An Open-label, Randomized, Parallel Group, Single Dose Study to Investigate the PK and Safety of Belimumab 200 mg Intravenous and 200 mg Subcutaneous Via Auto-injector in Chinese Healthy Participants
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Sponsor: GlaxoSmithKline

2018N385241_01
CONFIDENTIAL
GlaxoSmithKline group of companies
209629
1
TITLE PAGE
Protocol Title: An open-label, randomized, parallel group, single dose study to 
investigate the PK and safety of belimumab 200 mg intravenous and 200 mg 
subcutaneous via auto-injector in Chinese healthy participants.
Protocol Number: 209629/Amendment 01
Compound Number:
GSK1550188
Study Phase: Phase 1
Short Title: Single dose study to investigate the PK and safety of belimumab 200 mg 
intravenous and 200 mg subcutaneous via auto-injector in Chinese healthy participants
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Sponsor Contact Address: 
GlaxoSmithKline (Shanghai) Research & Development Limited 
No. 18, 999 HuanKe Road, Zhangjiang, Pudong
Shanghai 201203, China
Medical Monitor Name and Contact Information
This information will be provided in the Study Reference Manual (SRM).
Approval Date: 27-JUN-2019
Copyright 2019 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
 
2020N435387_00

 
2020N435387_00
PPD
PPD

2018N385241_01
CONFIDENTIAL
209629
3
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
DNG Number
Amendment01
27-Jun-2019
2018N385241_01
Original Protocol
18-Mar-2019
2018N385241_00
Amendment 01 27-June-2019
Overall Rationale for the Amendment: The changes made aim to increasing
operational feasibility and consistency with clinical study practice at the study site. Key 
changes including: 

Time of pre-dose blood sampling changed from point to a time window.

Changing method to collect blood pressure, body temperature; and pulse rate is 
replaced by heart rate to better reflect clinical practice.

