A Multi-Centre, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subcutaneously Administered Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Systemic Lupus Erythematosus (SLE)
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Sponsor: GlaxoSmithKline

 
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TITLE PAGE 
Protocol Title: 
A Multi-Centre, Open-Label Study to Evaluate the Pharmacokinetics and Safety of 
Subcutaneously Administered Belimumab Plus Standard Therapy in Chinese Paediatric 
Participants with Systemic Lupus Erythematosus (SLE)  
Protocol Number: 217091 / Amendment 02 
Compound Number 
or Name: 
GSK1550188   
Brief Title: Evaluate Pharmacokinetics of Subcutaneous Belimumab in Chinese 
Paediatric Participants with Systemic Lupus Erythematosus (SLE). 
Study Phase: Phase 1 
 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Manufacturer:  
The autoinjector components are manufactured by Scandinavian Health Limited (SHL) 
and assembled with the pre-filled syringe at GlaxoSmithKline (GSK), Barnard Castle, 
United Kingdom (UK). 
Regulatory Agency Identifying Number(s):NA 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
 
SPONSOR SIGNATORY     
Deepak Assudani MD 
Senior Clinical Development Director 
Clinical Science (Immunology)  
GSK 
 
Approval Date: 24 Jan 2024 
 
©2024 GSK group of companies or its licensor. 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 
Amendment 02 
24 Jan 2024 
Amendment 01 
3 Jan 2023 
Original protocol 
31 Jan 2022 
 
Amendment 02:24 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 current 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 
Move the section from 10.8 of 
previous version (amend 01) to 
the beginning of the protocol  
 
Delete Trademark Information 
 
Addition or update of 
definitions for 
several terms, including 
Investigational Product, 
Standard of Care, Background 
treatment, Adverse Drug , 
Reaction, SUSAR, Legal 
guardian 
 
 
To comply with an update 
to the internal GSK 
protocol process and template. 
10.6 Appendix 6: 
Liver Safety: 
Required Actions 
and Follow-up 
Assessments and 
Study Intervention 
Restart/Rechallenge 
Guidelines 
 
 
 
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. 
10.8. Appendix 8: 
Protocol 
Amendment History 
 
Add a section to overview 
protocol amendment history 
 
  
Overview protocol amendment history. 

 
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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY ........................................................................................ 12 
1.1. 
Synopsis ..................................................................................................... 12 
1.2. 
Schema ...................................................................................................... 14 
1.3. 
Schedule of Activities (SoA) ........................................................................ 15 
1.3.1. 
Body weight ≥50 kg, Dose 200 mg QW ........................................ 15 
1.3.2. 
Body weight ≥30 kg - <50 kg, Dose 200 mg Q10d ....................... 17 
1.3.3. 
Body weight ≥15 kg - <30kg, Dose 200 mg Q2W ......................... 18 
2. 
INTRODUCTION .................................................................................................... 21 
2.1. 
Study Rationale .......................................................................................... 21 
2.2. 
Background ................................................................................................ 21 
2.2.1. 
Efficacy of IV Belimumab in Paediatric SLE participants .............. 22 
2.2.2. 
Safety of IV Belimumab in Paediatric SLE participants ................ 22 
2.2.3. 
Pharmacokinetics of IV Belimumab.............................................. 23 
2.2.4. 
Pharmacodynamics of IV Belimumab .......................................... 23 
2.2.5. 
Belimumab IV in Chinese paediatric SLE Participants 
(Study 213560) ............................................................................ 23 
2.3. 
Benefit/Risk Assessment ............................................................................ 24 
2.3.1. 
Risk Assessment ......................................................................... 25 
2.3.2. 
Benefit Assessment ..................................................................... 30 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 30 
3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS ....................................... 31 
4. 
STUDY DESIGN .................................................................................................... 33 
4.1. 
Overall Design ............................................................................................ 33 
4.2. 
Scientific Rationale for Study Design .......................................................... 33 
4.3. 
Justification for Dose .................................................................................. 34 
4.4. 
End of Study Definition ............................................................................... 35 
5. 
STUDY POPULATION ........................................................................................... 36 
5.1. 
Inclusion Criteria ......................................................................................... 36 
5.2. 
Exclusion Criteria ........................................................................................ 37 
5.3. 
Lifestyle Considerations .............................................................................. 38 
5.4. 
Screen Failures........................................................................................... 38 
5.5. 
Criteria for Temporarily Delaying 
Enrolment/Randomization/Administration of Study Intervention .................. 38 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 39 
6.1. 
Study Intervention(s) Administered ............................................................. 39 
6.1.1. 
Medical Devices ........................................................................... 39 
6.2. 
Preparation, Handling, Storage and Accountability ..................................... 40 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 40 
6.4. 
Study Intervention Compliance ................................................................... 40 
6.4.1. 
Compliance with Subcutaneous Administration of 
Belimumab ................................................................................... 41 
6.4.2. 
Missed Doses .............................................................................. 41 
6.5. 
Dose Modification ....................................................................................... 42 

 
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6.6. 
Continued Access to Study Intervention after the End of the Study ............ 42 
6.7. 
Treatment of Overdose ............................................................................... 42 
6.8. 
Concomitant Therapy.................................................................................. 43 
6.8.1. 
Permitted Medications and Non-Drug Therapies .......................... 43 
6.8.2. 
Prohibited Concomitant Therapy .................................................. 44 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 46 
7.1. 
Discontinuation of Study Intervention .......................................................... 46 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 46 
7.1.2. 
IgG Stopping Criteria ................................................................... 48 
7.1.3. 
Rechallenge ................................................................................. 49 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 49 
7.3. 
Lost to Follow Up ........................................................................................ 49 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 51 
8.1. 
Screening and Critical Baseline Assessments ............................................ 51 
8.1.1. 
Baseline Assessments ................................................................. 53 
8.1.2. 
Scheduled Visit Assessments ...................................................... 53 
8.1.3. 
Unscheduled Visit Assessments .................................................. 53 
8.1.4. 
Early Withdrawal and Follow-up Visit Assessments ..................... 53 
8.1.5. 
Missed Study Visits ...................................................................... 53 
8.2. 
Efficacy and/or Immunogenicity Assessments ............................................ 53 
8.3. 
Safety Assessments ................................................................................... 54 
8.3.1. 
Physical Examinations ................................................................. 54 
8.3.2. 
Vital Signs .................................................................................... 54 
8.3.3. 
Electrocardiograms ...................................................................... 55 
8.3.4. 
Clinical Safety Laboratory Tests .................................................. 55 
8.3.5. 
Pregnancy Testing ....................................................................... 55 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 55 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 56 
8.4.2. 
Method of Detecting AEs and SAEs ............................................. 56 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 57 
8.4.4. 
Regulatory Reporting Requirements for SAEs ............................. 57 
8.4.5. 
Pregnancy ................................................................................... 58 
8.4.6. 
Medical Device Deficiencies ........................................................ 58 
8.5. 
Pharmacokinetics ....................................................................................... 59 
8.6. 
Genetics ..................................................................................................... 60 
8.7. 
Biomarkers ................................................................................................. 60 
8.8. 
Immunogenicity Assessments ..................................................................... 60 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics .................................................................................................. 61 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 62 
9.1. 
Statistical Hypotheses................................................................................. 62 
9.2. 
Analysis Sets .............................................................................................. 62 
9.3. 
Statistical Analyses ..................................................................................... 62 
9.3.1. 
General Considerations ............................................................... 62 
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis ................................. 62 
9.3.3. 
Secondary Endpoint Analysis ...................................................... 63 

 
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9.4. 
Interim Analysis .......................................................................................... 63 
9.5. 
Sample Size Determination ........................................................................ 63 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 65 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 65 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 65 
10.1.2. 
Financial Disclosure ..................................................................... 66 
10.1.3. 
Informed Consent and Assent Process ........................................ 66 
10.1.4. 
Data Protection ............................................................................ 67 
10.1.5. 
Dissemination of Clinical Study Data ........................................... 67 
10.1.6. 
Data Quality Assurance ............................................................... 68 
10.1.7. 
Source Documents ...................................................................... 69 
10.1.8. 
Study and Site Start and Closure ................................................. 69 
10.1.9. 
Publication Policy ......................................................................... 70 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 71 
10.2.1. 
Adverse Event and Laboratory Value Severity Grade 
Table ........................................................................................... 73 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 79 
10.3.1. 
Definition of AE ............................................................................ 79 
10.3.2. 
Definition of SAE .......................................................................... 80 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 81 
10.3.4. 
Reporting of SAE to GSK ............................................................. 83 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 85 
10.4.1. 
Definitions: ................................................................................... 85 
10.4.2. 
Contraception Guidance: ............................................................. 86 
10.4.3. 
Collection of Pregnancy Information: ........................................... 87 
10.5. 
Appendix 5: Genetics .................................................................................. 88 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments and Study Intervention Restart/Rechallenge 
Guidelines ................................................................................................... 89 
10.7. 
Appendix 7: Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting in Medical Device Studies ................ 92 
10.7.1. 
Definition of Medical Device AE and ADE .................................... 93 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE ................. 93 
10.7.3. 
Definition of Device Deficiency ..................................................... 94 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies ................................................................................. 94 
10.7.5. 
Reporting of SAEs ....................................................................... 96 
10.7.6. 
Reporting of SADEs ..................................................................... 97 
10.7.7. 
Reporting of Medical Device Deficiencies for Associated 
Person ......................................................................................... 97 
10.8. 
Appendix 8: Protocol amendment history .................................................... 99 
11. REFERENCES ..................................................................................................... 103 

 
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 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
List of Abbreviations 
ACR 
American College of Rheumatology 
ADA 
Anti-drug antibodies 
ADE 
Adverse device effect 
ADL 
Activities of Daily Living 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUCss, 0-τ 
Area under the curve at steady-state to the end of the 
dosing period 
BLyS 
B lymphocyte Stimulator 
BW 
Body weight 
Cavg 
Average concentration 
Cavgss 
Average serum concentration at steady state 
CDE 
Centre for Drug Evaluation 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL 
Clearance 
Cmax 
Maximum concentration 
Cmaxss 
Maximum serum concentrations during the dosing 
interval at steady state 
Cmin 
Minimum concentration 
Cminss 
Minimum serum concentrations at steady state 
CPK 
Creatinine phosphokinase 
CRF 
Case report form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
dL 
Deciliter 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EU 
European Union 
FDA 
Food and Drug Administration 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Glutamyl transferase 
GSK 
GlaxoSmithKline 
HB 
Hepatitis B 
HBsAg 
Hepatitis B surface antigen 
HBc 
Hepatitis B core 

 
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HBcAb 
Hepatitis B core antibody 
HGS 
Human Genome Sciences, Inc 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
Hpf 
High power field 
HRT 
Hormonal replacement therapy 
IA 
Intraarticular 
IB 
Investigator’s Brochure 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IL-6 
Interleukin-6 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IIV 
Inter-individual variability 
IM 
Intramuscular 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IVIG 
Intravenous immunoglobulin 
IWRS 
Interactive web response system 
Kg 
Kilogram 
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal 
Mg 
Milligram 
mL 
Milliliter 
MCID 
Minimally clinically important difference 
g 
Microgram 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
MDR 
Medical Device Regulation 
MMF 
Mycophenolate mofetil 
MSDS 
Materials Safety Data Sheet 
N/A 
Not applicable 
NDA 
New drug application 
NSAIDs 
Non-steroidal anti-inflammatory drugs 
PAC 
Post approval commitment 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PML 
Progressive multifocal encephalopathy 
PO 
By mouth (per os) 

 
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PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QTL 
Quality tolerance limits 
QW 
Once a week 
Q10D 
Every 10 days 
Q2W 
Every 2 weeks 
Q4W 
Every 4 weeks 
RA 
Rheumatoid arthritis 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SADE 
Serious adverse device effect 
SAE 
Serious Adverse Event 
SC 
Subcutaneous/subcutaneously 
SELENA 
Safety of Estrogen in Lupus Erythematosus National 
Assessment  
SFI 
SLE Flare Index 
SHL 
Scandinavian Health Limited 
cSLE 
Childhood Onset Systemic Lupus Erythematosus 
SLE 
Systemic Lupus Erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index 
SLICC 
Systemic Lupus International Collaborating Clinics 
SoA 
Schedule of Activities 
SOC 
System Organ Classes 
SRI 
SLE Responder Index 
SRM 
Study Reference Manual 
TNF 
Tumor Necrosis Factor 
UK 
United Kingdom 
ULN 
Upper limit of normal 
US 
United States 
USA 
United States of America 
USADE 
Unanticipated SADE 
WBC 
White blood cell 
WOCBP 
Woman of childbearing potential 
 
