A laboratory value that is above the testing laboratory’s normal range will be 
considered a high abnormal laboratory value. A laboratory value that is below the 
testing laboratory’s normal range will be considered a low abnormal value. 


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4.4.3.2. 
Vital Signs 
A summary of vital signs and change from baseline of vital signs will be presented by 
visit. 
4.5. 
Pharmacokinetic Analyses 
4.5.1. 
Pharmacokinetic endpoint(s) 
• 
Median belimumab concentration levels at Day 0, 7 and 14 days post first dose, and 
pre-infusion and post-infusion at Day 84 
• 
The PK will be evaluated with respect to clearance, volume of distribution and half-
life, and individual steady-state exposures (e.g., Cmin, Cavg, Cmax and AUC). 
4.5.2. 
Main analytical approach 
The PK analyses will be based on the PK Population, unless otherwise specified. 
4.5.2.1. 
Drug Concentration Measures 
Pharmacokinetic concentration data will be summarized descriptively, listed and plotted. 
Standard summary statistics will be calculated (i.e. mean, geometric mean and SD, 95% 
confidence intervals for mean/geometric means, CV%, median, minimum, and 
maximum) for Pharmacokinetic concentration data. It will be summarized at each 
sampling visit / time point. Individual subject concentration data will be listed. Median 
and geometric mean belimumab concentrations will be graphically presented. 
4.5.2.2. 
Population Pharmacokinetic (PopPK) Analyses 
Pharmacokinetic parameters data will be summarized and listed by population 
pharmacokinetic (PopPK) methods. Standard summary statistics will be calculated (i.e. 
arithmetic mean, standard deviation of the untransformed data, 95% confidence intervals 
for the arithmetic mean, median, minimum and maximum, geometric mean, standard 
deviation of the log-transformed data, 95% confidence intervals for geometric means, 
between subject coefficient of variation (%CVb)) for Pharmacokinetic parameters data. A 
by-subject listing of pharmacokinetic parameters will be produced. Since PK parameters 
will be calculated using population PK model, these outputs will be displayed in 
population PK modelling report. 
4.6. 
Other Endpoint(s) Analyses 
CCI


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4.8. 
Interim Analyses 
No formal interim analyses are planned. 
4.9. 
Changes to Protocol Defined Analyses 
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol amendment 04 (Dated: [22-JAN-2024]).  
5. 
SAMPLE SIZE DETERMINATION 
Focusing on serious infections, the incidence rate of the serious AE “Infections and 
Infestations” (SOC) was 7.5% (4/53 participants) in the 10 mg/kg-IV group of the global 
paediatric study (Study BEL114055).  
Under the assumption that the incidence rate of the serious infections is 7.5%, it is 
calculated that a study with 65 participants will have more than 99.0% probability to 
observe at least one serious infection. Under this sample size, for any other adverse 
CCI


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events, there are more than 90% probability to observe at least one event once the 
incidence rate is larger than 4%. Additionally, using the Exact method in PASS 2019 for 
the confidence interval (CI) around a single proportion: a sample size of 65 would have 
produced a 95% CI of [2.4%, 16.8%] when the incidence rate of the serious infections is 
7.5%. 
For the efficacy purpose, as one of the key efficacy endpoints, the estimated percentage 
of participants with ≥4-point reduction from baseline in SELENA SLEDAI at Week 52 is 
54.7% in BEL114055. Using the Exact method in PASS 2019 for the confidence interval 
(CI) around a single proportion: a sample size of 65 would produce a 95% CI of [41.9%, 
67.1%] when the estimate is 54.7%. Under the assumption that the percentage of 
participants with ≥4 points reduction from baseline in SELENA SLEDAI at week 52 is 
54.7%, it is calculated by simulation that a study with 65 participants will have more than 
95.0% probability to observe a percentage lager than 43.6%. 
5.1. 
PK Sample Size Determination 
The FDA recommends that for paediatric studies, the 95% confidence interval of the 
average CL and V estimates are within 60% to 140% of the geometric mean, with at least 
80% power [Wang, 2012]. The same principles are applied here, but for this study a more 
stringent criterion will be applied requiring the precision of the CL and V to be 
determined within 80% to 120% of the geometric mean with at least 80% power. It is 
recommended to collect PK blood samples from 25 Chinese paediatric patients, which is 
considered the minimum number to meet this more stringent condition and therefore 
enable a quantitative comparison with the PK in a Western paediatric population. 
The sampling of the PK from each subject will be sparse, but when the data is integrated 
with the population PK model previously developed for paediatrics, the belimumab 
clearance (CL) and volume of distribution (V) may be estimated for each subject as if the 
PK had been frequently sampled in these subjects. To show that PK samples from N=25 
evaluable Chinese paediatric patients should be sufficient to accurately determine the PK 
in a Chinese paediatric population, one needs to consider the precision of the average CL 
and V estimates derived from the N=25 individual values. 
The power to estimate the CL is calculated by integrating over all possible values of the 
estimated standard deviations, weighted by the probability density and for each value 
assigning one to the integrand if the 95% confidence interval is within the 80% to 120% 
range or zero otherwise:  
 