Correction of other inconsistency and typos.
Section # and 
Name
Description of Change
Brief Rationale
8 STUDY 
ASSESSMENTS 
AND 
PROCEDURES
In the table of Time assessment Window, 
change “-4 hrs” to “Any time before dosing”
Change note “a” to “Including physical 
examinations, vistal signs, local tolerance, 
ECG, clinical safety laboratory 
assessments and other applicable tests”. 
Delete superscripts and notes of “b” and “c” 
and make corresponding changes.
Change from time point to a time 
window of pre-dose blood 
sampling to increase site 
operation feasibility.
To describe safety evaluation in 
detail.
Delete urine tests that will not be 
done on Day 1 and Day 2-7.
8.5 
Pharmacokinetics
Delete “-4 h” in the first paragraph
Ensure consistent with Section 
8.
5.2 Exclusion 
Criteria
In item 10, change systolic and diastolic BP 
position from “supine” to “sitting”
To increase the feasibility at site 
operation level.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
4
Section # and 
Name
Description of Change
Brief Rationale
8.2.2 Vital Signs
Change from “supine” to “sitting position”, 
from “pulse rate” to “heart rate”, and from 
“axillary” to “tympanic” temperature.
To increase the feasibility at site 
operation level.
9.3.2.3 Vital signs
Change from “pulse rate, body 
temperature” to “heart rate, tympanic 
temperature”,
Ensure consistent with Section 
8.2.2
1.3 SoA
In note “f”, changed from “supine” to “sitting 
position”, from “pulse rate” to “heart rate”,
from “body” to “tympanic”.
Add “Standing and supine BP will be 
additionally collected on Day -1”
Ensure consistent with Section 
8.2.2. 
Describe standing and supine 
BP to be collected for exclusion 
criteria assessment.
1.3 SoA
Delete “-4 h” in the column of “Pre-dose”
Ensure consistent with Section 8
10.3 Appendix 3:  
Clinical 
Laboratory Tests
Delete “The results of each test must be 
entered into the CRF”.
Delete “HTLV-1 antibody” in Table 2.
Results of Screening items are 
not required to be entered.
HTLV-1 antibody is not included 
in screening tests.
2.2 Background
2.3 Benefit/Risk 
Assessment and 
11. Reference
Change Belimumab IB version to 
2011N128591_05, IB Version 15；delete
IB supplement number in Section 2.3 and 
11.
Update to latest IB version
Title page
Change “China” to “Shanghai” in Sponsor 
Contact Address
Corrections.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
5
TABLE OF CONTENTS
PAGE
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE.....................................3
1.
PROTOCOL SUMMARY..........................................................................................8
1.1.
Synopsis.......................................................................................................8
1.2.
Schema ......................................................................................................10
1.3.
Schedule of Activities (SoA)........................................................................11
2.
INTRODUCTION....................................................................................................14
2.1.
Study Rationale ..........................................................................................14
2.2.
Background ................................................................................................14
2.3.
Benefit/Risk Assessment ............................................................................15
2.3.1.
Risk Assessment .........................................................................17
2.3.2.
Benefit Assessment.....................................................................20
2.3.3.
Overall Benefit:Risk Conclusion...................................................20
3.
OBJECTIVES AND ENDPOINTS...........................................................................20
4.
STUDY DESIGN ....................................................................................................20
4.1.
Overall Design ............................................................................................20
4.2.
Scientific Rationale for Study Design ..........................................................20
4.3.
Justification for Dose ..................................................................................21
4.4.
End of Study Definition ...............................................................................21
5.
STUDY POPULATION...........................................................................................21
5.1.
Inclusion Criteria.........................................................................................22
5.2.
Exclusion Criteria........................................................................................23
5.3.
Lifestyle Considerations..............................................................................25
5.3.1.
Meals and Dietary Restrictions ....................................................25
5.3.2.
Alcohol, and Tobacco ..................................................................25
5.3.3.
Activity .........................................................................................25
5.3.4.
Other restrictions .........................................................................25
5.4.
Screen Failures...........................................................................................25
6.
STUDY INTERVENTION(S)...................................................................................26
6.1.
Study Intervention(s) Administered .............................................................26
6.1.1.
Medical Devices...........................................................................27
6.2.
Preparation/Handling/Storage/Accountability..............................................27
6.3.
Measures to Minimize Bias: Randomization and Blinding ...........................28
6.4.
Study Intervention Compliance ...................................................................28
6.5.
Concomitant Therapy..................................................................................28
6.5.1.
Permitted Medications .................................................................28
6.5.2.
Prohibited Medications and Non-Drug Therapies.........................29
6.6.
Dose Modification .......................................................................................29
6.7.
Intervention after the End of the Study........................................................29
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL.....................................................................29
7.1.
Discontinuation of Study Intervention..........................................................29
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
6
7.1.1.
Liver Chemistry Stopping Criteria ................................................29
7.1.2.
QTc Stopping Criteria ..................................................................29
7.1.3.
Temporary Discontinuation ..........................................................30
7.2.
Participant Discontinuation/Withdrawal from the Study ...............................30
7.3.
Lost to Follow Up........................................................................................30
8.
STUDY ASSESSMENTS AND PROCEDURES .....................................................31
8.1.
Efficacy Assessments.................................................................................32
8.2.
Safety Assessments ...................................................................................32
8.2.1.
Physical Examinations.................................................................33
8.2.2.
Vital Signs....................................................................................33
8.2.3.
Local tolerance evaluation ...........................................................33
8.2.4.
Electrocardiograms......................................................................33
8.2.5.
Clinical Safety Laboratory Assessments ......................................33
8.3.
Adverse Events and Serious Adverse Events.............................................34
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information...................................................................................34
8.3.2.
Method of Detecting AEs and SAEs.............................................34
8.3.3.
Follow-up of AEs and SAEs.........................................................35
8.3.4.
Regulatory Reporting Requirements for SAEs .............................35
8.3.5.
Pregnancy ...................................................................................35
8.3.6.
Medical Device Incidents (Including Malfunctions).......................36
8.3.6.1.
Time Period for Detecting Medical Device 
Incidents.....................................................................36
8.3.6.2.
Follow-up of Medical Device Incidents........................36
8.3.6.3.
Prompt Reporting of Medical Device Incidents 
to Sponsor..................................................................36
8.3.6.4.
Regulatory Reporting Requirements for 
Medical Device Incidents............................................37
8.4.
Treatment of Overdose...............................................................................37
8.5.
Pharmacokinetics .......................................................................................37
8.5.1.
Sample Analysis ..........................................................................38
8.6.
Pharmacodynamics ....................................................................................38
8.7.
Genetics .....................................................................................................38
8.8.
Biomarkers .................................................................................................38
8.9.
Health Economics OR Medical Resource Utilization and Health 
Economics..................................................................................................38
9.
STATISTICAL CONSIDERATIONS........................................................................38
9.1.
Sample Size Determination ........................................................................38
9.1.1.
Sample Size Assumptions ...........................................................38
9.1.2.
Sample Size Sensitivity................................................................39
9.1.3.
Sample Size Re-estimation..........................................................39
9.2.
Populations for Analyses ............................................................................40
9.3.
Statistical Analyses.....................................................................................40
9.3.1.
Pharmacokinetic Analyses...........................................................40
9.3.2.
Safety Analyses...........................................................................40
9.3.2.1.
Adverse events...........................................................40
9.3.2.2.
Clinical laboratory evaluation......................................41
9.3.2.3.
Vital signs...................................................................41
9.3.2.4.
12-lead ECG...............................................................41
9.3.3.
Interim Analyses ..........................................................................41
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
7
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS...............................................................................................42
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................42
10.1.1.
Regulatory and Ethical Considerations ........................................42
10.1.2.
Financial Disclosure.....................................................................42
10.1.3.
Informed Consent Process ..........................................................43
10.1.4.
Data Protection............................................................................43
10.1.5.
Committees Structure ..................................................................43
10.1.6.
Dissemination of Clinical Study Data ...........................................44
10.1.7.
Data Quality Assurance ...............................................................44
10.1.8.
Source Documents ......................................................................45
10.1.9.
Study and Site Closure ................................................................45
10.1.10. Publication Policy.........................................................................46
10.2.
Appendix 2: Contraceptive Guidance and Collection of Pregnancy 
Information..................................................................................................47
10.3.
Appendix 3:  Clinical Laboratory Tests........................................................50
10.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................52
10.4.1.
Definition of AE............................................................................52
10.4.2.
Definition of SAE..........................................................................53
10.4.3.
Recording and Follow-Up of AE and SAE....................................54
10.4.4.
Reporting of SAE to GSK.............................................................56
10.5.
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments ..............................................................................................57
10.6.
Appendix 6: Medical Device Incidents: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......................................59
10.7.
Appendix 7: Abbreviations and Trademarks................................................61
11. REFERENCES.......................................................................................................63
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
8
1.
PROTOCOL SUMMARY
1.1.
Synopsis
Protocol Title: An open-label, randomized, parallel group, single dose study to 
investigate the PK and safety of belimumab 200 mg intravenous and 200 mg 
subcutaneous via auto-injector in Chinese healthy participants.
Short Title: Single dose study to investigate the PK and safety of belimumab 200 mg 
intravenous and 200 mg subcutaneous via auto-injector in Chinese healthy participants.
Rationale:
The purpose of this study is to characterize the pharmacokinetic profile and safety profile
of 200 mg single dose of belimumab, administered either intravenously or
subcutaneously via auto-injector in Chinese healthy participants. In the global 
development program, both belimumab intravenous (IV) and belimumab subcutaneous
(SC) administration of belimumab have been evaluated. Following the global SC 
formulation development, this Phase I study in healthy Chinese participants will 
investigate the safety and PK of belimumab after single dose SC administration of a 
200 mg/mL liquid formulation. The dose used in this study is the same as the dose used 
in the Phase III study (study BEL112341) in the global development of belimumab SC.
The same dose, 200 mg, given IV will also be tested to compare the safety and 
pharmacokinetic profile between the subcutaneous and intravenous administrations. All 
PK data collected from the study will be combined with other PK data available and 
analyzed using a population PK (POPPK) model. The POPPK analysis results will be 
reported separately. The data from this study, and the planned POPPK analysis will be 
used to support belimumab SC for China regulatory market application in SLE and other 
autoimmune disease.
Objectives and Endpoints:
Objectives
Endpoints
Primary
To characterize the PK profile of belimumab
200 mg after intravenous and subcutaneous 
administration via auto-injector in healthy 
Chinese participants
Individual concentration-time profiles, and 
median/mean profiles of belimumab by 
treatment groups.
Secondary
To evaluate the safety and tolerability of IV
and SC administration via auto-injector of 
belimumab 200 mg in healthy Chinese 
participants
Safety parameters including vital signs, ECGs, 
clinical laboratory test, local tolerance 
evaluation (injection site), and adverse events.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
9
Overall Design:
This is an open-label, randomized, parallel group, single dose study in Chinese healthy 
participants. Each participant will receive single dose of belimumab administered either 
intravenously or subcutaneously. Intravenous dose will be administered over 
approximately 1 hour. The diluted solution volume for IV will be 250 mL in total. The 
subcutaneous dose will be administered in the thigh via prefilled auto-injector device.
The injection may take up to 15 seconds to complete.  
Disclosure Statement: 
This is parallel group 2 arm, open-label study.
Number of Participants:
Thirty-six participants will be enrolled.
Intervention Groups and Duration:
Treatment Groups and Duration: Participants will be assigned to Group A or B as 
shown in the following table in accordance with the randomization. Randomization will 