 
 
 
 
 
 
 
 
 
 

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

 
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legal guardian 
Parent(s) (preferably both if available or as per local requirements), 
legally appointed guardian(s), or legally acceptable 
representative(s), as defined by national and local laws and 
regulations, who consent(s) on behalf of the minor. For the purposes 
of this study, all references to informed consent and assent refer to 
the pediatric participant (child) and his or her legal guardian who 
have provided consent (and assent as applicable) according to the 
Informed Consent Process and Assent Form described in Section 
10.1.3 Informed Consent and Assent Process 
 
 

 
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1. 
PROTOCOL SUMMARY 
1.1. Synopsis 
Protocol Title: A Multi-Centre, Open-Label Study to Evaluate the Pharmacokinetics and 
Safety of Subcutaneously Administered Belimumab Plus Standard Therapy in Chinese 
Paediatric Participants with Systemic Lupus Erythematosus (SLE)  
Brief Title: Evaluate Pharmacokinetics of Subcutaneous Belimumab in Chinese 
Paediatric Participants with Systemic Lupus Erythematosus (SLE). 
Rationale: The purpose of this study is to evaluate the pharmacokinetic (PK) 
characteristics and safety of repeat doses of 200 mg belimumab subcutaneous (SC) in 
Chinese paediatric participants by leveraging the China belimumab IV paediatric study 
(213560), such that paediatric participants completing 48 weeks belimumab IV treatment 
could be rolled over to this belimumab SC study. The PK data derived from this study 
will contribute to the update of previous population PK model, and on the basis of the 
updated population PK model, an appropriate dose regimen of belimumab SC (i.e., dose 
frequency according to body weight) for Chinese paediatric participants will be 
determined by simulation.  
Objectives and Endpoints and Estimands: 
Objectives 
Endpoints 
Primary - Pharmacokinetics 
• To characterize belimumab exposure 
following belimumab 200 mg SC in 
Chinese paediatric systemic lupus 
erythematosus (SLE) participants who 
have previously been treated with IV 
belimumab 
• Exposure parameters: AUCss, 0-τ, Cavg, ss, 
Cmin, ss, Cmax, ss 
Secondary - Safety 
• To evaluate the safety and tolerability of 
belimumab 200mg SC in paediatric 
participants with SLE who have 
previously been treated with IV 
belimumab 
• Occurrence of adverse events, serious 
adverse events and adverse events of 
special interest through Week 12. 
AUCss, 0-τ = Area under the curve at steady-state to the end of the dosing period, Cavg, ss= Average serum 
concentration at steady state, Cmin, ss = Minimum serum concentrations at steady state, Cmax, ss = Maximum 
serum concentrations during the dosing interval at steady state 
 
Overall Design: 
This is a single arm, multi-centre open label study of belimumab plus standard of care in 
participants with SLE who have completed 48 weeks belimumab IV treatment in 213560 

 
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study, to evaluate the PK and safety of subcutaneously administered belimumab over 12 
weeks in approximately 17 paediatric participants aged 5-17 years and weighing ≥15 kg.  
Brief Summary: 
213560 study is an open label study to evaluate the safety, efficacy and pharmacokinetics 
of belimumab (10 mg/kg) IV with standard therapy in Chinese paediatric participants 
aged 5 to 17 years with active SLE. The participants in study 217091 will be those who 
have completed the 48-week treatment of 213560 study and who, in the investigator’s 
judgement will benefit from continuing treatment with belimumab. The targeted aim for 
this study will be to recruit participants in study 213560 who have IV PK samples 
collected. However, if the targeted number of participants cannot be met, additional 
participants from the non-PK population in 213560 will also be included. The PK sample 
right after the last IV dose in 213560 and pre-dose PK sample of study 217091 will be 
collected from each patient to ensure the belimumab PK profile leading up to and 
following the switch to SC dosing can be accurately characterized for each participant.  
Participants who have completed Week 52 assessment in study 213560, will receive the 
first SC dose in study 217091 no more than 4 weeks after the last IV dose (administered 
at week 48 visit of study 213560). The study will include: 
• 
Open-label, 12-week treatment phase. 
• 
Post-treatment follow-up assessments at 8 weeks and 16 weeks after the last dose 
of SC belimumab 
Number of Participants: 
Approximately 17 participants will be enrolled to study intervention. 
Note: Enrolled means a participant's (if applicable) and their legally acceptable 
representative’s, agreement to participate in a clinical study following completion of the 
informed consent process and screening. Potential participants who are screened for the 
purpose of determining eligibility for the study, but do not participate in the study, are not 
considered enrolled, unless otherwise specified by the protocol. A participant will be 
considered enrolled if the informed consent is not withdrawn prior to participating in any 
study activity after screening. 
Intervention Groups and Duration: 
The total maximum duration of study participation for each participant is 33 weeks 
(screening:5 weeks, treatment: up to 12 weeks and follow-up: 16 weeks). 
Administration of belimumab 200 mg SC will be as follows: 
• 
Participants 50 kg body weight will receive belimumab 200 mg SC weekly.  
• 
Participants 30 kg to <50 kg body weight will receive belimumab 200 mg SC 
every 10 days. 

 
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• 
Participants 15 kg to <30 kg body weight will receive belimumab 200 mg SC 
every 2 weeks. 
The dosing frequency fixed according the baseline body weight. 
 
 
Data Monitoring/ Other Committee: No 
1.2. Schema 
 
 Participants 50 kg body weight will receive belimumab 200 mg SC weekly 
 Participants 30 kg to <50 kg body weight will receive belimumab 200 mg SC 
every 10 days 
 Participants 15 kg body to <30 kg weight will receive belimumab 200 mg SC 
every 2 weeks 
* PK sampling 
# Participants will roll over from study 213560 thus the screening period of this study 
will have an overlap with study 213560. 
Note: For those participants who don’t have PK samples in study 213560, 3 
additional PK samples will be collected within 4 hours, at 7 days (±2 days) and 14 
days (±2 days) after last belimumab IV infusion at Week 48 of study 213560. 
 

 
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1.3. Schedule of Activities (SoA) 
1.3.1. 
Body weight ≥50 kg, Dose 200 mg QW 
  
Body weight ≥50 kg, Dose 200 mg QW 
  
  
 
  
Site Visit 
V1 
V2 
V3 
V4 
V5, V6 
V7 
V8-10 
V11 
V12-
13 
V14 
V15 
V16 
V17 
V18 
Procedure 
Scree
ning  
Treatment Period (12 weeks) 
Follow-Up 
Period1,2 
Study Day/Week 
 -35 
days 
Day 
1 
Day 
4±1 
Day 
8±2 
Day 
15, 22 ±2 
Day 
29±2 
Day 
36, 43, 
50±2 
Day 
57±2 
Day 
64, 
71±2 
Day 
78±1 
Day 
81±1 
Day 
85±2
/ 
EW1 
8-
Week± 
7 -Day 
Follow 
up1 
16-
Week 
±7-
Day 
Follow
-up1,2 
Wk 
0 
 
Wk 1 
Wk 2-3 
Wk 4 
Wk 5-7 Wk 8 
Wk 
9-10 
Wk 11 
 
Wk 
12 
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 
 
Symptom Driven 
Physical Exam3 
X 
X 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight 
X 
X6 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Height 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Body weight ≥50 kg, Dose 200 mg QW 
  
  
 
  
Site Visit 
V1 
V2 
V3 
V4 
V5, V6 
V7 
V8-10 
V11 
V12-
13 
V14 
V15 
V16 
V17 
V18 
Procedure 
Scree
ning  
Treatment Period (12 weeks) 
Follow-Up 
Period1,2 
Study Day/Week 
 -35 
days 
Day 
1 
Day 
4±1 
Day 
8±2 
Day 
15, 22 ±2 
Day 
29±2 
Day 
36, 43, 
50±2 
Day 
57±2 
Day 
64, 
71±2 
Day 
78±1 
Day 
81±1 
Day 
85±2
/ 
EW1 
8-
Week± 
7 -Day 
Follow 
up1 
16-
Week 
±7-
Day 
Follow
-up1,2 
Wk 
0 
 
Wk 1 
Wk 2-3 
Wk 4 
Wk 5-7 Wk 8 
Wk 
9-10 
Wk 11 
 
Wk 
12 
Adverse Events 
 
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 
Device Incidents 
malfunctions 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Laboratory Assessments 
Haematology 
X5 
X5 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
Chemistry 
X5 
X5 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
Urinalysis 
X5 
X5 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
Pregnancy Test4 
X5 
X5 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
IgA, IgG and IgM 
X 
X5 
 
 
 
X 
 
X 
 
 
 
X 
X 
 
Belimumab Administration and PK Sampling 
PK Sampling 
X7  
X8 
X10 
X8, 11 
 
 
 
 
 
X8 
X 
X 
 
 
Administration of 
Belimumab 
 
X9 
 
X9 
X 
X 
X 
X 
X 
X 
 
  
 
 
 
 

 
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Protocol Amendment 2 
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17 
1.3.2. 
Body weight ≥30 kg - <50 kg, Dose 200 mg Q10d 
Site Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7, 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
Procedure 
Screening 
Treatment Period (12 weeks) 
Follow-Up Period1,2 
Study Day/Week 
 -35 days 
Day 
1 
Day 
4± 1 
Day 
11± 2 
Day 
21± 2 
Day 
31± 2 
Day  
41, 
51± 2 
Day 
61± 2 
Day 
71± 1 
Day 
74± 1 
Day 
81± 2 
/ EW1 
8-Week ±7-
Day Follow-
up1 
16-Week± 7-
Day Follow-
up 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
Medication 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Symptom Driven 
Physical Exam3 
X 
X 
 
 
 
X 
 
X 
 
 
X 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight  
X 
X6 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Height 
 
X 
 
 
 
X 
 
X 
 
 
X 
X 
 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Serious Adverse 
Events 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Device Incidents 
malfunctions 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Haematology 
X5 
X5 
 
 
 
X 
 
X 
 
 
X 
X 
 
Chemistry 
X5 
X5 
 
 
 
X 
 
X 
 
 
X 
X 
 
Urinalysis 
X5 
X5 
 
 
 
X 
 
X 
 
 
X 
X 
 

 
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Protocol Amendment 2 
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18 
Site Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7, 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
Procedure 
Screening 
Treatment Period (12 weeks) 
Follow-Up Period1,2 
Study Day/Week 
 -35 days 
Day 
1 
Day 
4± 1 
Day 
11± 2 
Day 
21± 2 
Day 
31± 2 
Day  
41, 
51± 2 
Day 
61± 2 
Day 
71± 1 
Day 
74± 1 
Day 
81± 2 
/ EW1 
8-Week ±7-
Day Follow-
up1 
16-Week± 7-
Day Follow-
up 
Pregnancy Test4 
X5 
X5 
 
 
 
X 
 
X 
 
 
X 
X 
 
IgA, IgG and IgM 
X 
X5 
 
 
 
X 
 
X 
 
 
X 
X 
 
PK Sampling 
X7 
X8 
X10 
X8, 11 
 
 
 
 
X8 
X 
X 
 
 
Belimumab 
administration 
 
X9 
 
X9 
X 
X 
X 
X 
X 
 
  
 
 
 
1.3.3. 
Body weight ≥15 kg - <30kg, Dose 200 mg Q2W 
Site Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
 V12 
Procedure 
Screening  
Treatment Period (12 weeks) 
Follow-Up Period1,2 
Study Day/Week 
 -35 days 
Day 
1 
Day 
4±1  
Day 
15±2  
Day 
29±2  
Day 
43±2  
Day 
57±2  
Day 
71±1  
Day 
74±1  
Day 
85±2 
/EW1 
8-Week ±7-
Day Follow-
up1 
16-Week±7-
Day Follow-
up1,2 
Wk 0 
  
Wk 2 
Wk 4 
Wk 6 
Wk 8 
Wk 
10 
  
Wk 
12 
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 
 

 
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Protocol Amendment 2 
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19 
Site Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
 V12 
Procedure 
Screening  
Treatment Period (12 weeks) 
Follow-Up Period1,2 
Study Day/Week 
 -35 days 
Day 
1 
Day 
4±1  
Day 
15±2  
Day 
29±2  
Day 
43±2  
Day 
57±2  
Day 
71±1  
Day 
74±1  
Day 
85±2 
/EW1 
8-Week ±7-
Day Follow-
up1 
16-Week±7-
Day Follow-
up1,2 
Wk 0 
  
Wk 2 
Wk 4 
Wk 6 
Wk 8 
Wk 
10 
  
Wk 
12 
Symptom Driven Physical 
Exam3 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight  
X 
X6 
 