where    
 
The results from this power calculation show N=25 paediatric subjects with evaluable PK 
results in at least 80% power to estimate the CL and V with 95% confidence intervals 
within 80% to 120% of their geometric mean values (blue line, Figure 1). In this regard 


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the precision of the CL and V estimates in a Chinese paediatric population can be 
considered sufficient for this study design to compare against the corresponding 
parameters derived in a Western paediatric population. Additionally, there is 100% power 
the same sample size will estimate CL and V with 95% confidence intervals within the 
wider window of 60%-140% of their geometric means (red line, Figure 1). 
Figure 1 
The power to estimate CL and V versus sample size 
 
The power to estimate the 95% confidence interval within 80% to 120% of the 
geometric mean is shown (blue solid line). The power calculation was also repeated 
for the less stringent criteria requiring the 95% confidence interval to be within 
60% to 140% of the geometric mean (red solid line). 


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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
The ITT population will be used to summarize the study population data. 
6.1.1. 
Participant Disposition 
A summary of the number and percentage of participants who completed the study as 
well as those who prematurely withdrew from the study will be provided. Reasons for 
study withdrawal will be summarized. Additionally, the cumulative number and 
percentage of subjects who withdrew from the study by visit will be displayed. 
A summary of study intervention status will be provided. This display will show the 
number and percentage of participants who have completed the scheduled study 
intervention or have discontinued study intervention prematurely, as well as primary 
reasons for discontinuation of study intervention. Additionally, the cumulative number 
and percentage of subjects who discontinued study intervention by study visit will be 
displayed. 
The summary of study visit impacted by COVID-19 will be provided. 
Using the screened population, the number of subjects in each population (Screened, 
Enrolled, ITT, and PK will be summarized. A summary of the reasons for the screen 
failures will be provided along with a listing of the subjects who were screen failures. 
A listing of subject disposition will be provided showing completion status and whether 
or not they are included in each population. A listing of subjects who withdrew from the 
study, including reason and date of withdrawal will also be provided. 
6.1.2. 
Demographic and Baseline Characteristics 
Descriptive statistics will be used to summarize the continuous demographic and baseline 
characteristics of age at screening (years), height (cm), weight (kg), BMI (kg/m2) and 
vital signs (temperature, heart rate and blood pressure).  
Counts and percentages of the following categorical demographic and baseline 
characteristics will be presented: sex, age group at screening (<13 years and ≥13 years), 
cardiovascular history (family history [yes/no/ unknown]), tobacco use (never smoked, 
current smoker, former smoker). A summary of the number and percentage of subjects 
reporting each general medical history term will also be provided. 
The summary of demographic and baseline characteristics will be repeated for the age 
subgroups, as defined in Section 4.7.1. 
Demographic and baseline characteristics will be listed for all subjects. 
A summary of baseline disease activity will be provided, including counts and 
percentages for the following variables: 


