A Multi-Center, Open-Label Trial to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Subcutaneously Administered Belimumab, a Human Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Participants With Systemic Lupus Erythematosus (SLE)
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: GlaxoSmithKline

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GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: A Multi-Center, Open-Label Trial to Evaluate the Pharmacokinetics, 
Safety, and Pharmacodynamics of Subcutaneously Administered Belimumab, a Human 
Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Participants with 
Systemic Lupus Erythematosus (SLE) 
Protocol Number: 200908/Amendment 04 
Compound 
Number: 
GSK1550188 
Study Phase: Phase 2 
Short Title: Open label study of Subcutaneous Belimumab in Pediatric Participants with 
Systemic Lupus Erythematosus (SLE) 
Acronym: PLUTO-SC 
 
Sponsor Name and Legal Registered Address:  
GSK Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s): 
IND: 009970 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual. 
Sponsor Signatory:  
Emad Yanni, MD 
Clinical Development Director, Immunology 
Clinical Science Lupus 
GSK  
Approval Date: 14 Dec 2022 
Copyright 2022 the GSK group of companies.  All rights reserved.  Unauthorised 
copying or use of this information is prohibited. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 4 
14 Dec 202214 Dec 2022 
TMF-15202454 
Amendment 3 
14-Jul-2021 
TMF-13827130 
Amendment 2 
24-Apr-2020 
2018N373284_03 
Amendment 1/GER-1 
22-Nov-2019 
2018N373284_02 
Amendment 1 
24-Jul-2019 
2018N373284_01 
Original protocol (00) 
29-Apr-2019 
2018N373284_00 
 
Amendment 4 : 14 Dec 2022 
Overall Rationale for the Amendment:  
The purpose of this amendment is to accurately reflect the end of study definition as the 
last subject last visit occurring during the optional access extension phase vs. Part A and 
Part B of the study.    
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 4.4, End 
of Study 
Definition 
Revised end of study definition 
from last participant in Part A 
and Part B of the study to last 
participant in optional access 
extension phase. 
To accurately reflect last subject last visit 
occurring during the optional access 
extension phase. 
Section 6.7, 
Intervention after 
the End of the 
Study (previous) 
Modified Section heading to: 
6.7. Intervention after 
completion of Part A and Part B  
To accurately reflect last subject last visit 
occurring during the optional access 
extension phase. 
Appendix 10.3.4, 
Reporting of SAE 
to GSK 
Revised statement as follows: 
• 
After Part B of the study 
is completed at a given site, the 
electronic data collection tool 
will be taken off-linelocked to 
prevent the entry of new data or 
changes to existing data. 
Due to the end of study definition being 
revised to last participant in the optional 
access extension phase. 
Appendix 10.11, 
Abbreviations 
and Trademarks 
Removed GSK from the list of 
abbreviations 
Due to corporate rebranding 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Global 
Replaced GlaxoSmithKline with 
GSK throughout the document. 
Due to corporate rebranding 

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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schema ...................................................................................................... 10 
1.3. 
Schedule of Activities (SoA) ........................................................................ 11 
1.3.1. 
SOA 1.Part A - Cohort 1 (body weight 50 kg at baseline) 
and Cohort 3 (body weight <30 kg at baseline) ............................ 11 
1.3.2. 
SOA 2 Part A Cohort 2 (Body weight 30 kg - <50 kg at 
baseline) ...................................................................................... 15 
1.3.3. 
SOA 3 Part B  - Applies to all participants who enter Part 
B .................................................................................................. 19 
1.3.4. 
SOA 4 Optional Access Extension Phase - Applies 
exclusively to eligible participants who complete Part B ............... 23 
2. 
INTRODUCTION .................................................................................................... 25 
2.1. 
Study Rationale .......................................................................................... 25 
2.2. 
Background ................................................................................................ 26 
2.2.1. 
Study of IV Belimumab in Pediatric SLE Study Participants ......... 26 
2.3. 
Benefit/Risk Assessment ............................................................................ 28 
2.3.1. 
Risk Assessment ......................................................................... 29 
2.3.2. 
Benefit Assessment ..................................................................... 34 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 34 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 35 
4. 
STUDY DESIGN .................................................................................................... 35 
4.1. 
Overall Design ............................................................................................ 35 
4.2. 
Scientific Rationale for Study Design .......................................................... 37 
4.3. 
Justification for Dose .................................................................................. 38 
4.4. 
End of Study Definition ............................................................................... 42 
5. 
STUDY POPULATION ........................................................................................... 42 
5.1. 
Inclusion Criteria ......................................................................................... 42 
5.2. 
Exclusion Criteria ........................................................................................ 44 
5.3. 
Lifestyle Considerations .............................................................................. 47 
5.4. 
Screen Failures and Rescreening ............................................................... 47 
5.5. 
Repeat Assessments during the 35 Day Screening Period ......................... 47 
6. 
STUDY INTERVENTION ........................................................................................ 48 
6.1. 
Study Intervention Administered - Belimumab ............................................ 48 
6.1.1. 
Medical Devices ........................................................................... 48 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 49 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 49 
6.4. 
Subcutaneous Administration of Belimumab ............................................... 50 
6.4.1. 
Compliance with Subcutaneous Administration of 
Belimumab ................................................................................... 50 
6.4.2. 
Missed Doses .............................................................................. 51 
6.5. 
Concomitant Therapy.................................................................................. 52 
6.5.1. 
Permitted Concomitant Therapy .................................................. 52 

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6.5.2. 
Prohibited Concomitant Therapy .................................................. 54 
6.6. 
Dose Modification ....................................................................................... 54 
6.7. 
Intervention after completion of Part A and Part B ...................................... 55 
6.7.1. 
Optional Access Extension Phase ............................................... 55 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 59 
7.1. 
Discontinuation of Study Intervention .......................................................... 59 
7.1.1. 
IgG Stopping Criteria ................................................................... 60 
7.1.2. 
Liver Chemistry Stopping Criteria ................................................ 60 
7.1.3. 
Temporary Discontinuation .......................................................... 61 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 62 
7.3. 
Lost to Follow-Up ........................................................................................ 62 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 63 
8.1. 
Screening Assessments ............................................................................. 63 
8.2. 
Baseline Assessments ................................................................................ 65 
8.3. 
Scheduled Visit Assessments ..................................................................... 65 
8.4. 
Unscheduled Visit Assessments ................................................................. 66 
8.5. 
Early Withdrawal and Follow-up Visit Assessments .................................... 66 
8.6. 
Missed Study Visits ..................................................................................... 66 
8.7. 
Pharmacokinetic Assessments ................................................................... 66 
8.8. 
Safety Assessments ................................................................................... 66 
8.8.1. 
Physical Examinations ................................................................. 66 
8.8.2. 
Vital Signs .................................................................................... 67 
8.8.3. 
Electrocardiograms ...................................................................... 67 
8.8.4. 
Clinical Safety Laboratory Assessments ...................................... 67 
8.8.5. 
Suicidal Ideation and Behavior Risk Monitoring ........................... 68 
8.9. 
Adverse Events and Serious Adverse Events ............................................. 68 
8.9.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 68 
8.9.2. 
Method of Detecting AEs and SAEs ............................................. 69 
8.9.3. 
Follow-up of AEs and SAEs ......................................................... 69 
8.9.4. 
Regulatory Reporting Requirements for SAEs ............................. 69 
8.9.5. 
Pregnancy ................................................................................... 70 
8.9.6. 
Medical Device Incidents (Including Malfunctions) ....................... 70 
8.9.7. 
Medical Device Malfunctions........................................................ 71 
8.10. 
Efficacy Assessments ................................................................................. 72 
8.11. 
Treatment of Overdose ............................................................................... 72 
8.12. 
Pharmacodynamics and Biomarkers ........................................................... 72 
8.13. 
Genetics ..................................................................................................... 73 
8.14. 
Immunogenicity........................................................................................... 73 
8.15. 
Health Economics ....................................................................................... 73 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 73 
9.1. 
Statistical Hypotheses................................................................................. 73 
9.2. 
Sample Size Determination ........................................................................ 73 
9.3. 
Statistical Analyses ..................................................................................... 74 
9.3.1. 
Pharmacokinetic Analyses ........................................................... 74 
9.3.2. 
Safety Analyses ........................................................................... 75 
9.3.3. 
Pharmacodynamic Analyses ........................................................ 75 
9.3.4. 
Other Analyses ............................................................................ 75 

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9.4. 
Interim Analyses ......................................................................................... 76 
9.4.1. 
GSK Safety Review Team (SRT) ................................................. 76 
9.4.2. 
GSK Pharmacokinetics Review Team (PRT) ............................... 76 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 77 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 77 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 77 
10.1.2. 
Financial Disclosure ..................................................................... 77 
10.1.3. 
Informed Consent Process .......................................................... 78 
10.1.4. 
Data Protection ............................................................................ 78 
10.1.5. 
Publication Policy ......................................................................... 78 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 79 
10.1.7. 
Data Quality Assurance ............................................................... 79 
10.1.8. 
Source Documents ...................................................................... 80 
10.1.9. 
Study and Site Closure ................................................................ 80 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 81 
10.2.1. 
Adverse Event and Laboratory Value Severity Grade 
Table ........................................................................................... 83 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 91 
10.3.1. 
Definition of AE ............................................................................ 91 
10.3.2. 
Definition of SAE .......................................................................... 92 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 93 
10.3.4. 
Reporting of SAE to GSK ............................................................. 95 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 97 
10.4.1. 
Definitions: ................................................................................... 97 
10.4.2. 
Contraception Guidance: ............................................................. 98 
10.5. 
Appendix 5 Liver Safety: Required Actions and Follow-up 
Assessments and Study Intervention Restart Guidelines .......................... 100 
10.5.1. 
Restart Following Transient Resolving Liver Stopping 
Events Not Related to Study Intervention................................... 103 
10.6. 
Appendix 6: Medical Device Incidents: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 104 
10.7. 
Appendix 7: Country-specific requirements ............................................... 106 
10.8. 
Appendix 8: Country-specific Protocol Amendment 02 
Requirements ........................................................................................... 108 
10.9. 
Appendix 9: ACR Criteria .......................................................................... 110 
10.10. Appendix 10: SELENA SLEDAI Disease Assessment Scale..................... 111 
10.11. Appendix 11: Abbreviations and Trademarks ............................................ 112 
10.12. Appendix 12: Protocol Amendment History ............................................... 115 
11. REFERENCES ..................................................................................................... 122 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Multi-Center, Open-Label Trial to Evaluate the Pharmacokinetics, 
Safety, and Pharmacodynamics of Subcutaneously Administered Belimumab, a Human 
Monoclonal Anti-BLyS Antibody, Plus Standard Therapy in Pediatric Participants with 
Systemic Lupus Erythematosus (SLE) 
Short Title: Open label Study of Subcutaneous Belimumab in Pediatric Participants with 
Systemic Lupus Erythematosus (SLE) 
Rationale: The purpose of this study is to evaluate the pharmacokinetics (PK), safety, 
and pharmacodynamics (PD) of repeat doses of 200 mg belimumab administered 
subcutaneously (SC) in pediatric participants 5 to 17 years of age with systemic lupus 
erythematosus (SLE) on a background of standard of care therapy. This bridging PK 
study is part of an extrapolation strategy to support the use of SC belimumab in pediatric 
SLE patients, based on the completed adult SLE study with SC belimumab and the 
pediatric SLE study with IV belimumab, and is a component of a post-approval 
commitment to EMA (EMA-000520-PIP02-13-M01) and FDA (postmarketing 
requirement 3239-1 under BLA 761043). 
Objectives and Endpoints: 
Objective 
Endpoint 
Primary - Pharmacokinetics 
• To characterize the PK profile of 
belimumab 200 mg SC in pediatric SLE 
participants. 
• Observed belimumab concentrations at 
Week 12. 
• Steady-state PK parameters: Cavg 
(AUC), Cmax, Cmin (based on 
population PK estimates). 
Secondary - Safety 
• To evaluate the safety and tolerability of 
belimumab 200 mg SC in pediatric SLE 
participants. 
• Incidence of adverse events, serious 
adverse events and adverse events of 
special interest through Week 52. 
Secondary - Biomarkers 
• To characterize the pharmacodynamic 
profile of SC belimumab 200 mg SC in 
pediatric SLE participants. 
• Change from baseline in biomarkers 
(C3/C4, anti-dsDNA, B cell subsets, and 
immunoglobulins) at Weeks 12 and 52. 
 
Other - Efficacy 
• To characterize the impact on disease 
activity of belimumab 200 mg SC in 
pediatric SLE participants 
• Percent of subjects with a ≥ 4 point 
reduction from baseline in SELENA 
SLEDAI at Weeks 12 and 52. 

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Overall Design: 
This is a single arm, multi-center open-label study to evaluate the PK, safety, and PD of 
SC belimumab plus background standard therapy in approximately 28 pediatric 
participants ages 5 to 17 years of age and weighing 15 kg with active SLE. The study 
will include: 
• 
Part A: Open-label, 12-week treatment phase. 
• 
Part B: Optional 40-week open-label continuation phase for any participant who 
completes Part A. 
• 
Post-treatment follow-up assessments at 8 and 16 weeks after the last dose of SC 
belimumab. 
• 
Optional Access Extension Phase: Optional post-Week 52 extension phase 
exclusively for eligible participants who complete Part B (e.g., participants from 
countries where the IV formulation is not approved for pediatric use; or 
participants in whom IV Benlysta is not suitable due to medical reasons or 
significant logistical challenges). 
Disclosure Statement: This is a single group, treatment study with one arm with no 
masking. 
Number of Participants: 
It is expected that 36 participants will need to be screened to enroll approximately 28 
participants aiming to achieve 24 evaluable participants at Week 12. Enrollment and 
study withdrawals will be closely monitored and if there is an impact on continuation of 
participants in the study due to the Coronavirus SARS-CoV-2 (COVID-19) pandemic, 
more than 36 participants may be screened, and more than 28 may need to be enrolled, to 
ensure the ability to achieve the evaluable target at Week 12. 
Intervention Groups and Duration: 
The total maximum duration of study participation (Part A and Part B) for each 
participant is 73 weeks (screening:5 weeks, treatment: up to 52 weeks [12 weeks Part A 
plus 40 weeks extension phase] and follow-up: 16 weeks). 
Cohort 1 will include participants 50 kg body weight, Cohort 2 will include participants 
30 to <50 kg body weight and Cohort 3 will include participants <30 kg body weight at 
baseline. In Part A Cohort 1 will receive weekly doses of belimumab 200 mg SC, 
Cohort 2 will receive belimumab 200 mg SC every 10 days and Cohort 3 will receive 
belimumab 200 mg SC every 2 weeks. 
In Part B, the dosing frequency may change according to pre-defined criteria based on 
changes in body weight of the participant. 
The optional access extension phase is to provide a mechanism for continued access to 
belimumab SC from Week 52 onwards and is exclusive only for eligible participants who 
complete Part B of the study (e.g., participants from countries where the IV formulation 

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is not approved for pediatric use; or participants in whom IV Benlysta is not suitable due 
to medical reasons or significant logistical challenges for full eligibility criteria). The 
duration of this optional access extension phase will depend on age of the participants 
and the conditions for eligibility.  During the access extension phase, the dosing 
frequency may change based on changes in body weight of the participant. Participants 
who are enrolled into the optional access extension phase will be withdrawn from 
treatment if they reach the age of 18 years, if Belimumab SC or IV becomes licensed and 
commercially available for pediatric use in the participant’s country. 
Safety Review Team (SRT) 
An internal GSK Safety Review Team will monitor and perform in-stream review of 
safety data throughout Part A and Part B of the study. The optional access extension 
phase will not be part of this in-stream review. 
Pharmacokinetic Review Team (PRT) 
An internal GSK Pharmacokinetic Review Team will review in-stream PK data during 
Part A and Part B and if necessary recommend dose adjustments. 

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1.2. 
Schema 
 

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1.3. 
Schedule of Activities (SoA) 
1.3.1. 
SOA 1.Part A - Cohort 1 (body weight 50 kg at baseline) and Cohort 3 (body weight <30 kg at baseline) 
Note: In Part B and in the optional accesss extension phase, participants may need to switch dosing frequency according to changes in 
body weight (See Section 6.6 Dose Modification)  
Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 1 and Cohort 3] 
Screening to Day 85 (Week -5 to 12)  
Screening 
and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 8 
2 days 
Day 15 
2 days 
Day 29 
2 days 
Day 57 
2 days 
Day 85 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
Study Week 
 
Wk 0 
Wk 1 
Wk 2 
Wk 4 
Wk 8 
Wk 
12/EW1 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
X 
 
 
 
 
 
 
 
SELENA SLEDAI 
X 
X 
 
 
 
 
X 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight + Height  
X 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECG  
X 
 
 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
X 
X 
 

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Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 1 and Cohort 3] 
Screening to Day 85 (Week -5 to 12)  
Screening 
and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 8 
2 days 
Day 15 
2 days 
Day 29 
2 days 
Day 57 
2 days 
Day 85 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
Study Week 
 
Wk 0 
Wk 1 
Wk 2 
Wk 4 
Wk 8 
Wk 
12/EW1 
Adverse Events4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device 
incidents/malfunctions 
 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Assessments 
Hematology 
X 
X 
 
 
X 
X 
X 
X 
 
Urinalysis 
X 
X 
 
 
X 
X 
X 
X 
 
Chemistry  
X 
X 
 
 
X 
X 
X 
X 
 
Spot Urine 
(protein:creatinine) 
X 
X 
 
 
X 
X 
X 
X 
 
Pregnancy Test5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BLyS Protein8 
 
X 
 
 
 
 
 
 
 
PT/PTT 
X 
 
 
 
 
 
 
 
 
C3/C4, CRP8 
X 
X 
 
 
X 
X 
X 
X 
 

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Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 1 and Cohort 3] 
Screening to Day 85 (Week -5 to 12)  
Screening 
and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 8 
2 days 
Day 15 
2 days 
Day 29 
2 days 
Day 57 
2 days 
Day 85 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
Study Week 
 
Wk 0 
Wk 1 
Wk 2 
Wk 4 
Wk 8 
Wk 
12/EW1 
B-Cells8 
 
X 
 
X 
X 
X 
X 
X 
 
Anti-dsDNA, ANA8 
X 
X 
 
 
X 
X 
X 
X 
 
Immunogenicity 
 
X 
 
 
X 
 
X 
X 
 
IgA, IgG and IgM8 
X 
X 
 
 
X 
X 
X 
X 
 
Hepatitis B, Hepatitis C, 
HIV  
X 
 
 
 
 
 
 
 
 
Belimumab Administration and PK Sampling 
Training - Use of 
Autoinjector 
X 
X 
 
 
 
 
 
 
 
In Clinic Administration of 
Belimumab (Cohort 1 
≥50 kg)6 
 
X 
X 
X 
X 
X 
X9 
 
 
In Clinic Administration of 
Belimumab (Cohort 3 
<30 kg)7 
 
X 
 
X 
X 
X 
X9 
 
 
PK Sampling8 
 
 
X 
X 
X 
X 
X 
X 
 
 

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1. 8- and 16-week follow-up is required for participants who withdraw from study treatment prior to the end of Part A and for participants who complete Part A but do not wish to 
continue into Part B. For participants who withdraw from treatment prior to Week 12, in addition to the 8- and 16-week follow-up visit and assessments, an early withdrawal visit 
(EW) should be completed. The EW visit requires identical assessments and procedures to the Week 12 visit. 
2. 16-week follow-up requires a phone call to collect AEs, concomitant medications and the results of home urine pregnancy test (if applicable) for female participants. NOTE: the 16-
week follow-up may be performed at a clinic visit per local requirement. 
3. Full Physical Examination is required at screening (Section 8.1). An abbreviated/symptom-driven exam can be done thereafter. 
4. Please refer to Section 8.9.1.for the time period for collection of AEs/SAEs 
5. 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. 
6. Cohort 1 (50 kg at baseline): Study drug to be administered weekly in Part A. Administration in clinic is mandated where specified in the Schedule of Activities (SOA), otherwise 
at home self-administration is encouraged (see Section 6.4). For the first 2 doses (Day 1 and Week 0) participants must be observed for 3h post belimumab injection (see Section 
6.4). 
7. Cohort 3 (<30 kg at baseline): Study drug to be administered every 2 weeks in Part A. Administration in clinic is mandated where specified in the SOA, otherwise at home self-
administration is encouraged (see Section 6.4). For the first 2 doses (Day 1 and Week 1), participants must be observed for 3h post belimumab injection (see Section 6.4).  
8. Samples must be taken pre-dose. 
9. Dosing only occurs for participants who elect to continue in Part B. 
10. Participants in Cohort 3 (<30 kg) will have the screening blood collection and testing split across 2 visits separated by at least 2 weeks and between the 2nd screening and Day 1 
visits to ensure the blood volume collected remains within local guidelines. Note: This may also apply to particpants ≥30kg according to local guidelines. 
 