X 
X 
X 
X 
X 
 
X 
X 
 
Height 
 
X 
 
 
X 
 
X 
 
 
X 
X 
 
12-Lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Serious Adverse Events 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Device Incidents 
malfunctions 
 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
Laboratory Assessments 
Haematology 
X5 
X5 
 
 
X 
 
X 
 
 
X 
X 
 
Chemistry 
X5 
X5 
 
 
X 
 
X 
 
 
X 
X 
 
Urinalysis 
X5 
X5 
 
 
X 
 
X 
 
 
X 
X 
 
Pregnancy Test4 
X5 
X5 
 
 
X 
 
X 
 
 
X 
X 
 
IgA, IgG and IgM 
X 
X5 
 
 
X 
 
X 
 
 
X 
X 
 
Belimumab Administration and PK Sampling 
PK Sampling 
X7 
X8 
X10 
X8, 11 
 
 
 
X8 
X 
X 
 
 
Administration of 
Belimumab 
 
X9 
 
X9 
X 
X 
X 
X 
 
  
 
 
ECG: Electrocardiogram, IgA: Immunoglobulin A, IgG: Immunoglobulin G, IgM: Immunoglobulin M, PK: Pharmacokinetic. Note: 

 
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Protocol Amendment 2 
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20 
1. 8-week and 16-week follow-up is required for participants who withdraw from study treatment prior to Week 12 (Month 3) or completed 12 weeks of treatment. For participants who 
withdraw from treatment prior to Week 12 (Month 3), in addition to the 8-week and 16-week follow-up visit and assessments, an early withdrawal visit (EW) should be completed 
within 4 weeks of the decision to withdraw. The EW visit requires identical assessments and procedures to the Week 12 visit (Month 3). 
2. The 16-week follow-up requires a phone call to collect adverse events (AEs) and the results of home urine pregnancy test (if applicable) for female participants. The 16-week follow-
up may be performed at a clinic visit per local requirement. 
3. Full Physical Examination is required at screening. An abbreviated/symptom-driven exam can be done thereafter as described in Section 8.3.1. 
4. Serum pregnancy test required at screening for all females of childbearing potential. Urine pregnancy test is sufficient for all subsequent visits. A home pregnancy test (urine) will be 
provided to participants for the 16-week follow-up pregnancy assessment.  
5. Laboratory assessments in visit 1 (screening) and visit 2 (Day 1) would share with study 213560 visit 16 (Week 48) and visit 17 (Week 52) laboratory assessments respectively.  
6. The participant's weight at Day 1 should be calculated to decide dosing frequency for each following visit to be administered.  
7. For those participants who don’t have IV PK samples in study 213560, 3 additional PK samples will be collected within 4 hours, at 7 days (±2 days) and 14 days (±2 days)  after 
last belimumab IV infusion at week 48 of study 213560.  
8. Samples must be taken pre-dose.  
9. For the first 2 doses participants must be observed for 3 h post belimumab injection.10. If the PK sample collection on visit 3 was missed, then that PK sample collection should be 
rescheduled at 3 ±1 day after any of the next doses. 
11. If the PK sample collection on visit 4 was missed, then that PK sample collection should be rescheduled to when participants take the next dose and the sample must be taken pre-
dose. 
 
 
 
 

 
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21 
2. 
INTRODUCTION 
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with multisystem 
involvement characterised by autoantibody production and abnormal B lymphocyte 
function. Paediatric SLE shares similar pathogenesis with adult SLE that includes a 
complex interaction of genetics, environment, and hormones that leads to immune-
tolerance damage, resulting in autoantibody production, inflammation and organ injury. 
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 IV was first approved in the United States 
of America (USA) in 2011 as an add-on treatment for adult participants with active 
autoantibody positive SLE despite standard therapy. It is now approved in over 70 
countries. Belimumab IV 10mg/kg for the treatment of SLE in paediatric population from 
5-17 years of age was approved in the United States (US), Japan and the European Union 
(EU) in 2019 and in China on 02 December 2020.  
Belimumab 200 mg once weekly SC administered injection formulation (ready to use 
pre-filled syringe and autoinjector) was first approved in July 2017 in the US and is now 
licensed in over 30 countries. The New drug application (NDA) of Belimumab SC for 
adult SLE in China was accepted by China’s Centre for Drug Evaluation (CDE) on 01 
December 2020. An oversea bridging PK study (200908) is currently ongoing to evaluate 
the pharmacokinetics (PK), safety, and pharmacodynamics (PD) of 200 mg belimumab 
SC in paediatric participants 5 to 17 years of age with SLE. Data generated from the 
current study (217091) using the SC formulation in Chinese paediatric participants ages 
5-17 years will be estimated via a population PK approach to determine a dosing regimen 
for Benlysta 200 mg solution for SC injection that enables appropriate exposures to be 
reached to achieve efficacy in Chinese children with SLE. 
2.1. 
Study Rationale 
The purpose of this study is to evaluate the pharmacokinetic characteristics and safety of 
repeat doses of 200 mg belimumab subcutaneous in Chinese paediatric participants by 
leveraging the China belimumab IV paediatric study (213560), such that paediatric 
participants completing 48 weeks belimumab IV treatment can switch to SC treatment by 
joining the SC PK bridging study. The PK data derived from this study will contribute to 
the update of previous population PK model, and on basis of the updated population PK 
model, appropriate dose regimen of belimumab SC (i.e., dose frequency according to 
body weight) for Chinese paediatric participants will be determined by simulation.  
2.2. Background 
Paediatric SLE is an important subgroup of lupus, manifested as an autoimmune disease 
with multisystem involvement characterized by widespread inflammation of blood 
vessels and connective tissue [Petty, 2005]. Paediatric SLE is often treated with high 
doses of corticosteroids and immunosuppressant’s including IV cyclophosphamide than 
adult SLE, contributing to the increased incidence and earlier onset of long-term organ 
damage in children [Mina, 2013, Chatham , 2001; Silva, 2016]. Development of safe and 

 
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22 
effective treatments for paediatric SLE therefore remains an area of high-unmet need. 
Belimumab was first approved for adults in 2011 in the USA, which can not only reduce 
disease activity and SLE flares but also reduce the dosage of steroids [Furie, 2011; 
Navarra, 2011; Stohl, 2012]. Although the IV formulation of belimumab is approved for 
the treatment of adult and paediatric participants in China, the SC formulation is still 
particularly needed to allow at-home administration and reduce the burden of IV infusion 
and consequently required hospital visits for participants, their families and hospitals. 
Further information on the safety and efficacy of belimumab is provided in the current IB 
and investigator’s brochure (IB) supplement(s) (if applicable) and product label. 
2.2.1. 
Efficacy of IV Belimumab in Paediatric SLE participants 
Belimumab efficacy in SLE participants has been established in Chinese adults with SLE 
in the adult IV study in Northeast Asia (BEL113750) and has been demonstrated to be 
comparable to efficacy in overseas adults (C1056, C1057, BEL112341) and overseas 
paediatrics (BEL114055). Therefore, a comparable efficacy would be expected in 
paediatric participants from China. 
The SLE Responder Index (SRI) Response rate at Week 52 in study BEL114055 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 participants 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 participants (95% CI: 0.42, 4.18) to OR 1.67 in Asian participants (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. 
2.2.2. 
Safety of IV Belimumab in Paediatric SLE participants 
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 studies) and the North East Asian adult studies (BEL113750). Also, 
consistency was demonstrated between paediatric and adult studies safety results. 
The safety of belimumab in paediatric participants has been evaluated in the double-blind 
phase of study BEL114055, 82.5% of participants experienced at least 1 AE in placebo 
group and 79.2% in the belimumab 10 mg/kg group. 35.0% of participants experienced at 
least 1 serious adverse events (SAE) in placebo group and 17.0% in the belimumab 
group. The system organ class (SOC) with the highest incidence of SAEs was infections 
and infestations (12.5%, placebo; 7.5%, belimumab). Adverse events of special interest 
(AESI) 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 

 
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23 
similar between treatment groups. No participants in either treatment group experienced 
an AESI of malignancy. 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%) participant 
in the placebo group experienced a fatal SAE (pancreatitis acute), while no death 
occurred in the belimumab group. 
2.2.3. 
Pharmacokinetics of IV 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, 200909 and 209629). Population PK analyses have been 
conducted in both adults (Report No. HGS1006-POPPK) and paediatrics (BEL114055 
POPPK). The results showed belimumab PK to be body-weight-dependent, dose-
proportional and time-invariant after IV administration, similar to many monoclonal 
antibodies targeting soluble ligands. Geometric mean values of steady-state maximum 
concentration (Cmax), minimum concentration (Cmin), average concentration (Cavg), 
and area under the curve (AUC) were estimated to be 315 g/mL, 50 g/mL, 108 g/mL, 
and 3012 day·g/mL respectively 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, indicating no great 
difference exists in steady-state exposure between paediatric and adult populations. The 
slightly decreased exposure in younger participants was expected due to the allometric 
effect of lower body weight combined with weight proportional dosing. Because of body 
weight difference between Asian and Caucasian adult participants, there is small 
difference in exposure of belimumab when the same weight proportional 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]. 
2.2.5. 
Belimumab IV in Chinese paediatric SLE Participants (Study 
213560) 
The registration of Benlysta for paediatrics in China, approved in December 2020, was 
based on extrapolation of efficacy from results of the overseas paediatric population 
study (BEL114055), the Northeast Asian Phase 3 study with Chinese adult data 
(BEL113750) and other overseas Phase 3 studies (C1056, C1057). Following a 
requirement from CDE, GSK is conducting a post approval commitment (PAC) study 
(213560) to further evaluate the effectiveness, safety and PK profile of belimumab IV in 
Chinese paediatric SLE participants. Study 213560 is a multi-centre, open-label study 
targeting to enrol approximately 65 Chinese paediatric participants with active SLE aged 
5 to 17 years, and to characterise the pharmacokinetic profile in a subset (target N=25) of 

 
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Protocol Amendment 2 
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24 
the study population. 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.  
2.3. Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of belimumab may be found in the current IB and IB 
supplement(s) (if applicable) and product label. 
 

 
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Protocol Amendment 02 
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25  
2.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product - GSK1550188/belimumab 
Infections 
As with other immunomodulators, the 
mechanism of action of belimumab, which 
results in a reduction in B-cells and IgG, may 
increase risk for the development of infections 
including severe infections, opportunistic 
infections and progressive multifocal 
encephalopathy (PML). Fatal infections have 
been reported in participants with SLE receiving 
immunosuppressant therapy, including 
belimumab. 
The rate of serious infections for SLE is 5% of 
participants receiving either belimumab or 
placebo. 
Exclusions (see Section 5.2) based on history of 
primary immunodeficiency, IgA deficiency (IgA 
level <10 mg/dL), acute or chronic infections 
requiring management, serologic evidence of 
Hepatitis B, Hepatitis C or Human 
immunodeficiency virus (HIV) infection, and 
grade 3 (or greater) hypo gammaglobulinemia 
or (if unrelated to SLE) grade 3 (or greater) 
neutropenia, lymphopenia, leukopenia will be 
applied. 
Participants whose IgG level falls below 
250 mg/dL will have belimumab treatment 
withheld (See Section 10.2 Clinical Laboratory 
Assessments), and the appropriateness to 
continue dosing must be discussed and agreed 
with the Medical Monitor before the next dose. 
Any participant whose IgG level falls below 
250 mg/dL and is associated with a severe or 
serious infection will have study agent 
permanently discontinued. 
A diagnosis of PML should be considered in any 
participant presenting with new-onset or 
deteriorating neurological signs and symptoms. 

 
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Protocol Amendment 02 
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26  
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
The participant should be referred to a 
neurologist or other appropriate specialist for 
evaluation. If PML is confirmed, discontinuation 
of belimumab should be considered. If PML is 
suspected, this should be reported to the 
Medical Monitor within 24 hours. The 
appropriateness of continuing belimumab 
dosing while the case is being assessed, should 
be discussed. 
SC Injection-Related reactions, Hypersensitivity Reactions and Immunogenicity 
Administration of belimumab may result in 
infusion or injection-related systemic reactions 
and allergic/hypersensitivity reactions. 
Administration of belimumab may result in 
infusion and hypersensitivity reactions, which 
can be severe and can be fatal. Delay in the 
onset of serious hypersensitivity reactions can 
occur. Belimumab has been associated with 
delayed type non-acute hypersensitivity reaction 
(HSR)/serum sickness, although no relationship 
to anti-drug antibody (ADA) has been 
established. 
Infusion or injection-related systemic reactions 
and hypersensitivity reactions occur more 
frequently with the first two doses and tend to 
decrease with subsequent doses. In studies 
involving subcutaneous administration, injection 
site reactions occurred more frequently 
following subcutaneous administration than with 
intravenous infusion. The most frequent 
Participants with a history of an anaphylactic 
reaction to parenteral administration of contrast 
agents, human or murine proteins, or 
monoclonal antibodies or to any of the 
excipients of the study drug will be excluded 
from this study. 
Participants will remain under clinical 
supervision for 3 hours after completion of the 
first 2 belimumab injections. 
Participants will be made aware of the potential 
risk, the signs and symptoms of such reactions, 
and the importance of immediately seeking 
medical attention. Participants will be given an 
alert card for hypersensitivity/allergic reactions. 