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• 
SLE disease duration category (≤0.5, >0.5-<1.5, 1.5-<3, ≥3) 
• 
SLE disease duration category (<2, ≥2) 
• 
SELENA SLEDAI category (≤12, ≥13) 
• 
SELENA SLEDAI category (≤7, ≥8) 
• 
SELENA SLEDAI category (≤5, ≥6) 
• 
PGA category (0-1, >1 – 2.5, >2.5) 
• 
ParentGA category (0-2.5, >2.5 – 5, >5 – 7.5, >7.5) 
• 
Proteinuria category (≤0.5, >0.5-<1, 1-<3, ≥3) 
Descriptive statistics (N, Min, Median, Max, Mean, SD, 25th and 75th percentiles) for 
the continuous scores will be presented for the following variables: 
• 
SELENA SLEDAI 
• 
PGA 
• 
ParentGA 
• 
Proteinuria levels 
The summary of baseline disease activity will be repeated for the age subgroups, as 
detailed in Section 4.7.1. 
The following indicators of disease activity will also be summarized at baseline: 
• 
SLE disease duration (years)  
• 
SELENA SLEDAI category by organ domain and item (count and percentage with 
each item present) 
• 
 
 
• 
• 
• 
 
. 
• 
Allowable SLE medication usage– counts and percentages by class (Steroids, Anti-
malarials, and Other Immunosuppressive/Immunomodulatory Agents) and drug as 
well as summary statistics for average daily prednisone dose (mg/day) at baseline. 
CCI
CCI
CCI


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• 
Steroid, Anti-malarial and Immunosuppressant Use at Baseline – counts and 
percentages by class (Steroid Only, Immunosuppressant Only, Anti-malarial Only, 
Steroid and Immunosuppressant Only, Steroid and Anti-malarial Only, 
Immunosuppressant and Anti-malarial Only, Steroid and Immunosuppressant and 
Anti-malarial) 
6.1.3. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan. 
• 
Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset.  
• 
This dataset will be the basis for the summaries and listings of protocol deviations. 
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 
All violations will be discussed and adjudicated as important or not important. Full 
details describing important deviations are given in the Protocol Deviation Management 
Plan (PDMP) 
In addition to the overall summary of important protocol deviations, separate summaries 
will be produced for important protocol deviations related to COVID-19, and important 
protocol deviations not related to COVID-19 respectively. 
Visits and assessments missed due to the COVID-19 pandemic, together with visits 
conducted remotely, will be summarized. 
6.1.4. 
Prior and Concomitant Medications 
Concomitant medications will be coded according to drug name as defined in the GSK 
Drug Dictionary, and classified according to the GSK-Drug ATC classification level 1 
and ATC level 4. 
A summary of the number and percentage of subjects with concomitant medications by 
ATC level 1 term and ATC level 4 term will be displayed. A further summary of 
concomitant medications by ATC level 4 term and preferred term will be provided. A 
listing of all concomitant medication data will be displayed by subject. 


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Prior medication is any medication that started before first dose of study treatment. 
Concomitant medications include any medication that was taken at some point during the 
study period (post first dose of study treatment), regardless of whether it was started prior 
to the first dose of study treatment or not. Unless otherwise stated, all concomitant 
medications summaries will use the “while on treatment” approach, i.e., any concomitant 
medications which are taken post intervention period will be excluded. Medications 
which are taken post intervention period will be considered post-treatment. 
The number and percentage of subjects who receive a protocol-prohibited medication 
will be summarized. 
6.1.5. 
Study Intervention Compliance 
A summary of overall compliance based on the exposure data will be produced. Overall 
compliance will be summarized using descriptive statistics. 
Study intervention Compliance (%) = (Number of infusions prescribed- Number of 
infusions missed / Number of infusions prescribed])*100. 
6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Analysis age 
Screening Age 
For screening age, three variables are required in the dataset: age in years, age in months, 
and age in years and months (e.g. “12 yrs 9 mo”). 
Age in years will be used for the demography summary. Age in months is required to 
derive age in years and months, which will be displayed in the listing. 
Screening age (years) will be calculated as: 
INTCK (‘YEAR’, Date of birth, Screening Date, ’C’). 
Screening age in months will be calculated as follows: 
INTCK (‘MONTH’, Date of birth, Screening Date, ’C’). 
For age in months and years, the year component will be equivalent to age in years. The 
number of additional months will be calculated as follows: 
Age in months – (Age in years * 12) 
Baseline Age 
Baseline age (years) will be calculated as: 
INTCK (‘YEAR’, Date of birth, Treatment Start Date, ’C’). 
The baseline age(years) will be used in subgroup analyses. 