be stratified by body weight (<65 kg and ≥65 kg). In each stratum, the participants will be 
allocated to the two treatment groups by 1: 2 (IV:SC) ratio.
Group A (N=12)
Group B (N=24)
belimumab 200 mg single IV
belimumab 200 mg single SC
Data Monitoring Committee: No.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
10
1.2.
Schema
Figure 1
Study Design
In patient, 
sampling
Outpatient
SC, 200 mg, N=24
Enrollment and 
Randomization 
IV, 200 mg, N=12
Day -1
Day -14
Screening
Admission
Day 5
Unit discharge(IV)
Day 71
End of study
Day 8
Unit discharge(SC)
Day 1
Dosing
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
11
1.3.
Schedule of Activities (SoA)
Study Day
Screening
(-14~-1)
-1
1
2
3
4
Hour (Relative to dose completion)
Pre-
dose
-1 h
-30 
min
0 h
1 h
2 h
4 h
6 h
12 h
24 h
36 h
48 h
60 h
72 h
84h
Informed consent
X
Outpatient visit
X
Admission to unit
X
Demographics and Medical historya
X
Body weight and BMIb
X
X
Height 
X
Inclusion/Exclusion Criteria 
X
X
X
Randomization
X
Laboratory and Clinical
Urine Drug Screen
X
Alcohol Breath Test
X
HIV, syphilis, HepB and HepC Screen
X
Chest X-Ray
X
QuantiFERON-TB Gold Test
X
Pregnancy test (female with fertility) c
X
Xc
12-lead ECG d
X
Hematological/Chemical/Urinalysis tests
X
Xo
IgA, IgM and IgG
X
Physical examination
X
X
Xe
Xe
Xe
Xe
Vital signs f
X
X 
X
X
X
X
X
X
X
X
X
X
X
AE, SAE assessment g
=============================================================================================
Concomitant drug review
=============================================================================================
Dosing and PK Sampling 
Study Treatment Dosing IV only
1 h h
Study Treatment Dosing SC
X
PK blood sample IV
X
Xn
X
X
X
X
X
X
PK blood sample SC
X
X
X
X
X
Local tolerance evaluation (SC only) j
Xk
X
X
Xl
Xl
Xl
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
12
Study Day
5
6
7
8
11i,m
15 i,m
22 i,m
29 i,m
43 i,m
57 i,m
71/Follow-up i,m
Hour (Relative to dose completion)
96 h
120 h
144 h
168 h
240 h
336 h
504 h
672 h
1008 h
1344 h
1680 h
Outpatient visit
Xm
Xi
X
X
X
X
X
X
Discharge
Xm
Xi
Laboratory and Clinical
Pregnancy test (Only for female with 
fertility) C
X
X
X
12-lead ECGd
X
Hematological/Chemical/Urinalysis tests
X
X
X
X
IgA, IgM and IgG
X
X
X
X
AE, SAE assessment g
============================================================================
Concomitant drug review
============================================================================
Physical examination
Xe
Xie
Xie
Xe
Xie
Xe
Xe
Xe
Xe
Xe
X
Vital signs
X 
Xi
Xi
X
Xi
X
X
X
X
X
X
PK blood sample IV
X
X
X
X
X
X
X
X
PK blood sample SC
X
X
X
X
X
X
X
X
X
X
X
Local tolerance evaluation (SC only) j
Xl
a.
Medical history includes allergy history, alcohol and smoking history, use of concomitant medication, blood donation history, other clinical trials attendance 
history, general condition and other which would be assessed as related to the Inclusion/Exclusion Criteria listed in Section 5.1 and Section 5.2.
b.
Body weight on day-1 would be used for study stratification.
c.
Pregnancy (serum or urine) test is only for female participants with fertility. Urine pregnancy test is required at screening visit, Day 29, Day 57 and Day 71. 
Serum pregnancy test is required at Day -1. Only conduct serum pregnancy test for subjects screened on Day -1. Pregnancy beyond Day 71 and within 16 
weeks will be assessed with a home kit and participants can report the results via phone to site.
d.
Single ECG, or triplicate ECGs obtained over a brief recording period. 
e.
Symptom-driven physical examination.
f.
Vital signs include BP (sitting position), heart rate and tympanic temperature. Standing and supine BP will be additionally collected on Day -1. 
g.
SAE collection will start from inform consent, AE collection will start from study treatment administration. Injection site reactions (e.g., induration, erythema, 
edema, rash, pruritis, pain) are to be recorded on the AE form of CRF.
h.
The IV infusion time will be over and close to 1hour. It’s important to record the actual infusion start time and completion time in the medical notes.
i.
SC only. The outpatient visits planned for SC is on Day 11,15, 22, 29, 43, 57,71.
j.
Local tolerance evaluation: inspection of injection site reactions (e.g., induration, erythema, edema, rash, pruritis, pain) are to be recorded on the AE form of 
CRF.
k.
Immediately after injection completed.
l.
Local tolerance evaluation windows on Day 2,3,4,5 are ±4hrs. 
m.
IV only. The outpatient visits planned for IV is on Day 8,15,22,29,43,57,71.
n.
The -30 min PK timepoint is calculated at 30 mins after the start of belimumab IV infusion. 
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
13
o.
Clinical laboratory test results at screening visit will be used for inclusion/exclusion assessment. For subjects who screened on Day-1, only conduct laboratory 
tests once on the same day. 
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
14
2.
INTRODUCTION
2.1.
Study Rationale
Belimumab (belimumab) is a recombinant, human, immunoglobulin G1 lambda (IgG1λ) 
monoclonal antibody that binds and antagonizes the biological activity of soluble B 
lymphocyte stimulator (BLyS) protein, a member of the tumor necrosis factor (TNF) 
ligand superfamily that promotes the survival of B lymphocytes and stimulates the 
differentiation of B cells into immunoglobulin-producing plasma cells. The biologic 
profile of belimumab suggests that it may have therapeutic benefit in the treatment of 
autoimmune diseases where BLyS appears to play a role in disease pathogenesis. In the 
treatment of systemic lupus erythematosus (SLE), corticosteroids are generally indicated. 
The initial dose is determined according to the severity of disease. In active cases with 
severe visceral lesions, coadministration of immunosuppressants is considered. For these 
treatments, there are concerns about adverse reactions or lack of efficacy in refractory 
cases. Thus, there is an urgent need for drugs with improved efficacy and safety for the 
treatment of SLE.
In the global development program, both intravenous (IV) and subcutaneous (SC) 
administration of belimumab have been evaluated. The first market product was 
belimumab IV, which was initially approved in the US on 09 March 2011 for the 
treatment of adult patients who had active, autoantibody-positive SLE and were receiving 
standard therapy. The approved dosing regimen is 10 mg/kg by intravenous infusion over 
1 hour every 2 weeks for 3 doses and then every 4 weeks thereafter. Overall, marketing 
approval of Benlysta IV has been achieved in over 65 countries by the end of 2016.
Following Benlysta IV, Benlysta SC has been approved in US and other countries since 
2017. 
In the China development program, the clinical trials for Benlysta IV including a 
completed phase I study (study number 200909_single dose PK study in SLE patients,
GlaxoSmithKline Document number 2017N342008_00) and a completed regional phase 
III study (study number BEL113750_regional study to evaluate the efficacy and safety of 
belimumab IV 10 mg/kg in subjects with active SLE of Northeast Asia, GlaxoSmithKline 
Document number, 2014N216965_01 ). The planned study described in this protocol will 
assess the safety, pharmacokinetic profile of 200 mg IV and 200 mg SC in Chinese 
healthy participants. The data of this study will be used to bridge other Benlysta IV and 
SC clinical data to support the registration of belimumab SC administration in China.
2.2.
Background
In vitro and in vivo studies of belimumab have demonstrated its ability to bind BLyS and
inhibit its activity, while animal models and ex vivo data collected from patients with 
RA, SLE, Sjogren’s Syndrome, ITP and ANCA-associated vasculitis (e.g., Wegner’s 
granulomatosis) suggest that elevated BlyS levels may be associated with the 
pathogenesis of these autoimmune diseases in which B cells are dysregulated as 
evidenced by pathogenic autoantibody production [Zhang, 2001; Cheema, 2001; Groom, 
2002; Sanders, 2006; Emmerich, 2007; Petri, 2008; Bosello, 2008; Schneeweis, 2010]. In 
cynomolgus monkeys, belimumab has been shown to significantly reduce B cell 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
15
representation in lymphoid tissue after 1 month of treatment and reduce peripheral blood 
B cells after 3 months of treatment. The ability of belimumab to reduce B cells led may 
be helpful for the reduction of B lymphocyte activity in patients with autoimmune 
disease. A detailed description of the chemistry, pharmacology, efficacy, and safety of 
belimumab is provided in the Investigator Brochure (IB) [GlaxoSmithKline Document 
number 2011N128591_05, IB Version 15].
2.3.
Benefit/Risk Assessment
Belimumab has been generally well tolerated in the clinical trial populations studied.
In a Phase I study (Study BEL114448), including both SC and IV formulations of 
belimumab in 118 healthy participants, the most frequent AEs were injection site pain, 
headache, injection site erythema, diarrhea, and pharyngitis. In the SC multiple-dose 
groups, 2 SAEs were reported. One subject experienced serious appendicitis (possibly 
related, resolved) on Day 13 (after 2 injections) resulting in discontinuation of study 
agent and another subject with a history of a torn anterior cruciate ligament and right 
knee pain reported moderate pain in extremity (not related) that occurred on Day 1. There 
were no serious or severe injection site reactions reported, and most reports of pain were 
mild and occurred immediately after the injection. No hypersensitivity reactions or deaths 
were reported.
In a Phase I SC study (BEL116119, GlaxoSmithKline Document Number 
2012N137242_00) including 16 healthy male Japanese subjects who were randomized 
and treated with a single dose of 200 mg belimumab administered by either IV infusion 
or SC injection. In total, 7 AEs were observed in 5 subjects. All events were mild or 
moderate in intensity. Six AEs were reported in 4 subjects in the IV group, and 1 AE was 
reported in the SC group. No AEs related to injection site reactions were reported during 
the study. Among 7 AEs, one event (cellulitis) reported in the IV group was judged to be 
related to the belimumab. No SAEs or deaths were reported during this study. There were 
no withdrawals, and all 16 subjects completed the study. No clinically significant changes 
were noted in vital sign, electrocardiogram (ECG) or laboratory test except those judged 
as AEs.
In Phase III IV study(BEL113750) of the Northeast Asia, the incidences of AEs during 
the double-blind period in the belimumab group were similar with or lower than those in 
the placebo group. SAEs were reported overall for 18.3% and 12.3% of participants in 
the placebo and belimumab 10 mg/kg IV groups, respectively. The SAE with overall 
highest incidence was infections and infestations (5.5% placebo, 5.3% belimumab). No 
clinically meaningful differences were observed between treatment groups with regards
to the incidence of SAEs. In sub-group analysis of the China cohort, SAEs were reported 
for 14.4% and 9.0% of subjects in the placebo and belimumab10 mg/kg groups, 
respectively. In both treatment groups, the incidence of SAEs in the China cohort was 
lower than the Overall population (18.3% placebo, 12.3% belimumab) and the Not-China 
cohort (30.9% placebo, 23.8% belimumab). The incidence of SAE in infections and 
infestations was 5.6% for placebo and 3.6% for belimumab).
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
16
Identified risks include hypersensitivity/infusion reactions and infections. Potential risks 
include malignancies; immunogenicity; effects on immunizations, including interactions
with live vaccine; and psychiatric events including depression and suicidality.
Malignancy and immunogenicity risks are theoretically associated with long-term use.
Further details about the potential risks and expected benefits of belimumab can be found 
in the IB [GlaxoSmithKline Document number 2011N128591_05, IB Version 15]
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
17
2.3.1.
Risk Assessment
Known/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) [GSK 1550188]
Hypersensitivity and Post-Injection and 
Infusion Reactions
Administration of belimumab may result in 
infusion and hypersensitivity reactions, which 
can be severe and can be fatal. Serious infusion 
and hypersensitivity reactions affected less than 
1% of patients and included: anaphylactic 
reaction, bradycardia, hypotension, angioedema, 
and dyspnoea. Delays in the onset of 
hypersensitivity reactions have been observed. 
Infusion reactions following administration of 
belimumab occurred more frequently on the first 
2 infusion days and tended to decrease with 
subsequent administrations. Delayed-type, non-
acute hypersensitivity reactions have also been 
observed and included symptoms such as rash, 
nausea, fatigue, myalgia, headache, and facial 
oedema.
In the clinical study for BENLYSTA administered 
subcutaneously, the frequency of injection site 
reactions was 6.1% (34/556) for patients 
receiving BENLYSTA plus standard therapy and 
2.5% (7/280) for patients receiving placebo plus 
standard therapy. These injection site reactions 
(most commonly pain, erythema, hematoma,
Exclusion of participants with a history of atopy 
or anaphylactic reaction to any food, drug or 
insect bite/sting or a history of allergic reaction to 
parenteral administration of contrast agents, 
foreign proteins, or monoclonal antibodies.
Participants will remain under medical 
supervision in the institute at least up to the 96 
hours post dose assessments, which should 
be long enough to detect early reactions to the 
study drug.
Participants will be made aware of the potential 
risk, the signs and symptoms of such reactions, 
and the importance of immediately seeking 
medical attention. Belimumab will be 
administered by a healthcare professional 
prepared to treat hypersensitivity reactions 
including anaphylaxis.
The local injection site reaction will be evaluated 
for SC group during the study.  
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
18
Known/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
pruritus, and induration) were mild to moderate in 
severity. The majority did not necessitate 
discontinuation of treatment.
Infections
Infections occurred in a slightly greater 
proportion of participants treated with belimumab 
compared with placebo. Infections occurring in at 
least 3% of patients receiving belimumab and at 
least 1% more frequently than patients receiving 
placebo were nasopharyngitis, bronchitis, 
pharyngitis, cystitis, and gastroenteritis viral.  
Serious infections occurred in 5% of patients 
receiving either belimumab or placebo
Exclude participants with a history of any 
infection requiring hospitalization, antivirals or 
antibiotics within 4 weeks prior to Day 1., a 
history of or positive test at screening for HIV, 
Grade 3 or 4 lymphopenia, Grade 3 or 4 IgG or 
IgA deficiency. Patients will be excluded for 
serologic evidence of Hepatitis C (positive test) 
and evaluated for serologic evidence of Hepatitis 
B (HB) infection (HbsAg and anti-HbcAb). 
Patients with a positive HbsAg or a positive anti-
HbcAb will be excluded.  
Monitor patients for signs and symptoms of 
infection, monitor laboratory values, and request 
that patients report signs of infection.  Treat 
infections immediately and appropriately. 
If patient becomes hepatitis B core antibody 
positive and/or develop an ALT and/or AST >2.5
x ULN, obtain quantitative hepatitis B virus 
Deoxyribonucleic acid (DNA). If the quantitative 
hepatitis B virus DNA result shows detectable 
viral loads, then the participant must be treated 
immediately and appropriately.
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
19
Known/Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Effects on immunizations including reactions 
with live vaccines
No data are available on the secondary 
transmission of infection from persons receiving 
live vaccines to patients receiving belimumab.
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.  Limited data suggest that belimumab 
does not significantly affect the ability to maintain 
a protective immune response to immunizations 
received prior to administration of belimumab. 
The study will exclude patients who have 
received a live vaccine within 30 days of Day 1
or anticipate receipt of a live vaccine during the 
study.
Do not administer live vaccines concurrently.
Malignancies
As with other immunomodulating agents, the 
mechanism of action of belimumab may increase 
the potential risk for the development of 
malignancies.
Exclude patients with a history of malignant 
neoplasm within the last 5 years, except for 
adequately treated basal or squamous cell 
cancers of the skin, or carcinoma in situ of the 
uterine cervix.
Monitor patients for signs and symptoms of 
malignancy, monitor laboratory values, request 
that patients report signs and symptoms. Treat 
appropriately.
 