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1.3.2. 
SOA 2 Part A Cohort 2 (Body weight 30 kg - <50 kg at baseline) 
Note: In Part B and in the optional access extension phase, participants may need to switch dosing frequency according to changes in 
body weight (See Section 6.6 Dose Modification)  
Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 2] 
Screening to Day 81 (Week -5 to 119)  
Screening and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 11 
2 days 
Day 21 
2 days 
Day 31 
2 
days 
Day 61 
2 
days 
Day 811 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
Written Informed Consent 
X 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
 
 
 
SELENA SLEDAI 
X 
X 
 
 
 
 
X 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight + Height  
X 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECG  
X 
 
 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse Events4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 2] 
Screening to Day 81 (Week -5 to 119)  
Screening and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 11 
2 days 
Day 21 
2 days 
Day 31 
2 
days 
Day 61 
2 
days 
Day 811 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
Device incidents/malfunctions 
 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Assessment 
Hematology 
X 
X 
 
 
X 
X 
X 
X 
 
Urinalysis 
X 
X 
 
 
X 
X 
X 
X 
 
Chemistry  
X 
X 
 
 
X 
X 
X 
X 
 
Spot Urine (protein:creatinine) 
X 
X 
 
 
X 
X 
X 
X 
 
Pregnancy Test5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BLyS Protein8 
 
X 
 
 
 
 
 
 
 
PT/PTT 
X 
 
 
 
 
 
 
 
 
C3/C4, CRP8 
X 
X 
 
 
X 
X 
X 
X 
 
B-Cells8 
 
X 
 
X 
X 
X 
X 
X 
 
Anti-dsDNA, ANA8 
X 
X 
 
 
X 
X 
X 
X 
 
Immunogenicity 
 
X 
 
 
X 
 
X 
X 
 

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Procedure 
Part A - Subcutaneous PK/PD Safety [Cohort 2] 
Screening to Day 81 (Week -5 to 119)  
Screening and 
eligibility  
-35 days10 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 1 
Day 11 
2 days 
Day 21 
2 days 
Day 31 
2 
days 
Day 61 
2 
days 
Day 811 
2 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7 days1,2 
IgA, IgG and IgM8 
X 
X 
 
 
X 
X 
X 
X 
 
Hepatitis B, Hepatitis C, HIV  
X 
 
 
 
 
 
 
 
 
Belimumab Administration and PK Sampling 
Training - Use of Autoinjector 
X 
X 
 
 
 
 
 
 
 
In Clinic Administration of 
Belimumab (Cohort 2 ≥30 - 
<50kg)6 
 
X 
X 
X 
X 
X 
X7 
 
 
PK Sampling8 
 
 
X 
X 
X 
X 
X 
X 
 
1. 8- and 16-week follow-up is required for participants who withdraw from study treatment prior to the end of Part A and for participants who complete Part A but do not wish to 
continue into Part B. For participants who withdraw from treatment prior to Day 81 (Week 11), in addition to the 8- and 16-week follow-up visit and assessments, an early 
withdrawal visit (EW) should be completed. The EW visit requires identical assessments and procedures to the Day 81 visit. 
2. 16-week follow-up requires a phone call to collect AEs, concomitant medications and the results of home urine pregnancy test (if applicable) for female participants. NOTE – 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 8.8.1 
4. Adverse Event collection: Please refer to Section 8.9.1 
5. 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. 
6. Cohort 2 (30 - <50 kg): Study drug to be administered every 10 days in Part A (see Section 6.4). Administration in clinic is mandated where specified in the Schedule of Activities 
(SOA), otherwise at home self-administration is encouraged (see Section 6.4). For the first 2 doses (Day 1 and Day 11) participants must be observed for 3h post belimumab 
injection (see Section 6.4). Note the visit schedule for Cohort 2 participants differs from Cohorts 1 and 3 but aligns with dosing schedule without adding additional visits.  
7. Dosing occurs only for participants who elect to continue in Part B. 
8. Samples must be taken pre-dose where the dose is administered on a clinic visit day. 

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9. Note – Study weeks are not shown for Cohort 2 as the weeks for this cohort do not align with those for Cohorts 1 and 3 for all visits. The visits for Cohort 2 should be planned 
according to the Study Days shown in the header. 
10. Participants in Cohort 2 (30-<50 kg) may have the screening blood collection and testing split across 2 visits separated by at least 2 weeks and between the 2nd screening and 
Day 1 visits to ensure the blood volume collected remains within local guidelines. 

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1.3.3. 
SOA 3 Part B  - Applies to all participants who enter Part B 
Note: Participants may need to switch dosing frequency according to change in body weight (See Section 6.6 Dose Modification)  
 
Procedure 
Part B - Optional Treatment Extension - Days 86-365 (Weeks 13-52) [All participants] 
Treatment Period 
Follow-Up Period 
Study Day 
Day 113 
7 days 
Day 141 
7 days 
Day 169 
7 days 
Day 211 
7 days 
Day 253 
7days 
Day 309 
7days 
Day 365 
7 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7days 1,2 
Study Week 
Wk 16 
Wk 20 
Wk 24 
Wk 30 
Wk 36 
Wk 44 
Wk 52/EW1 
Wk 60 
Wk 682 
SELENA SLEDAI 
 
 
 
 
 
 
X 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight +Height  
X 
X 
X 
X 
X 
X 
X 
X 
 
Symptom Driven 
Physical Exam3 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse Events4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Collection of device 
events/malfunctions 
X 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Assessments 
Hematology  
X 
X 
X 
X 
X 
X 
X 
X 
 

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Procedure 
Part B - Optional Treatment Extension - Days 86-365 (Weeks 13-52) [All participants] 
Treatment Period 
Follow-Up Period 
Study Day 
Day 113 
7 days 
Day 141 
7 days 
Day 169 
7 days 
Day 211 
7 days 
Day 253 
7days 
Day 309 
7days 
Day 365 
7 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7days 1,2 
Study Week 
Wk 16 
Wk 20 
Wk 24 
Wk 30 
Wk 36 
Wk 44 
Wk 52/EW1 
Wk 60 
Wk 682 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry  
X 
X 
X 
X 
X 
X 
X 
X 
 
Spot Urine (protein 
to creatinine ratio) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy Test5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C3/C4, CRP10 
 
 
X 
 
 
 
X 
X 
 
B-Cells10 
 
 
X 
 
 
 
X 
X 
 
Anti-dsDNA and 
ANA10 
 
 
X 
 
 
 
X 
X 
 
Immunogenicity 
 
 
X 
 
 
 
X 
X 
 
IgA, IgG and IgM10 
X 
X 
X 
X 
X 
X 
X 
X 
 
Belimumab Administration and PK Sampling 
Cohort 1 
Administration of 
Belimumab (Body 
weight ≥50 kg)6,9 
Once weekly (2 days) until Week 51 (inclusive)  
 
 
 

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Procedure 
Part B - Optional Treatment Extension - Days 86-365 (Weeks 13-52) [All participants] 
Treatment Period 
Follow-Up Period 
Study Day 
Day 113 
7 days 
Day 141 
7 days 
Day 169 
7 days 
Day 211 
7 days 
Day 253 
7days 
Day 309 
7days 
Day 365 
7 days 
8-Week 
Follow-up 
7 days1 
16-Week 
Follow-up 
7days 1,2 
Study Week 
Wk 16 
Wk 20 
Wk 24 
Wk 30 
Wk 36 
Wk 44 
Wk 52/EW1 
Wk 60 
Wk 682 
Cohort 2 
Administration of 
Belimumab (Body 
weight 30 kg to 
<50kg)7,9 
Every 10 days( 2 days) until Day 361 (inclusive) 
 
 
 
Cohort 3 
Administration of 
Belimumab (Body 
weight <30kg)8,9 
Every 2 weeks (2 days) until Week 50 (inclusive) 
 
 
 
PK Sampling10 
X 
 
X 
 
X 
 
X 
X 
 
1. If participants withdraw from treatment prior to Week 52, in addition to the 8- and 16-week follow-up visit and assessments, an early withdrawal (EW) visit should, if possible, be 
completed. The EW visit requires identical assessments and procedures to the Week 52 visit. The 8- and 16-week follow-up visits are NOT required for participants who are 
eligible for and are enrolled into the optional access extension phase. 
2. 16-week follow-up requires a phone call to collect AEs, concomitant medications and report results of home urine pregnancy test (if applicable) for female participants. NOTE – the 
16-week follow-up may be performed at a clinic visit per local requirement. 
3. An abbreviated/symptom-driven exam can be done as described in Section 8.8.1 
4.  Please refer to Section 8.9.1 for the time period for collection of AEs/SAEs. 
5. Urine pregnancy test is sufficient for all visits in Part B. A home pregnancy test (urine) will be provided to participants for the 16-week follow-up pregnancy assessment.  
6. Cohort 1 (50 kg at baseline): Study drug to be administered weekly. Wherever the dosing days coincide with clinic visits IP administration in clinic is mandated. PK and/or 
biomarker sample collection, where specified, must be pre-dose at these visits. 
7. Cohort 2 (30 kg - <50 kg at baseline): Study drug to be administered every 10 days. Wherever the dosing days coincide with clinic vists IP administration in clinic is mandated.  
PK and/or biomarker sample collection, where specified, must be pre-dose at these visits. 
8. Cohort 3 (15 - <30 kg at baseline): Study drug to be administered every 2 weeks. Wherever the dosing days coincide with clinic visits IP administration in clinic is mandated. PK 
and/or sample collection, where specified, must be pre-dose at these visits. 

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9. In Part B the dosing frequency may be switched according to any change in body weight. Please refer to Section 6.6 Dose Modification. IF a participant switches dosing frequency 
due to weight changes during Part B, the last IP administration will be according to the schedule provided at Week44. Individual cases will be consulted with and resolved by the 
Medical Monitor.  
10. Samples must be taken pre-dose where the dose is administered on a clinic visit day. 
 

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1.3.4. 
SOA 4 Optional Access Extension Phase - Applies exclusively to eligible participants who complete Part B 
Note: Participants may need to switch dosing frequency according to changes in body weight (See Section 6.6 Dose Modification)  
Procedure 
Optional Access Extension phase - From Week52 [Eligible participants only] 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 365 
7 days 
Visit Every 12 Weeks until the end 
of Access Extension 7 days1 
End of 
access 
extension 
/EW1 
8-Week 
Follow-
up 
7 
days1,2 
16-Week 
Follow-
up 7 
days1,2 
Study Week 
Wk 52 
Access Extension Phase Specific 
Eligibility Criteria 
X 
 
 
 
 
Access Extension Phase -Specific  
Written Informed Consent 
X 
 
 
 
 
Weight3  
X 
X 
 
 
 
Serious Adverse Events4 
X 
X 
X 
X 
X 
Collection of device 
events/malfunctions 
X 
X 
X 
 
 
Laboratory Assessments 
Pregnancy Test5 
X 
X 
X 
X 
X 
Belimumab Administration 
Administration of Belimumab (Body 
weight ≥50 kg)6,9 
X 
X 
 
 
 
Administration of Belimumab (Body 
weight 30 kg to <50kg)7,9 
X 
X 
 
 
 

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Procedure 
Optional Access Extension phase - From Week52 [Eligible participants only] 
Treatment Period 
Follow-Up Period1,2 
Study Day 
Day 365 
7 days 
Visit Every 12 Weeks until the end 
of Access Extension 7 days1 
End of 
access 
extension 
/EW1 
8-Week 
Follow-
up 
7 
days1,2 
16-Week 
Follow-
up 7 
days1,2 
Study Week 
Wk 52 
Administration of Belimumab (Body 
weight <30kg)8,9 
X 
X 
 
 
 
 
1. If participants withdraw from treatment at anytime during the optional access extension phase, in addition to the 8- and 16-week follow-up visits, an early withdrawal (EW) visit 
should, if possible, be completed.  
2. 8 and 16-week follow-up requires a phone call to collect SAEs, and the results of home urine pregnancy test (if applicable) for female participants. NOTE: the 8-Week and 16-
week follow-up may be performed at a clinic visit per local requirement. 
3. Any changes in body weight that lead to a change in dosing frequency should be noted and requested in the IWRS system as per Section 6.7.1.5(see SRM for details). 
4. Please refer to Section 6.7.1.5for SAE reporting in the optional access extension phase and Section 8.9.1.for the time period for collection of SAEs. 
5. For females of childbearing potential: urine pregnancy tests will be provided by sites. Participants will be required to perform a urine pregnancy test every 4 weeks throughout the 
treatment period (1 onsite and 2 at home). Home urine pregnancy tests will also be provided for the 8-week and 16-week follow-up period. The results of urine pregnancy tests 
conducted at home will be recorded in the subject diary cards and stored as part of the investigator’s source documents. Only positive pregnancy test results will be reported to 
GSK during the optional access extension phase and will follow the guidance in Section 8.9.5.  
6. Participants 50 kg at the start of the access extension phase: Study drug to be administered weekly. At home self-administration is encouraged. 
7. Participants 30 kg - <50 kg at the start of the access extension phase: Study drug to be administered every 10 days. At home self-administration is encouraged.  
8. Participants <30 kg at start of the access extension phase: Study drug to be administered every 2 weeks. At home self-administration is encouraged.  
9. In the optional access extension phase the dosing frequency may be switched according to any change in body weight. Please refer to Section 6.6 Dose Modification.  

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2. 
INTRODUCTION 
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 and SC formulations) is approved for 
the treatment of adult patients with active autoantibody positive systemic lupus 
erythematosus (SLE), a chronic autoimmune disorder characterized by autoantibody 
production and abnormal B lymphocyte function. 
Three pivotal trials have been conducted to support the approval of belimumab for the 
treatment of adult participants SLE, including two Phase 3 trials using intravenous (IV) 
belimumab [Furie, 2011; Navarra, 2011] and one Phase 3 trial using the subcutaneous 
(SC) formulation [Stohl, 2017]. In these studies, belimumab treatment led to significant 
improvements in the SLE Responder Index (SRI) [Furie, 2009]. Pooled analyses 
demonstrated steroid sparing and decreased risk of severe flares over 52 weeks. Data 
from completed clinical studies are provided in the current Investigator Brochure (IB) 
and IB supplement(s) (if applicable). Clinical trial data for belimumab since its approval 
continue to show efficacy in the treatment of SLE through decreased SLE flares and 
decreased disease activity across multiple organ systems. 
A multi-center randomized double-blind placebo-controlled clinical trial of IV 
belimumab in pediatric participants (BEL114055) is currently being conducted (see 
Section 2.2.1) in order to fulfill post-approval commitments to the FDA and EMA. Data 
generated from the current open-label study using the SC formulation in pediatric 
participants ages 5-17 years will be used to support extrapolation of safety and PK from 
the IV pediatric and SC adult randomized trials, in order to support an alternative mode 
of administration of belimumab to pediatric SLE patients. 
Further information on the safety and efficacy of belimumab is provided in the current IB 
and IB supplement(s) (if applicable) and product label. 
2.1. 
Study Rationale 
BENLYSTA for SC use is licensed in over 30 countries for the treatment of adult patients 
with active, autoantibody-positive SLE who are receiving standard of care therapy. The 
approved dose is 200 mg weekly SC and is available in a prefilled syringe and an 
autoinjector device. The purpose of this study is to evaluate the pharmacokinetics (PK), 
safety, and pharmacodynamics (PD) of repeat doses of 200 mg belimumab administered 
subcutaneously (SC) in pediatric participants 5 to 17 years of age with SLE on a 
background of standard of care therapy. This bridging PK study is part of an 
extrapolation strategy to support the use of SC belimumab in pediatric SLE patients, 
based on the completed adult SLE study with SC belimumab and the pediatric SLE study 
with IV belimumab, and is a component of a post-approval commitment to EMA (EMA-
000520-PIP02-13-M01) and FDA (PMR 3239-1, BLA 761043). Availability of SC 
belimumab could potentially benefit the pediatric SLE population by allowing at-home 
administration and reducing the burden of IV infusions and time spent at the doctor’s 
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2.2. 
Background 
Like other rheumatic diseases of childhood, childhood-onset SLE (cSLE) is not identical 
to adult-onset SLE [Lehman, 2007]. Compared with adult SLE, cSLE patients have more 
active disease both at the time of diagnosis and over time. cSLE is associated with more 
rapid accrual of organ damage, and a higher degree of morbidity compared with adult 
onset SLE [Brunner, 2008; Tucker, 2008]. Several studies suggest that 
glomerulonephritis is more prevalent in cSLE compared to adult-onset SLE [King, 1977; 
Barron, 1993; Fish, 1977]. In addition, cSLE has a significantly higher occurrence of 
neurological involvement at the time of diagnosis [Tucker, 2008]. Development of safe 
and effective treatments for cSLE therefore remains an area of high unmet need. 
2.2.1. 
Study of IV Belimumab in Pediatric SLE Study Participants 
BEL114055 is the first randomized placebo-controlled trial to test for treatment effect on 
disease activity outcomes in pediatric SLE. BEL114055 is a three-part study. In Part A 
(52-week double-blind treatment phase), participants were randomized to receive IV 
belimumab or placebo in addition to standard of care SLE therapy. Participants who 
completed Week 52 of Part A were eligible to participate in Part B, a 10-year open-label 
continuation phase. Participants discontinuing study agent in Part A or Part B were 
eligible for enrollment into Part C, the long-term safety follow-up phase. Parts B and C 
are ongoing. Part A was completed in January 2018. Due to the rarity of SLE in children 
and the resulting recruitment challenges, BEL114055 was not powered by design, and 
therefore no hypothesis testing was performed. Of the 93 participants enrolled in 
BEL114055, 40 participants were randomized to placebo and 53 participants to IV 
belimumab in Part A. Thirteen participants were 5 to 11 years of age and 80 participants 
were 12 to 17 years of age at the time of screening. Within the limits of the 1-year data 
analyzed to date, the risk/benefit profile of IV belimumab 10 mg/kg in pediatric SLE 
patients appears consistent with that of the adult patient population. 
2.2.1.1. 
Efficacy of IV Belimumab in Pediatric SLE Study Participants 
Similar to the pivotal adult IV [Furie, 2011; Navarra, 2011] and SC [Stohl, 2017] studies, 
the primary endpoint for Part A of BEL114055 was the SRI at Week 52. A major 
secondary endpoint was the Week 52 PRINTO/ACR Juvenile SLE Response Evaluation 
(PRINTO), a novel pediatric-specific composite endpoint used for the first time in a 
placebo-controlled clinical trial. The PRINTO tool assessed percent improvement from 
baseline to Week 52 in the following five domains: 1) SELENA SLEDAI, 2) Physician’s 
Global Assessment, 3) Parent’s Global Assessment, 4) 24-hour proteinuria, and 5) 
Pediatric Quality of Life physical functioning. Other major secondary endpoints included 
the individual PRINTO components, the proportion of participants with a sustained SRI 
response, and the proportion of participants with a sustained parent global assessment 
(parent GA) response. Risk of lupus flares was also assessed.  