 
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27  
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
injection site-related event was pain at the site 
of injection. 
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 participants for signs and symptoms of 
malignancy, monitor laboratory values, request 
that participants report signs and symptoms. 
Treat appropriately. 
Interactions with Vaccinations 
Because of its mechanism of action, belimumab 
may interfere with the response to 
immunizations. 
The efficacy of concurrent vaccination in 
participants 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 Participants with SLE receiving 
belimumab compared with those not receiving 
treatment at the time of vaccination. 
Immunization with live or live attenuated 
vaccines is prohibited from 30 days prior to 
Day 1 and during belimumab use. 
Participants’ vaccination status should be 
assessed and current immunization guidelines 
followed; all necessary vaccinations should be 
administered no later than 30 days prior to 
Day 1. 
Psychiatric Events 
Psychiatric events including depression and 
suicidality. 
 In a recent one-year, randomized, double-blind, 
placebo-controlled post marketing study 
(BEL115467) of 4,003 participants with SLE (1:1 
randomization): Serious adverse events (SAE) 
of suicidal ideation or behavior or self-injury 
Participants who, in the investigator’s opinion, 
pose a significant suicide risk will be excluded. 
Monitor participants for psychiatric signs and 
symptoms, request that participants report 

 
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28  
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
were reported in 0.7% (n= 15) of participants 
receiving belimumab intravenously 10 mg/kg 
(IV) vs. 0.2% (n=5) of participants taking 
placebo. No suicide-related deaths were 
reported. SAEs of depression were reported in 
0.3% (n=7) of participants 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) participants on belimumab 
10 mg/kg IV reported suicidal ideation or 
behavior and 2.0% (n=39) participants on 
placebo reported suicidal ideation or behavior. 
psychiatric symptoms. Treat psychiatric 
symptoms immediately and appropriately. 
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 belimumab. 
Autoinjector device 
Injury due to injection device, i.e., needle stick 
injury, intradermal injection, intramuscular 
injection, and/or infection at injection site due to 
improper cleaning of site and/or contamination 
of injection needle during handling (e.g., 
dropped onto floor). 
A comprehensive risk assessment for use of the 
devices during self-administration has been 
performed in accordance with International 
Organization for Standardization (ISO) 14971, 
“Application of Risk Management to Medical 
Devices.” Accordingly, all potential risks posed 
by the user during operation of device for self-
administration have been identified and 
evaluated. 
The participant and their caregiver will be 
educated by the staff prior to self-administration 
and their first 3 scheduled doses will be 
supervised in the clinic. 

 
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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
The possible risks identified are based on those 
observed during formative human factors 
studies, benchmarking similar devices on the 
market, and theoretical misuse scenarios. For 
those risks identified as unacceptable, risk 
control measures have been identified and 
implemented to mitigate the risk through 
optimizing the device design and/or instructions 
for use. 
 
 

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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 participants 
with SLE (BEL114055) was consistent with that seen in adult participants. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures that will be implemented to minimize risk to 
participants participating in this study, the potential risks associated with SC 
administration of belimumab are justified by the anticipated benefits that may be afforded 
to pediatric participants with SLE who choose to participate in this trial. 

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3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS 
Objectives 
Endpoints 
Primary - Pharmacokinetics 
• To characterize belimumab exposure 
following belimumab 200 mg SC in 
Chinese paediatric systemic lupus 
erythematosus (SLE) participants who 
have previously been treated with IV 
belimumab 
•  Exposure parameters; AUCss, 0-τ, Cavg,ss, 
Cmin,ss, Cmax,ss,  
Secondary - Safety 
• To evaluate the safety and tolerability of 
belimumab 200mg SC in paediatric 
Participants with SLE who have 
previously been treated with IV 
belimumab 
• Occurrence of adverse events, serious 
adverse events and adverse events of 
special interest through Week 12. 
AUCss, 0-τ = Area under the curve at steady-state to the end of the dosing period, Cavg, ss= Average serum 
concentration at steady state, Cmin, ss = Minimum serum concentrations at steady state, Cmax, ss = Maximum 
serum concentrations during the dosing interval at steady state 
 
Primary estimands 
For estimand strategy in primary endpoint. The estimand is described by the following 
attributes: 
 
Population 
Chinese paediatric participants 5-17 years of age with SLE who have 
previously been treated with IV belimumab 
Treatment 
• Repeat doses of 200mg belimumab administered SC over 12 weeks 
on a background of standard of care therapy 
Endpoints 
• Exposure parameters; AUCss, 0-τ, Cavg,ss, Cmin,ss, Cmax,ss, 
Summary 
Measure 
•  Geometric mean 
Intercurrent 
events and 
strategies 
The anticipated key intercurrent events and corresponding strategies 
are: 
• Discontinuation of study medication: while-on-treatment 
strategy. The PK data after study medication discontinuation 
(except for PK data from EW visit) will not be used in analysis. 
Specially, to maximize PK data to support the estimation of 

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exposure parameters, the PK data from EW visit will be used in 
analysis. 
• Interruption of study medication: treatment policy strategy. The 
PK data after interruption of study medication will be used in 
analysis. 
• Using of prohibited medications or therapies: while-on-treatment 
strategy. Only the PK data before initiation of prohibited 
medications or therapies will be used in analysis.  
Rationale for estimand: Interest lies in the exposure parameters when participants have 
actually taken study medication irrespective of interruption of study medication. For 
using of prohibited medications or therapies, the while-on-treatment strategy is motivated 
by the potential confounding of PK data after using prohibited medications or therapies. 
For estimand strategy in secondary endpoint. The estimand is described by the following 
attributes: 
Population 
Chinese paediatric participants 5-17 years of age with systemic lupus 
erythematosus (SLE) who have previously been treated with IV 
belimumab 
Treatment 
• Repeat doses of 200mg belimumab administered subcutaneously 
(SC) over 12 weeks on a background of standard of care therapy 
Endpoints 
• Occurrence of adverse events, serious adverse events and adverse 
events of special interest through Week 12. 
Summary 
Measure 
•  Frequency and percentage 
Intercurrent 
events and 
strategies 
• Discontinuation of study medication, addressed with while-on-
treatment strategy. Safety data in the 12-week on-treatment period 
will be used in analysis. The definition of on-treatment period will be 
provided in reporting and analysis plan (RAP). 
Rationale for Estimand: This attempts to estimate on-treatment safety effects likely to be 
attributable to the drug. 
In addition to estimand strategy in secondary endpoint, an additional analysis will be 
performed based on all safety data including 12-week on-treatment period and 16-week 
post-treatment follow-up period. 
Further details on estimand strategy will be provided in the RAP. 

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4. 
STUDY DESIGN 
4.1. Overall Design 
This is a single arm, multi-centre open label study of belimumab plus standard of care in 
participants with SLE who have completed 48 weeks belimumab IV treatment in 213560 
study to evaluate the PK and safety of subcutaneously administered belimumab over 12 
weeks in approximately 17 paediatric participants ages 5-17 years and weighing ≥15 kg.  
213560 study is an open label study to evaluate the safety, efficacy and pharmacokinetics 
of belimumab (10 mg/kg) IV with standard therapy in Chinese paediatric participants 
aged 5 to 17 years with active SLE. The participants in study 217091 will be those who 
have completed the 48-week treatment phase of 213560 study and who, in the 
investigator’s judgement will benefit from continuing treatment with belimumab. The 
targeted aim for this study will be to recruit participants in Study 213560 who have IV 
PK samples collected. However, if the targeted number of participants cannot be met 
additional participants from the non-PK population in 213560 will also be included. The 
PK sample right after the last IV dose in 213560 and pre-dose PK sample of study 
217091 will be collected from each patient to ensure the belimumab PK profile leading 
up to and following the switch to SC dosing can be accurately characterized for each 
participant.  
Participants who have completed Week 52 assessment in study 213560, will receive the 
first SC dose in study 217091 no more than 4 weeks after the last IV dose (administered 
at week 48 visit of study 213560). The study will include: 
• 
Open-label, 12-week treatment phase. 
• 
Post-treatment follow-up assessments at 8 weeks and 16 weeks after the last dose 
of SC belimumab 
4.2. Scientific Rationale for Study Design 
Paediatric SLE is a severe autoimmune disease with multisystem involvement and wide 
heterogeneity of disease manifestations. It shares similar pathogenesis with adult SLE 
that includes a complex interaction of genetics, environment, and hormones that leads to 
immune-tolerance damage, resulting in autoantibody production, inflammation and organ 
injury. Disease follows an unpredictable course of relapses (flares) and remissions, and 
there is currently no cure [Moulton, 2017]. Regardless of age of onset or time of 
diagnosis, Participants with SLE share many immunogenetic and serologic similarities 
[Aggarwal, 2015; Barron, 1993; Mina, 2013]. 
Belimumab efficacy in participants with SLE has been established in Chinese adults with 
SLE in the adult IV study in Northeast Asia (BEL113750) and has been demonstrated to 
be comparable to efficacy in overseas adults (C1056, C1057, BEL112341) and 
paediatrics (BEL114055). A clinical pharmacology study 209629, in which PK of both 
IV and SC in Chinese healthy volunteers were collected, demonstrated that belimumab 
exposures in Chinese adults after administering 200 mg QW SC and 10 mg/kg Q4W IV 
are comparable.  

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In addition, GSK is initiating a study to investigate the effectiveness, safety and PK 
profile of belimumab IV in Chinese paediatric Participants with SLE (213560). This 
study was requested as a PAC by CDE during assessment of the NDA to register 
Benlysta IV for children with SLE aged 5 years and older (Approval letter number 
2020S00808/2020S00809).  
The purpose of this study (217091) is to evaluate the PK characteristics and safety of 
repeat doses of 200 mg belimumab SC in Chinese paediatric participants by leveraging 
study 213560, such that paediatric participants completing 48 weeks of IV treatment can 
switch to SC treatment by joining the SC PK bridging study. 
As SLE pathogenesis and disease progression in paediatrics is similar to adults, and the 
efficacy of belimumab IV 10 mg/kg has been established in Chinese adults, simulation 
based on the previous population PK model was used to determine the body weight-based 
dose regimens to be used in study 217091. In order to confirm or optimise the SC dosing 
regimen for Chinese children with SLE, the population model will be updated when the 
data from this study are available, and a simulation will be performed to establish 
comparable SC exposure in Chinese paediatrics with exposure seen in adults following a 
belimumab IV 10 mg/kg dosing [GSK Document Number 2020N427517_00].  
4.3. Justification for Dose 
The dose and dosing regimens selected for SC administration in this study are based on 
calculations intended to achieve a similar average exposure as observed with the weekly 
200 mg SC dosing regimen in adult Participants with SLE, estimated from a population 
PK analysis of SC study data in adults, where the estimated bioavailability (F) was 74.2% 
without inter-individual variability (IIV) and clearance (CL) was 204 mL/day with 30.2% 
(CV%) IIV [GSK Document Number 2016N291332_00]. For a fixed belimumab dose 
(e.g. 200 mg SC), the exposure increases as body weight decreases, as observed in adults 
and supported by the population PK model developed from the paediatric IV study 
BEL114055. To accommodate children between the ages of 5 to 17 years, specifically to 
ensure that participants with lower body weight are not over-exposed, 3 belimumab SC 
dose groups were proposed and defined by body weight for study 200908 in non-Chinese 
paediatric participants. Paediatric participants weighing 50 kg or more will receive 200 
mg belimumab once a week (QW), as per the recommended dosing regimen in adults. 
Paediatric participants who weigh between 30 to 50 kg will receive as 200 mg belimumab 
administered once every ten days (Q10d). Paediatric participants weighing less than 30 
kg will receive 200 mg belimumab once every two weeks (Q2W). Belimumab exposure 
(Css, avg) in paediatrics is predicted to be very similar across the three dose groups, as 
shown in the exposures projected in overseas paediatrics (Figure 1 ). According to the 
recommended dose regimen, a higher peak-trough ratio is expected in participants with 
lower body weight; however, safety is not considered as an issue because even greater 
PK fluctuation was observed in the participants following 10 mg/kg every four weeks 
(Q4W) IV belimumab. The effects of body weight on belimumab PK are expected to be 
the same in overseas participants as in Chinese participants. Therefore, the proposed 
three-tier dosing regimen used in study 200908, with Q2W dosing for participants <30 
kg, Q10d dosing for participants between 30 and <50 kg, and QW dosing for participants 
≥50 kg is considered appropriate for use in this study in Chinese paediatric participants. 