 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
20
2.3.2.
Benefit Assessment
Participants enrolled into this study are Chinese healthy participants. The participants’ 
involvement will contribute to the PK and safety profiles of belimumab IV and SC in the 
Chinese population.
2.3.3.
Overall Benefit:Risk Conclusion
This study will be conducted in healthy participants. Risk mitigation measures have been 
taken to minimise the risk to participants in this study. 
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To characterize the PK profile of belimumab
200 mg after intravenous and subcutaneous 
administration via auto-injector in healthy 
Chinese participants 
Individual concentration-time profiles, and 
median/mean profiles of belimumab by 
treatment groups.
Secondary
To evaluate the safety and tolerability of IV 
and SC administration via auto-injector of 
belimumab 200 mg in healthy Chinese 
participants
Safety parameters including vital signs, ECGs, 
clinical laboratory test, local tolerance 
evaluation (injection site), and adverse events.
4.
STUDY DESIGN
4.1.
Overall Design
This is an open-label, randomized, parallel group, single dose study in healthy Chinese 
participants. Each participant will be randomized at 1:2 ratio to receive one treatment of 
either IV or SC administration of belimumab 200 mg.  The intravenous dose will be 
administered over approximately 1 hour. The diluted solution volume for IV will be 
250 mL in total. The subcutaneous dose will be administered in the front of the thigh via
auto-injector device within approximately 15 seconds. The total study duration is 
approximately 13 weeks.
Protocol waivers or exemptions are not allowed with the exception for immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Schedule of activities (SOA) Table Section 1.3, are essential and required 
for study conduct.
4.2.
Scientific Rationale for Study Design
This is an open label study in which belimumab will be administered either intravenously 
or subcutaneously to each participant. A parallel design is selected as the t1/2 of 
belimumab is longer than 2 weeks (18-19 days) based on the POPPK analysis, and 
therefore a washout of at least 10 weeks would have been required for a crossover design.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
21
4.3.
Justification for Dose
An international Phase III study (BEL112341, GlaxoSmithKline Document Number,
2014N216963_01) of the SC formulation of belimumab over 52 weeks has been 
completed in 2016, and the efficacy and safety have been confirmed. belimumab SC was 
received FDA approval in 2017 to treat adult patients who had active, 
autoantibody-positive SLE and were receiving standard therapy. China had conducted a 
regional Phase III study BEL113750 for IV formulation and the data will be used to 
support the belimumab IV in China Market application. In addition, there is a completed 
single dose Phase I study 200909 which investigated the safety, tolerability and PK/PD of 
single dose IV belimumab 10 mg/kg in Chinese participants with SLE. 
Following a single SC administration of the 200 mg/mL solution belimumab product in 
healthy non-Chinese participants (study BEL114448), the absolute bioavailability of 
belimumab ranged from 72%-76%. As expected, IV dosing results in higher steady-state 
Cmax and lower steady-state Cmin than SC dosing. 
Following the global SC formulation development, this Phase I study in healthy Chinese 
participants will investigate the safety and PK of belimumab after single dose SC 
administration of a 200 mg/mL liquid formulation. The dose used in this study is the 
same as that used in the Phase III study in the global development of SC belimumab. The 
200 mg IV dose will also be tested to compare the safety and pharmacokinetic profiles
between the SC and IV administrations. There are observed differences between Chinese 
and western populations related to e.g. body weight in that exposure in Chinese subjects 
are on average higher, but the difference is clinically insignificant because of the safety 
profiles of belimumab (up to 20 mg/kg IV and 240 mg SC dose regimens were tested in 
previous studies). The distribution of individual steady-state average concentration 
(Cavg_ss) observed following 10 mg/kg IV dosing every 4 weeks and those estimated 
from 200 mg SC weekly dosing (from post-hoc of POPPK analysis, based on data from 
study C1056, C1057 and BEL113750) are largely overlapping, supporting the potential 
efficacy of the SC 200 mg QW dosing. Therefore, the two dosing regimens of IV 
10 mg/kg Q4W and 200 mg QW chosen for this PK study is considered reasonable. 
The data from this study will be used to support belimumab SC in China regulatory 
application including SLE and other autoimmune disease.
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the follow-up visit.
The end of the study is defined as the last participant’s last visit.
5.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
22
5.1.
Inclusion Criteria
Informed Consent
1.
Capable of giving signed informed consent as described in Appendix 1 which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
Age 
2.
Chinese healthy male or female between 18 and 45 years of age inclusive, at the time 
of signing the informed consent.
Type of Participant
3.
Healthy as defined as being free from clinically significant illness or disease as 
determined by a responsible and experienced physician, based on a medical 
evaluation including medical history, physical examination, vital sign, laboratory 
tests and ECG. A subject with a clinical abnormality or laboratory parameter(s) 
which is/are not specifically listed in the inclusion or exclusion criteria, outside the 
reference range for the population being studied, may be included only if the 
investigator (in consultation with the GSK medical monitor if necessary) agree and 
document that the finding is unlikely to introduce additional risk factors and will not 
interfere with the study procedures.  
4.
Non-smoker or ex-smoker having ceased smoking for at least 6 months
Weight
5.
Body weight ≥45.0 kg for females, ≥50.0 kg for males, and BMI (body mass index) 
within the range 19.0≤-≤26.0kg/m2.
Sex
6.
Both male and female subjects are eligible to participate.
A female participant is eligible to participate if she is not pregnant (see Appendix 2), 
not breastfeeding, and at least one of the following conditions applies:
i.
Not a woman of childbearing potential (WOCBP) as defined in Appendix 2
OR
ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2
during the treatment period and for at least 16 weeks after the last dose of 
belimumab.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
23
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Laboratory Assessment
1.
A positive test for syphilis, positive Hepatitis C antibody, HIV antigen /antibody, at
screening. For Hepatitis B: participants with a positive HbsAg and/or a positive anti-
HBc result will be excluded. 
2.
A positive result of pre-study drug screen (including at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines).
3.
Alanine transaminase (ALT) or Alanine phosphatase(AST)>1.2x upper limit of 
normal (ULN).  
4.
Bilirubin >1.2xULN (isolated bilirubin >1.2xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%). 
5.
QTc >450 msec based on single ECG. 
NOTES:

The QTc is the QT interval corrected for heart rate according to Bazett’s 
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-
read or manually over-read.

The specific formula that will be used to determine eligibility and 
discontinuation for an individual subject should be determined prior to initiation 
of the study. In other words, several different formulae cannot be used to 
calculate the QTc for an individual subject and then the lowest QTc value used 
to include or discontinue the subject from the trial.
6.
Immunoglobulin (M, A, G) level is < Lower limit of normal (LLN) at screening.
Medical Conditions
7.
Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert’s syndrome or asymptomatic gallstones).
8.
History of major organ transplant: e.g., heart, lung, kidney, liver, or hematopoietic 
stem cell transplant. 
9.
History of malignant neoplasm within the last 5 years, except for adequately treated 
basal or squamous cell cancers of the skin, or carcinoma in situ of the uterine cervix. 
10. Participants with a sitting position systolic blood pressure <90 mmHg or ≥140 
mmHg and/or a sitting diastolic blood pressure <50 mmHg or ≥90 mmHg and/or 
systolic blood pressure drop from supine to standing of >30 mmHg.
11. Symptomatic herpes zoster within 3 months prior to screening. 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
24
12. Evidence of active or latent tuberculosis (TB) as documented by medical history and 
examination, chest X-rays (posteroanterior) and a positive (not indeterminate) 
QuantiFERON-TB Gold test.
NOTE: The use of QuantiFERON-TB Gold test is dependent on previous 
treatment(s). This test may not be suitable if previous treatment(s) produced 
significant immunosuppression.
13. History of any infection requiring hospitalization or treatment with antivirals, 
antibiotics, anti-fungals, anti-parasitic agents or vaccination within 30 days prior to 
the administration of study medication.
14. History of regular alcohol consumption exceeding, on an average, 14 drinks/week for 
men or 7 drinks/week for female (1 drink = 5 ounces [150 mL] of wine or 350 mL of 
beer or 1.5 ounces [45 mL] of 80 proof distilled spirits) within 6 months of 
screening.
Prior/Concurrent Clinical Study Experience
15. The participant had participated in a clinical study or post-marketing study with an 
investigational or a non-investigational product during the previous 4 months or 5 
half-lives (whichever is longer) preceding the administration of study medication of 
this study.
16. Exposure to more than 4 new chemical entities within 12 months prior to the dosing 
day.
17. The participant planned to concurrently participate in another clinical study or post-
marketing study.
Prior/Concomitant Therapy
18. Use of any prescription or non-prescription medications including vitamins, herbal 
and dietary supplements within the 14 days or 5 half-lives (whichever is longer) prior 
to the administration of study medication. 
19. History of B cell targeted therapy (rituximab, other anti-CD20agents, anti-CD22 
[epratuzumab], anti-CD52 [alemtuzumab], BlyS-receptor fusion protein [BR3], 
TACI-Fc, LY2127399 [anti-BAFF] or belimumab) at any time.
20. Have received a live vaccine within 30 days of Day 1 or anticipate receipt of a live 
vaccine during the study or within 120 days after the last dose administration of 
study drug. 
Other Exclusions
21. History of sensitivity to any of the study medications, or components thereof or a 
history of drug or other allergy (excluding pollen allergy) without current symptoms.
22. History of anaphylactic reaction to any food, drug, or insect bite/sting.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
25
23. History of allergic reaction to parenteral administration of contrast agents, foreign 
proteins, or monoclonal antibodies.
24. Donation of blood or blood products or significant blood loss in excess of 400 ml 
within 4 months or 200 ml within 2 months prior to administration
25. Participant is mentally or legally incapacitated, or unwillingness or inability 
(including mentally or legally incapacity) to follow the procedures outlined in the 
protocol.
5.3.
Lifestyle Considerations
5.3.1.
Meals and Dietary Restrictions

Each participant must visit the medical institution at Day -1, 8 (IV group only), 29, 
57 and 71 in a fasted state for clinical laboratory tests.
5.3.2.
Alcohol, and Tobacco

Participants will abstain from ingesting alcohol for 24 hours before the start of 
dosing until final follow-up examination.

Use of tobacco products is not allowed from the time a participant gives consent to 
participate in the study until after the final follow-up visit.
5.3.3.
Activity

Participants will abstain from strenuous exercise for 48 hours before each blood 
collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (e.g., watching television, reading).
5.3.4.
Other restrictions

Participants must refrain from taking any other medication (prescription, 
nonprescription, herbal and dietary supplements) from administration of study 
medication until the study period, with the exception for medication for treatment of 
adverse event permitted by investigator/sub-investigator.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized 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 
Study Intervention includes demography, screen failure details, eligibility criteria, and 
any serious adverse events (SAEs). Laboratory retest is allowed if required or if 
investigator judged any error in lab result.
Individuals who do not meet the criteria for participation in this study (screen failure) 
may not be rescreened.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
26
6.
STUDY INTERVENTION(S)
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol.
6.1.
Study Intervention(s) Administered
Study Intervention
Product name:
Belimumab 400 mg vial for IV
Belimumab 200 mg/mL auto-
injector for SC
Formulation description:
Belimumab 400 mg per vial 
plus excipients (Citric acid 
monohydrate / Sodium citrate 
dehydrate / Sucrose / 
Polysorbate 80)
200 mg/mL belimumab in 
0.65 mg/mL L-histidine, 
1.2 mg/mL L-histidine 
monohydrochloride, 6.7 mg/mL 
sodium chloride, 5.3 mg/mL 
L-arginine hydrochloride, 
0.1 mg/mL polysorbate 80, with 
pH 6.0.
Dosage form:
Lyophilized cake for 
reconstitution and dilution in 
normal saline
Sterile, liquid product
Unit dose 
strength(s)/Dosage level(s):
400 mg per vial (to contain 
80 mg/mL when reconstituted 
with 4.8 mL sterile water for 
injection [SWFI]) /200 mg per 
dose
200 mg/mL; 1 mL (deliverable)
Route/ Administration/ 
Duration
Intravenous / Single dose
SC injection/single dose
Dosing instructions:
Should be infused 
approximately over 1 hr
Single dose in the front of the 
thigh 
Physical description:
White to off-white cake in a 
20 mL vial
Clear to opalescent, colorless 
to pale yellow sterile solution 
sterile solution for SC injection 
in a single-use, prefilled 
syringe contained within an 
auto-injector device
Manufacturer/source of 
procurement:
Drug substance: manufactured 
by GSK GMS BIOPHARM US 
(Rockville).
Drug Product: manufactured by 
GSK Parma, Italy.
The auto-injector components 
are manufactured by 
Scandanavian Health Limited 
(SHL) and assembled with the 
prefilled syringe at GSK, 
Barnard Castle, UK
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
27
Study Intervention
Method for individualizing 
dosage:
Solution volume will be 
adjusted by a pharmacist in the 
institute
(Calculated dose is diluted into 
a normal saline IV bag for 
infusion)
No adjustment
Device
Intravenous cannula and 
infusion equipment (provided 
by clinical site)
Auto-injector
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 is injection device the auto-injector.