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From the double-blind (Part A) phase of BEL114055, the following results have been 
reported [Brunner, 2018]: 
• 
A numerical benefit of belimumab 10 mg/kg was shown over placebo for the 
primary efficacy endpoint of SRI response rate at Week 52. The treatment difference 
(belimumab vs. placebo) at Week 52 was consistent with those observed in adult IV 
belimumab studies and the results for SRI6 and sustained SRI response also favored 
belimumab. 
• 
The key secondary PRINTO/ACR endpoints indicated a greater benefit of 
belimumab with 4 of the 5 individual components (percent change in ParentGA, 
PGA, SELENA SLEDAI, and proteinuria) showing a numerical benefit of 
belimumab compared with placebo. 
• 
A higher percentage of belimumab participants had a sustained ParentGA response at 
Weeks 44-52 vs. placebo. 
• 
Participants in the belimumab group had a lower risk of experiencing a severe SFI 
flare compared with the placebo group. 
• 
More than 50% of pediatric participants exceeded the MCID for improvement in the 
PedsQL generic total score, with no difference between the belimumab and placebo 
groups. 
2.2.1.2. 
Pharmacokinetics of IV Belimumab in Pediatric SLE Study Participants 
Following IV administration of 10 mg/kg on Days 0, 14, and 28 and every 4 weeks 
thereafter, the approved adult SLE dosing regimen, belimumab exposures were similar 
between pediatric and adult SLE participants [GSK document number 2017N34326_00]. 
Steady-state geometric mean Cmax, Cmin, Cavg, and AUC values were, respectively, 
315, 50, 108 g/mL, and 3012 day g/mL in the overall pediatric population; 305, 42, 92 
g/mL, and 2569 day g/mL in the 5-11-year-old group, and 317, 52, 112 g/mL, and 
3126 day g/mL in the 12-17-year-old group compared to 311, 46, 100 g/mL, and 2811 
day g/mL in adults. The slightly decreased exposure in younger participants was 
expected due to their lower BMI and allometric principles. 
2.2.1.3. 
Pharmacodynamics of IV Belimumab in Pediatric SLE Study 
Participants 
Similar to results of adult IV [Stohl, 2012] and SC [Doria, 2018] studies, reductions in 
overall B cells, naive B cells, other B cell subsets, and immunoglobulins were observed 
following IV belimumab administration in pediatric participants in Part A of BEL114055 
[GSK document number 2017N34326_00]. 
2.2.1.4. 
Safety of IV Belimumab in Pediatric SLE Study Participants 
In the double blind phase (Part A) of BEL114055, treatment with IV belimumab plus 
standard of care was generally well-tolerated. Overall, no new safety concerns were 
identified during Part A, relative to the known safety profile of IV and SC belimumab in 
adult SLE clinical trials as described in the current IB and IB supplement(s) (if 
applicable).  

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The proportion of participants withdrawn from Part A due to an adverse event was 12.5% 
of placebo participants compared with 5.7% of belimumab participants. Serious adverse 
events were reported in 35.0% of placebo participants compared with 17.0% of 
belimumab participants, and only lupus nephritis led to discontinuation in more than 
1 participant (2 [5%] placebo, 1 [1.9%] belimumab). 
The most common AE reported in both treatment groups during the study was headache 
(27.5% placebo, 13.2% belimumab). AEs reported in >5% of belimumab-treated 
participants and at an incidence at least 3% greater than that observed with placebo were 
diarrhea, rash, neutropenia, and increased transaminases.  
The system organ class (SOC) with the highest incidence in both treatment groups was 
infections and infestations for AEs (70.0% placebo, 56.6% belimumab) and SAEs (12.5% 
placebo, 7.5% belimumab). Opportunistic infections, including active tuberculosis and 
herpes zoster, were not reported in the placebo group and one (1.9%) participant in the 
belimumab group had an opportunistic herpes zoster infection. There were no 
malignancies reported. During Part A, there were no deaths in the belimumab group and 
one subject in the placebo group died of acute pancreatitis. 
2.3. 
Benefit/Risk Assessment 
Overall, the positive benefit/risk profile of IV belimumab in the BEL114055 pediatric 
SLE cohort appears consistent with that of adult IV and SC study populations. More 
detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of belimumab may be found in the current IB and IB 
supplement(s) (if applicable) and product label. 
 

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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 PML. Fatal infections have been 
reported in SLE patients receiving 
immunosuppressant therapy, including 
belimumab. 
The rate of serious infections for SLE is 5% of 
participants receiving either belimumab or 
placebo. 
Exclusions (see Section 5.1) 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 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 8.8.4 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. 
The participant should be referred to a 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
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 in Part A. 
The presence of ADAs will be monitored with 
collection at baseline, Weeks 4, 12, 24, 52, and 
8-week post-treatment follow-up. 
Participants will be made aware of the potential 
risk, the signs and symptoms of such reactions, 
and the importance of immediately seeking 
medical attention. Patients will be given an alert 
card for hypersensitivity/allergic reactions. 

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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 patients for signs and symptoms of 
malignancy, monitor laboratory values, request 
that patients report signs and symptoms. Treat 
appropriately. 
Interactions with Vaccinations 
Because of its mechanism of action, belimumab 
may interfere with the response to 
immunizations. 
The efficacy of concurrent vaccination in 
patients receiving belimumab is not known; 
however, in the belimumab vaccination trial, 
evaluation of the impact of belimumab treatment 
on response to on-treatment vaccination with 
23-valent pneumococcal vaccine revealed that 
immune responses to the different serotypes 
were similar in SLE patients receiving 
belimumab compared with those not receiving 
treatment at the time of vaccination. 
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 subjects with SLE (1:1 
randomization): Serious adverse events (SAE) 
Participants who, in the investigator’s opinion, 
pose a significant suicide risk will be excluded. 
Monitor participants for psychiatric signs and 
symptoms, request that patients report 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
of suicidal ideation or behavior or self-injury 
were reported in 0.7% (n= 15) of subjects 
receiving belimumab intravenously 10 mg/kg 
(IV) vs. 0.2% (n=5) of subjects taking placebo. 
No suicide-related deaths were reported. SAEs 
of depression were reported in 0.3% (n=7) of 
subjects receiving belimumab 10 mg/kg IV vs. 
<0.1% (n=1) taking placebo. On the Columbia-
Suicide Severity Rating Scale (C-SSRS), 2.4% 
(n=48) subjects on belimumab 10 mg/kg IV 
reported suicidal ideation or behavior and 2.0% 
(n=39) subjects 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 ISO 14971, 
“Application of Risk Management to Medical 
Devices.” Accordingly, all potential risks posed 
by the user during operation of device for self-
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 
administration have been identified and 
evaluated. 
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 SLE Responder Index and time to first severe flare endpoints. 
Overall efficacy of IV belimumab in a randomized placebo-controlled clinical trial in 
pediatric patients with SLE (BEL114055) was consistent with that seen in adult patients 
(see Section 2.2.1.1).  
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures that will be implemented to minimize risk to patients 
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 
patients with SLE who choose to participate in this trial. 

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3. 
OBJECTIVES AND ENDPOINTS 
Objective 
Endpoint 
Primary - Pharmacokinetics 
• To characterize the PK profile of 
belimumab 200 mg SC in pediatric SLE 
participants. 
• Observed belimumab concentrations at 
Week 12. 
• Steady-state PK parameters: Cavg 
(AUC), Cmax, Cmin (based on 
population PK estimates). 
Secondary - Safety 
• To evaluate the safety and tolerability of 
belimumab 200 mg SC in pediatric SLE 
participants. 
• Incidence of adverse events, serious 
adverse events and adverse events of 
special interest through Week 52. 
Secondary - Biomarkers 
• To characterize the pharmacodynamic 
profile of belimumab 200 mg SC in 
pediatric SLE participants. 
• Change from baseline in biomarkers 
(C3/C4, anti-dsDNA, B cell subsets, and 
immunoglobulins) at Weeks 12 and 52. 
Other - Efficacy 
• To characterize the impact of 
belimumab 200 mg SC on disease 
activity in pediatric SLE participants.  
• Percent of subjects with a ≥ 4 point 
reduction from baseline in SELENA 
SLEDAI at Weeks 12 and 52. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
Please refer also to the study Schema (Section 1.2). 
This is a single arm, multi-center open-label study to evaluate the PK, safety, and PD of 
SC belimumab plus background standard therapy in approximately 28 pediatric 
participants 5 to 17 years of age and weighing 15 kg with active SLE. The study will 
include: 
• 
Part A: Open-label, 12-week treatment phase 
• 
Part B: Optional 40 week open-label continuation phase for any participant who 
completes Part A 
• 
Post-treatment follow-up assessments at 8 and 16 weeks after the last dose of SC 
belimumab 
• 
Optional Access extension Phase: Optional post-Week 52 extension phase 
exclusively for eligible participants who complete Part B (e.g., participants from 
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participants in whom IV Benlysta is not suitable due to medical reasons or 
significant logistical challenges;see Section 6.7.1).  
Part A is an open label 12-week treatment phase to evaluate the PK, safety, and PD of 
200 mg belimumab administered SC via autoinjector in pediatric participants with active 
SLE (SLE diagnosis confirmed by revised ACR criteria and SELENA SLEDAI score 6 
at screening, with at least 12 participants with a SELENA SLEDAI score of 8 at 
screening). Approximately 28 participants will be enrolled and allocated to treatment 
cohorts based on their body weight at baseline. The total enrolment is aimed to ensure 
that approximately 24 participants are evaluable at Week 12 to have sufficient data to 
accurately characterize the PK in this pediatric population. Enrollment and study 
withdrawals will be closely monitored and if there is an impact on continuation of 
participants in the study due to the Coronavirus SARS-CoV-2 (COVID-19) pandemic, 
more than 36 participants may be screened and more than 28 may need to be enrolled, to 
ensure the ability to achieve the evaluable target at Week 12. 
 
Administration of belimumab 200 mg SC in Part A will be as follows: 
Cohort 
Body weight at baseline (kg) 
Dosing frequency 
1 
50  
Every week (QW) 
2 
30 to <50  
Every 10 days (Q10d) 
3 
<30  
Every 2 weeks (Q2W) 
 
Cohort 1, Cohort 2, and Cohort 3 will be recruited in parallel.  
Belimumab will be administered in addition to standard of care therapy for SLE. 
Participants and/or caregivers will be trained to use the autoinjector to administer the 
study agent. The first three doses will be administered under observation in the clinic and 
the first two doses must also be followed by 3 hours post dose clinical observation (see 
Section 6.4). Subsequent doses may be administered away from the clinic except where 
in clinic dosing is specified in the SoA (Section 1.3). 
Blood samples for PK, PD, and safety monitoring will be obtained as indicated in the 
SoA (Section 1.3). For participants not continuing to Part B, an 8-week follow-up visit 
will take place and in addition, AEs, concomitant medications and the results of a home 
urine pregnancy test will be collected by phone (or at the clinic as per local requirement) 
at the 16-week post treatment follow-up assessment. 
Part B is an optional 40-week open-label continuation phase, open to all participants who 
have completed Part A. Dosing of SC belimumab may continue at the same frequency in 
Part B or may require a change in frequency according to changes in participant body 
weight (see Section 6.6 for details). Participants will return to the clinic for safety 

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assessments at regular intervals as defined in the SoA (Section 1.3). Samples for PK 
analysis and for immunogenicity and biomarkers will be obtained as indicated in the SoA 
(Section 1.3). AEs, concomitant medications and the results of a home urine pregnancy 
test will be collected by phone (or at the clinic as per local requirement) at the 16-week 
post-treatment follow-up. 
The study Medical Monitor and members of the GSK Safety Review Team (SRT) 
(Section 9.4.1) will perform in-stream review of all safety data throughout Part A and 
Part B of the study. 
In parallel, a GSK PK Review Team (PRT) (Section 9.4.2) will review all available PK 
data after the first 6 participants in Cohorts 1 (50 kg) or 2 (30 kg to <50kg) have 
completed Week 12. For Cohort 3 (<30 kg), preliminary PK data will be reviewed by the 
PRT based on a data cut triggered by the first Cohort 3 participant having completed 
Week 12. The primary objective of the PRT meetings will be to either confirm the initial 
dose or to recommend any adjustments. 
Participants may withdraw or discontinue from the study at any time for any reason (see 
Section 7.2). 
The total maximum duration of study participation for each participant is 73 weeks 
(screening:5 weeks, treatment: up to 52 weeks [12 weeks Part A plus 40 weeks extension 
phase] and follow-up: 16 weeks) unless they are included in the optional access extension 
phase. 
Optional Access Extension Phase is an optional extension phase to provide a 
mechanism for continued access to belimumab SC from Week 52 and is exclusive only 
for eligible participants who complete Part B of the study. The conditions of eligibility 
into the optional access extension phase will be reviewed against the access extension 
specific eligibility criteria, detailed in Section 6.7.1. The duration of this phase is 
dependent upon participants’ ages and the conditions of eligibility to the optional access 
extension phase. Participants who are enrolled into the optional access extension phase 
will be withdrawn from treatment if they reach the age of 18 years, if Belimumab SC or 
IV becomes licensed and commercially available for pediatric use in the participant’s 
country (see Section 6.7.1.4for full withdrawal criteria). 
In the optional access extension phase, after Week 52 visit, participants will return to the 
clinic every 12 weeks to receive their autoinjectors for at home administration and safety 
assessments, as defined in the SoA (Section 1.3). Dosing of SC belimumab may continue 
at the same frequency or may require a change in frequency according to changes in 
participant body weight (see Section 6.6 for details). At 8 and 16-week follow-up visits, 
SAEs and the results of home urine pregnancy tests will be collected by phone (if 
applicable). The 8-Week and 16-week follow-up may be performed at a clinic visit per 
local requirement. 
4.2. 
Scientific Rationale for Study Design 
The results from study BEL114055 (Section 2.2.1) are consistent with a positive risk 
benefit of IV belimumab 10 mg/kg for the treatment of SLE in pediatric population from 

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5 to 17 years of age and are consistent also with the positive risk benefit of belimumab IV 
and SC formulations in the adult population. This study aims to confirm that belimumab 
SC formulation in the pediatric study population has consistent PK and safety profile 
with belimumab in adult population, and with IV belimumab in pediatric population. 
The study is to support the use of belimumab SC in the pediatric population, thereby 
providing treatment options and allowing patients the potential to administer their 
medication at home, and decreasing the burden of visits to an infusion center. 
The 12-week open-label PK, safety, and PD study of SC belimumab will be followed by 
an optional open-label 40-week continuation phase. The open-label trial design, in 
combination with a partial PK extrapolation strategy, is expected to provide longer term 
data on belimumab SC formulation in this trial population. 
4.3. 
Justification for Dose 
The dose and dosing regimens selected for SC administration in this pediatric population 
are intended to achieve a similar average exposure as observed with the weekly 200 mg 
SC dosing regimen in adult SLE patients, estimated at 104 µg/mL from a population PK 
analysis of SC study data in adults [GSK Document Number 2015N263802_01]. 
For a fixed belimumab dose the exposure increases as body weight decreases, as 
observed in adults and supported by the population PK model developed from the 
pediatric IV study BEL114055. To accommodate children between the ages of 5 to 17, 
specifically to ensure lower body weight subjects are not over-exposed, three belimumab 
SC dose groups are proposed and defined by body weight. Pediatric subjects weighing 50 
kg or more will receive 200 mg belimumab once a week (QW), as per the recommended 
dosing regimen in adults. Pediatric participants who weigh between 30 to 50 kg will 
receive as 200 mg belimumab administered once every ten days (Q10d). Pediatric 
participants weighing less than 30 kg will receive 200 mg belimumab once every two 
weeks (Q2W).  
The proposed 30 and 50 kg weight thresholds approximately correspond to the age 
groups 5-9 years, 9-14 years, and 14 years or older - according to the CDC growth chart 
9.3 and 14.2-year-old girls have median weights of 30.1 and 50.0 kg, respectively. 
[https://www.cdc.gov/growthcharts/clinical_charts.htm#Set1]. 
The pediatric population PK model for IV administration, developed from the pediatric 
IV study data (BEL114055 CSR), was extended to include SC dosing by incorporating 
the absorption components of the adult SC PK model [GSK Document Number 
2015N263802_01]. The resulting model was used to simulate the three dose groups for 
200 mg SC: (1) Q2W for <30 kg; (2) Q10d for ≥30 kg and <50 kg; (3) QW for ≥50 kg 
subjects. The simulations sampled a pediatric population biased towards females (90%) 
which is typical of an SLE population. Body size parameters (body weight and BMI) 
were sampled from the NHANES 2015-2016 database and restricted to pediatric subjects 
between the ages of 5 and 18 years. Other covariates which form model input parameters 
were sampled from the pediatric study BEL114055 dataset. 
For the proposed dosing regimen, the range of exposures in the three dose groups (Q2W 
<30kg, Q10d 30 to <50kg, QW 50kg) are very similar (Figure 1, Table 1). At the 30 

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kg threshold exposure is predicted to be ~15% below and above the target concentration, 
namely 88 g/mL (Q2W) and 123 g/mL (Q10d) relative to the 104 g/mL target. 
Similarly, at the 50 kg threshold subjects receiving belimumab Q10d also have exposures 
15% below the target value (90 g/mL vs 104 g/mL target). For 50 kg subjects 
receiving QW dosing the exposure is a little higher, predicted to be ~25% above the 
target (129 g/mL vs 104 g/mL target). However, this specific value represents the 
largest deviation from the target along the exposure-weight relationship for body weights 
>15 kg (the cut-off weight for enrolment) and does not constitute an “over-exposure” 
considering the much larger between-subject variability not explained by body weight. In 
addition, several adults weighed less than 50 kg, similar to pediatrics, and were not 
considered to have unjustifiably large exposures even though the adults received 200 mg 
QW. 
The exposures across the three dose groups are generally centred about the target value 
(104 g/mL), with almost identical between subject variability at steady state (Figure 2). 
Additionally, the variability in the average exposure in any of the three dose groups, as 
expressed by the 90% prediction interval (light grey region, Figure 1), does not fall 
outside the range of exposures observed in adults (blue points, Figure 1). As a result, 
since no exposure-response relationship for safety was apparent in the adult SC 
population analysis, or in the pediatric IV study BEL114055, no safety concerns are 
expected in any of the three dose groups based on the PK predicted for pediatrics. 
In summary, belimumab PK in pediatrics is predicted to be very similar across the three 
dose groups. Within each group, steady state concentrations are centred on the target 
value (104 g/mL), between-subject variability is consistent with observed adult data, 
and deviations from the target exposure are within acceptable limits (≤25% at the body 
weight thresholds). Therefore, the three-tier dosing regimen, with Q2W dosing for 
subjects <30 kg, Q10d dosing for subjects between 30 and <50 kg, and QW dosing for 
subjects ≥50 kg is considered appropriate for study 200908. 