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Figure 1 
Average serum concentrations at steady state versus body weight 
projected in overseas paediatrics 
 
 
Pediatric predictions for the median (solid black line), inter-quartile range (dark grey shaded region) and 90% prediction 
interval (light grey shaded area) are compared with the post-hoc adult estimates (blue points) and the population adult 
estimate (broken red, 104 ug/mL). The median pediatric concentrations at the 30 mg and 50 mg body weight 
thresholds are shown (red diamonds 88 and 123 ug/mL at 30 kg, 90 and 129 ug/mL at 50 kg). 
4.4. End of Study Definition 
A participant is considered to have completed the study if he/she has completed treatment 
phase (12 weeks) of the study. 
The end of the study is defined as the date of the last assessment (16-week post-treatment 
follow-up) of the last participant in the study. 

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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, 
also known as protocol waivers or exemptions, is not permitted. 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Between 5 and 17 years of age inclusive, at the time of informed consent 
Type of Participant and Disease Characteristics 
2. Chinese paediatric participants with SLE, who have completed 48 weeks 
treatment in study 213560 and who, in the opinion of the investigator, may benefit 
from treatment with GSK1550188.  
Weight 
3. Body weight ≥15kg, at the time of signing the informed consent. 
Sex and Contraceptive/Barrier Requirements 
4. Male and/or female 
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: 
o Is not a woman of childbearing potential (WOCBP)  
OR 
o Is a WOCBP and is using a contraceptive method that is highly effective, with 
a failure rate of <1%, as described in 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 have a negative highly sensitive [Appendix 2] pregnancy test 
(serum or as required by local regulations) within 35 days before the first dose of 
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• 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 
5. Participant signs and dates a written age appropriate assent form (in accordance 
with applicable regulations) and the parent or legal guardian (or emancipated 
minor) that has the ability to understand the requirements of the study, provides 
written informed consent (including consent for the use and disclosure of 
research-related health information) that the participant will comply with the 
study protocol procedures (including required study visits). 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Have developed clinical evidence of significant, unstable or uncontrolled, acute or 
chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, 
gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases), or 
experienced an AE in 213560 study that could, in the opinion of the principal 
investigator, put the participant at undue risk. 
2. Have developed any other medical diseases (e.g., cardiopulmonary), laboratory 
abnormalities, or conditions that, in the opinion of the principal investigator, makes 
the participant unsuitable for the study. 
3. Have an estimated glomerular filtration rate as calculated by Schwartz Formula of 
less than 30 mL/min. 
4. Have an IgA deficiency (IgA level <10 mg/dL). 
5. Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale 
(Section 10.2.1) except for the following that are allowed: 
a) Stable Grade 3 hypoalbuminemia due to lupus nephritis and not related to 
liver disease or malnutrition. 
b) Any grade proteinuria 
c) 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 alanine transaminase (ALT) 
and/or aspartate aminotransferase (AST) must be Grade 2. 
d) Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 
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Diagnostic Assessments 
6. Developing a positive test for HIV antibody after inclusion into 213560, per 
investigator’s discretion according to clinical need. 
7. Developing hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as 
Hepatitis B surface antigen positive (HBsAg+) OR Hepatitis B core antibody positive 
(HBcAb+) after inclusion into 213560, per investigator’s discretion according to 
clinical need. 
8.  Developing a positive test for Hepatitis C antibody after inclusion into 213560, per 
investigator’s discretion according to clinical need. 
Prior/Concomitant Therapy 
9. Have received a live or live-attenuated vaccine within 30 days of Day 1. 
Other Exclusions 
10. Are unable or unlikely, in the opinion of the investigator, to administer belimumab by 
SC injection and have no reliable source to administer the injection. 
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 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, any protocol deviations. 
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. Criteria for Temporarily Delaying 
Enrolment/Randomization/Administration of Study Intervention 
Not Applicable. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
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 
Table 1 
Study Intervention(s) Administered 
ARM Name 
Open label arm 
Intervention Name Belimumab 
Type  
Biologic 
Dose Formulation 
SC Injection 
Unit Dose 
Strength(s) 
200 mg/mL  
Dosage Level(s) 
Dose weight 50 kg: 200 mg weekly;  
Dose weight 30 kg - <50 kg: 200 mg every 10 days; 
Dose weight 15 kg - <30 kg: 200 mg every 2 weeks 
Route of 
Administration 
SC injection (autoinjector) 
Sourcing 
Provided centrally by the Sponsor 
Packaging and 
Labelling 
Belimumab will be provided as an autoinjector 
Manufacturer: 
Autoinjector: The autoinjector components are manufactured by 
Scandinavian Health Limited (SHL) and assembled with the pre-filled 
syringe at GSK, Barnard Castle, UK. 
Device 
Single use autoinjector 
 
6.1.1. 
Medical Devices 
• The GSK manufactured medical devices (or devices manufactured for GSK by a 
third party) provided for use in this study are injection devices: an autoinjector 
device. 

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• GSK medical device incidents, including those resulting from malfunctions of the 
device, must be detected, documented, and reported by the investigator 
throughout the study. 
6.2. Preparation, Handling, Storage and Accountability 
1. The investigator or designee must confirm 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. Only participants enrolled in the study may receive study intervention and only 
authorized 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 labeled storage conditions with 
access limited to the investigator and authorized 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 autoinjectors are 
provided in the Study Reference Manual (SRM). 
5. 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. 
6. 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. 
7. The excipients used in the pediatric formulation are safe for administration in the 
pediatric population participating in the study. 
6.3. Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study without randomization and blinding. 
6.4. Study Intervention Compliance 
“Self-administration” is defined as administration of study drug either by the study 
participant or by the participant’s parent/caregiver. All participants less than 12 years old 
must have the study drug administered by their parent/caregiver. Whether the study drug 
is administered by the participant for those 12 years and older will be determined by the 
participant and his/her parents/caregivers. 
Participants or their caregivers should not administer the study agent until they receive 
proper training in subcutaneous injection technique. Participants and caregivers who do 
not feel adequately trained with self-injection may return to the site for further training. 
Participants or caregivers who cannot administer the study drug may have subsequent 

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subcutaneous injections delivered by qualified study site personnel. Ideally, the injection 
site should be rotated between the left or right thigh and the abdomen. 
6.4.1. 
Compliance with Subcutaneous Administration of Belimumab 
Participants, caregivers or medical staff will be provided with an injection diary (refer to 
SRM). Dosing compliance must be reviewed with the participant/caregiver/medical staff 
at each site visit, the injection diary must be reviewed by study site staff and the entries 
transcribed to the electronic case report form (eCRF). Participants and caregivers are also 
required to return all used and any malfunctioning autoinjector devices. All unused 
autoinjectors, including spare devices, must be returned as described in the SRM.  
When participants are dosed at the investigative site with belimumab, immediately after 
the injection, medical staff who inject the drug will complete the injection diary recording 
the date and time of injection, the injection site and whether or not the entire dose was 
administered. These injection diary entries will be transcribed into the eCRF by the site 
staff. 
When participants self-administer study treatment(s) at home, immediately after the 
injection, participants or caregivers will complete the injection diary recording the date 
and time of injection, the injection site and whether or not the entire dose was 
administered. Participants must bring their injection diary with them to site visits and 
compliance with belimumab treatment will be assessed by the site staff through review of 
the injection diary and transcription of the entries into the eCRF.  
A record of the number of belimumab autoinjectors dispensed to and taken by each 
participant and of unused autoinjectors returned by each participant must be maintained 
and reconciled with study treatment and compliance records. Used autoinjectors should 
be placed in a sharps container and returned to the site as described in the SRM. Any 
returned malfunctioning autoinjectors will be marked to distinguish them from the used 
autoinjectors (see SRM for details). 
6.4.2. 
Missed Doses 
If the participant has not taken the scheduled dose on the due date, the following rules 
apply: 
Weekly dosing – if the scheduled dose has not been administered during the scheduled 
window the dose should be SKIPPED and dosing should be resumed on the next 
scheduled date. 
10-day dosing – if the scheduled dose has not been administered during the scheduled 
window it may be administered up to 3 DAYS later. If the dose is not administered 
within 3 days, the dose should be SKIPPED and dosing should be resumed on the next 
scheduled date. 
2 weekly dosing - if the scheduled dose is not administered during the scheduled window 
it may be administered up to 7 DAYS later. If the dose is not administered within 7 days 
the dose should be SKIPPED and dosing should be resumed on the next scheduled date. 

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The participant should not administer 2 doses on the same day and 2 doses should not be 
administered to make up for a dose missed. 
If a participant misses 2 consecutive doses of belimumab or 3 non-consecutive doses of 
belimumab, then the Investigator must contact the Medical Monitor to discuss whether 
the participant should continue in the study (see SRM for details).  
6.5. Dose Modification 
No dose modifications of belimumab are allowed. Dosing frequency are fixed according 
the baseline body weight.  
Dosing cohort 
Dosing frequency 
BW 50 kg at baseline 
Every week 
BW 30 kg and <50 kg at baseline 
Every 10 days 
BW  15 kg and <30 kg at baseline 
Every 2 weeks 
BW= Body weight 
 
6.6. Continued Access to Study Intervention after the End of the 
Study 
Following the end of treatment at Week 12 or early withdrawal from the study, the 
participant will follow standard of care for SLE as determined by the investigator. 
6.7. 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. 
GSK does not recommend specific treatment for an overdose of belimumab. 
In the event of a belimumab overdose, the investigator should: 
• 
Contact the Medical Monitor immediately. 
• 
Closely monitor the participant for AEs/SAEs. 
• 
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 

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6.8. Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
screening 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, route and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1. 
Permitted Medications and Non-Drug Therapies 
The investigator may adjust concurrent medications (add, eliminate, change dose 
level/frequency) as clinically required during the study unless specifically excluded. 
6.8.1.1. 
Anti-malarials 
A new anti-malarial (e.g., hydroxychloroquine, chloroquine, quinacrine) may be started 
at any time during the study. 
The dose of an anti-malarial may be reduced or increased as clinically required at any 
time during the study. 
An anti-malarial may be replaced by another anti-malarial due to documented toxicity or 
lack of availability at any time during the study. 
Anti-malarial drugs should be given according to local guidance (see SRM for further 
details).  
NOTE: The use of anti-malarials for either SLE management or malarial prophylaxis is 
permitted. 
6.8.1.2. 
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. 
Systemic Steroids for SLE-related Disease Activity 
The total dose of systemic steroids may be increased or decreased as clinically indicated 
at any time during the study. 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 American College of Rheumatology (ACR), for steroid 
dose/duration of induction therapy [Liang, 2004]. 

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Intra-articular Injections of Corticosteroids 
Participants may receive intraarticular (IA) corticosteroid injections at any time during 
the study. 
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.  
6.8.1.3. 
Other Immunosuppressive/Immunomodulatory Agents 
Starting any new allowable immunosuppressive/immunomodulatory agent is permitted at 
any time during the study. 
The dose of existing immunosuppressive/immunomodulatory agents may be increased or 
decreased, as clinically required, at any time during the study. 
An immunosuppressive/immunomodulatory agent may be replaced with 1 of the 
abovementioned agents due to documented toxicity or lack of availability. New topical 
immunosuppressive agents (e.g., eye drops, topical creams) are allowed at any time 
during the study.  
6.8.1.4. 
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) 
During the study, 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. 
6.8.2. 
Prohibited Concomitant Therapy 
Participants who start prohibited medications or therapies at any time during the study 
will be considered a 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 (except study 213560) 

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• Anti- Tumor Necrosis Factor (TNF) or anti-IL-6 therapy (e.g., adalimumab, 
etanercept, infliximab, certolizumab, tocilizumab, golimumab). 
• All biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist). 
• Janus kinase (JAK) inhibitors. 
• 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). 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
If study intervention is permanently discontinued, the participant will complete the early 
withdrawal and follow-up visits as described in Section 8.1.4 and Section 1.3 (SoA) and 
will be withdrawn from the study. 
Participants may be withdrawn from study agent and from the study if at any time: 
• 
It is the wish of the participant (or their legally acceptable representative) for any 
reason. 
• 
The investigator judges it necessary due to medical reasons. 
• 
Consecutive belimumab injections (Section 6.4.2) or consecutive clinic visits are 
missed, consult to medical monitor to decide withdrawn or not (Section 8.1.4). 
Furthermore, participants will be withdrawn from study agent and subsequently 
withdrawn from the study if at any time they: 
• 
Become pregnant. 
• 
Receive prohibited therapy  
• 
Experience unacceptable toxicity 
• 
Participate in another interventional clinical trial except Study 213560 
• 
Trigger liver chemistry stopping criteria and/or IgG stopping criteria. 
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 10.6 (Appendix 6) 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 10.6 (Appendix 6) for required Liver Safety Actions and Follow-up 
Assessments  
7.1.2. 
IgG Stopping Criteria 
Any participant who has a Grade 4 IgG level (<250 mg/dL), 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 1.3). 