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6.2.2. 
Study Period 
Assessments and events will be classified according to the time of occurrence relative to 
the study intervention period.  
Pre-Treatment is defined as time prior to the first dose of study intervention. 
On-Treatment is defined as time from first dose to Week 52 Visit Date/Early 
withdrawal Date/IP Discontinuation Date + 28 days (i.e., Study Treatment Start Date ≤ 
Event Start Date  ≤ Week 52 Visit Date/Early withdrawal Date/IP Discontinuation Date + 
28 days.  
• 
For Subjects who did not withdraw early from IP: 
Event onset date is on/after IP start date & on/before Week 52 Date. 
(IP Start Date ≤ Event Start Date ≤ Week 52 Date) 
• 
For Subjects who withdrew early from IP: 
Event onset date is on/after IP start date & on/before the earliest of Early Withdrawal 
Date/IP Discontinuation Date + 28 days. 
(IP Start Date ≤ Event Start Date ≤ the earliest of Early withdrawal Date/IP 
Discontinuation Date + 28 days) 
Post-Treatment is defined as any time post on-treatment window, i.e. > Week 52 Visit 
Date/Early withdrawal Date/IP Discontinuation Date + 28 days.  
6.2.3. 
Study Day and Reference Dates 
The safety reference date is the study intervention start date and will be used to calculate 
study day for safety measures.  
The efficacy reference date is the study intervention start date and will be used to 
calculate study day for efficacy measures and baseline characteristics, as well as efficacy 
durations.  
The study day is calculated as below: 
• 
Assessment Date = Missing              → Study Day = Missing  
• 
Assessment Date < Reference Date → Study Day = Assessment Date – Ref Date 
• 
Assessment Data ≥ Reference Date → Study Day = Assessment Date – Ref Date + 1     
6.2.4. 
Assessment Window  
Data will be analysed as per the planned visit assignment. 
Early withdrawal and unscheduled visits will be slotted to the appropriate planned visit.  
The assigned visit will be based on the interval in which the Study Day for the early 
withdrawal or unscheduled visit falls according to intervals provided below. 


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For data summaries by visit, the planned (nominal) visit description will be used. 
Unscheduled, Safety FU and Early withdrawal visit data will be slotted into a target visit 
based on visit window defined in the table below using the visit Study Day. If there are 
multiple assessments within the same visit window, a scheduled visit assessment will be 
prioritized over un-scheduled visits. If all assessments within the same window are from 
unscheduled visits, the value closest to the target day for that window will be used. 
If the Early withdrawal visit is slotted into the same visit as the visit prior to Early 
withdrawal, slot the Early withdrawal visit to the next scheduled visit. For example, if the 
subject’s last visit prior to the Early withdrawal visit was Week 12 and the Early 
withdrawal visit mapped as another Week 12, map the Early withdrawal visit to Week 16. 
Analysis Visit 
Analysis 
Visit Number 
Target Study 
Day 
Analysis Window 
Beginning 
Timepoint 
Ending 
Timepoint 
Screening 
10 
up to -35 days 
na 
na 
Week 0 
20 
1 
na 
na 
Week 1 
30 
8 
2 
11 
Week 2 
40 
15 
12 
21 
Week 4 
50 
29 
22 
42 
Week 8 
60 
57 
43 
70 
Week 12 
70 
85 
71 
98 
Week 16 
80 
113 
99 
126 
Week 20 
90 
141 
127 
154 
Week 24 
100 
169 
155 
182 
Week 28 
110 
197 
183 
210 
Week 32 
120 
225 
211 
238 
Week 36 
130 
253 
239 
266 
Week 40 
140 
281 
267 
294 
Week 44 
150 
309 
295 
322 
Week 48 
160 
337 
323 
350 
Week 52 
170 
365 
351 
378 
16 Week post last 
dose Follow-Up 
180 
449 
379 
na 
6.2.5. 
Multiple measurements at One Analysis Time Point 
When triplicate ECG assessments are taken, mean of the measurement will be calculated 
first and summary statistics will be based on the calculated mean. This will apply to 
baseline assessments. 
For lab tests on a study day, if more than one assessment is taken on the same day, the 
test from a central lab will be taken over the test from a local lab. If multiple assessments 
are taken from the same type of lab, the worst case will be used. 