The auto-injector components are manufactured by Scandanavian Health Limited 
(SHL).  The auto-injector components are assembled with the prefilled syringe at 
GSK Barnard Castle.

Instructions for use of these injection devices are provided in the Study Reference 
Manual (SRM).

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 8.3.6).
6.2.
Preparation/Handling/Storage/Accountability
1.
The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment.
2.
Only participants enrolled in the study may receive study treatment and only 
authorized site staff administer study treatment. All study treatments 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. Study treatment is to be stored at 2-8°C 
(refrigerator) /protected from direct sunlight/etc. Maintenance of a temperature log 
(manual or automated) is required.
3.
The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). The 
investigator or the head of the medical institution, or designated site staff (IP storage 
manager) must maintain study treatment accountability records throughout the 
course of the study. The responsible person(s) will document the amount of study 
treatment received from and returned to GSK and the amount administered to 
Participants. The required accountability unit for this study will be vial/syringe. 
Discrepancies are to be reconciled or resolved.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
28
4.
A description of the methods and materials required for reconstitution of solution for 
IV dose are provided in the SRM.
5.
Further guidance and information for the final disposition of unused study treatment 
are provided in the SRM.
6.
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.
7.
Precaution will be taken to avoid direct contact with the study treatment. A 
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. Take adequate precautions to avoid direct eye or 
skin contact and the generation of aerosols or mists. Notify the GSK medical monitor 
of any unintentional occupational exposure.
6.3.
Measures to Minimize Bias: Randomization and Blinding
This is a randomized open-label study. A randomization schedule will be generated prior 
to the study by the study statistician, using an internal validated software (i.e. RandAll
NG). Participants will be randomly assigned to either IV group or SC group at 1:2 ratio.
The randomization is stratified by body weight (<65 kg and ≥65kg). 
6.4.
Study Intervention Compliance

Participants will be dosed at the site. They will receive the study intervention directly 
from the investigator or designee, under medical supervision. The date and time of 
each dose administered in the clinic will be recorded in the source documents and 
reported in the CRF. The dose of study intervention and study participant 
identification will be confirmed at the time of dosing by a member of the study site 
staff other than the person administering the study intervention.
6.5.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded along with the:

reason for use

dates of administration including start and end dates

dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy.
6.5.1.
Permitted Medications
Concomitant medications and non-drug therapy other than the investigational drug will 
not be permitted from 14 days or 5 half-lives before the first dose to the completion of the 
post-study screen (or additional/follow-up examination) other than at the discretion of the 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
29
investigator/sub investigator for instances of emergency treatment (Exclusion Criteria
Section 5.2).
6.5.2.
Prohibited Medications and Non-Drug Therapies
Live vaccine is not allowed during the study. 
6.6.
Dose Modification
There is no specific adjustment / stopping criteria for the study. Each participant will 
receive a single dose, either intravenously or subcutaneously in the study.
6.7.
Intervention after the End of the Study
Participants will not receive any additional treatment from GSK after completion of the 
study because only healthy participants are eligible for study participation.
The investigator is responsible for ensuring that consideration has been given to the 
post-study care of the participant’s medical condition, whether or not GSK is providing 
specific post-study treatment.
7.
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
7.1.1.
Liver Chemistry Stopping Criteria
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology.
These protocol guidelines are in alignment with FDA premarketing clinical liver safety 
guidance: 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf
Liver Safety Required Actions and Follow up Assessments Section can be found in
Appendix 5.
7.1.2.
QTc Stopping Criteria

The same QT correction formula must be used for each individual participant to 
determine eligibility for and discontinuation from the study.  This formula may not 
be changed or substituted once the participant has been enrolled.

For example, if a participant is eligible for the protocol based on QTcB, then 
QTcB must be used for discontinuation of this individual participant as well.

Once the QT correction formula has been chosen for a participant’s eligibility, 
the same formula must continue to be used for that participant for all QTc data 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
30
being collected for data analysis.  Safety ECGs and other non-protocol specified 
ECGs are an exception.  

The QTc should be based on the average of triplicate ECG readings obtained over a 
brief (e.g., 5-10 minute) recording period.  
A participant that meets the criteria below will be withdrawn from the study intervention.

QTcB or QTcF >500 msec
Withdrawal decisions are to be based on an average QTc value of triplicate ECGs. If an 
ECG demonstrates prolonged QTc interval, obtain 2 more ECGs over a brief period, and 
then use the averaged QTc values of the 3 ECGs to determine whether the participant 
should be discontinued from the study.
See the SoA for data to be collected at the time of intervention discontinuation and 
follow-up and for any further evaluations that need to be completed.
If participants who completed dosing of study medication meet the stopping criteria, they 
may continue safety monitoring and PK blood sampling as described in SoA, at the 
discretion of the investigators.
7.1.3.
Temporary Discontinuation
If a participant does not complete the dose of investigational product(s), the participant 
will be considered to have prematurely discontinued investigational product(s). The 
investigator must make every effort to perform the follow up assessments.
7.2.
Participant Discontinuation/Withdrawal from the Study

A participant may withdraw from the study at any time at his/her own request,
or may be withdrawn at any time at the discretion of the investigator for safety
behavioural, compliance or administrative reasons.

If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent.

If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records.

If a participantwithdraws or is withdrawn from the study, all assessments 
scheduled for the final visit should be completed, if the participant consents to 
this being done.
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:
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
31

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
8.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA. 

Detailed procedures for obtaining each assessment are provided in the SRM.

For the IV group, the end time of the infusion will be designated as Time 0. Both the 
start time and the end time of infusion should be documented in the source 
document. 

Whenever two or more examinations are scheduled for the same nominal time, the
timing of the assessments should allow the blood draw for PK analysis to occur at the 
exact nominal time. It’s essential that the exact time of blood sampling, however, 
should still be accurately recorded. 

Time assessment window of each examination is as follows:
Study Day
Hrs relative to dose
Safety examinations a
Blood sampling for
PK
Day-1
Previous day
-24 hrs
Any time
Day 1
Pre-dose
Any time before dosing
Any time before dosing
Day 1
30 mins after the start of IV 
NA
±5min
Day 1
0 h
For local tolerance 
evaluation, conduct
immediately after SC 
injectionc
+5min b
Day 1
1hrs after dose completion
±10 min
±5 min
Day 1
2-4 hrs after dose completion
±15 min
±5min
Day 1
6 hrs after dose completion
±30 min
±10 min
Day 1-2
12-24 hrs after dose completion
±1 h
±15 min
Day 2-7
36-144 hrs after dose completion ±2 h
±30 min
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
32
Study Day
Hrs relative to dose
Safety examinations a
Blood sampling for
PK
Day 8-15
168-336 hrs after dose completion± 1day b
±4 hc
± 1day b
±4 h c
Day 22-57
504-1344 hrs after dose
completion
±1 day
±1 day
Day 71
1680 hrs after dose completion
±2 days
±2 days
a.
Including physical examinations, vistal signs, local tolerance, ECG, clinical safety laboratory assessments and 
other applicable tests
b.
IV group
c.
SC group

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 treatment.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 

Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA.

The following demographic parameters will be captured: date of birth, gender, race
and ethnicity. Medical/medication/alcohol history, allergy to any drug, use of
concomitant medication, blood donation, participation in clinical trials during the
past 4 months, smoking, presence of participant’s general practitioner, general
condition, food habit will be assessed as related to the eligibility criteria listed in
Section 5.

Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples.
8.1.
Efficacy Assessments
Not applicable.
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
33
8.2.1.
Physical Examinations

A complete physical examination will include, at a minimum, assessments of the 
Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. 
Height and weight will also be measured and recorded at screening visit and/or 
day-1 per SoA.

Investigators should pay special attention to clinical signs related to previous 
serious illnesses.
8.2.2.
Vital Signs

Systolic and diastolic blood pressure (sitting position), heart rate, and tympanic
temperature will be measured. Timepoints of measurements of vital signs are 
specified in the SoA(see Section 1.3). At the discretion of the Investigator, vital 
signs may be assessed at unscheduled visits.
8.2.3.
Local tolerance evaluation

On Day 1, inspection of injection site reactions (e.g., induration, erythema, 
edema, rash, pruritis, pain) will be assessed and recorded.  All measurement 
timings are detailed in the SoA (Section 1.3) and further details is in SRM. 
8.2.4.
Electrocardiograms

A Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) 
using an ECG machine that automatically calculates the heart rate and measures 
PR, QRS, QT, and QTc intervals. Refer to Section 7.1.2 for QTc withdrawal 
criteria and additional QTc readings that may be necessary.