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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 are not allowed. 
7.2. Participant Discontinuation/Withdrawal from the Study 
The legal guardian and the paediatric participant have the right to withdraw permission 
(consent or assent, respectively) at any time during the study. If the study staff identify 
any reluctance in the legal guardian or paediatric participant (e.g., signs of verbal or 
physical dissent) about continued participation in the study, the paediatric participant’s 
continuation in the study should be re-evaluated. The same principles that govern 
permission/assent/consent also govern its withdrawal.  
A participant will be withdrawn from the study for any of the following reasons: 
• Withdrawal of consent or assent if applicable (A paediatric participant’s dissent 
should be respected.) 
• 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, or compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA. See SoA 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 from the study intervention and 
the study at that time. 
• If the participant 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, he/she 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/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 fail 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, counsel the participant on the importance of maintaining the 

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assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 
• 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.  

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized 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.  
• Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of informed consent form (ICF) 
may be utilized for screening or baseline purposes provided the procedure met the 
protocol-specified criteria and was performed within the timeframe defined in the 
SoA. 
8.1. 
Screening and Critical Baseline 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 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 (if applicable, in accordance with local regulation). A participant may have 
treatment assigned when all screening procedures have been completed and eligibility 
criteria confirmed. 

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Screening Assessments 
Study assessments and procedures will include the following and are detailed in the 
Schedule of Activities (SOA). 
• Demographic information including gender, ethnic origin, race, date and year of 
birth. 
• Medical history. 
• Complete physical examination, including height and weight 
• Vital signs including temperature, sitting blood pressure, and heart rate 
• Confirm classification of SLE disease (based on ACR criteria) by reviewing 
previously documented clinical records. 
•  A single 12-lead ECG will be obtained for screening purposes only as outlined in 
the SoA (see Section 1.3) using an ECG machine that automatically calculates the 
heart rate and measures PR, QRS, and QT intervals. If the screening ECG is 
abnormal, the Investigator may at their discretion exclude the participant from the 
study and/or contact the Medical Monitor to discuss the appropriateness of 
including the participant. 
• Device Incidents malfunctions 
• Blood samples for: 
o Haematology. 
o Modified Chem 20 (non-fasting).  
o Serum pregnancy test - defined as a pre-menarcheal female who has not 
yet entered puberty as evidenced by lack of breast development (palpable 
glandular breast tissue); or a female who has documentation (medical 
report verification) of a hysterectomy, has both ovaries surgically removed 
or tubal ligation. 
o PK sampling. 
o Serum immunoglobulin (IgG, IgA and IgM). 
• Urine sample for: 
o Routine urinalysis 

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8.1.1. 
Baseline Assessments 
Procedures at the Baseline Visit are listed in the SOA (Section 1.3). They include clinical 
assessments and laboratory tests. The interim medical history, including concomitant 
medications should be reviewed to ensure the participant’s eligibility for the study has 
not changed. 
Additional information about these procedures are provided in Section 8.4 (and in the 
SRM). 
8.1.2. 
Scheduled Visit Assessments 
Procedures at the Scheduled Visits are listed in the SoA (Section 1.3). They include 
clinical assessments, laboratory tests and pharmacokinetics. Time windows are provided 
for each study visit to allow flexibility in site and participant scheduling. All study visits 
should occur within the visit window of the scheduled study visit. Additional information 
about these procedures are provided in Section 8.4 (and in the SRM). 
8.1.3. 
Unscheduled Visit Assessments 
Unscheduled visits may be performed for a variety of reasons, including safety. The 
specific procedures to be performed at an Unscheduled Visit depend on the reason for the 
Unscheduled Visit. Additional information on the procedures to be performed at an 
Unscheduled Visit is provided in the SRM. 
8.1.4. 
Early Withdrawal and Follow-up Visit Assessments 
Participants who discontinue belimumab treatment and withdraw from the study, are 
required to complete an Early Withdrawal Visit (within 4 weeks of the decision to 
withdraw) in addition to the 8-week and 16-week follow-up visit and assessments (see 
also Section 1.3). If participants are unwilling to return for the 8-week follow-up visit, the 
early withdrawal visit should be completed at the point of withdrawal and every effort 
should be made to obtain the results of the home pregnancy assessment, if applicable, and 
AE collection 16 weeks following the last dose of belimumab. 
8.1.5. 
Missed Study Visits 
If a participant misses consecutive study visits, the Investigator should contact the 
Medical Monitor to discuss whether the participant should continue in the study or be 
withdrawn (additional guidance is provided in the SRM). 
8.2. Efficacy and/or Immunogenicity Assessments 
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8.3. Safety Assessments 
o Adverse Event (including injection-related and hypersensitivity reactions, 
infections and malignancies) reported throughout the 12-week treatment 
period and 16-week follow-up. 
o Haematological and clinical chemistry parameters (including urinalysis) 
throughout the 12-week treatment period. 
o Vital signs (i.e., pulse rate and systolic and diastolic blood pressure) 
throughout the 12-week treatment period and 16-week follow-up. 
o Physical examination 
o Additional safety tests (such as vital signs, physical examinations and 
laboratory safety tests) or change in timing or addition of assessments may 
be performed during the course of the study based on newly available data 
to ensure appropriate safety monitoring. 
o 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. 
Physical Examinations 
• 
A complete physical examination will be conducted at screening, see Section 
8.1. 
• 
Abbreviated, symptom-driven examinations will include at a minimum, 
assessment of the skin, lungs, cardiovascular system, and abdomen (liver and 
spleen), as well as other relevant organ systems based on participants’ 
symptoms. The abbreviated symptom driven examination will be performed as 
specified in the SoA (Section 1.3). 
• 
Height and Weight will be measured and recorded as specified in the SoA 
(Section 1.3). Every effort should be made to maintain a similar practice to 
measure height and weight throughout the study e.g. shoes on or off, level of 
clothing to minimize any impact of alteration of these condition on any potential 
change in height or weight. 
• 
At the discretion of the Investigator, physical and neurological examinations 
may be performed at unscheduled visits. 
8.3.2. 
Vital Signs 
• 
Systolic and diastolic blood pressure (sitting), heart rate, and body temperature 
will be measured. Measurements of vital signs will be taken as specified in the 
SoA (Section 1.3). When belimumab dosing is scheduled to occur in clinic (see 
Section 1.3), vital signs will be collected pre-dose. 
 
• 
At the discretion of the Investigator, vital signs may be assessed at unscheduled 
visits. 

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8.3.3. 
Electrocardiograms 
• 
ECG is obtained at screening only, see Section 8.1. 
8.3.4. 
Clinical Safety Laboratory Tests 
• See Appendix 2 for the list of clinical laboratory tests to be performed and the 
SoA for the timing and frequency.  
• The investigator must review the laboratory report, document this review, and 
record any clinically significant changes occurring during the study as an AE. The 
laboratory reports must be filed with the source documents.  
• 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.  
o 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 tests, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 
8.3.5. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at monthly intervals during study intervention period. 
• Pregnancy testing (urine or serum as required by local regulations) for all females 
of childbearing potential 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. 
8.4. Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting 
The definitions of adverse events (AEs) or serious adverse events (SAEs) can be found in 
Section 10.3. 

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The definitions of device-related safety events, adverse device effects (ADEs) and serious 
adverse device effects (SADEs), can be found in Section 10.7. Device deficiencies are 
covered in Section 8.4.6. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized 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 belimumab. 
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. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All AEs and SAEs will be collected from the start of treatment intervention until the 
follow-up visit at the time points specified in the SoA (Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical 
conditions not as AEs. 
• 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 Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• Investigators are not obligated to actively seek information on AEs or SAEs after 
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 
• Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-
ended and nonleading verbal questioning of the participant is the preferred method to 
inquire about AE occurrence.  
• Study-site staff should instruct the legal guardians and caregivers, on how to report 
signs and symptoms (e.g., crying and pain) in the individual pediatric participant. 
They will be instructed to report both specific and non-specific symptoms (including 
vomiting, diarrhea, sleepiness, variation in the intensity and pattern of crying, etc.). 
These non-specific symptoms may be the only manifestations of some adverse 
reaction observed in 5-17 years age participants. Care should be taken that the clinical 
presentation of adverse reactions is not misinterpreted as the manifestation of a pre-
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• Moreover, symptoms that are dependent on participant communication ability (e.g., 
nausea, pain, mood alterations) in younger or mentally-disabled children could 
potentially be at risk for under- or mis-reporting. 
• These events may or may not have been noted in the participant diary. 
 
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 AESI (i.e., post-injection 
systemic reactions and hypersensitivity reactions, infections of special interest, 
malignancies, and depression/suicidality/self-injury), will be followed until the event is 
resolved, stabilized, 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. 
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. 
• 
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 SAE) 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. 

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8.4.5. 
Pregnancy 
• Details of all pregnancies in female participants and, if indicated, will be collected 
after the start of study intervention and until time period for reporting pregnancies 
should align with the time period for post-intervention contraception determined in 
Section 5.1. 
• If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the [female 
participant or female partner of male participant (after obtaining the necessary signed 
informed consent from the female partner)] pregnancy. 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. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in Section 
8.4.4. 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 in the study will 
discontinue study intervention or be withdrawn from the study. 
8.4.6. 
Medical Device Deficiencies 
Medical devices are being provided for use in this study as the study intervention. To 
fulfil regulatory reporting obligations worldwide, the investigator is responsible for the 
detection and documentation of events meeting the definitions of device deficiency that 
occur during the study with such devices.  
The definition of a medical device deficiency can be found in Section 10.7. 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 10.3 of the protocol.  
8.4.6.1. 
Time Period for Detecting Medical Device Deficiencies 
• Medical device deficiencies that result in an incident will be detected, 
documented, and reported during all periods of the study in which the medical 
device is used.  
• If the investigator learns of any device deficiency at any time after a participant 
has been discharged from the study, and such a device deficiency is considered 

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reasonably related to a medical device provided for the study, the investigator will 
promptly notify the sponsor. 
• Medical device deficiencies and any associated AE/SAEs for associated person 
(i.e., spouse, caregiver, site staff) will be collected. The associated person will be 
provided with a safety reporting information and authorisation letter. 
• The method of documenting medical device deficiencies is provided in Section 
10.7. 
8.4.6.2. 
Follow-up of Medical Device Deficiencies 
• Follow-up applies to all participants, including those who discontinue study 
intervention or the study, and associated persons. 
• The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
• New or updated information will be recorded on the originally completed form with 
all changes signed and dated by the investigator. 
8.4.6.3. 
Prompt Reporting of Medical Device Deficiencies to the Sponsor 
• Device deficiencies will be reported to the sponsor within 24 hours after the 
investigator determines that the event meets the protocol definition of a device 
deficiency. 
• The medical device deficiency report form will be sent to the sponsor by email (see 
SRM for details). If email is unavailable, then paper form should be utilized. 
• The sponsor will be the contact for the receipt of device deficiency reports. 
8.4.6.4. 
Regulatory Reporting Requirements for Device Deficiencies 
• The investigator will promptly report all device deficiencies occurring with any 
medical device provided for use in the study in order for the sponsor to fulfil the legal 
responsibility to notify appropriate regulatory authorities and other entities about 
certain safety information relating to medical devices being used in clinical studies. 
• The investigator, or responsible person according to local requirements (e.g., the head 
of the medical institution), will comply with the applicable local regulatory 
requirements relating to the reporting of device deficiencies to the IRB/IEC. 
8.5. Pharmacokinetics 
• Blood samples will be collected for measurement of serum concentrations of 
belimumab as specified in the SoA (Section 1.3) and Table 2. Instructions for the 
collection and handling of biological samples will be provided by the sponsor. The 
actual date and time (24-hour clock time) of each sample will be recorded. 
• Samples collected for analyses of belimumab serum concentrations may also be used 
to help evaluate safety or efficacy questions arising during or after the study. 