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6.2.6. 
Handling of Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing 
displays.   
• 
However, where necessary, display macros may impute dates as 
temporary variables for sorting data in listings only. In addition, 
partial dates may be imputed for ‘slotting’ data to study phases or 
for specific analysis purposes as outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to 
onset or duration (e.g., time to onset or duration of adverse 
events), or elapsed time variables (e.g., time since diagnosis). In 
addition, imputed dates are not used for deriving the last contact 
date in overall survival analysis dataset. 
Adverse Events 
• 
Partial dates for AE recorded in the CRF will be imputed using the 
following conventions: 
Missing start 
day 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then 
set start date = 1st of month. 
Else if study intervention start date is not missing: 
o If month and year of start date = month and 
year of study intervention start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention start 
date, then set start date= 1st of month. 
▪ 
Else set start date = study intervention 
start date. 
Else set start date = 1st of month. 
Missing start 
day and month 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then 
set start date = January 1. 
Else if study intervention start date is not missing: 
If year of start date = year of study intervention 
start date, then 
If stop date contains a full date and stop date is 
earlier than study intervention start date, then set 
start date = January 1. 
Else set start date = study intervention start 
date.       


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Element 
Reporting Detail 
Else set start date = January 1. 
Missing end 
day  
A '28/29/30/31' will be used for the day (dependent 
on the month and year). 
Missing end 
day and month 
No Imputation 
Completely 
missing 
start/end date 
No imputation 
Concomitant 
Medications/Medical 
History 
• 
Partial dates for any concomitant medications recorded in the CRF 
will be imputed using the following convention: 
Missing start 
day 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then 
set start date = 1st of month. 
Else if study intervention start date is not missing: 
o If month and year of start date = month and 
year of study intervention start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention start 
date, then set start date= 1st of month. 
▪ 
Else set start date = study intervention start 
date. 
Else set start date = 1st of month. 
Missing start 
day and month 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then 
set start date = January 1. 
Else if study intervention start date is not missing: 
o If year of start date = year of study 
intervention start date, then 
▪ 
If stop date contains a full date and stop 
date is earlier than study intervention start 
date, then set start date = January 1. 
▪ 
Else set start date = study. intervention 
start date.       
Else set start date = January 1. 


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Element 
Reporting Detail 
Missing end 
day 
▪ 
A '28/29/30/31' will be used for the day 
(dependent on the month and year).  
Missing end 
day and month 
▪ 
A '31' will be used for the day and 'Dec' 
will be used for the month. 
Completely 
missing 
start/end date 
▪ 
No imputation 
6.2.7. 
Average Daily Prednisone Equivalent 
Average daily prednisone equivalent dose will be expressed in milligrams per day 
(mg/day). To determine average daily prednisone equivalent, all steroid dosages are 
converted to a prednisone equivalent in milligrams at each visit. See Table 1 for 
conversion factors and detail of how values should be converted. 
The average daily prednisone equivalent dose takes into account all steroids taken IV, 
intramuscularly (IM), subcutaneously (SC), intradermally and orally for both SLE and 
non-SLE reasons. The total systemic steroid dose is defined as the average daily dose of 
all steroids taken IV, IM, SC, intradermally and orally for all reasons. 
A concomitant medication is identified as a steroid if at least one associated ATC code 
(ATCCD1 – ATCCD6) begins with ‘H02.’ 
• 
The following routes are considered to provide systemic exposure: oral, 
subcutaneous, intramuscular, intradermal and intravenous steroids. Topical routes of 
administration are excluded (e.g., topical, conjunctival, intranasal). 
• 
At data base release and in-stream, all preferred terms identified with an ATC code 
beginning with ‘H02’ will be reviewed to ensure a conversion factor and dosing 
frequency exist for all terms with a systemic route of administration. 
• 
Similarly, all routes of administration for preferred terms with an ATC code 
beginning with ‘H02’will be reviewed to ensure all systemic routes have been 
identified in the list above. 
• 
In order to be converted, the frequency and dose of the steroid must be present with 
the unit dose in milligrams (mg). 
• 
Reported dose for systemic steroid is converted to prednisone equivalent dose using 
conversion factor for each particular medication (refer to online calculator 
http://www.globalrph.com/corticocalc.htm). 
Daily Prednisone Equivalent Dose (mg) = Collected Dose (mg) x Conversion Factor x 
Frequency Factor 