At each time point at which triplicate ECG are required, 3 individual ECG 
tracings should be obtained as closely as possible in succession, but no more 
than 2 minutes apart. The full set of triplicates should be completed in less than 
4 minutes.
8.2.5.
Clinical Safety Laboratory Assessments

Refer to Appendix 3 for the list of clinical laboratory tests to be performed and 
to the SoA 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 71 days after the last dose of study 
treatment should be repeated until the values return to normal or baseline or are 
no longer considered significantly abnormal by the investigator or medical 
monitor. 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
34

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 3, must be 
conducted in accordance with the laboratory manual and the SoA.
8.3.
Adverse Events and Serious Adverse Events
The definitions of an AE or SAE can be found in Appendix 4.
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7). 
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information

All SAEs will be collected from the signing of the ICF until the follow-up visit
at the time points specified in the SoA (Section 1.3). 

All AEs will be collected from the start of study treatment until the follow-up 
visit at the time points specified in the SoA (Section 1.3).

Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the case report form (CRF) not the AE section.

All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 4. 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 in former study 
participants. 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 treatment or study 
participation, the investigator must promptly notify the sponsor.
8.3.2.
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 4.

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. 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
35
8.3.3.
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, AEs 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 4.
8.3.4.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met. 

The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators.

Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary.

An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE ) from the 
sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate according to local requirements.
8.3.5.
Pregnancy

Details of all pregnancies in female participants will be collected after the start of 
study treatment and until 16 weeks following last dose.

If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy. Pregnancy beyond Day 71 and within 16 weeks will be 
assessed with a home kit and participants can report the results via phone to site. The 
pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child. Pregnancy complications and elective 
terminations for medical reasons must be reported as an AE or SAE. Spontaneous 
abortions must be reported as an SAE.
Any SAE occurring in association with a pregnancy, brought to the investigator’s (or 
sub-investigator’s) attention after the participant has completed the study and 
considered by the investigator (or sub-investigator) as possibly related to the IP, must 
be promptly reported to GSK.
If a participant has a positive pregnancy test during study participation, complete a 
Pregnancy Notification Form and fax it to GSK. Follow the participant to determine 
the outcome of the pregnancy and forward the outcome information using a 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
36
Pregnancy Follow-up Form to GSK no later than 6 to 8 weeks following the 
estimated delivery date.

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE.
8.3.6.
Medical Device Incidents (Including Malfunctions)
Medical device (Auto-injector) is being provided for use in this study. In order to fulfil
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 8.3.3 and Appendix 4 of the protocol. 
8.3.6.1.
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.

The method of documenting Medical Device Incidents is provided in Appendix
6.
8.3.6.2.
Follow-up of Medical Device Incidents

All medical device incidents involving an AE will be followed and reported in 
the same manner as other AEs (see Section 8.3.3). 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.
8.3.6.3.
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 will be sent to the sponsor by 
electronic data collection tool. If electronic system is unavailable for greater 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
37
than 24 hours, the site will use the paper SAE data collection tool and fax it to 
the SAE contactor.

The same individual will be the contact for the receipt of medical device reports 
and SAE.
8.3.6.4.
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.
8.4.
Treatment of Overdose
For this study, any dose of belimumab >200 mg within a 24-hour time period will be 
considered an overdose. GSK does not recommend specific treatment for an overdose. 
The investigator will use clinical judgment to treat any overdose.
In the event of an overdose, the investigator should:
1.
Contact the Medical Monitor immediately.
2.
Closely monitor the participant for AE/SAE and laboratory abnormalities until 
belimumab can no longer be detected systemically (at least 71 days).
3.
Obtain a serum sample for PK analysis within 71 days from the date of the last dose 
of study intervention if requested by the Medical Monitor (determined on a case-by-
case basis).
4.
Document the quantity of the excess dose as well as the duration of the overdosing in 
the CRF.
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.
8.5.
Pharmacokinetics
Whole blood samples will be collected for measurement of serum concentrations of 
belimumab as specified in the SoA. 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. Briefly, PK samples from approximately 
24 subjects in belimumab SC group will be collected at pre-dose , 6 h, 24 h, 48 h, 72 h, 
96 h, 120 h, 144 h, 168 h, 240 h, 336 h, 504 h, 672 h, 1008 h, 1344 h, and 1680 h. In 
belimumab IV group, PK samples from approximately 12 subjects will be collected at 
pre-dose , -30 mins (after the start of belimumab IV infusion), 0 h (end of infusion), 1 
h, 6 h, 24 h, 48 h, 72 h, 96 h, 168 h, 336 h, 504 h, 672 h, 1008 h, 1344 h, and 1680 h.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
38
Samples will be used to evaluate the PK of belimumab. Each serum sample will be 
divided into 2 aliquots (1 each for PK and a back-up). Samples collected for analyses of 
belimumab serum concentration may also be used to evaluate safety or efficacy aspects 
related to concerns arising during or after the study.
Details of PK blood sample collection (including volume to be collected), processing, 
storage and shipping procedures are provided in the SRM.
Non-compartmental PK analysis will not be performed for this study.
8.5.1.
Sample Analysis
PK sample would be sent to a local bioanalytical laboratory (Covance Laboratories Inc.)
and analysed using a validated method (details provided in the SRM).
8.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7.
Genetics
Genetics are not evaluated in this study.
8.8.
Biomarkers
Serum immunoglobin (IgG, IgA and IgM) analysis will be conducted per SoA. 
Since none of the SLE patients dosed with belimumab 200 mg SC tested positive for anti-
belimumab antibodies in the double-blind phase of Study BEL11234, and 
immunogenicity risks are theoretically associated with long-term use, immunogenicity 
analysis will not be investigated in this study. 
8.9.
Health Economics OR Medical Resource Utilization and 
Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study. 
9.
STATISTICAL CONSIDERATIONS
9.1.
Sample Size Determination
9.1.1.
Sample Size Assumptions
The primary objective of this study is to characterize the PK profile of belimumab 200 
mg after intravenous and subcutaneous administration in health Chinese participants.
There are no formal hypothesis to be tested and no power calculation performed. The 
sample size is determined based on following considerations, first to meet the sample size 
of 20 requirement per Chinese regulatory guidance [China FDA, 2005] for new chemical 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
39
entity, therefore, it is aimed to evaluate 20 subjects in SC group. In addition, considering 
a lower variability observed for IV group in the previous studies, the sample size for IV
group is adjusted as 10 participants. In Japan PK study BEL116119 with similar design, 
the observed Coefficient of variance (CV)% of Cmax in IV group was 17.0%, which was 
lower than the data in SC group (32.7%).  Considering the observed CV% in this PK 
study would probably be similar with it in BEL116119, the estimated 95% conference 
interval will be within 17% of point estimation of Cmax for SC group, and within 13% 
for IV group. 
The sample size is further increased to 36 assuming a drop-out rate of 20%. At least 
36 participants (30 evaluable participants) will be enrolled into the study and assigned to 
SC arm and IV arm at 2:1 ratio under each weight stratification category to obtain 
approximately 20 and 10 evaluable participants in SC and IV treatment arm, respectively.
9.1.2.
Sample Size Sensitivity
The above sample size is chosen to meet regulatory requirement for PK studies. No 
sample size sensitivity analysis will be performed.
9.1.3.
Sample Size Re-estimation
No sample size re-estimation will be performed
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
40
9.2.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign the ICF
Safety
All randomized participants who take at least 1 dose of study 
treatment. Participants will be analyzed according to the treatment 
they actually received.
Pharmacokinetic Population
The PK Population will include all participants in the Safety 
population for whom at least one evaluable PK sample will be 
obtained and analysed.
9.3.
Statistical Analyses
9.3.1.
Pharmacokinetic Analyses
Serum concentrations of belimumab will be listed and summary statistics, including 
mean, median, standard deviations per GSK IDSL standard, will be calculated by 
treatment group and nominal time. Individual concentration-time profiles and 
median/mean profiles by treatment group will be plotted on both a linear and semilog 
scale. PK analysis, e.g. non-compartmental analysis, will not be performed for this study 
alone. All PK data collected from the study will be combined with other PK data 
available and analyzed using a population PK (POPPK) model. The POPPK analysis 
results will be reported separately.
9.3.2.
Safety Analyses
All safety analyses will be performed on the Safety Population. 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards.
9.3.2.1.
Adverse events
Adverse Events will be coded using MedDRA and summarized by System Organ Class 
(SOC) and Preferred Term (PT). The number and percentage of participants with any 
adverse events occurring on or after the treatment start date will be summarized by 
treatment group.  The listing of all adverse events will be prepared. The adverse events 
related to injection site reactions will be identified on the listing.
When adverse events leading to discontinuation, fatal or non-fatal serious adverse events, 
or other significant adverse events are observed, a listing will be prepared separately.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
41
9.3.2.2.
Clinical laboratory evaluation
For clinical laboratory data, summary statistics will be calculated by treatment group and 
all observed values will be listed. The change from baseline for each parameter will be 
also summarized.
9.3.2.3.
Vital signs 
For systolic and diastolic blood pressure, heart rate, tympanic temperature and body
weight, summary statistics will be calculated by treatment group and all observed values
will be listed. The change from baseline for each variable will be also summarized.
9.3.2.4.
12-lead ECG
The ECG findings will be summarized by treatment group and the listing of ECG findings
will be prepared. For 12-lead ECG parameters, HR, PR, QRS, QT and QTc, summary
statistics will be calculated by treatment group and all observed values will be listed. The
change from baseline for each parameter will be also summarized.
9.3.3.
Interim Analyses
No interim analysis is planned in the study. 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
42
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.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
43
10.1.3.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study to 
the participant or 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 was enrolled in 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. 