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Figure 1 
Average serum concentrations at steady state versus body weight. 
 
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 g/mL). The median pediatric concentrations at the 30 kg and 50 kg body weight thresholds 
are shown (red diamonds 88 and 123 g/mL at 30 kg, 90 and 129 g/mL at 50 kg). 
 

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Table 1 
Average serum concentrations at steady state as a function of body 
weight. 
Regimen 
Dose 
Body Weight (kg) 
Serum Concentration (g/mL) 
30/50 kg body weight 
thresholda 
Q2W <30kg 
30 
88 
Q10d 30-50 kg 
30 
123 
50 
90 
QW ≥50 kg 
50 
129 
Adults 
QW 
67 
104b 
a. 
1-week dosing period switches to 1 dose every 10-days at 50 kg and then to 1 dose every 2-weeks at 30 kg. 
b. 
Estimate based on population parameters from the adult population PK model for SC belimumab administration. 
 
Figure 2 
Time course profiles for the three dose groups defined by 30 kg and 
50 kg weight thresholds. 
 
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 population adult estimate (broken red, 104 g/mL). 
 

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4.4. 
End of Study Definition 
A participant is considered to have completed the primary study if he/she has completed 
Part A and Part B of the study up to and including the Week 52 visit. Participants who 
elect not to join the optional Part B will be considered to have completed Part A of the 
study if all visits up to Week 11/12 (Day 81-85) are completed. Eligible participants who 
complete Part B may be enrolled into the optional access extension phase of the study 
from Week 52 (Section 6.7.1).  
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 optional access extension phase. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to eligibility criteria, also known as protocol 
waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in Parts A and B of the study only if all of the 
following criteria apply: 
Age 
1. Participant must be between 5 and 17 years of age inclusive, at the time of Day 1. 
Type of Participant and Disease Characteristics 
2. Participants who meet the 1997 American College of Rheumatology (ACR) criteria 
for the classification of SLE (Appendix 8) 
a.  Have or have had in series 4 or more of the 11 ACR criteria for the 
classification of SLE  
3. Have active SLE disease defined as a SELENA SLEDAI score 6 at screening 
(Appendix 9). 
4. Have documented positive autoantibody test results within the study screening 
period, defined as an ANA titre ≥ 1:80 and/or a positive anti-dsDNA (30 IU/mL) 
serum antibody test based on EITHER the study’s central laboratory results OR the 
local laboratory results. Only unequivocally positive values as defined in the 
laboratory’s reference range are acceptable; borderline values will not be accepted. 
5. Are on a stable SLE treatment regimen. 
“Stable treatment at baseline” consists of any of the following medications (alone or in 
combination) administered for a period of at least 30 days prior to Day 1: 
• 
Corticosteroids (prednisone or prednisone equivalent up to 0.5 mg/kg/day): 

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• 
For those participants on alternating day doses of steroids, use the average of 2 daily 
doses to calculate the average daily steroid dose.  
• 
Other immunosuppressive or immunomodulatory agents including methotrexate, 
azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, 
mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin 
inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-
mercaptopurine or thalidomide. 
• 
Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine) 
• 
Non-steroidal anti-inflammatory drugs (NSAIDs) 
• 
New SLE therapy must not be added within 30 days of Day 1. 
Weight 
6. Body weight 15 kg. 
Sex 
7. Male and/or female 
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
Male Participants 
No contraceptive measures are required for male participants. 
Female participants: 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
• 
Is not a woman of childbearing potential (WOCBP) (See Appendix 4) 
OR 
• 
Is a WOCBP and is using a contraceptive method that is highly effective, with a 
failure rate of <1%, as described in 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 
belimumab. 
• 
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. 

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Informed Consent 
8. 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 Parts A and B of the study if any of the following criteria 
apply: 
Medical Conditions 
1. Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz 
Formula [Schwartz, 2009] of less than 30 mL/min. 
2. Have acute severe nephritis defined as significant renal disease (e.g., the presence of 
urinary sediments and other lab abnormalities) that, in the opinion of the study 
investigator, may lead to the participant requiring induction therapy during the first 
12 weeks of the trial. 
Note:  Clinically stable lupus nephritis which can be managed with medications 
allowed in the study will not exclude participants from participating in the trial (nor 
will any maximum level of proteinuria exclude participants). Clinical assessment and 
medical management of nephritis will be at the discretion of the study investigator. 
3. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or 
hematopoetic stem cell/marrow transplant. 
4. Have clinical evidence of significant, unstable or uncontrolled, acute or chronic 
diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, 
gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) 
which, in the opinion of the investigator, could confound the results of the study or 
put the participant at undue risk. 
5. Have a planned surgical procedure or a history of any other medical disease 
(e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous 
access) that, in the opinion of the investigator, makes the participant unsuitable for 
the study. 
6. Have a history of malignant neoplasm within the last 5 years. 
7. Have evidence of serious suicide risk including any history of suicidal behavior in 
the last 6 months, or who in the investigator’s opinion, pose a significant suicide risk. 
8. Have a history of a primary immunodeficiency. 

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9. Have an IgA deficiency (IgA level <10 mg/dL). 
10. Have acute or chronic infections requiring management, as follows: 
• 
Currently on any suppressive therapy for a chronic infection (such as 
tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes 
zoster and atypical mycobacteria). 
• 
Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, 
or anti-parasitic agents) for infection within 60 days of Day 1. 
11. Have a Grade 3 or greater laboratory abnormality based on the protocol defined 
Adverse Event and Laboratory Value Severity Grade scale (Appendix 2, Section 
10.2.1) except for the following that are allowed: 
• 
Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. 
• 
Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and 
not related to liver disease or anti-coagulant therapy. 
• 
Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver 
disease or malnutrition. 
• 
Any grade proteinuria. 
• 
Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus 
hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes or viral 
hepatitis. If present, any abnormalities in the ALT and or AST must be ≤ Grade 
2. 
• 
Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 
leukopenia, due to SLE. 
12. Have 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. 
Prior/Concomitant Therapy 
13. Have ever received treatment with belimumab (BENLYSTA). 
14. Have received any of the following within 364 days of Day 1: 
• 
Treatment with any B-cell targeted therapy (e.g., rituximab, other anti-CD20 
agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor 
fusion protein [BR3], TACI-Fc) 
• 
Abatacept. 
• 
Any biologic investigational agent  
15. Have required 3 or more courses of systemic corticosteroids for concomitant 
conditions (e.g., asthma, atopic dermatitis) within 90 days of Day 1 (topical or 
inhaled steroids are permitted). 
16. Have received any of the following within 90 days of Day 1: 

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• 
Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab). 
• 
Interleukin-1 receptor antagonist (anakinra). 
• 
Intravenous immunoglobulin (IVIG). 
• 
Plasmapheresis. 
17. Have received any of the following within 30 days of Day 1: 
• 
Intravenous (IV) cyclophosphamide. 
• 
A non-biologic investigational agent (30 day window OR 5 half-lives, 
whichever is greater). 
• 
Any new immunosuppressive/immunomodulatory agent. 
• 
High dose prednisone or equivalent (>1.5 mg/kg/day) or any intramuscular or 
intravenous steroid injection. 
• 
Note: New inhaled steroids, intraarticular steroids, and new topical 
immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any 
NSAID use for  1 week is allowed. 
18. Have received a live or live-attenuated vaccine within 30 days of Day 1.  
19. Have active central nervous system (CNS) lupus (including seizures, psychosis, 
organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS 
vasculitis) requiring therapeutic intervention within 60 days of Day 1. 
20. Have required renal replacement therapy (e.g. hemodialysis, peritoneal dialysis) 
within 90 days of Day 1 or are currently on renal replacement therapy. 
Prior/Concurrent Clinical Study Experience 
21. Participation in an interventional clinical study either concurrently or within 
6 months of screening. Participation in an observational study may be permitted. 
Diagnostic assessments 
22. Positive immunodeficiency virus (HIV) antibody test. 
23. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B 
surface antigen positive (HBsAg+) OR Hepatitis B core antibody positive 
(HBcAb+). 
24. Hepatitis C: Positive test for Hepatitis C antibody confirmed on an additional blood 
sample by RNA PCR assay. Participants who are positive for Hepatitis C antibody 
and negative when the Hepatitis C RNA-PCR assay is performed on an additional 
sample will be eligible to participate. Participants who are positive for Hepatitis C 
antibody and have a positive result for the HCV when the Hepatitis C RNA PCR 
assay is performed on the additional sample will not be eligible to participate. 
(Institution or country specific guidelines for blood sample volume limits must be 
followed in collection of the additional blood sample.) 
 

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Other Exclusions 
25. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol 
abuse or dependence within 364 days prior to Day 1. 
26. 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. 
27. Children in Care:  A Child in Care (CiC) is a child who has been placed under the 
control or protection of an agency, organisation, institution or entity by the courts, 
the government or a government body, acting in accordance with powers conferred 
on them by law or regulation. The definition of a CiC can include a child cared for 
by foster parents or living in a care home or institution, provided that the 
arrangement falls within the definition above. The determination of whether a child 
meets the definition of CiC should be made with the study centre staff in 
consultation with the responsible IRB/Ethics Committee. 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required during the course of this study. 
5.4. 
Screen Failures and Rescreening 
Screen failures are defined as participants who consent to participate in the clinical study 
but following the screening assessments are not subsequently enrolled 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, and any serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once at the investigator’s discretion following discussion with the 
Medical Monitor. Such participants will be assigned a new participant number and have 
all screening assessments repeated. 
5.5. 
Repeat Assessments during the 35 Day Screening Period 
Laboratory assessments may be repeated if determined necessary by the investigator, for 
example: (a) in cases of technical malfunction (e.g., loss of laboratory specimen), (b) in 
the event of a value close enough to the exclusionary threshold that it may reasonably lie 
within the degree of variability of the assay; (c) if there is reason to believe the result may 
be false (e.g. contradicts recent result for the same parameter). 
These are repeat assessments and not rescreening events. If the original result was 
exclusionary and is confirmed by repeat testing, the participant will be excluded. 

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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention Administered - Belimumab 
ARM Name 
Open label arm 
Intervention 
Name 
Belimumab 
Type  
Biologic 
Dose Formulation 
SC Injection 
Unit Dose 
Strength(s) 
200 mg/mL  
Dosage Level(s) 
Cohort 1 (50 kg): 200 mg weekly;  
Cohort 2 (30 kg - <50 kg): 200 mg every 10 days; 
Cohort 3 (<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 in cartons (1 autoinjector/carton). Each carton 
will be labeled as required per country requirement. 
Manufacturer: 
Pre-filled syringe: Pre-filled syringe components are procured from 
Becton Dickinson. Pre-filled syringe is filled with drug product and 
assembled at GSK, Barnard Castle, UK. 
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: a pre-filled syringe 
contained within 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 (see Section 8.9.6). 
6.1.1.1. 
Training for Use of Autoinjectors 
Instructions for autoinjector use are provided in the Study Reference Manual. Training 
will also be provided to sites as described in the Study Reference Manual. Sites will 
provide training to participants and caregivers and will also provide them with an 
Instructions for Use. A link for online directions on how to use the autoinjector is 
provided for reference by site personnel so they are better able to instruct 
participants/caregivers on correct use. 
6.2. 
Preparation/Handling/Storage/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 by the Interactive Web Response System 
(IWRS) 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. 
• 
Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor and/or 
GSK study contact. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study with a single treatment arm. The treatment (belimumab) to be 
taken by a participant will be centrally assigned using an IWRS. The site will contact the 
IWRS prior to the start of belimumab administration for each participant.  

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6.4. 
Subcutaneous Administration of Belimumab 
“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. 
During screening and on Day 1 (prior to the participant receiving their first dose), 
qualified study site personnel must review study drug handling and administration 
techniques with the participant and their caregiver(s). After the first injection of 
belimumab on Day 1, all subsequent injections should be administered according to the 
schedule shown in the SOA Section 1.3 ±2 days. Please refer to Section 6.4.2 for 
guidance regarding missed doses. 
If possible, the participant or their caregiver will administer the study agent by SC 
injection even if administered at the clinic visit. The first three doses will be administered 
under observation in the clinic. In the post-marketing setting with IV belimumab, delayed 
onset of symptoms of acute hypersensitivity reactions have been observed. Therefore, at 
each of the first 2 scheduled administrations of belimumab, participants will be observed 
by qualified site staff during dosing and will remain under observation at the clinic for 
3 hours post-dose. Should symptoms of acute hypersensitivity occur, an extended period 
of monitoring may be appropriate, based on clinical judgement. Participants and 
caregivers should be made aware of the potential risk, the signs and symptoms of such 
reactions, and the importance of immediately seeking medical attention. 
Following the 3rd scheduled administration, where allowed by the schedule of activities 
(see Section 1.3 for definition of which scheduled belimumab injections must be done in 
clinic), at the discretion of the investigator, participants and caregivers who are 
adequately trained should administer subsequent doses of belimumab at home following 
the instructions provided. 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 subcutaneous injections delivered by qualified study site personnel, 
although self-administration should be strongly encouraged. 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 
6.4.1.1. 
Parts A and B 
In Parts A and B, participants and caregivers will be provided with an injection diary 
(refer to SRM). Dosing compliance must be reviewed with the participant/caregiver at 
each site visit, the injection diary must be reviewed by study site staff and the entries 
transcribed to the 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.  

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When participants are dosed at the investigative site with belimumab, 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. 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. 
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 during Part A, then the Investigator must contact the Medical Monitor to 
discuss whether the participant should continue in the study   (see SRM for details). 
If a participant misses 3 or more consecutive doses of belimumab or 4 or more non-
consecutive doses of belimumab during Part B, then the Investigator must contact the 
Medical Monitor to discuss whether the participant should continue in the study. If the 
participant is allowed to continue they must receive their next dose of belimumab in the 

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clinic and remain in the clinic for at least 3 hours for observation, as described in Section 
6.4 for the initial 2 doses of belimumab. 
6.4.2.1. 
Partial Doses 
If a participant has administered a partial dose or was unable to completely self-
administer a dose of belimumab due to malfunction of the autoinjector or user error, the 
participant/caregiver should be instructed to SKIP additional attempts and not re-inject 
for that period’s belimumab dose. Thereafter, the participant should resume self-
administering belimumab injections according to their next scheduled day of 
administration. The participant should not self-administer 2 doses on the same day, even 
if they believe that they did not receive any medication from the first administration 
attempt. (See Section 8.9.7– Medical Device Malfunctions). 
6.5. 
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. 
6.5.1. 
Permitted Concomitant Therapy 
Participants must be on a stable SLE treatment regimen for at least 30 days prior to 
Day 1. Corticosteroids may be added as new medications or their doses adjusted only up 
to 30 days prior to Day 1. 
Once the participant has treatment assigned by the IWRS and receives the first dose of 
belimumab on Day 1, the investigator may adjust concurrent medications (add, eliminate, 
change dose level/frequency) as clinically required; however, changes in certain 
medications (as outlined below) may result in the participant being withdrawn from the 
study. 
6.5.1.1. 
Anti-malarials 
• 
A new anti-malarial (e.g., hydroxychloroquine, chloroquine, quinacrine) may be 
started between Day 1 and the 16-week follow-up assessment. 
• 
The dose of an anti-malarial may be reduced or increased as clinically required, 
between Day 1 and the 16-week follow-up assessment. 
• 
An anti-malarial may be replaced by another anti-malarial due to documented 
toxicity or lack of availability at any time during the study. 

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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. 
6.5.1.2. 
Steroids 
6.5.1.2.1. Systemic Steroids for SLE-related Disease Activity 
• 
The total dose of systemic steroids may be increased or decreased as clinically 
indicated from Day 1 through the 16-week post-treatment follow-up assessment (see 
Section 1.3). Treatment of SLE Flares with Steroids: If a participant has an SLE flare 
requiring an increase in steroid dose the investigator should consider the guidelines 
prepared for the ACR, for steroid dose/duration of induction therapy [Ad Hoc 
Working Group on Steroid-Sparing Criteria in Lupus, 2004]. 
6.5.1.2.2. Intra-articular Injections of Corticosteroids 
• 
Participants may receive intraarticular (IA) corticosteroid injections at any time 
between Day 1 and the 16-week follow-up assessment. 
6.5.1.2.3. Steroids for Reasons Other Than SLE Disease Activity 
Inhaled and topical steroids are allowed throughout the course of the study. 
Steroids may be given for reasons other than SLE disease activity (such as asthma, 
contact dermatitis) as clinically indicated.  
6.5.1.3. 
Other Immunosuppressive/Immunomodulatory Agents 
• 
Starting any new allowable immunosuppressive/immunomodulatory agent is 
permitted from Day 1 through the 16-week post-treatment follow-up assessment (See 
guidance in the SRM). 
• 
The dose of existing immunosuppressive/immunomodulatory agents may be 
increased or decreased, as clinically required, from Day 1 through the 16-week post-
treatment follow-up assessment. 
An immunosuppressive/immunomodulatory agent may be replaced with 1 of the agents 
above due to documented toxicity or lack of availability. New topical immunosuppressive 
agents (e.g., eye drops, topical creams) are allowed from Day 1 through the 16-week 
follow-up visit.  
6.5.1.4. 
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) 
• 
NSAIDs may be given within 30 days prior to Day 1 only if given for <1 week. 
From Day 1 through the 16-week follow-up visit NSAIDs may be given as clinically 
indicated (even if >1 week). An NSAID may be replaced with another NSAID due to 
documented toxicity or lack of availability 
• 
Anti-thrombotic doses of aspirin are permitted at any time during the study. 