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Table 1 
Prednisone Conversion Factors (mg) 
Preferred term 
Conversion factor for converting to a 
prednisone-equivalent dose 
BETAMETHASONE 
8.333 
BETAMETHASONE 
DIPROPIONATE  
8.333 
BETAMETHASONE SODIUM 
PHOSPHATE 
8.333 
BETAMETHASONE VAL 
8.333 
BETROSPAM  
8.333 
CELESTONA BIFAS 
8.333 
CORTISONE  
0.2 
CORTISONE ACETATE 
0.2 
CRONOLEVEL  
8.333 
DEFLAZACORT 
0.8333 
DEPO-MEDROL MED LIDOKAIN 
1.25 
DEXAMETHASONE 
6.667 
DEXAMETHASONE ACETATE 
6.667 
DEXAMETHASONE SODIUM 
PHOSPHATE 
6.667 
FLUOCORTOLONE 
3 
HYDROCORTISONE 
0.25 
HYDROCORTISONE ACETATE 
0.25 
0.25 
HYDROCORTISONE SODIUM 
SUCCINATE 
0.25 
MEPREDNISONE 
1.25 
METHYLPREDNISOLONE 
1.25 
METHYLPREDNISOLONE ACEP  
1.25 
METHYLPREDNISOLONE 
ACETATE 
1.25 
METHYLPREDNISOLONE 
SODIUM SUCCINATE 
1.25 
PARAMETHASONE 
2.5 
PREDNISOLONE 
1 
PREDNISOLONE SODIUM 
PHOSPHATE 
1 
PREDNISOLONE SODIUM 
SUCCINATE 
1 
PREDNISONE 
1 


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Preferred term 
Conversion factor for converting to a 
prednisone-equivalent dose 
PREDNISONE ACETATE 
1 
TRIAMCINOLONE 
1.25 
TRIAMCINOLONE ACETATE 
1.25 
TRIAMCINOLONE ACETONIDE 
1.25 
BUDESONIDE 
0.333 
Table 2 
Frequency Factors 
Frequency Factor 
Factor 
BID  
2 
BIW  
2/7 
OAM 
 1/30 
Once 
 1 
PRN  
null 
Q2H 
 12 
Q2W  
1/14 
Q3H  
8 
Q3MO 
 1/84 
Q3w  
1/21 
Q4H  
6 
Q4W  
1/28 
Q6H 
 4 
Q8H  
3 
Q12H  
2 
QAM  
1 
QD  
1 
QH  
24 
QHS  
1 
QID  
4 
QM  
1 
QOD  
½ 
QPM  
1 
QW 
 1/7 
QWK  
1/7 
TID  
3 
TIW  
3/7 
UNK  
Null 
2 TIMES PER WEEK  
2/7 