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Table 2 
PK visit days and sample times for study participants 
Sampling 
Body weight ≥50 kg Body weight ≥30 kg to <50 kg Body weight ≥15 kg to <30 
kg 
Belimumab 200 mg 
weekly 
Belimumab 200 mg SC every 
10 days 
Belimumab 200 mg SC every 
2 weeks 
Visit 
Day 
Visit 
Time  
Visit 
Time  
Additional 
PKa  
V1a 
Screening 
V1a 
Screening 
V1a 
Screening 
1 
V2b 
Day1  
V2b 
Day1  
V2b 
Day1  
2 
V3c 
Day4±1 
V3 c 
Day4±1 
V3 c 
Day4±1 
3 
V4b, d 
Day8±2 
V4b, d 
Day11±2 
V4b, d 
Day15±2 
4 
V14b 
Day78±1 
V10b 
Day71±1 
V8b 
Day71±1 
5 
V15 
Day81±1 
V11 
Day74±1 
V9 
Day74±1 
6 
V16 
Day85±2 
V12 
Day81±2 
V10 
Day85±2 
a. For those participants who don’t have IV PK samples in study 213560, 3 additional 
PK samples will be collected within 4 hours, at 7 days (±2 days) and 14 days (±2 
days) after last belimumab IV infusion at week 48 of study 213560.  
b. Samples must be taken pre-dose where the dose is administered on a clinic visit day. 
If sampling for PK is missed at Visits 3 and Visit4, the impact will be minimized by 
attempting to reschedule the missing PK sampling to ensure sufficient precision of PK 
characterization in Chinese paediatric participants: 
ꟷ 
c. For the scenario that if the sample collection on visit 3 (Day 4 ± 1 day) was 
missed, then that PK sample collection should be rescheduled at 3±1 day after 
any of the next doses.  
ꟷ 
d. For the scenario that if the sample collection on visit 4 (Day 8/11/15 ± 2 day) 
was missed, the PK sample collection should be rescheduled to when 
participants take the next dose and the sample must be taken pre-dose. 
Further guidance and information on PK sampling and PK reschedule is provided in SRM. 
8.6. Genetics 
Genetics are not evaluated in this study. 
8.7. Biomarkers 
Biomarkers are not evaluated in this study. 
8.8. Immunogenicity Assessments 
Immunogenicity parameters are not evaluated in this study. 

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8.9. Health Economics OR Medical Resource Utilization and Health 
Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. Statistical Hypotheses 
The study is designed to descriptively evaluate the PK and safety of belimumab plus 
standard therapy, and as such no formal statistical hypothesis testing is planned. 
9.2. Analysis Sets 
• The following populations are defined: 
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. 
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 analyzed. 
 
9.3. Statistical Analyses 
9.3.1. 
General Considerations 
No formal hypothesis testing is planned in the study; all analyses are descriptive.  
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis 
All pharmacokinetic analyses will be performed on the PK Population. Primary PK 
analysis will be performed after PK sample collection in all participants has been 
completed. A population PK analysis will be carried out based on dataset combining PK 
and demographic data collected in this study (217091) and from studies 213560, 
BEL114055 and 200908. Individual belimumab exposure parameters (AUCss 0-τ, Cavg,ss, 
Cmin,ss, Cmax,ss) for study 217091 participants will be derived using the population PK 
model and a statistical summary on these parameters will be performed. 
Endpoint 
Statistical Analysis Methods 
Primary 
Endpoints:  
• Belimumab exposure parameters: AUCss, 0-τ, Cavg,ss, Cmin,ss, Cmax,ss 
Analysis:  

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Endpoint 
Statistical Analysis Methods 
Descriptive statistics(arithmetic mean, standard deviation of the 
untransformed data, 95% confidence intervals for the arithmetic mean, 
median, 25th and 75th percentiles, minimum and maximum, geometric 
mean, standard deviation of the log-transformed data, 95% confidence 
intervals for geometric means, between subject coefficient of variation 
(%CVb, if applicable) will be used to summarize the belimumab exposure 
parameters: AUCss, 0-τ, Cavg,ss, Cmin,ss, Cmax,ss 
Belimumab exposure parameters (AUCss, 0-τ,Cavg,ss, Cmin,ss, Cmax,ss) estimated for all subjects 
of this study will be summarised and reported in the clinical study report (CSR) of this 
study. The belimumab exposure parameters will be estimated using a population PK 
approach based on the integrated dataset including the PK and demographic information 
from study 213560, 217091, 200908, BEL114055, and may also include PK from other 
relevant studies in adults. The detailed information about the methods, the results e.g. 
parameter estimation, goodness of fit, etc. will be reported separately in a model report.  
Further details on the population PK analysis will be discussed in the population PK 
reporting and analysis plan. 
9.3.3. 
Secondary Endpoint Analysis 
All safety analyses will be performed on the ITT population.  
Endpoint 
Statistical Analysis Methods 
Secondary 
(Safety) 
Endpoints:  
Occurrence of adverse events, serious adverse events and adverse events 
of special interest through Week12. 
Analysis:  
Descriptive statistics (frequency and percentage) will be used to summarize 
AEs, SAEs, and AESIs. The frequency of AEs will be tabulated by MedDRA 
SOC and preferred term (PT). 
 
9.4. Interim Analysis 
No formal interim analyses are planned. 
9.5. Sample Size Determination 
There are no formal calculations of power for this study. The sample size justification for 
study 217091 is based on the precision in the estimate of the geometric mean of Cavg,ss, 
over all study participants. The coefficient of variation (CV) for between-subject 
variability in Cavg,ss was approximated to 35.5%, equal to the variability evaluated in 
overseas children receiving belimumab IV in study BEL114054 [Dimelow, 2020], on the 

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basis that bioavailability for SC dosing is similar in all subjects and does not significantly 
increase variability in exposure. 
Cavg,ss is expected to be log-normally distributed and the 95% confidence interval (CI) 
relative to the geometric mean is given by exp(±t97.5, N-1×sd/√N), where t97.5, N-1 is the 
97.5th percentile of the t-distribution with N-1 degrees of freedom, sd is the standard 
deviation in the logarithm of Cavg,ss equal to 0.345 for 35.5% CV, and N is the number 
of subjects. 
For N of 14, the 95% confidence interval in Cavg,ss relative to the geometric mean is 
82% to 122%. The 95% CI therefore lies within 22% of the point estimate for Cavg and 
this level of precision is considered adequate to characterise belimumab exposure in 
Chinese children receiving belimumab SC.  
Considering the withdrawal rate in the previous and ongoing Benlysta paediatric studies 
in overseas and China, the withdrawal rate in the current study is estimated to be 20%. To 
account for a 20% withdrawal rate, the total sample size is 17.  

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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 Organizations of 
Medical Sciences (CIOMS) international ethical guidelines 
Applicable International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) guidelines 
Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, 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.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
o 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 
o Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, 
the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), European Medical Device Regulation 2017/745 for clinical 
device research (if applicable), and all other applicable local regulations, 
o The investigator will be responsible for reporting cases of suspected child 
abuse and/or neglect according to local medical association (e.g., 
American Academy of Pediatrics [AAP], EU Academy of Pediatrics 
[EAP]) or Health Department guidelines. 

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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. 
10.1.3. 
Informed Consent and Assent Process 
• The investigator, or a person designated by the investigator, will provide the legal 
guardian (refer to Abbreviations and Definitions) with the written ICF and the 
participant with the assent if applicable. They must be informed that participation 
is voluntary. The legal guardian will be required to sign written consent, and the 
participant if applicable will be required to sign written 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 center after the nature of the study has been fully explained 
and before performance of any study-related activity. 
• Assent requirements for pediatric participants may vary across regions and 
countries; local regulations should be followed as appropriate. 
• 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 centrer.  
• The medical record must include a statement that written informed consent from 
the legal guardian and assent from the pediatric participant (if deemed appropriate 
by local ethics review or local regulations) were obtained before the participant 
was enrolled in the study and the date the written consent and assent were 
obtained. The medical record should describe how the clinical investigator 
determined that the person signing the ICF was the participant’s legal guardian. 
The authorized person obtaining the informed consent must also sign the ICF and 
assent form attesting that the pediatric participant did not show signs of dissent 
particularly in those studies including toddlers and small children; it should be 
written in language appropriate to the child’s developmental and functional status. 
• Participants and their legally authorised representative (parent/guardian) must be 
reconsented and re-assented to the most current version of the ICF(s) during their 
participation in the study.  
• Minor participants who assent to a study and later withdraw that assent should not 
be maintained in the study against their will, even if their legal guardian still 
wants them to participate. 
• Minor participants must be re-consented if they reach the age of majority during 
the course of the study, in order to continue participating. 

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• A copy of the ICF(s) must be provided to the participant or the participant’s 
parent/guardian. 
• As appropriate, participants may be given the opportunity to meet privately with a 
member of the site staff to ask confidential questions and to decline assent for 
confidential reasons, which, at their request, would not be shared with their legal 
guardian, unless required by local law. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• There will be no attempt to recontact the participant at adulthood. However, the 
participant retains the right to withdraw assent/consent for storage of samples 
unless specified, e.g., if adolescent becomes legal age during the study, they 
should be reconsented.  
• Stored samples will be coded throughout the sample storage and analysis process 
and will not be labeled with personal identifiers. Participants may withdraw their 
consent/assent for their samples to be stored for research. 
• If follow-up information from a treating physician or other licensed medical 
practitioner is required for a medical device incident with an AE/SAE involving 
an associated person(s), the Associated Person Safety Reporting Information and 
Authorization Letter must be signed by the associated person to obtain consent.  
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 authorized 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. 
• GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators what treatment their 
participants’ received. The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 

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• Under the framework of the SHARE initiative, GSK intends to make anonymized 
participant-level data from this study available to external researchers for 
scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and 
understanding. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
10.1.6. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRFs 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.  
• Guidance on completion of CRFs will be provided in eCRF guideline. 
• Quality tolerance limits (QTLs) will be pre-defined in the QTL plan to identify 
systematic issues that can impact participant safety and/or reliability of study 
results. These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
• 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 including definition of study critical data 
items and processes (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. Detailed information about study data 
collection and management process including systems used can be found in the 
study equivalent Contract Research Organization (CRO) document]. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
• 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 sponsor. 
No records may be transferred to another location or party without written 
notification to the sponsor.  

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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 and its origin can be found in [Source 
Data Acknowledgment]. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized 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.  
 
10.1.8. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first participant screened and will be the study start 
date. 
Study/Site Termination 
GSK or 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: 
For study termination: 

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• Discontinuation of further study intervention development 
For site termination: 
• 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 or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator 
• 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 organization(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 subject 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 
support publication of multicenter 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 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. 
• 
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: 
Mean corpuscular volume 
(MCV) 
Mean corpuscular 
haemoglobin (MCH) 
%Reticulocytes 
White blood cell (WBC) 
count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red blood cell (RBC) 
Count 
Haemoglobin 
Haematocrit 
 
 
Clinical 
Chemistry1 
Calcium 
Potassium 
Aspartate 
Aminotransferase 
Total bilirubin 

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Laboratory 
Assessments 
Parameters 
(AST)/ Serum 
Glutamic-Oxaloacetic 
Transaminase (SGOT) 
 
Calcium 
corrected for 
Albumin 
Inorganic 
Phosphate 
Sodium 
Alanine 
Aminotransferase 
(ALT)/ Serum Glutamic-
Pyruvic Transaminase 
(SGPT) 
Total Protein 
 
Carbon 
dioxide 
Magnesium 
Alkaline phosphatase 
Albumin 
 
Glucose 
(nonfasting) 
Creatine 
phosphokinase 
(CPK) 
Gamma glutamyl 
transpeptidase (GGT) 
Creatinine 
 
Uric acid 
Blood urea 
nitrogen (BUN) 
BUN/creatinine ratio 
Estimated Creatinine 
Clearance/glomerular 
filtration rate 
(Schwartz3) 
Routine Urinalysis • 
pH, glucose, protein, blood, ketones, occult blood by dipstick 
• 
Microscopic examination 
Urine Pregnancy2 
• 
Urine pregnancy if applicable 
Immunoglobulins 
• 
Serum immunoglobulin isotypes: IgG, IgM, IgA 
PK 
• 
Blood collection 
Other Screening 
Tests 
• 
Highly sensitive human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)3 
• 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], anti-HBs 
Antibody, anti-HBc antibody and hepatitis C virus antibody) 
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 7.1.1 and Appendix 6. 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. 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, LLLN = Lower Limit of Normal 
**Lymphopenia calculated from Common Terminology Criteria for Adverse Events (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 
 
FEV = Forced expiratory volume 
 
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: AEs and SAEs: 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 unfavorable 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 
For efficacy studies, include the penultimate bullet, and for nonefficacy studies involving 
marketed products in established indications, include the final bullet. 
• Any abnormal laboratory test results (hematology, 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 condition 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 intervention- intervention 
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. 
 