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Paracetamol (acetaminophen) is primarily an analgesic and lacks the anti-inflammatory 
properties of other NSAIDs. The use of paracetamol is recommended when possible to 
treat non-SLE related conditions, in the absence of a pre-existing hepatic function 
deficiency. 
6.5.2. 
Prohibited 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. 
• 
 Anti-TNF or anti-IL-6 therapy (e.g., adalimumab, etanercept, infliximab, 
certolizumab, tocilizumab, golimumab). 
• 
All biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist). 
• 
Intravenous immunoglobulin (IVIG). 
• 
IV cyclophosphamide (oral cyclophosphamide is permitted). 
• 
Plasmapheresis, leukapheresis. 
• 
Any live or live attenuated vaccines. (Participants who require a live or live 
attenuated vaccine during the study should have belimumab discontinued prior 
to receiving the vaccine). 
Note: 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. 
6.6. 
Dose Modification 
No dose modifications of belimumab are allowed. An exception is for a participant whose 
body weight changes within pre-defined criteria. 
The participant must be weighed prior to dosing at each clinic visit and dosing frequency 
for the next period adjusted according to the criteria below. Site personnel should ensure 
they provide the participant with sufficient autoinjectors for possible home use prior to 
the next clinic visit. (See additional details in the SRM). 

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Part A 
Part B and Optional Access Extension Phase 
Dosing cohort 
Dosing 
frequency 
Body weight 
(BW) 
Dosing 
frequency 
Note 
Cohort 1 (BW 
50 kg at baseline) 
Every week 
Remains 50 kg 
Every week 
 
Decreases to 
<50 kg 
Every 10 days 
Revert to every 
week if BW 
increases to 
53 kg 
Cohort 2 (BW 
30 kg and <50 kg 
at baseline) 
Every 10 days 
Remains 30 kg 
and <50 kg 
Every 10 days 
 
Increases to 
53 kg  
Every week 
Revert to every 
10 days if BW 
decreases to 
<50 kg 
Decreases to 
<30 kg 
Every 2 weeks 
Revert to every 
10 days if BW 
increases to 
33 kg 
Cohort 3a (BW 
<30 kg at baseline) 
Every 2 weeks 
Remains <30 kg 
Every 2 weeks 
 
Increases to 
33 kg 
Every 10 days 
Revert to every 2 
weeks if BW 
decrease to 
<30 kg 
a. 
If BW drops below 15 kg at any time, suspend dosing and discuss with Medical Monitor to determine if 
participant should be withdrawn from the study. 
 
6.7. 
Intervention after completion of Part A and Part B 
Following the end of treatment at Week 52 or early withdrawal from the study, the 
participant will return to standard of care for SLE as determined by the investigator. 
Eligible participants who complete Part B (Section 6.7.1.1 and Section 6.7.1.2) may be 
enrolled into the optional access extension phase of the study from Week 52. 
 
6.7.1. 
Optional Access Extension Phase 
Access extension is an optional extension phase for 200908 to provide a mechanism for 
continued access to belimumab SC from Week 52 exclusively for eligible participants 

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(Section 6.7.1.1 and Section 6.7.1.2). The duration of this optional access extension phase 
depends on the age of participants when they are enrolled into the access extension phase 
and whether the circumstances leading to their eligibility change at any time (Section 
6.7.1.3). 
6.7.1.1. 
 Optional Access Extension Phase Process 
If per investigator’s judgement a participant meets the eligibility criteria to enroll into the 
Optional Access Extension Phase, the Medical Monitor should be notified prior to 
enrolling any participant. The Investigator would be required to submit information 
related to their eligibility (see SRM for details), as determined by the specific inclusion 
and exclusion criteria (Section 6.7.1.2and Section 6.7.1.3). Eligibility information will be 
reviewed by the Medical Monitor and enrollment into the Optional Access Extension 
Phase can only proceed following Medical Monitor approval.  
6.7.1.2. 
Optional Access Extension Phase Inclusion Criteria 
1. Male or female participants who complete Week 52 visit of the 200908 study. 
2. Age <18 years at completion of Week 52. 
3. Documented evidence of clinical benefit in 200908 study per investigator’s 
judgement. 
4. Able to comply with clinic visits and required assessments. 
5. Intravenous (IV) Benlysta not currently licensed for the pediatric use in the 
participant’s country; OR documented evidence of the rationale for IV Benlysta not 
being suitable for this participant requiring continued treatment with belimumab SC 
(including but not limited to: medical reasons, significant logistical challenges, or 
other legitimate reasons [discuss with medical monitor]). 
6. Participant eligibility agreed with the Medical Monitor prior to enrolling the 
participant into the optional access extension phase. 
7. Participant signs and dates a written age appropriate assent form specific for the 
access extension phase (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 specific to the access 
extension. 
6.7.1.3. 
Optional Access Extension Phase Exclusion Criteria 
1. Female participant has positive urine pregnancy test at Week 52 visit. 
2. Female participant wishes to become pregnant at or within 4 months of Week 52 
visit. 
3. Participant has experienced any change in his/her medical history that, per the 
investigator’s judgement, continued administration of belimumab therapy would be 
contraindicated. 
4. Participant received a live vaccine within 30 days prior to Week 52 

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6.7.1.4. 
Optional Access Extension Phase Withdrawal Criteria 
A participant may be withdrawn from the optional access extension phase by the 
investigator and/or Sponsor for reasons including but not limited to: 
1. Participant reaches the age of 18 years. 
2. Depending on the condition the participant was eligible for the optional access 
extension phase: 
a. Belimumab SC (or IV) becomes licensed and commercially available for 
pediatric use in the participant’s country. 
b. The reason for which IV Benlysta was not suitable for this participant is 
no longer valid. 
3. Participant becomes pregnant. 
4. Participant receives prohibited therapy (See Section 6.5.2). 
5. Participant experiences unacceptable toxicity per investigator’s judgement. 
6. Participant participates in another interventional clinical trial. 
7. Three Consecutive belimumab injections (see Section 6.4.2) or consecutive clinic 
visits (see Section 8.5) are missed. 
8. Participant is no longer experiencing clinical benefit from belimumab per the 
documented medical judgement of the investigator. 
9. Participant develops new or worsening of existing medical condition for which, in 
the opinion of the investigator or medical monitor, the risk of continued 
administration of belimumab outweighs clinical benefit to the participant; including 
liver chemistry stopping criteria (see Section 7.1.2) and/or IgG stopping criteria (see 
Section 7.1.1). 
10. Sponsor becomes aware of new safety data that would preclude continued 
administration of SC belimumab. 
11. It is the wish of the participant (or their legally acceptable representative) to 
withdraw for any reason. 
Withdrawal from the optional access extension phase results in discontinued access to 
belimumab SC. 
6.7.1.5. 
Optional Access Extension Phase Study Assessments and Procedures 
• 
Study procedures and their timing during the optional access extension phase are 
summarized in the SoA (see Section 1.3.4).  
• 
Visit frequency in the access extension is every 12 weeks ( 7 days) after Week 52 
and for the entire duration of the optional access extension phase. 
• 
Body weight should be checked at the beginning of each clinic visit and should be 
noted in the Investigators source documents. As the dosing frequency may change 
due to changes in participant’s body weight, Section 6.6 should be followed for any 

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dose modifications. Any changes in body weight that lead to a change in dosing 
frequency should be noted and requested in the IWRS system (see SRM for details).  
• 
No efficacy assessments are required during the optional access extension phase. The 
investigator will use their judgement to determine and continue to evaluate the 
clinical benefit from belimumab SC and pariticipants who are no longer experiencing 
clinical benefit will be withdrawn. 
• 
Although routine safety laboratory monitoring is not required during the optional 
access extension phase, local laboratory assessments can be performed as part of the 
participant’s routine evaluation or can be triggered by the investigator should a 
safety signal warrant further investigation per the investigator’s judgement. Any 
abnormal results will be noted in the Investigator’s source documents. The GSK 
Medical Monitor should be informed of any result that meets the safety stopping 
criteria (e.g. Liver Stopping Criteria in Section 7.1.2 and Grade 4 IgG level Section 
7.1.1).  
• 
Serious adverse event (SAE) definition and reporting during the optional access 
extension phase will follow the guidance in Section 8.9. During the optional access 
extension phase, SAEs will be reported to GSK via paper CRF only (see Section 
10.3.4).  
• 
For females of childbearing potential: urine pregnancy tests will be provided by sites 
at the scheduled visits in SOA (Section 1.3). Participants will be required to perform 
a urine pregnancy test every 4 weeks throughout the treatment period (1 onsite and 2 
at home). Home urine pregnancy tests will also be provided for the 8-week and 16-
week follow-up period. The results of urine pregnancy tests conducted at home will 
be recorded in the subject diary cards and stored as part of the investigator’s source 
documents. Only positive pregnancy test results will be reported to GSK during the 
optional access extension phase and will follow the guidance in Section 8.9.5. 
• 
Participants and caregivers will be provided with a subject diary card (refer to SRM 
for details). Participants must complete the subject diary card and bring it with them 
to each site visit. Compliance for all dosing, pregnancy testing and autoinjector 
malfunctions will be assessed and reviewed by the Investigator or site staff, with the 
participant/caregiver at each site visit. For any dosing or pregnancy testing 
conducted at the investigative site, participants or caregivers will complete the 
subject diary card. Results will not be reported and the completed subject diary card 
will be stored in the Investigator’s source documents.  
• 
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. Participants 
and caregivers are required to return all used and unused autoinjector devices to the 
site, for their local disposal and destruction. All used autoinjectors should be placed 
in a sharps container and returned to site (see SRM for details). Any returned 
malfunctioning autoinjectors will be marked to distinguish them from the used 
autoinjectors (see SRM for details). 
• 
Medical device incidents and malfunction reporting during the optional access 
extension phase will follow the guidance in Section 8.9.6 and Section 8.9.7. 

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• 
If participants withdraw from treatment at any time during the optional access 
extension phase, an early withdrawal (EW) visit should be completed. Additionally, 
8 and 16-week follow-up visits are required via phone call to collect SAEs, and the 
results of home urine pregnancy test (if applicable) for female participants. 
 
6.7.1.6. 
Optional Access Extension Phase Statistical Analyses and Reporting 
• 
There are no formal statistical analyses being performed in the optional access 
extension phase. 
• 
Summary of SAEs, pregnancies and medical device incidents reported in the safety 
database during the optional access extension phase will be provided in a synoptic 
clinical study report after conclusion of the optional access extension phase. 
 
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 8.5 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 (see Section 6.4.2) or consecutive clinic 
visits (see Section 8.5) are missed. 
Furthermore, participants will be withdrawn from study agent and subsequently 
withdrawn from the study if at any time they: 
• 
Become pregnant. 
• 
Receive prohibited therapy (See Section 6.5.2) 
• 
Experience unacceptable toxicity 
• 
Participate in another interventional clinical trial 
• 
Trigger liver chemistry stopping criteria (see Section 7.1.2) and/or IgG stopping 
criteria (see Section 7.1.1). 

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7.1.1. 
IgG Stopping Criteria 
Any participant who has a Grade 4 IgG level, by the protocol defined Adverse Event and 
Laboratory Value Severity Grade Scale (see Appendix 2, Section 10.2.1), will have 
dosing with study agent withheld, and the appropriateness to continue study treatment 
must be discussed with the Medical Monitor before the next dose. Any participant who 
has a Grade 4 IgG level associated with a severe or serious infection will have study 
agent discontinued and should complete the follow-up assessments as described in the 
SoA (Section 1.3). 
7.1.2. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.  
Discontinuation of study treatment is required when: 
• 
a participant meets one of the conditions outlined in Algorithm A or Algorithm B  
OR 
• 
when in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the investigator believes study treatment discontinuation is in the best 
interest of the participant. 
 
Algorithm A: Phase III-IV Liver Chemistry Stopping and Increased Monitoring 
Algorithm 
 
Abbreviations: ALT = alanine transaminase; bili = bilirubin; INR = international normalized ratio; SAE = serious adverse 
event; ULN = upper limit of normal. 

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See Appendix 5 for liver safety required actions and follow-up assessments. 
Algorithm B: Phase III-IV Liver Chemistry Increased Monitoring Algorithm with 
Continued Therapy for ALT 3xULN but <8xULN 
 
Abbreviations: ALT = alanine transaminase; bili = bilirubin; INR = international normalized ratio; SAE = serious adverse 
event; ULN = upper limit of normal. 
 
See Appendix 5 for liver safety required actions and follow-up assessments. 
7.1.2.1. 
Study Intervention Restart or Rechallenge After Liver Stopping Criteria 
Met 
After liver stopping criteria are met, restart or rechallenge is not permitted.  
7.1.3. 
Temporary Discontinuation 
In the event of a participant experiencing an AE or SAE, the investigator may at their 
discretion choose to instruct the participant/caregiver to skip one or more scheduled 
administrations of belimumab. Please also refer to Section 6.4.2. 
In the event a participant tests positive for COVID-19, or if no testing is available and a 
participant exhibits symptoms consistent with COVD-19, withhold dosing of belimumab 
until symptoms resolve and contact the Medical Monitor to discuss reinitiating 
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7.2. 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons. This is expected to be 
uncommon. 
• 
At the time of discontinuing from the study, if participants are unwilling to 
return for the 8- and 16-week follow-up assessment then, if possible, an early 
withdrawal visit (as shown in the SoA - see Section 1.3 and Section 8.5) should 
be conducted at the time of withdrawal and every effort made to collect the 
results of a home pregnancy test (if applicable) and AEs 16 weeks after the last 
dose of belimumab. 
• 
The participant will be permanently discontinued both from the study 
intervention and from the study at that time. 
• 
If the participant‘s parent/caregiver withdraws consent for disclosure of future 
information, the sponsor may retain and continue to use any data collected 
before such a withdrawal of consent. 
• 
If a participant withdraws from the study, her/his parent/caregiver may request 
destruction of any samples taken and not tested, and the investigator must 
comply and document this in the site study records. 
7.3. 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA (see Section 1.3).  
• 
Protocol waivers or exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.  
• 
The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
local guidelines. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples (see also Section 5.5). 
8.1. 
Screening Assessments 
Information collected during the screening phase assessments represent key data that 
identify and define participant baseline status. This information is critical for evaluation 
of subsequent safety assessments. 
Informed Consent 
Informed consent will be obtained from the participant’s parent/legally appointed 
representative 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. Participants who turn 18 years old during the course of the study will provide their 
own informed consent. 
Participants who give written consent will enter a screening period of up to 35 days. A 
participant may have treatment assigned when all screening procedures have been 
completed and eligibility criteria confirmed.  
Screening Assessments 
During the screening period the following assessments will be performed: 
Demographic parameters will be captured: Date and year of birth, sex, race, and 
ethnicity. 
Medical history/medication will be assessed as related to the exclusion criteria listed in 
Section 5.2. A complete medical history will be taken at the Screening Visit. Information 

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from the medical history is important to establish the baseline condition of the 
participant, and will impact the safety monitoring assessments during the study. Any 
significant medical conditions affecting the participant in the past 5 years should be 
recorded on the Medical conditions page of the eCRF. The history should include the 
following: 
• 
Past or current conditions 
• 
Prior surgical procedures 
• 
Pharmacotherapy and chronic or current use of any medication or herbal 
preparation 
• 
Prior use of belimumab 
• 
Allergies and significant allergic reactions 
• 
Significant infections, or history of recurrent infection, including urinary and 
respiratory tract infections 
• 
Smoking history (current or previous smoker, number of cigarettes smoked per 
day) 
• 
Cardiovascular medical history/risk factors (as detailed in the eCRF). 
Pregnancy Test 
A serum pregnancy test will be performed for females of child-bearing potential at the 
Screening Visit and a urine pregnancy test will be performed during each subsequent 
clinic visit. Refer to the pregnancy section (Section 8.9.5). 
Full Physical Examination, Height, Weight, and Vital Signs 
The full physical examination will include complete assessment of all organ systems 
including assessments of the head and neck (including eyes, ears, nose, throat, and 
thyroid gland), skin, musculoskeletal (including evaluation of both small and large 
joints), neurological, respiratory, and cardiovascular systems, gastrointestinal system, and 
abdomen (including liver and spleen), lymph nodes and extremities. 
Height and weight, and vital signs (systolic and diastolic blood pressure [sitting], heart 
rate, and body temperature) will be measured and recorded. 
Electrocardiogram 
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. 

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Laboratory Tests 
The following laboratory tests will be performed by the central laboratory at screening, as 
related to the eligibility criteria described in Section 5. 
• 
Autoantibodies (anti-dsDNA, ANA), complement (C3, C4) and CRP 
• 
HIV, hepatitis B and Hepatitis C screen 
• 
Immunoglobulins (IgG, IgA, IgM) 
• 
Urinalysis (including drug and alcohol screen) 
• 
Hematology, PT/PTT and blood chemistry 
• 
Urine protein:creatinine ratio 
• 
Pregnancy test (serum) 
• 
NOTE: To maintain the volume of blood collection with local guidelines, the 
screening assessments for particpants <30 kg will be split across 2 visits 
separated by a minimum of 2 weeks. There must also be a minimum of 2 weeks 
between the second screening and the Day 1 blood draws (see SRM for details). 
This may also apply to particpants 30 kg according to local guidelines. 
Disease Activity Index 
The SELENA SLEDAI (Appendix 9) will be performed at screening to assess the level of 
SLE severity. 
Suicidality Assessment 
Possible suicidal behavior or ideation will be assessed at screening (see also Section 5.2). 
8.2. 
Baseline Assessments 
Procedures at the Baseline Visit are listed in the SOA (Section 1.3). They include clinical 
assessments, laboratory tests, biomarkers and immunogenicity. 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 8.7 to Section 8.14 
(and in the SRM). 
8.3. 
Scheduled Visit Assessments 
Procedures at the Scheduled Visits are listed in the SoA (Section 1.3). They include 
clinical assessments, laboratory tests, pharmacokinetics, biomarkers, and blood samples 
for immunogenicity. 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 8.7 to Section 8.14 (and in the SRM). 