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Frequency Factor 
Factor 
3 TIMES PER WEEK  
3/7 
4 TIMES PER WEEK  
4/7 
5 TIMES PER WEEK  
5/7 
5 TIMES PER DAY  
5 
EVERY 2 WEEKS 
 1/14 
EVERY 3 WEEKS  
1/21 
EVERY 4 WEEKS  
1/28 
EVERY WEEK  
1/7 
6.2.7.1. 
Baseline Prednisone Dose 
At baseline, the average daily prednisone equivalent dose is the sum of all prednisone 
doses over 7 consecutive days up to, but not including Day 1, divided by 7. 
6.2.7.2. 
Average Daily Prednisone Dose Between Visits 
The average daily prednisone dose between visits will be calculated for each scheduled 
post-baseline visit by summing all prednisone doses since the previous visit (previous 
visit date +1) up to and including the current visit and then dividing by the number of 
days in this period (Date of current visit – Date of previous scheduled visit). Days on 
which a subject does not have prednisone use recorded will be considered as 0 mg for the 
day in the calculation of average daily prednisone dose. 
For subjects who withdraw from the study prior to a scheduled visit, the average dose 
from the previous scheduled visit will be used in order to have complete data between 
visits. 
6.2.7.3. 
Average Daily Prednisone Dose at the Visit 
While on treatment, the average daily prednisone dose at the visit is the sum of all 
prednisone doses over 7 consecutive days up to and including the day of interest, divided 
by 7, unless otherwise specified. Days on which a subject does not have prednisone use 
recorded will be considered as 0 mg for the day in the calculation of average daily 
prednisone dose. 
The average daily prednisone equivalent dose will be calculated for each scheduled visit. 
For subjects who withdraw from the study prior to a scheduled visit, the average dose 
will be calculated at the date of withdrawal. 


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6.2.8. 
SLE Allowable Medication Categories  
Medication Category 
Rule 
Anti-malarials 
Set to "ANTIMALARIALS" if the preferred term 
begins with "QUINACRINE", "QUININE", 
"HYDROXYCHLOROQUINE","MEPACRINE", or 
"CHLOROQUINE" AND the route of administration 
is not 'TOPICAL','VAGINAL', 'CONJUNCTIVAL', 
'INTRANASAL', 'INHALATION', 'INTRA-
OCULAR', 'INTRATRACHEAL', 'EPIDURAL', 
'INTRAARTICULAR', or 'OTHER'. 
Steroids 
Set to ‘STEROIDS’ if at least one associated ATC 
code (ATCCD1 – ATCCD6) begins with ‘H02’ AND 
Route of administration is 
"INTRADERMAL", "INTRAMUSCULAR", 
"INTRAVENOUS", "ORAL", "SUBCUTANEOUS", 
or "INTRA-ARTICULAR". 
Immunosuppressants 
Set to ‘IMMUNOSUPPRESSANTS’ if at least one 
associated ATC code (ATCCD1 – ATCCD6) begins 
with ‘L04A’ or the preferred term begins with 
“CYCLOPHOSPHAMIDE” (oral and parenteral 
routes) or “MERCAPTOPURINE” (oral route) AND 
route of administration is not “TOPICAL”. Chinese 
patent medicines will be identified by clinical 
physicians and should be excluded from this category. 
For example, the preferred term begins with 
"TRIPTERYGIUM", etc. Specially, if 
ADECOD="CICLOSPORIN" and 
CMROUTE="INTRAOCULAR", it will be excluded 
from this category. 
NSAIDs 
Set to NSAIDs if at least one associated ATC code 
(ATCCD1 – ATCCD6) begins with ‘M01A’. Chinese 
patent medicines will be identified by clinical 
physicians and should be excluded from this category. 
For example, the preferred term begins with " 
FORSYTHIA", " MORUS", 
"SCROPHULARIA","DRYNARIA", "ACONITUM", 
etc.  
Aspirin 
Set to "ASPIRIN" if CMDECOD contains 
"ACETYLSALICYLIC ACID" or 
"ACETYLSALICYLATE LYSINE". Chinese patent 
medicines will be identified by clinical physicians and 
should be excluded from this category. For example, 
the preferred term begins with "TRIPTERYGIUM", 
"PAEONIA", etc. 