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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 condition. 
• 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 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. 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. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(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 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 

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An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that 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. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
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. 
• 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 required form. 
• 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. 

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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to one of the following categories:  
• Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Moderate: Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting self-
care ADL. Self care ADL refers to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden. 
 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment 
to determine the relationship. 
• 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. 
• 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. 
 

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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 submitted 
documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
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) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 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 Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool 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. 

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SAE Reporting to GSK via Paper Data Collection Tool 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in SRM. 
 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
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 

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10.5. 
Appendix 5: Genetics 
Not applicable 

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10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments and Study Intervention Restart/Rechallenge 
Guidelines 
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 

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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 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form 
• Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications. 
• Record alcohol use on the liver event 
alcohol intake case report form (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 

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the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM. 
 
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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10.7. 
Appendix 7: Deficiencies: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting in Medical 
Device Studies 
• The definitions and procedures detailed in this appendix are in accordance with 
ISO 14155 and the European Medical Device Regulation (MDR) 2017/745 for 
clinical device research (if applicable).  
• Both the investigator and the sponsor will comply with all local medical device 
reporting requirements for medical devices. 
• The detection and documentation procedures described in this protocol apply to 
all GSK medical devices provided for use in the study (see Section 6.1.1 for the 
list of GSK medical devices). 

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10.7.1. 
Definition of Medical Device AE and ADE 
Medical Device AE and ADE Definition  
• 
A medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether or not considered related to the investigational medical 
device. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of an investigational medical device. This 
definition includes events related to the investigational medical device or 
comparator and events related to the procedures involved except for events in 
users or other persons, which only include events related to investigational 
devices. 
• 
An adverse device effect (ADE) is defined as an AE related to the use of an 
investigational medical device. This definition includes any AE resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device 
as well as any event resulting from use error or from intentional misuse of the 
investigational medical device. 
 
10.7.2. 
Definition of Medical Device SAE, SADE and USADE 
A Medical Device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
• A life-threatening illness or injury. 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. 
• A permanent impairment of a body structure or a body function. 
• Inpatient or prolonged hospitalization. Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
• Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
• Chronic disease (MDR 2017/745). 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 

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A Medical Device SAE is any serious adverse event that: 
d. Is a suspected transmission of any infectious agent via a medicinal product 
SADE definition 
• A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of an SAE. 
• Any device deficiency that might have led to an SAE if appropriate action had not 
been taken, intervention had not occurred, or circumstances had been less fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is 
defined as a serious adverse device effect that by its nature, incidence, severity or 
outcome has not been identified in the current version of the risk analysis report 
(see Section 2.3). 
 
10.7.3. 
Definition of Device Deficiency 
Device Deficiency Definition 
• 
A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and inadequacy of the information supplied by 
the manufacturer. 
10.7.4. 
Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies 
AE, SAE and Device Deficiency Recording 
• 
When an AE/SAE/device deficiency occurs, it is the responsibility of the 
investigator to review all documentation (e.g., hospital progress notes, laboratory 
reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE/device deficiency 
information in the participant’s medical records, in accordance with the 
investigator’s normal clinical practice, and on the appropriate form. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to in lieu of completion of the AE/SAE/device deficiency form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by medical monitor. 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 the medical monitor. 

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AE, SAE and Device Deficiency Recording 
• 
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. 
• 
For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the deficiency. 
o A remedial action is any action other than routine maintenance or servicing of 
a medical device where such action is necessary to prevent recurrence of a 
device deficiency. This includes any amendment to the device design to 
prevent recurrence. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE/SAE/device 
deficiency reported during the study and assign it to one of the following categories:  
• Mild:  Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Moderate:  Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• Severe:  Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting self-
care ADL. Self-care ADL refers to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden. 
Other measures to evaluate AEs and SAEs may be used (e.g., National Cancer Institute 
Common Terminology Criteria for Adverse Events [NCI-CTCAE]). 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency. The investigator will use 
clinical judgment to determine the relationship. 
• 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. 
• 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. 

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Assessment of Causality 
• The investigator will also consult the IB, in his/her assessment. 
• For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency 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/SAE/device deficiency 
• 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/SAE/device deficiency as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• New or updated information will be recorded in the originally completed form. 
• The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
10.7.5. 
Reporting of SAEs 
SAE Reporting to GSK via an Electronic Data Collection Tool 
• The primary mechanism for reporting an 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 table) 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. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken offline to prevent the entry of new data or changes to existing data. 

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SAE Reporting to GSK via an Electronic Data Collection Tool 
• 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 GSK medical monitor/SAE coordinator by telephone. 
• Contacts for SAE reporting can be found in SRM. 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE paper data collection tool within the designated 
reporting time frames. 
• Contacts for SAE reporting can be found in SRM. 
10.7.6. 
Reporting of SADEs 
SADE Reporting to GSK  
NOTE: There are additional reporting obligations for medical device deficiencies 
that are potentially related to SAEs that must fulfill the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  
• Any device deficiency that is associated with an SAE must be reported to GSK 
within 24 hours after the investigator determines that the event meets the definition 
of a device deficiency. 
• GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
• Refer to the paper medical device deficiency report form for details on transmission 
of this information to the sponsor. 
 
10.7.7. 
Reporting of Medical Device Deficiencies for Associated Person 
Reporting to GSK  
If an Associated Person (i.e. e.g. spouse, caregiver, site staff) experiences a device 
deficiency, the medical device deficiency information, and any associated AE/SAE 
information will be reported to GSK. The associated person will be provided with the 
authorization to contact physician letter. 
If follow up information is required, authorization to contact physician (or other 
licensed medical practitioner’ must be signed to obtain consent. 

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Reporting to GSK  
• Medical device deficiencies that are not related to an AE or SAE should be 
reported via email to gsk-rd.complaints@gsk.com, using the medical device 
deficiency report form.  
 
• If the medical device deficiency is related to a non-serious AE and not linked to an 
SAE, please send the medical device deficiency report form with details of the 
associated AE via email to gsk-rd.complaints@gsk.com only. 
 
• If the device incident is linked to an SAE, please email the medical device 
deficiency report form, within 24 hours, to both uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822) and gsk-rd.complaints@gsk.com. 
The associated SAE form should also be reported to uk.gsk-rd-gcsp-ctsm-
admin@gsk.com (or fax +44(0)20 8754 7822). 
 
• GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported 
to the regulatory authorities and IRBs/IECs as required by national regulations. 
 
• Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 
 
 
 
 
 

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10.8. 
Appendix 8: Protocol amendment history 
 
Amendment 01:24 Jan 2024 
Overall Rationale for the amendment: 
The main purpose of this protocol amendment is to add an additional two PK sampling 
points after the last IV dose of study 213560 for the non-PK participants of that study who 
then enrol into the SC study (217091) in order to better characterise the PK parameter 
estimation and precision.  
The study sample size has been increased from 14 to 17 to take into account an estimated 
participant withdrawal rate of 20%.  
Further guidance is provided for the rescheduling timeframe for PK sampling visits that 
have been missed to ensure sufficient precision of PK characterization. 
Other minor amendments are included to provide additional clarification and to reflect 
local clinical practice and GCP requirements in China.  
 
 
 

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Section # and 
Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
Overall 
Design 
Number of 
Participants 
Updated sample size number 
from 14 to 17. 
 
Updated wording in the 1st 
sentence of “Note” as below, 
Enrolled means a participant's 
(if applicable) and their legally 
acceptable representative’s, 
agreement to participate in a 
clinical study following 
completion of the informed 
consent process and screening. 
 
Enlarged sample size to account for 
estimated 20% withdrawal rate. 
 
According to China regulations, not every 
paediatric participant needs to sign the 
ICF but their legally acceptable 
representative’s signing ICF is 
mandatory. 
 
 
 
1.2 Schema 
Added “Note” as below, 
Note: For those participants 
who don’t have IV PK samples 
in study 213560, 3 additional 
PK samples will be collected 
within 4 hours, at 7days (±2 
days) and 14 days (±2 days) 
after last belimumab IV infusion 
at week 48 of study 213560. 
 
To mitigate the risk of insufficient 
precision of bioavailability in participants 
enrolled from non-PK subjects in study 
213560 additional PK sampling points 
have been included. 

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1.3 Schedule of 
Activities (SoA) 
Shorten visit window from ±2 
days to ±1 day on V3 for each 
cohort of Body Weight (BW). 
Shorten visit window from ±2 
days to ±1 day on V14 and 
V15 in cohort of BW ≥50 kg, 
V10 and V11 in cohort of BW 
≥30 kg and <50 kg, V8 and V9 
in cohort of BW ≥15 kg and 
<30 kg respectively. 
 
Increased height recording in 
each visit with Laboratory 
Assessments 
 
Deleted superscript 8 (samples 
must be taken pre-dose) for PK 
sampling visits as below: 
 BW ≥50 kg at V16 
 BW ≥30 kg and <50 kg at V12 
 BW ≥15 kg and <30 kg at V10  
 
Updated information in footnote 
7 as below: 
For those participants who don’t 
have IV PK samples in study 
213560, 3 additional PK 
samples will be collected within 
4 hours, at 7 days (±2 days) 
and 14 days (±2 days) after last 
belimumab IV infusion at week 
48 of study 213560. 
 
Deleted “(Day1 and Week1)” in 
footnote 9.  
 
 
Added footnote 10 and 11 for 
PK sampling reschedule as 
below,  
10. If the PK sample collection 
on visit 3 was missed, then that 
PK sample collection should be 
rescheduled at 3 ±1 day after 
any of the next doses. 
To minimize the fluctuation of the 
sampling time and avoid possible overlap 
of study visits. 
 
 
 
 
 
 
 
 
 
For eGFR calculation in safety visits. 
 
 
 
Corrected to account for no dose 
administration at this visit. 
 
 
 
 
 
To mitigate the risk of insufficient 
precision of bioavailability in participants 
enrolled from non-PK subjects in study 
213560. 
 
 
 
 
 
 
 
To reflect that depending on the body 
weight cohort, this is not always at Week 
1. 
 
To help investigator further understand 
rescheduling the missing PK sampling. 
 

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11. If the PK sample collection 
on visit 4 was missed, then that 
PK sample collection should be 
rescheduled to when 
participants taken the next dose 
and sample must be taken pre-
dose. 
4.1 Overall 
Design 
Updated sample size number 
from 14 to 17.  
Enlarged 20% of sample size to mitigate 
the risk of 20% drop-out rate.  
 
6.8.2 Prohibited 
Concomitant 
Therapy 
Added “Janus kinase (JAK) 
inhibitors” as prohibited 
concomitant therapy. 
JAK inhibitors are more commonly used 
as target therapy in SLE in China, 
however there is no safety evidence on 
JAK inhibitors combine with belimumab. 
Add JAK inhibitors as prohibited 
concomitant therapy to reduce drug 
interactions. 
 
8.1. Screening 
and Critical 
Baseline 
Assessments 
 
Updated the 2nd sentence of 
“Informed Consent” as below,  
The participant will provide their 
assent to participate in the 
study at the same time (if 
applicable, in accordance with 
local regulation).   
 
According to China regulations and GCP, 
not every paediatric participant needs to 
sign the ICF. 
8.5 
Pharmacokinetics  
Added a new table (table 2) and 
footnotes to summarize the PK 
visit days and sample times. 
 
To help investigator understand the PK 
sampling points more clearly.  
9.5. Sample Size 
Determination 
Added new wording as below, 
Considering the withdrawal rate 
in the previous and ongoing 
Benlysta paediatric studies in 
overseas and China, the 
withdrawal rate in the current 
study is estimated to be 20%. 
To account for a 20% 
withdrawal rate, the total 
sample size is 17. 
 
Previous sample size did not take 
withdrawal rate into consideration.  
10.2. Appendix 2: 
Clinical 
Laboratory Tests 
Updated the table number from 
2 to 3.  
Updated the table number for adding a 
new Table 2 in Section 8.5 
 
 

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11. 
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Signature Page for  217091 TMF-17752964 v1.0
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Date of signature: 24-Jan-2024 09:47:25 GMT+0000
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