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8.4. 
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. 
8.5. 
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- 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. 
8.6. 
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). 
8.7. 
Pharmacokinetic Assessments 
• Blood samples will be collected for measurement of serum concentrations of 
belimumab as specified in the SoA (Section 1.3). 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. 
8.8. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.8.1. 
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 

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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. 
8.8.2. 
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. 
8.8.3. 
Electrocardiograms 
• 
ECG is obtained at screening only, see Section 8.1. 
8.8.4. 
Clinical Safety Laboratory Assessments 
• 
A central laboratory will be used in this study. 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and 
to the SoA (Section 1.3) for the timing and frequency. 
• 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 60 days after the last dose of study 
intervention should be repeated until the values return to normal or baseline or 
are no longer considered significantly abnormal by the investigator or medical 
monitor.  
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA. 
• 
Laboratory toxicity will be graded using the Adverse Event and Laboratory 
Value Severity Grading Table (Appendix 2, Section 10.2.1). The Table is based 
upon publicly available Tables from the National Institute of Allergy and 
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(www.niaid.nih.gov) and Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0 (U.S. Department of Health and Human Services, 2010). 
• 
Note: If a laboratory value is reported that requires withholding of further 
dosing, the site personnel must contact the parent/caregiver promptly to ensure 
no further injections are administered until reviewed with the investigator if the 
next administration would be away from the clinic. 
8.8.5. 
Suicidal Ideation and Behavior Risk Monitoring 
Some autoimmune diseases have an increased risk of suicidal behavior and/or ideation 
[Bachen, 2009; Timonen, 2003; Stenager, 1992]. Investigators are reminded of the 
importance to clinically assess for suicidality at every visit given that SLE patients are (or 
autoimmune disease patients may be) at increased risk of suicidal behavior and/or 
ideation. There have been reports of suicidal ideation or behavior symptoms, as reported 
in the product label in some patients being treated with belimumab for SLE. A high risk 
of suicidality is exclusionary in this study. 
Participants being treated with belimumab should be monitored appropriately and 
observed closely for suicidal ideation and behavior or any other unusual changes in 
behavior. Consideration should be given to withholding belimumab dosing and 
investigating further in participants who experience signs of suicidal ideation or behavior. 
Families and caregivers of participants being treated with belimumab should be alerted 
about the need to monitor participants for the emergence of unusual changes in behavior, 
as well as the emergence of suicidal ideation and behavior and to report such symptoms 
immediately to the study investigator. 
If evidence of suicidal behavior or ideation by a participant is detected at any visit, it is 
recommended that the Investigator consider mental health consultation or referral. The 
Medical Monitor should be notified when these events occur. In addition, the possible 
suicidality related event (PSRAE) form must be completed in the eCRF in Part A and B 
of the study. 
8.9. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
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 or study 200908 (see 
Section 7). 
8.9.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of treatment until the follow-up visit at 
the time points specified in the SoA (Section 1.3). However, any SAEs assessed 
as related to study participation (e.g., study intervention, protocol-mandated 

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procedures, invasive tests, or change in existing therapy) or related to a GSK 
product will be recorded from the time a participant consents to participate in 
the study. 
• 
All AEs will be collected from the start of treatment until the follow-up visit in 
Part B of the study 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 on the Medical History/Current 
Medical Conditions section of the CRF, and not within the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
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 AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
8.9.2. 
Method of Detecting AEs and SAEs 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3. 
• 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence. 
8.9.3. 
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 non-serious and 
serious AEs of special interest (AESI) (i.e., post-injection systemic reactions and 
hypersensitivity reactions, infections, malignancies, and 
depression/suicidality/self-injury) will be followed until the event is resolved, 
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 
Appendix 3. 
8.9.4. 
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 

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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. 
8.9.5. 
Pregnancy 
• 
If a pregnancy in a female participant is reported, the investigator should inform 
GSK within 24 hours of learning of the pregnancy and should follow the procedures 
outlined in Appendix 4. 
• 
A pregnancy is not considered to be an SAE, although abnormal pregnancy 
outcomes or complications (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered to be SAEs. 
• 
There is no requirement to collect pregnancy information from female partners of 
male participants. 
8.9.6. 
Medical Device Incidents (Including Malfunctions) 
Medical devices (i.e. belimumab autoinjectors) are being provided for use in this study 
for the purposes of administering belimumab from a pre-filled syringe contained within 
an autoinjector device. In order to fulfill regulatory reporting obligations worldwide, the 
investigator is responsible for the detection and documentation of events meeting the 
definitions of incident or malfunction that occur during the study with such devices.  
The definition of a Medical Device Incident can be found in Appendix 6. 
NOTE: Incidents fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 8.9.3 and Appendix 3 of the protocol.  
8.9.6.1. 
Time Period for Detecting Medical Device Incidents 
• 
Medical device incidents or malfunctions of the device 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 incident at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to 
a medical device provided for the study, the investigator will promptly notify the 
sponsor. 

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• 
The method of documenting Medical Device Incidents is provided in Appendix 
6. 
8.9.6.2. 
Follow-up of Medical Device Incidents 
• 
All medical device incidents involving an AE or SAE will be followed and 
reported in the same manner as other AEs (see Section 8.9.3). This applies to all 
participants, including those who discontinue study intervention or the study. 
• 
The investigator is responsible for ensuring that follow-up includes any 
supplemental investigations as indicated to elucidate the nature and/or causality 
of the incident. 
• 
New or updated information will be recorded on the originally completed form 
with all changes signed and dated by the investigator. 
8.9.6.3. 
Prompt Reporting of Medical Device Incidents to Sponsor 
• 
Medical device incidents will be reported to the sponsor within 24 hours after 
the investigator determines that the event meets the protocol definition of a 
medical device incident. 
• 
The Medical Device Incident Report Form and Device Malfunction/Failure 
Reporting Form will be sent to the sponsor by email (see SRM for details). If 
email is unavailable, then a paper form should be utilized. 
• 
The Device Malfunction/Failure Reporting Form will be sent to the sponsor 
along with the Medical Device Incident Form (see SRM). 
8.9.6.4. 
Regulatory Reporting Requirements for Medical Device Incidents 
• 
The investigator will promptly report all incidents occurring with any medical 
device provided for use in the study in order for the sponsor to 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. 
• 
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 incidents to the IRB/IEC. 
8.9.7. 
Medical Device Malfunctions 
Medical devices (Belimumab Autoinjector) that are provided for use in this study for the 
purposes of self-administration of study treatment may malfunction during use (e.g., parts 
missing, device leaking, needle bent). The information provided in this section applies to 
occurrence and reporting of device malfunctions that are NOT associated with an 
AE/SAE. 
If when using an autoinjector, the participant experiences a device malfunction, the 
participant or their caregiver should stop using the device and SKIP additional attempts 
and not re-inject for that week’s belimumab dose. (See Section 6.4.2.1 for additional 

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instruction regarding administration of study treatment following a device malfunction). 
Note: if a malfunction has been noticed before any attempt to use it e.g., cap missing, 
then the autoinjector can be set aside for return to GSK and a new autoinjector can be 
used. 
The participant or caregiver should record the malfunction in their injection diary and 
contact the site the same day or as soon as possible to report the device malfunction. The 
study site should record the malfunction on the Device Malfunction/Failure Reporting 
Form and forward the information to GSK as described on the form as soon as possible 
(see SRM). The participant should return the malfunctioned device to the study site at the 
next scheduled visit for shipment back to GSK for evaluation. 
8.10. 
Efficacy Assessments 
The SELENA SLEDAI (Appendix 9) will be perfomed at the visits indicated in the SOA 
(Section 1.3). 
8.11. 
Treatment of Overdose 
There is limited experience with overdosage of belimumab. Adverse reactions reported in 
association with cases of overdosage have been consistent with those expected for 
belimumab. 
Two doses up to 20 mg/kg administered 21 days apart by IV infusion have been given to 
humans with no increase in incidence or severity of adverse reactions compared with 
doses of 1, 4 or 10 mg/kg. 
GSK does not recommend specific treatment for an overdose of belimumab. 
In the event of a belimumab overdose, the investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for AEs/SAEs. 
3. Document the quantity of the excess dose as well as the duration of the overdosing. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
8.12. 
Pharmacodynamics and Biomarkers 
Pharmacodynamic parameters and biomarkers will be evaluated in this study according to 
the SOA (Section 1.3). Laboratory evaluations will include the following: 
• 
Autoantibodies: anti-dsDNA, ANA 
• 
Serum immunoglobulin isotypes: IgG, IgM, IgA. 
• 
Serum complement (C3, C4). 

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• 
Peripheral lymphocytes including B lymphocytes (CD20+, CD20+/27+ 
memory, CD20+/27– naïve, CD19+/27br/38br ‘SLE subset’). 
• 
BLyS protein (analyzed at a laboratory contracted by GSK other than the central 
laboratory). 
Samples will be collected pre-dose when taken at dosing visits. All biomarker samples 
will be analyzed by the central laboratory unless otherwise stated. 
8.13. 
Genetics 
Genetics are not analyzed in this study.  
8.14. 
Immunogenicity 
The presence of antibodies to belimumab will be evaluated in serum samples collected 
from all participants according to the SoA (Section 1.3). These samples will be analyzed 
at a laboratory contracted by GSK other than the central laboratory). 
8.15. 
Health Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The study is designed to descriptively evaluate the PK, safety, and PD of belimumab 
during Parts A and B, and as such no formal statistical hypothesis testing is planned. 
9.2. 
Sample Size Determination 
Assuming a 20% screen-failure rate, it is expected that 36 participants will need to be 
screened in order that approximately 28 participants will be enrolled (treated with at least 
one dose of study treatment) aiming for 24 evaluable participants at Week 12. Enrollment 
and study withdrawals will be closely monitored and if there is an impact on continuation 
of participants in the study due to the Coronavirus SARS-CoV-2 (COVID-19) pandemic, 
more than 36 participants may be screened and more than 28 may need to be enrolled, to 
ensure the ability to achieve the evaluable target at Week 12. 
The sample size of 24 participants and the specified sampling schedule allow estimation 
of central clearance and volume of distribution with a 95% confidence interval within 
60% and 140% [Wang, 2012] with a power of 99.9% and 99.7%, respectively (mean 95% 
confidence intervals were 83.8-116.2% and 80.5-119.5%, respectively). The 95% CI 
were derived by simulating pediatric PK data and estimating clearance and volume of 
distribution with a population PK model for 2000 trial replicates (power estimates based 
on 1843 model estimates with successful covariance step). The following assumptions 
were used: (i) the simulations were based on participant data and the population PK 
parameters from pediatric IV study BEL114055 (see Section 2.2.1) augmented by the 

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subcutaneous absorption parameters obtained from adult SC population PK model 
[Struemper, 2018]; (ii) PK data for 24 participants were simulated for Part A of the study 
only (including the 8-week follow-up visit); (iii) the population PK model used for 
parameter estimation was a linear one-compartment model with first-order absorption. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Screened 
All participants whose parent/caregiver sign the ICF 
Enrolled 
All participants assigned treatment by the IWRS.  
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 for whom at least one post belimumab 
treatment PK sample was obtained and analyzed. 
9.3. 
Statistical Analyses 
9.3.1. 
Pharmacokinetic Analyses 
All pharmacokinetic (PK) analyses will be performed on the PK Population. 
Endpoint 
Statistical Analysis Methods 
Primary 
Endpoints:  
Observed belimumab concentrations at Week 12. 
Steady-state PK parameters: Cavg (AUC), Cmax, Cmin (based on population 
PK estimates). 
Analysis:  
Descriptive statistics will be used to summarize the observed belimumab 
concentrations at Week 12. 
Descriptive statistics will be used to summarize the steady-state PK 
parameters: Cavg (AUC), Cmax, Cmin (based on population PK estimates). 
Further details on the population PK analysis will be discussed in the reporting and 
analysis plan. 

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9.3.2. 
Safety Analyses 
All safety analyses will be performed on the ITT Population.  
Endpoint 
Statistical Analysis Methods 
Secondary 
Endpoints:  
Incidence of adverse events, serious adverse events, and adverse events of 
special interest (AESI) through Week 52. 
Analysis:  
Descriptive statistics will be used to summarize AEs, SAEs, and AESIs. The 
frequency of AEs will be tabulated by MedDRA system organ class (SOC) and 
preferred term. 
9.3.3. 
Pharmacodynamic Analyses 
All pharmacodynamic analyses will be performed on the ITT Population.  
Endpoint 
Statistical Analysis Methods 
Secondary 
Endpoints:  
Change from baseline in biomarkers (C3/C4, anti-dsDNA, B cell subsets, and 
immunoglobulins) at Weeks 12 and 52. 
Analysis:  
Descriptive statistics will be used to summarize change from baseline in 
biomarkers (C3/C4, anti-dsDNA, B cell subsets, and immunoglobulins) at 
Weeks 12 and 52. 
9.3.4. 
Other Analyses 
Other analyses will be performed on the ITT Population.  
Endpoint 
Statistical Analysis Methods 
Other 
Endpoint:  
Percent of subjects with a ≥ 4 point reduction from baseline in SELENA 
SLEDAI at Weeks 12 and 52. 
Analysis:  
Descriptive statistics will be used to summarize the number and percentage of 
subjects with a  ≥ 4 point reduction from baseline in SELENA SLEDAI at 
Weeks 12 and 52. 
 

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Other biomarker analyses, efficacy analyses, and safety analyses will be described in the 
reporting and analysis plan.  
9.4. 
Interim Analyses 
No formal interim analyses are planned. In-stream review of the safety and PK data will 
be performed by the study Medical Monitor, members of the GSK Safety Review Team 
(SRT), and the GSK Pharmacokinetics Review Team (PRT). 
9.4.1. 
GSK Safety Review Team (SRT) 
The study Medical Monitor and members of the GSK SRT will perform in-stream review 
of all safety data throughout Part A and Part B of the study and make and communicate 
recommendations as appropriate. SAEs reported during the optional access extension 
phase will not be part of this in-stream review. 
9.4.2. 
GSK Pharmacokinetics Review Team (PRT) 
The GSK PRT will include the study Medical Monitor, Clinical Science Lead, 
Statistician, Safety Scientist/Physician, and Pharmacokineticist. Additional GSK 
scientists/physicians may also be invited to assist the PRT with data reviews. The PRT 
will review all available PK data after the first 6 participants in Cohort 1 (≥50 kg) or  
Cohort 2 (30 kg to <50 kg) have completed Week 12. For Cohort 3 (<30 kg), 
preliminary PK data will be reviewed by the PRT based on a data cut triggered by the 
first Cohort 3 participant having completed Week 12. The primary objective of the PRT 
meetings will be to either confirm the initial dose or to recommend an adjustment in 
dosing frequency if a substantial difference in exposure is observed compared to 
exposure in adult SLE participants receiving 200 mg SC belimumab every week. 
Recommendations will be made regarding dose confirmation or adjustment. The 
recommendations of the PRT will be summarized and distributed to study team members 
and Investigators. 

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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 ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 

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10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant and his/her legally authorized representative and answer all 
questions regarding the study. 
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent 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.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant entered the study and the date the written consent 
was obtained. The authorized person obtaining the informed consent must also 
sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• 
Participants must provide their own consent if they reach 18 years old during the 
course of the study. 
• 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative.  
• 
Participants who are rescreened are required to sign a new ICF. 
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.  
• 
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. 
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 

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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. 
10.1.6. 
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 the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• 
GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care. This helps ensure the 
data provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding. 
10.1.7. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  

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• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
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.  
• 
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.  
10.1.8. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
• 
Definition of what constitutes source data can be found in the Monitoring Plan. 
10.1.9. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 2 will be performed by the central laboratory.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• 
Pregnancy testing  
• 
Refer to Section 5.1 Inclusion Criteria for screening pregnancy criteria. 
• 
Pregnancy testing (urine or serum as required by local regulations) should 
be conducted at monthly intervals during intervention  
• 
Pregnancy testing (urine or serum as required by local regulations) should 
be conducted at the end of relevant systemic exposure.  
• 
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 2 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
Calcium 
Potassium 
Aspartate 
Aminotransferase 
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT) 
Total bilirubin 
 
Calcium 
corrected for 
Albumin 
Inorganic 
Phosphate 
Sodium 
Alanine 
Aminotransferase 
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total Protein 

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Laboratory 
Assessments 
Parameters 
 
Carbon dioxide 
Magnesium 
Alkaline 
phosphatase 
Albumin 
 
Glucose 
(nonfasting) 
 
Gamma glutamyl 
transpeptidase 
(GGT) 
Creatinine 
 
Uric acid 
Blood urea 
nitrogen (BUN) 
BUN/creatinine 
ratio 
Estimated 
Creatinine 
Clearance/GFR 
(Schwartz2) 
Routine 
Urinalysis 
• pH, glucose, protein, blood, ketones, occult blood by dipstick 
• Microscopic examination (if blood or protein is abnormal) 
Biological 
markers 
• BLyS protein 
• Serum complement (C3 and C4) 
• C-Reactive Protein (CRP) 
• 
Peripheral lymphocytes including B lymphocytes (CD20+, CD20+/27+ 
memory, CD20+/27– naïve, CD19+/27br/38br ‘SLE subset’). 
Immunoglobulins • Serum immunoglobulin isotypes: IgG, IgM, IgA 
PK 
• Blood collection 
Immunogenicity 
• Blood collection 
Autoantibodies 
• ANA titer, Anti-dsDNA 
Other Screening 
Tests 
• Screening pregnancy 
• Urine alcohol and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines) 
• Highly sensitive human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2 
• Serology (HIV antibody, hepatitis B surface antigen [HBsAg], 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 7.1.2 and Appendix 5. All events of ALT 3 × upper limit of normal 
(ULN) and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized 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. 
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 
Hemoglobin 
> 9.5 - 11.0 g/dL > 8.0 – 9.5 g/dL 
6.5 - 8.0 g/dL 
< 6.5 g/dL 
Leukocytes 
3000-3999/mm3 2000-2999/mm3 1000-1999/mm3 
< 1000/mm3 
Absolute Neutrophil Count 
1500-1999/mm3 1000-1499/mm3 500-999/mm3 
< 500/mm3 
Platelets 
75,000 - 
99,999/mm3 
50,000 – 
74,999/mm3 
25,000 - 
49,999/mm3 
< 25,000/mm3 
Prothrombin Time (PT) 
> 1.0-1.25 x 
ULN* 
> 1.25-1.5 x ULN > 1.5-3.0 x ULN 
> 3.0 x ULN 
Partial Thromboplastin 
Time (PTT) 
> 1.0-1.66 x 
ULN 
> 1.66-2.33 x 
ULN 
> 2.33-3.0 x ULN > 3.0 x ULN 
Methemoglobin 
5.0-10.0 % 
10.1-15.0 % 
15.1-20.0 % 
> 20% 
 
Lymphocyte count** 
<LLN - 
800/mm3; <LLN 
- 0.8 
x 10e9 /L 
<800 - 500/mm3; 
<0.8 - 0.5 x 
10e9 /L 
<500 - 200/mm3; 
<0.5 - 0.2 x 
10e9 /L 
<200/mm3; <0.2 x 10e9 /L 
 
 
 
 
(continued) 
*ULN = Upper Limit of Normal 
**Lymphopenia calculated from CTCAE table 
 
 

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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 
hospitalization 
and treatment required 
Hypotension 
Transient 
orthostatic 
hypotension, no 
treatment 
Symptoms correctable  
with oral fluid treatment 
IV fluid req, 
no hospitalization 
req 
 
Hospitalization req 
Hypertension 
Transient, 
increase 
> 20 mm/Hg; no 
treatment 
Recurrent; chronic 
increase 
> 20 mm/Hg, treatment 
req 
Acute treatment 
req; out subject 
hospitalization 
possible 
 
Hospitalization req 
Pericarditis 
Minimal effusion Mild/moderate 
asymptomatic effusion, 
no treatment 
Symptomatic 
effusion, 
pain, ECG changes 
 
Tamponade OR 
pericardiocentesis  
OR surgery req 
Hemorrhage, Blood 
Loss 
- 
Mildly symptomatic;  
no treatment required 
Gross blood loss 
OR 
1-2 units transfused 
Massive blood loss OR 
> 2 units transfused 
 
 
 
 
 
(continued) 
 
 