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6.2.9. 
Prohibited Medications and Non-Drug Therapies 
Participants who start prohibited medications or therapies at any time during the study 
will be considered protocol violation. Belimumab will be discontinued and participants 
will be withdrawn from the study.  
The following medications and therapies are prohibited at any time during the study: 
• 
Other investigational agents (biologic or non-biologic). Investigational applies to any 
drug not approved for sale in the country in which it is being used. 
• 
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). 
• 
All biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist). 
• 
Intravenous immunoglobulin (IVIG). 
• 
IV cyclophosphamide (oral cyclophosphamide is permitted). 
• 
Plasmapheresis, leukapheresis. 
• 
Any live or live attenuated vaccines. (Participants who require a live or live 
attenuated vaccine during the study should have belimumab discontinued prior to 
receiving the vaccine). 
Medication 
Category 
Rule 
Prohibited 
Set to "PROHIBITED" if any of the following conditions are met, 
if CMDECOD equals "INVESTIGATIONAL 
DRUG","ADALIMUMAB", "BELIMUMAB", "ETANERCEPT", 
"INFLIXIMAB", "CERTILIZUMAB”, “TOCILIZUMAB”, 
"GOLIMUMAB", "RITUXIMAB", 
"ABATACEPT","ANAKINRA","IMMUNOGLOBULIN"(IV 
route), “CYCLOPHOSPHAMIDE” (IV route), 
"PLASMAPHERESIS" or “LEUKAPHERSIS”. 
6.2.10. 
SLE Flare Index 
• 
SFI reports the first mild /moderate or severe flare occurrence since the last visit 
assessment. 
• 
The SLEDAI criteria will be assessed programmatically to determine if the SELENA 
SLEDAI criteria for a flare has been met and used for the assessment of flare, 
irrespective of what was recorded on the SFI form.  


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• 
Although there are boxes on the form for the investigator to classify the most recent 
flare to mild/moderate or severe, the classification will be re-derived from the 
subcategory scores. Flares originally marked severe will be downgraded to “Not 
Severe” if the only reason marked is a change in SELENA SLEDAI score to > 12. In 
this case, if any of the mild/moderate reasons are checked or if the SELENA 
SLEDAI score has a change from previous visit of at least 3, then the flare will be 
considered Mild/Moderate. 
• 
 Flares that are marked mild/moderate where the only reason checked is SELENA 
SLEDAI increase of at least 3 points but not more than 12 points will be re-derived 
using the SELENA SLEDAI score. If it’s found that the change is not actually ≥ 3, 
and no other reasons are checked, then the flare will not be counted. 
6.3. 
Appendix 3 Missing Data Imputation     
6.3.1. 
Multiple imputation under MAR assumption  
1. Set all data at each visit after the intercurrent event to missing. 
2. For all missing data(including intermittent missing data), generate 1000 multiply 
imputed datasets using a monotone regression imputation including terms for 
baseline value (this covariate will not be included in the model for endpoints related 
to SELENA SLEDAI), baseline age group (5-11 years vs.12-17 years) ,baseline 
SELENA SLEDAI score (≤12 vs. ≥13) , and all previous visit values, i.e. a model of 
the form: 
𝑦𝑖= 𝛼1𝑖+ 𝛼2𝑖𝑏𝑎𝑠𝑒+ 𝛼3𝑖𝑎𝑔𝑒+ 𝛼4𝑖𝑠𝑐𝑜𝑟𝑒+ 𝛽𝑖−1𝑦𝑖−1 + ⋯+ 𝛽1𝑦1 
where 𝑦𝑖 is the result at visit i, i=1, 2, 3,…,14. 
3. Derive the endpoint based on the imputed data and estimand as detailed in Section 
4.2.1, Sections 4.2.3, 4.2.4  and Section 4.3.1.1. 
4. Perform statistical analysis as detailed in Section 4.2.3 and Section 4.3.1.3. 
6.3.2. 
LOCF 
The last observation carried forward (LOCF) principle is applied whereby missing values 
will be replaced with the last previous non-missing value. If the first on-treatment 
assessment is missing, then the missing data will be imputed with the baseline value. 
If a subject has a visit but partial data of the endpoint are missing (including individual 
items of any component of the primary endpoint), LOCF will be used for the missing 
item or component.  
TRADEMARKS 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
BENLYSTA 
 
SAS 
 
 
WinNonlin 


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7. 
REFERENCES 
Wang Y, Jadhav PR, Lala M, Gobburu JV. Clarification on precision criteria to derive 
sample size when designing pediatric pharmacokinetic studies. Jr Clin Pharmacol. 
2012;52(10):1601-6.