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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 
   Hypokalemia 
3.0-3.4 meq/L 
2.5-2.9 meq/L 
2.0-2.4 meq/L 
< 2.0 meq/L 
   Hyperkalemia 
5.6-6.0 meq/L 
6.1-6.5 meq/L 
6.6-7.0 meq/L 
> 7.0 meq/L 
Phosphate 
   Hypophosphatemia 
2.0-2.4 mg/dL 
1.5-1.9 mg/dL 
1.0-1.4 mg/dL 
< 1.0 mg/dL 
Calcium- (Corrected For Albumin) 
   Hypocalcemia 
7.8-8.4 mg/dL 
7.0-7.7 mg/dL 
6.1-6.9 mg/dL 
< 6.1 mg/dL 
   Hypercalcemia 
10.6-11.5 mg/dL 
11.6-12.5 mg/dL 
12.6-13.5 
mg/dL 
>13.5 mg/dL 
Magnesium 
   Hypomagnesemia 
1.2-1.4 meq/L 
0.9-1.1 meq/L 
0.6-0.8 meq/L 
< 0.6 meq/L 
Albumin 
   Hypoalbuminemia 
3.00-3.49 g/dL 
2.50-2.99 g/dL 
2.00-2.49 g/dL 
< 2.00 g/dL 
Bilirubin (Total) 
   Hyperbilirubinemia (Total) 
> 1.0-1.5 x ULN 
> 1.5-2.5 x ULN 
> 2.5-5 x ULN 
> 5 x ULN 
Glucose 
   Hypoglycemia 
55-64 mg/dL 
40-54 mg/dL 
30-39 mg/dL 
< 30 mg/dL 
   Hyperglycemia  
116-160 mg/dL 
161-250 mg/dL 
251-500 mg/dL > 500 mg/dL 
   (nonfasting & no prior 
diabetes) 
 
 
 
 
   Triglycerides 
151-399 mg/dL 
400-750 mg/dL 
751-1200 
mg/dL 
> 1200 mg/dL 
Creatinine 
> 1.0-1.5 x ULN 
> 1.5-3.0 x ULN 
> 3.0-6.0 x ULN > 6.0 x ULN 
 
 

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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 
Hospitalization required 
Vomiting 
Mild OR 
transient;  
2-3 episodes/day 
OR  
mild vomiting 
lasting  
< 1 week 
Mod OR 
persistent;  
4-5 episodes per 
day;  
OR vomiting 
lasting  
 1 week 
Severe vomiting of 
all foods/fluids in 24 
hours  
OR orthostatic 
hypotension 
 OR IV treatment 
req 
Hypotensive shock OR 
hospitalization  
required for IV treatment req 
Diarrhea 
Mild or transient;  
3-4 loose stools 
per day  
OR mild diarrhea 
lasting  
< 1 week 
Mod OR 
persistent;  
5-7 loose stools 
per day  
or diarrhea lasting  
 1 week 
Bloody diarrhea;  
OR orthostatic 
hypotension  
OR > 7 loose 
stools/day  
OR IV treatment req 
Hypotensive shock  
OR hospitalization req 
Oral 
Discomfort/Dysphagia 
Mild discomfort, 
no difficulty 
swallowing 
Difficulty 
swallowing but 
able to eat and 
drink 
Unable to swallow 
solids 
Unable to drink fluids;  
IV fluids req 
Constipation 
Mild 
Moderate 
Severe 
Distention with vomiting 
 
 
 
 

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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; 
normalizes with 
bronchodilator;  
FEV1 50% to < 70%  
(or peak flow) 
 
No Normalization  
with bronchodilator;  
FEV 25% to < 50%  
(or peak flow), 
retractions 
Cyanosis; FEV1 < 25%  
(or peak flow) OR intubated 
Dyspnea 
Dyspnea on 
exertion 
Dyspnea with  
normal activity 
Dyspnea at rest 
Dyspnea requiring O2 therapy 
 
 
 
URINALYSIS 
 
GRADE 1 
GRADE 2 
GRADE 3 
GRADE 4 
MILD 
MODERATE 
SEVERE 
POTENTIALLY LIFE-
THREATENING 
Proteinuria 
 
Dispstick 
 
 
 
 
Protein 
 
1 + 
2-3 + 
4 + 
Nephrotic syndrome 
Spot Urine:    
Protein:Creatinine  
Ratio mg/mg 
0.2-1.0 
> 1.0-2.0 
> 2.0-3.5 
> 3.5 
24 Hour Urine: 
Protein 
200 mg - 1g 
loss/day 
 
> 1-2 g loss/day 
 
> 2-3.5 g loss/day 
 
Nephrotic syndrome 
OR > 3.5 g loss/day 
 
Hematuria 
Microscopic only 
> 3 to < 10 
RBC/hpf 
Gross, No clots 
 10 RBC/hpf 
Gross plus clots OR  
RBC casts 
Obstructive OR transfusion 
required 
 
RBC = red blood cell; hpf = high power field. 
 
 

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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 
Localized urticaria 
Generalized 
urticaria 
angioedema 
 
Anaphylaxis 
Cutaneous/Rash/ 
Dermatitis 
Erythema, 
pruritus rash  
OR dry 
desquamation 
Diffuse 
maculopapular  
OR dry 
desquamation 
Vesiculation OR 
moist 
desquamation 
ulceration 
ANY ONE: mucous 
membrane involvement, 
suspected  
Stevens-Johnson (TEN), 
erythema multiforme, necrosis 
req surgery, exfoliative 
dermatitis 
 
Local Reaction 
(secondary  
to parenteral 
treatment- not 
vaccination or skin 
test) 
 
Erythema 
Induration < 10 mm  
OR inflammation  
OR phlebitis 
Induration > 10 mm  
OR ulceration 
Necrosis of skin 
Fatigue 
Normal activity  
Reduced < 25% 
Normal activity  
Reduced 25-50% 
Normal activity  
reduced > 50%;  
cannot work 
Unable to care for self 
 
 
 

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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  
Hospitalization 
Paresthesia  
(burning, 
tingling, etc) 
Mild discomfort;  
no treatment 
needed 
Mod discomfort  
non-narcotic analgesia 
req 
Severe discomfort; 
OR narcotic 
analgesia req with 
symptomatic 
improvement 
 
Incapacitating; OR not 
responsive  
to narcotic analgesia 
Neuro-motor 
Mild weakness in 
muscle of feet but  
able to walk and/or 
mild increase or 
decrease in 
reflexes 
Mod weakness in feet 
(unable to walk on heels 
and/or toes), mild 
weakness in hands, still 
able to do most hand 
tasks and/or loss of 
previously present reflex 
or development of 
hyperreflexia  
and/or unable to do 
deep knee  
bends due to weakness 
 
Marked distal 
weakness (unable to 
dorsiflex toes or foot 
drop), and mod 
proximal weakness 
ie, in hands 
interfering with ADLs 
and/or requiring 
assistance to walk 
and/or unable to rise 
from chair 
unassisted 
Confined to bed or 
wheelchair  
because of muscle weakness 
Neuro-sensory Mild impairment 
sensations,  
(ie, vibratory, 
pinprick, hot/cold in 
great toes) in focal 
area or 
symmetrical 
distribution 
Mod impairment mod 
de-sensation,  
(ie, of vibratory, pinprick, 
hot/cold to ankles) 
and/or joint position or 
mild impairment that is 
not symmetrical. 
Severe impairment 
(dec or loss of 
sensation to knees 
or wrists) or loss of 
sensation of at least 
mod degree in 
multiple different 
body areas (ie, 
upper and lower 
extremities) 
Sensory loss involves limbs  
and trunk 
 
 
 
 
 
 
 

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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any 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 
• 
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 judgement of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE. Also, 
"lack of efficacy" or "failure of expected pharmacological action" constitutes an 
AE or SAE. 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition. 

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• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
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 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
• 
Results in death 
• 
Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during 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. 
Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 

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Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgement should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 
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 (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF in 
Parts A and B of the study. 

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• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
• 
Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event; and both AE and SAE can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
Other measures to evaluate AE and SAE may be utilized (see Appendix 2 - 
Adverse Event and Laboratory Value Severity Grade Tables). 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
The investigator will use clinical judgement to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 

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• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF in 
Parts A and B. 
• 
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 
• 
In Parts A and B , the primary mechanism for reporting SAE to GSK will be the 
electronic data collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF. 
• 
After Part B of the study is completed at a given site, the electronic data collection 
tool will be locked to prevent the entry of new data or changes to existing data. 

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• 
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 the SRM. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile/email transmission of the SAE paper CRF are the preferred method to 
transmit this information to the SAE coordinator (Further details are documented 
in the SRM). 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the Study Reference Manual. 
 

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10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A female 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, a single FSH measurement is 
insufficient.  
• Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen 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 enrollment. 
 

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10.4.2. 
Contraception Guidance: 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
Note: Vasectomized 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 (estrogen- 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 which 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. Male 
condom and female condom should not be used together (due to risk of failure with friction) 
 

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Female Participants who become pregnant 
• 
Any female participant who becomes pregnant while participating will discontinue 
study intervention and be withdrawn from the study. 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study.  
• 
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 fetal 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 a medical reason will be 
reported as an AE or SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  
• 
Any SAE occurring as a result of a post-study pregnancy which 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.  

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10.5. 
Appendix 5 Liver Safety: Required Actions and Follow-up 
Assessments and Study Intervention Restart Guidelines 
Phase III-IV liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event etiology  
Phase III-IV 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, stabilize, or return to within 
baseline (see MONITORING below) 
• Do not restart participant with study 
treatment. 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 
• Only in those with underlying chronic 
Hepatitis B at study entry (identified by 
positive Hepatitis B surface antigen) 
quantitative Hepatitis B DNA and 
Hepatitis delta antibody5. 
• Obtain blood sample for pharmacokinetic 
(PK) analysis, within 6 weeks after last 
dose6 
• Serum creatine phosphokinase (CPK) 
and lactate dehydrogenase (LDH). 

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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 hrs 
• Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
• A specialist or hepatology consultation is 
recommended 
For All other criteria:  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) 
and perform liver event follow-up 
assessments within 24-72 hrs  
• Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
• Fractionate bilirubin, if total 
bilirubin2xULN 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form 
• Record use of concomitant medications 
on the concomitant medications report 
form including acetaminophen, herbal 
remedies, other over the counter 
medications. 
• Record alcohol use on the liver event 
alcohol intake case report form (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. 
• Serum acetaminophen adduct high 
performance liquid chromatography 
(HPLC) assay (quantifies potential 
acetaminophen contribution to liver injury 
in participants with definite or likely 
acetaminophen use in the preceding 
week [James, 2009]). NOTE: not 
required in China  
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms. 
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 threshold value stated will not apply to participants receiving anticoagulants 

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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; 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. If hepatitis delta antibody assay cannot be performed,, it can be replaced with a polymerase chain reaction (PCR) 
of hepatitis D RNA virus (where needed) [Le Gal, 2005]. 
6. Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM.  
 
Phase III-IV 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 normalize or return 
to within baseline. 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, et al. 
Pharmacokinetics of acetaminophen-adduct in adults with acetaminophen overdose and 
acute liver failure. Drug Metab Dispos. 2009; 37:1779-84. 
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 

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patterns of virological response to interferon therapy in chronically infected subjects. 
J Clin Microbiol. 2005;43(5):2363–2369. 
10.5.1. 
Restart Following Transient Resolving Liver Stopping Events Not 
Related to Study Intervention 
After liver stopping criteria are met, restart or rechallenge is not permitted, see Section 
7.1.2.1.  

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10.6. 
Appendix 6: Medical Device Incidents: Definition and 
Procedures for Recording, Evaluating, Follow-up, and 
Reporting 
Definition and Documentation of Medical Device Incidents 
Definitions of a Medical Device Incident 
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 for the list of GSK medical 
devices).  
Medical Device Incident Definition 
• 
A medical device incident is any malfunction or deterioration in the characteristics 
and/or performance of a device as well as any inadequacy in the labeling or the 
instructions for use which, directly or indirectly, might lead to or might have led to 
the death of a participant/user/other person or to a serious deterioration in his/her 
state of health. 
• 
Not all incidents lead to death or serious deterioration in health. The 
nonoccurrence of such a result might have been due to other fortunate 
circumstances or to the intervention of health care personnel. 
 
It is sufficient that: 
• 
An incident associated with a device happened and 
• 
The incident was such that, if it occurred again, might lead to death or a serious 
deterioration in health. 
A serious deterioration in state of health can include any of the following: 
• 
Life-threatening illness 
• 
Permanent impairment of body function or permanent damage to body structure 
• 
Condition necessitating medical or surgical intervention to prevent one of the 
above  
• 
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Examples of incidents 
• 
A participant, user, caregiver, or healthcare professional is injured as a result of a 
medical device failure or its misuse. 
• 
A participant’s study intervention is interrupted or compromised by a medical 
device failure. 
• 
A misdiagnosis due to medical device failure leads to inappropriate treatment. 
• 
A participant’s health deteriorates due to medical device failure. 
 
Documenting Medical Device Incidents 
Medical Device Incident Documenting 
• 
Any medical device incident occurring during the study will be documented in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice, and on the appropriate form. 
• 
For incidents fulfilling the definition of an AE or an SAE, the appropriate AE/SAE 
CRF page will be completed as described in Appendix 3. 
• 
The form will be completed as thoroughly as possible and signed by the 
investigator before transmittal to the GSK. 
• 
It is very important that the investigator provides his/her assessment of causality 
(relationship to the medical device provided by GSK) at the time of the initial 
report and describes any corrective or remedial actions taken to prevent recurrence 
of the incident. 
• 
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 an 
incident. This includes any amendment to the device design to prevent recurrence. 
 

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10.7. 
Appendix 7: Country-specific requirements 
Country specific changes in Protocol Amendment 01 apply to Investigator Sites in Japan 
only. 
 
Summary of Country Specific Changes and Rationale 
 
Section  
Global Wording 
New Country Specific 
Wording 
Rationale 
Inclusion 
criterion #7 
• 
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. 
 
Of the allowed 
options for birth 
control in inclusion 
criterion  #7, the 
following are not 
approved and cannot 
be used in Japan: 
• 
Implantable 
progestogen-only 
hormone 
contraception 
associated with 
inhibition of 
ovulation 
• 
Combined 
(estrogen- and 
progestogen-
containing) 
hormonal 
contraception 
associated with 
inhibition of 
ovulation 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
• 
Injectable 
• 
Progestogen-only 
hormone 
contraception 
associated with 
inhibition of 
ovulation  
• 
Oral 
• 
Injectable 
To exclude 
contraceptive methods 
not approved in Japan 
Exclusion 
crierion #10 
Have acute or chronic 
infections requiring 
management, as 
follows: 
• 
Currently on any 
suppressive therapy for 
Participants are 
excluded if they have: 
• 
symptoms or 
signs which 
suggest active TB 
from medical 
To exclude 
participants with 
evidence of active TB 

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Section  
Global Wording 
New Country Specific 
Wording 
Rationale 
a chronic infection 
(such as tuberculosis, 
pneumocystis, 
cytomegalovirus, 
herpes simplex virus, 
herpes zoster and 
atypical mycobacteria). 
• 
Use of parenteral (IV or 
IM) antibiotics 
(antibacterials, 
antivirals, anti-fungals, 
or anti-parasitic agents) 
for infection within 60 
days of Day 1. 
 
history or on 
examination 
• 
recent close 
contact with a 
patient with active 
TB; 
• 
Evidence 
indicating TB 
infection on 
Interferon-gamma 
release assay 
(QuantiFERON, 
T-SPOT) or 
tuberculin skin 
test conducted 
within 5 weeks 
before the first 
dose of study 
treatment; 
• 
Chest X-ray or 
CT scan) taken 
within 3 months 
before first dose 
of study treatment 
showing evidence 
indicating active 
TB. 
 
 

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10.8. 
Appendix 8: Country-specific Protocol Amendment 02 
Requirements 
Country specific changes in Protocol Amendment 02 apply to Investigator sites in the 
Netherlands only. 
 
Summary of Country Specific Changes and Rationale 
 
Section  
Global Wording 
New Country 
Specific Wording 
Rationale 
7.2 Participant 
Discontinuation/Withdrawal 
from the Study 
• 
A participant 
may withdraw from the 
study at any time at 
his/her own request, or 
may be withdrawn at 
any time at the 
discretion of the 
investigator for safety, 
behavioral, compliance 
or administrative 
reasons. This is 
expected to be 
uncommon. 
• 
With 
younger children, 
careful attention 
should be paid to 
signs of resistance 
to (further) 
participation. In 
the event of signs 
of resistance, the 
participant will be 
permanently 
discontinued from 
the study. The 
Netherlands 
Association for 
Paediatric 
Medicine’s (NVK) 
code of conduct 
relating to 
expressions of 
objection by 
minors 
participating in 
medical research 
will be adhered to. 
To incorporate 
Netherlands 
required wording 
for studies 
involving 
children. 
8.9.4 Regulatory Reporting 
Requirements for SAEs 
• 
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 
• 
The 
sponsor will report 
the SAEs through 
the web portal 
ToetsingOnline to 
the accredited 
METC that 
approved the 
protocol, within 7 
days of first 
knowledge for 
SAEs that result in 
death or are life 
threatening 
followed by a 
period of 
To exclude 
participants with 
evidence of 
active TB 

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Section  
Global Wording 
New Country 
Specific Wording 
Rationale 
authority, Institutional 
Review Boards 
(IRB)/Independent 
Ethics Committees 
(IEC), and 
investigators. 
 
maximum of 8 
days to complete 
the initial 
preliminary report. 
All other SAEs 
will be reported 
within a period of 
maximum 15 days 
after the sponsor 
has first 
knowledge of the 
serious adverse 
events. 
 

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10.9. 
Appendix 9: ACR Criteria 
The ACR Criteria for the Classification of Systemic Lupus Erythematosus*  
[Tan, 1982; Hochberg, 1997] 
Criterion 
Definition 
1. Malar "butterfly" rash  
Fixed erythema, flat or raised, over the malar eminences, tending to spare the 
nasolabial folds. 
2. Discoid rash  
Erythematosus raised patches with adherent keratotic scaling and follicular 
plugging; atrophic scarring may occur in older lesions. 
3. Photosensitivity  
Skin rash as a result of unusual reaction to sunlight, by subject history or 
physician observation. 
4. Oral ulcers  
Oral or nasopharyngeal ulceration usually painless, observed by the 
physician. 
5. Nonerosive Arthritis  
Nonerosive arthritis involving 2 or more peripheral joints characterized by 
tenderness, swelling, or effusion. 
6. Serositis  
a. 
Pleuritis (convincing history or pleuritic pain or rub heard by physician or 
evidence of pleural effusion), OR 
b. 
Pericarditis (documented by ECG, rub, or evidence or pericardial 
effusion). 
7. Renal disorder  
a. 
Persistent proteinuria ( 0.5 grams/day or  3 + if quantitation not 
performed) OR 
b. 
Cellular casts (may be red cell, hemoglobin, granular, tubular, or mixed). 
8. Neurologic disorder  
a. 
Seizures (in the absence of offending drugs or known metabolic 
derangements; ie, uremia, ketoacidosis, or electrolyte imbalance) OR 
b. 
Psychosis (in the absence of offending drugs or known metabolic 
derangements; ie, uremia, ketoacidosis, or electrolyte imbalance. 
9. Hematologic disorder  
a. 
Hemolytic anemia (with reticulocytosis) 
 
OR 
b. 
Leukopenia ( 4000/mm3 total on 2 or more occasions), OR 
c. 
Lymphopenia ( 1500/mm3 on 2 or more occasions), OR 
d. 
Thrombocytopenia ( 100,000/mLmm3 in the absence of offending 
drugs). 
10. Immunologic disorder  
a. 
Anti-DNA (antibody to native DNA in abnormal titer), OR 
b. 
Anti-Sm (presence of antibody to Sm nuclear antigen), OR 
c. 
Positive-finding of antiphospholipid antibodies based on 1) an abnormal 
serum level of IgG or IgM anticardiolipin antibodies, 2) a positive test 
result for lupus anticoagulant using a standard method, or 3) a false-
positive serologic test for syphilis known to be positive for at least 6 
months and confirmed by Treponema pallidum immobilization (TPI) or 
fluorescent treponemal antibody (FTA) absorption test. 
11. Antinuclear antibody (ANA) 
Abnormal titer of ANA by immunofluorescence or an equivalent assay at any 
point in time and in the absence of drugs known to be associated with "drug-
induced lupus" syndrome. 
*The proposed classification is based on 11 criteria. For the purpose of identifying subjects in clinical studies, a 
person shall be said to have systemic lupus erythematosus if any 4 or more of the 11 criteria are present, serially or 
simultaneously, during any interval or observation. 
 
 

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10.10. 
Appendix 10: SELENA SLEDAI Disease Assessment Scale 
SELENA SLEDAI Score (adapted from [Petri, 2005; Bombardier, 1992]) Score if 
descriptor is present at time of visit or in the preceding 10 days. 
Wgt. 
Descriptor 
Definition 
8 
Seizure 
Recent onset (last 10 days). Exclude metabolic, infectious drug cause, or seizure 
due to past irreversible CNS damage. 
8 
Psychosis 
Altered ability to function in normal activity due to severe disturbance in the 
perception of reality. Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked illogical thinking, bizarre, 
disorganized, or catatonic behavior. Exclude uremia and drug causes. 
8 
Organic Brain 
Syndrome 
Altered mental function with impaired orientation, memory or other intellectual 
function with rapid onset and fluctuating clinical features. Include clouding of 
consciousness with reduced capacity to focus and inability to sustain attention to 
environment, plus at least 2 of the following: perceptual disturbance, incoherent 
speech, insomnia or daytime drowsiness, or increased or decreased psychomotor 
activity. Exclude metabolic, infectious, or drug causes. 
8 
Visual Disturbance 
Retinal and eye changes of SLE. Include cytoid bodies, retinal hemorrhages, 
serious exudate of hemorrhage in the choroid, optic neuritis, scleritis or episcleritis. 
Exclude hypertension, infection, or drug causes. 
8 
Cranial Nerve 
Disorder 
New onset sensory or motor neuropathy involving cranial nerves.  
Include vertigo due to lupus. 
8 
Lupus Headache 
Severe persistent headache: may be migrainous, but must be  
non-responsive to narcotic analgesia. 
8 
CVA 
New onset of CVA(s). Exclude arteriosclerosis or hypertensive causes. 
8 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual infarction, splinter 
hemorrhages, or biopsy or angiogram proof of vasculitis. 
4 
Arthritis 
More than 2 joints with pain & signs of inflammation (ie, tenderness, swelling or 
effusion). 
4 
Myositis 
Proximal muscle aching/weakness associated with elevated creatine 
phosphokinase/aldolase or electromyogram changes or a biopsy showing myositis. 
4 
Urinary Casts 
Heme-granular or red blood cell casts. 
4 
Hematuria 
 5 red blood cells/high power field. Exclude stone, infection, or other causes. 
4 
Proteinuria 
New onset or recent increase of more than 0.5 g/24 hours. 
4 
Pyuria 
 5 white blood cells/high power field. Exclude infection. 
2 
Rash 
New or ongoing inflammatory lupus rash. 
2 
Alopecia 
New or ongoing abnormal, patchy or diffuse loss of hair due to active lupus. 
2 
Mucosal Ulcers 
New or ongoing oral or nasal ulcerations due to active lupus. 
2 
Pleurisy 
Classic and severe pleuritic chest pain or pleural rub or effusion or new pleural 
thickening due to lupus. 
2 
Pericarditis 
Classic and severe pericardial pain or rub or effusion, or electrocardiogram 
confirmation. 
2 
Low Complement 
Decrease in CH50, C3, or C4 below the lower limit of normal for testing laboratory. 
2 
Increased DNA 
Binding 
 25% binding by Farr assay or above normal range for testing laboratory. 
1 
Fever 
 38°C. Exclude infectious cause. 
1 
Thrombocytopenia 
 100,000 platelets/mm3 
1 
Leukopenia 
 3,000 white blood cells/mm3. Exclude drug causes. 
 
TOTAL SCORE 
(Sum of weights next to descriptors marked present) 
 

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10.11. 
Appendix 11: Abbreviations and Trademarks 
aCL 
Anticardiolipin 
ACR 
American College of Rheumatology 
ADA 
Anti drug antibodies 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine amininotransferase 
ANA 
Anti-nuclear antibody 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
BLyS 
B lymphocyte Stimulator 
BW 
Body weight 
C3/C4 
Complement factor C3 and C4 
Cavg 
Average concentration 
CBC 
Complete blood count 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CiC 
Child in care 
Cmax 
Maximum concentration 
Cmin 
Minimum concentration 
CNS 
Central nervous system 
COVID-19 
Coronavirus SARS-CoV-2 (COrona Virus Disease -2019) 
CPK 
Creatinine phosphokinase 
CrCl 
Creatinine clearance 
CRP 
C-reactive protein 
CRF 
Case report form 
dL 
Deciliter 
dsDNA 
Double stranded deoxyribonucleic acid  
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
HB 
Hepatitis B 
HBsAg 
Hepatitis B surface antigen 
HBc 
Hepatitis B core 
HGS 
Human Genome Sciences, Inc 
HIV 
Human immunodeficiency virus 
hpf 
High power field 
IA 
Intraarticular 
IB 
Investigator’s Brochure 
ICH 
International Committee on Harmonization 
IEC 
Independent Ethics Committee 
IL-6 
Interleukin-6 

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IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
IUD 
Intrauterine device 
IV 
Intravenous 
IVIG 
Intravenous immunoglobulin 
IWRS 
Interactive web response system 
kg 
Kilogram 
LDH 
Lactate dehydrogenase 
mg 
Milligram 
mL 
Milliliter 
MCID 
Minimally clinically important difference 
g 
Microgram 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
MMF 
Mycophenolate mofetil 
MRI 
Magnetic Resonance Imagery 
MSDS 
N/A 
Materials Safety Data Sheet 
Not applicable 
NSAIDs 
Non-steroidal anti-inflammatory drugs 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PO 
By mouth (per os) 
PRINTO 
 
Pediatric Rheumatology International Trials 
Organization 
PRT 
Pharmacokinetic Review Team 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QW 
Once a week 
Q10D 
Every 10 days 
Q2W 
Every 2 weeks 
RA 
Rheumatoid arthritis 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious Adverse Event 
SC 
Subcutaneous 
SELENA 
Safety of Estrogen in Lupus Erythematosus National 
Assessment  
SFI 
SLE Flare Index 
cSLE 
Childhood Onset Systemic Lupus Erythematosus 

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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 
SRT 
Safety Review Team 
TACI Fc 
 
TB 
Transmembrane activator attached to the Fc portion of an 
immunoglobulin 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
ULN 
Upper limit of normal 
WOCBP 
Woman of childbearing potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
BENLYSTA 
 
MedDRA 
BLyS 
 
 
LymphoStat-B 
 
 
 

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10.12. 
Appendix 12: Protocol Amendment History 
Amendment 3 14-Jul-2021 
Overall Rationale for the Amendment:  
The purpose of this amendment is to add an optional access extension phase post 
Week 52 exclusively for eligible participants who complete Part B of the study (e.g., 
participants from countries where the IV formulation is not approved for pediatric use; or 
participants in whom IV Benlysta is not suitable due to medical reasons or significant 
logistical challenges; see Section 6.7.1 for full eligibility criteria). At the time of the 
200908 protocol development, belimumab IV formulation was expected to be licensed 
and available for SLE patients aged 5 years and older following completion of the study 
in all countries where the 200908 study is conducted. Currently in Mexico, belimumab 
IV is not approved for pediatric use in SLE patients. Additionally, in countries where IV 
Benlysta is approved, it might not be suitable for individual participants as post study 
treatment due to medical reasons or significant logistical difficulties. Therefore, this 
optional access extension phase has been introduced to provide a mechanism for 
continued access to belimumab SC from Week 52 onwards for eligible participants. 
Participants who are enrolled into the optional access extension phase will be withdrawn 
from treatment if they reach the age of 18 years or if Belimumab SC or IV becomes 
licensed and commercially available for pediatric use in the participant’s country (see 
Section 6.7.1.4for full withdrawal criteria).   
Section # and 
Name 
Description of Change 
Brief Rationale 
Synopsis 
Added information regarding 
optional access extension 
phase and updated wording to 
clarify items only pertaining to 
Part A and Part B 
The optional access extension phase 
was added to provide a mechanism for 
continued access to belimumab SC from 
week 52 onwards for eligible 
participants. This was added to study 
design and clarified items only pertaining 
to Part A and Part B 
Section 1.2, 
Schema 
Updated to include optional 
access extension phase 
The Schema was updated to reflect the 
added optional extension phase 
Section 1.3, 
Schedule of 
Activities 
Added wording in Note for 
Section 1.3.1 and Section 1.3.2 
for optional access extension 
phase. 
Added a note to Section 1.3.3 to 
clarify that 8- and 16-week 
follow-up visits are NOT 
required for participants who 
are eligible for and are enrolled 
List of the activites during the newly 
added optional access extension phase 
was added to the SOA. Wording was 
changed in the impacted sections of Part 
A and Part B. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
into the optional access 
extension phase. 
Added new table in Section 
1.3.4 with activities in optional 
access extension phase  
Section 4.1, 
Study Design 
Added information regarding 
optional access extension 
phase and updated wording to 
clarify applicability to Part A and 
B 
The optional access extension phase 
was added to the study design to provide 
a mechanism for continued access to 
belimumab SC from week 52 onwards 
for eligible participants. 
Section 4.4, End 
of Study 
Updated wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 5.1, 
Inclusion Criteria 
and Section 5.2, 
Exclusion Criteria 
Added wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 6.4.1, 
Compliance with 
Subcutaneous 
Administration of 
Belimumab 
Added subheading for “Parts A 
and B” and wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 6.6, Dose 
Modification 
Added optional access 
extension phase to Part B dose 
modification instructions  
To clarify dose modification instructions 
during the optional access extension 
phase 
Section 6.7, 
Intervention after 
the End of the 
Study 
Added wording to Section 6.7 
for eligibility in the optional 
access extension phase.  
Added new section for the 
Optional Access Extension 
Phase (6.7.1) and subsections 
for process (6.7.1.1), inclusion 
criteria (6.7.1.2), exculsion 
criteria (6.7.1.3), withdrawal 
criteria (6.7.1.4), and study 
assessments and procedures 
(6.7.1.5), and statistical 
analyses and reporting (6.7.1.6) 
Clarified that for eligible participants, the 
optional access extension phase was 
added to provide a mechanism for 
continued access to belimumab SC from 
week 52 onwards. The added sections 
clarify the process for enrolling eligible 
participants into the access extension 
phase, eligibility criteria, withdrawal 
criteria, study assessments and 
procedures and statistical analyses and 
reporting in the access extension phase. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 8.8.5, 
Suicidal Ideation 
and Behavior 
Risk Monitoring 
Added wording to clarify data 
collection for Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 8.9.1, 
Time Period and 
Frequency for 
Collecting AE and 
SAE information 
Added wording to clarify AE 
collection through follow-up in 
Part B 
To clarify AEs will only be collected in 
Parts A and B of the study 
Section 9.1, 
Statistical 
Hypotheses 
Updated wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 9.4.1, 
GSK Safety 
Review Team 
Updated wording to clarify 
applicability to Part A and B and 
to clarify that SAEs reported 
during the optional access 
extension phase will not be part 
of the GSK Safety Review 
Team (SRT) in-stream review. 
To clarify items pertaining only to Parts A 
and B 
Section 10.3.3, 
Recording and 
Follow-up of AE 
and SAE 
Updated wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
Section 10.3.4, 
Reporting of SAE 
to GSK 
Updated wording to clarify 
applicability to Part A and B 
To clarify items pertaining only to Parts A 
and B 
 

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Amendment 2 24-APR-2020 
Overall Rationale for the Amendment:  
This amendment adjusts the protocol in response to the COVID-19 pandemic.  The 
purpose of this amendment is to provide flexibility to protocol specified visits and 
assessments in accordance with guidance from regulatory agencies, while maintaining 
trial and data integrity.  
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1 Synopsis; 4.1 
Overall design; 
9.2 Sample Size 
Determination 
Flexibility added to allow more 
than 36 participants to be 
screened and additional 
participants enrolled to achieve 
the original number of 24 
evaluable participants. 
The flexibility has been added to allow 
for the possibility of higher than 
anticipated withdrawals due to the 
COVID-19 pandemic. 
1.2 Schema  
Schmatic updated to clarify 
study visits for Cohort 2 are 10 
days apart.  
The schematic had the same visits for 
all 3 cohorts with description indicating 
the different visit schedule for the 10 
day dosing cohort. The schematic was 
updated to align with the legend. 
1.3.1 SOA 
Cohorts 1 and 3, 
1.3.2 SOA Cohort 
2 and  
Visit windows were widened. 
To provide some more flexibility due to 
the COVID-19 pandemic, while 
maintaining the 3 different dosing 
schedules, visit windows were 
increased.  
1.3.3 SOA Part B 
All participants 
The PK sampling and 
belimumab administration 
windows were widened. 
To provide some more flexibility due to 
the COVID-19 pandemic, while 
maintaining the 3 different dosing 
schedules, PK sampling and belimumab 
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Section # and 
Name 
Description of Change 
Brief Rationale 
2.3.1 Risk 
Assessment; 5.2 
Exclusion criteria  
‘to any of the excipients of the 
study drug’ added 
To further clarify that a history of 
anaphylactic reaction also includes any 
of the excipients of the study drug. 
4.1 Overall 
design; 9.4.2 
GSK 
Pharmacokinetics 
Review Team 
The number of participants that 
triggered a data review by the 
pharmacokinetic team was 
changed from after the first 12 
participants, to now after the first 
6 participants in Cohorts 1 or 2 
have completed Week 12.  
If recruitment is slow, to ensure an early 
PK data review to determine whether a 
change in frequency of dosing is 
required.   
7.1.3 Temporary 
Discontinuation 
Addtion of requirement to 
temporarily discontinue study 
medication for COVID-19 
positive participants or if no 
testing is available for those 
exhibiting symptoms consistent 
with COVID-19 
Clarification of protocol specific 
procedures to be followed for COVID-19 
positive participants or those  exhibiting 
symptoms of COVID-19 with regards to 
study medication. 
10.8 Country 
Specific 
Requirements 
Addition of Netherlands country 
specific requirements regarding 
discontinuation/withdrawal from 
the study and regulatory 
reporting requirements for SAEs 
To comply with local requirements in the 
Netherlands for studies involving 
children. 
Throughout the 
protocol 
Administrative edits 
Minor edits such as updating the list of 
abbreviations. 

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Amendment 1 24-Jul-2019 
Overall Rationale for the Amendment:  
This amendment adjusts and clarifies the number of planned participants to ensure 
compliance with regulatory commitments. Additionally the following changes have been 
added: modification of the exclusion criterion pertaining to hepatitis B status to align 
with current GSK guidance, allowance for in clinic 16-week follow-up, splitting of 
screening testing for lower weight participants to ensure blood volume collection remains 
within local guidance, and other wording changes for clarification. Furthermore, an 
Appendix has the Japan country specific requirements that have been added to the 
inclusion/exclusion criteria. 
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1 Synopsis; 4.1 
Overall design; 
9.2 Sample Size 
Determination 
Adjustment and clarification of 
number of participants – now 
approximately 36 screened, 28 
enrolled aiming for 24 
evaluable. 
The number of participants screened 
and enrolled has been increased to allow 
for 24 evaluable participants 
1.3.1 SOA 
Cohorts 1 and 3; 
1.3.2 SOA Cohort 
2; 8.1 Screening 
– Lab tests 
Note added to indicate 
screening lab tests for 
participants < 30kg will be split 
over 2 visits separated by at 
least 2 weeks.Second screening 
and Day 1 visit also to be 
separated by 2 weeks.May also 
apply to particpants  30kg per 
local requirements. 
To allow for compliance with local 
guidance on limit to blood volume 
collected in single draw. 
1.3.1 SOA 
Cohorts 1 and 3, 
1.3.2 SOA Cohort 
2 and 1.3.3 SOA 
Part B All 
participants 
Location of pregnancy testing at 
Week 16 follow-up clarified 
The 16-week follow-up may be perfomed 
at an in clinic visit according to local 
requirement. 
1.3.1 SOA Cohort 
1 and 3 
Addtion of pregnancy test at 
Day 8 and Day 15 
To ensure pregnancy is ruled out at each 
clinic visit. 
1.3.2 SOA Cohort 
2 
Addtion of pregnancy test at 
Day 11 and Day 21 
To ensure pregnancy is ruled out at each 
each visit. 
2.2.2 Benefit 
Assessment 
Insertion of ‘in adults’ to 
description of IV and SC trial 
results description 
To clarify the results are from adult data 

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Section # and 
Name 
Description of Change 
Brief Rationale 
5.2 Exclusion 
Criteria 
Change in exclusion criterion for 
hepatitis B status #23 
To comply with GSK Hepatology Board 
guidance 
6.1.1.1 
Video link to guidance on use of 
autoinjector will be provided to 
site personnel only 
To clarify the video is for reference by 
site personnel only  
6.4.1 Compliance 
Requirement to record 
estimated proportion of a 
partially administered dose in 
the patient diary card removed 
Removal of ‘self’ as prefix to 
injection diary 
Estimation of the proportion of a partially 
administered dose is no longer required. 
 
To acknowledge injection with be given 
by parent/caregiver to participants under 
12 years old. 
6.4.2 Missed 
doses 
Rules to follow if a dose is 
missed have been modified. 
Clarification of wording to minimise gaps 
in scheduled dosing while maintaining 
weekly gap between doses. 
6.5.1 Permitted 
Concomitant 
therapy 
Re-wording of guidance on use 
of concomitant anti-malarials, 
steroids and NDSAIDs. 
To provide clearer guidance to 
investigator on permitted concomitant 
medication throughout the study. 
8.1.1 Treatment 
of Overdose 
Definition of belimumab 
overdose has been removed. 
The dosage of belimumab considered an 
overdose has not been defined. 
10.7 Country 
Specific 
Requirements 
Addition of Japan country 
specific requirements regarding 
inclusion/exclusion criteria  
To comply with local requirements in 
Japan 
11 References 
Addition of 2 new references  
References added to support included 
statements. 
 

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11. 
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