A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 
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.
Committees Structure
Publication Policy

The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.

The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
44
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 subjects, 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 participant-level data from this trial available 
to external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve participant care. This helps ensure 
the data provided by trial participants are used to maximum effect in the creation 
of knowledge and understanding
10.1.7.
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. 

The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations).
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
45

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 SRM 
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
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
46
10.1.10.
Publication Policy

The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.

The sponsor will comply with the requirements for publication of study results.
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement.

Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
47
10.2.
Appendix 2: Contraceptive Guidance and Collection of 
Pregnancy Information
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below)
Women in the following categories are not considered WOCBP
1.
Premenarchal
2.
Premenopausal female with ONE of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note:  Documentation can come from the site personnel’s review of 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-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.
Contraception Guidance
Female participants
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
Table 1.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
48
Table 1
Highly Effective Contraceptive Methods
Highly Effective Contraceptivea Methods 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 ovulationb

oral

intravaginal 

transdermal 
Progestogen-only hormonal contraception associated with inhibition of ovulationb

injectable 
Highly Effective Methods That Are User Independent 

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

bilateral tubal occlusion
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. 
Sexual abstinence 
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 drug. 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.
NOTES: 
a.
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies. 
b.
Hormonal contraception may be susceptible to interaction with the standard of care medications, which may 
reduce the efficacy of the contraceptive method. In this case two highly effective methods of contraception should 
be utilized during the treatment period and for at least 16 weeks after the last dose of belimumab. If stricter female 
or male contraception requirements are specified in the country-specific label for induction and/or maintenance 
standard of care medications, they must be followed.
Pregnancy Testing

WOCBP should only be included after a confirmed menstrual period and a negative 
highly sensitive serum pregnancy test.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
49

Additional pregnancy testing during the treatment period per the SoA and at 
16 weeks after the last dose of belimumab as required locally.

Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected.

Pregnancy testing using a serum sample, with a sensitivity of 5 mIU/mL will be 
performed and assayed at Day -1. Urine pregnancy test will be conducted for all 
other scheduled pregnancy tests and in accordance with instructions provided in its 
package insert.
Collection of Pregnancy Information
Female Participants who become pregnant

Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study. 

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 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 treatment by the investigator, will be reported to GSK
as described in Appendix 4. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting. 
Any participant who becomes pregnant while participating will discontinue study 
treatment or be withdrawn from the study. Participants who discontinue study treatment 
should be encouraged to continue to participate in study visits in accordance with the 
SoA (Section 1.3), especially all remaining safety evaluations.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
50
10.3.
Appendix 3: Clinical Laboratory Tests

The tests detailed in Table 2 will be performed by the local 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.
Table 2
Protocol-Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count 
WBC count with 
Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC Count
Hemoglobin
Hematocrit
Clinical 
Chemistry1
BUN
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT)
Total and direct 
bilirubin
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT)
Total Protein
Glucose (fasting)
Calcium
Alkaline 
phosphatase
Phosphorus
Gamma 
glutamyltransferase 
(GGT)
Uric acid
CK(CPK)
TG
Amylase
LDH
Albumin
Chloride
Total cholesterol
HDL Cholesterol
LDL cholesterol
Routine
Urinalysis

Specific gravity

pH, glucose, protein, occult blood and ketones by dipstick
Other 
Screening 
Tests

Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only)

Urine drug screen3（to include at minimum: amphetamines, barbiturates, 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
51
Laboratory 
Assessments
Parameters
cocaine, opiates, cannabinoids and benzodiazepines）

Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)2

Immunology3: HIV antibody, hepatitis B surface antigen [HbsAg], anti-
hepatitis B core antibody[HbcAb] and hepatitis C virus antibody, Syphilis

IgA, IgM and IgG

Alcohol breath test3
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 and Appendix 4. 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.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC.
3.
Screening and day -1.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
52
10.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.4.1.
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 judgment of the investigator (i.e., not related 
to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.
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.

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.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
53

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.
10.4.2.
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:
o
Results in death
o
Is life-threatening
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
Requires inpatient 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.
Is a congenital anomaly/birth defect
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
54
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.
10.4.3.
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.

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.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
55
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AE and SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals.

If a participant dies during participation in the study or during a 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.

The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
56
10.4.4.
Reporting of SAE to GSK
SAE Reporting to GSK via Electronic Data Collection Tool

The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

The investigator or medically-qualified sub-investigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of SAE 
entry into the eCRF.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor/SAE coordinator by telephone.

Contacts for SAE reporting can be found in SRM.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
57
10.5.
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments 
Phase I liver chemistry stopping criteria and required follow up assessments
Liver Chemistry Stopping Criteria 
ALT-absolute
ALT≥3xULN
If ALT≥3xULN AND bilirubin1,2 2xULN (>35% direct bilirubin) or INR >1.5, 
Report as an SAE.
See additional Actions and Follow Up Assessments listed below
Required Actions and Follow up Assessments 
Actions
Follow Up Assessments

Report the event to GSK within 24 hours

Complete the liver event CRF, and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the participant until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING below)
MONITORING:
If ALT≥3xULN AND bilirubin 2xULN or INR 
>1.5

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24 
hrs

Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline

A specialist or hepatology consultation is 
recommended
If ALT≥3xULN AND bilirubin < 2xULN and INR 
≤1.5:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-
72 hrs

Viral hepatitis serology3

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend

Obtain blood sample for pharmacokinetic 
(PK) analysis when investigators consider 
appropriate

Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH).

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications on 
the concomitant medications report form 
including acetaminophen, herbal remedies, 
other over the counter medications.

Record alcohol use on the liver event 
alcohol intake case report form
If ALT≥3xULN AND bilirubin 2xULN or INR 
>1.5:

Anti-nuclear antibody, anti-smooth muscle 
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
58
Liver Chemistry Stopping Criteria 

Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline
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]. 

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 treatment 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, if INR 
measured, which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated will 
not apply to participants receiving anticoagulants
3.
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis C 
RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody 
References
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
59
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 6.1.1 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 labelling 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 

Fetal distress, fetal death, or any congenital abnormality or birth defects
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
60
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.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
61
10.7.
Appendix 7: Abbreviations and Trademarks
ABBREVIATIONS
Ae
Urinary recovery of unchanged drug
AE
Adverse Event
ALT
Alanine aminotransferase (SGPT)
AST
Aspartate aminotransferase (SGOT)
BA
Bioavailability
BlyS
B lymphocyte Stimulator
BMI
Body mass index
BP
Blood pressure
BUN
Blood urea nitrogen
CBC
Complete blood count
CI
Confidence Interval
Cmax
Maximum observed concentration
CPK
Creatine phosphokinase
CRF
Case Report Form
CV
Coefficient of variance
DBP
Diastolic blood pressure
DNA
Deoxyribonucleic acid
ECG
Electrocardiogram
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma glutamyltransferase
GLP
Good Laboratory Practice
GSK
GlaxoSmithKline
HbsAg
Hepatitis B surface antigen
HIV
Human Immunodeficiency Virus
h/hr
Hour(s)
HR
Heart rate
IB
Investigator’s Brochure
ICH
International Conference on Harmonization of Technical
IDSL
Integrated Data Standards Library
Ig
Immunoglobulin
IND
Investigational New Drug
IP
Investigational Product
IRB
Institutional Review Board
IU
International Unit
IV
Intravenous
Kg
Kilogram
L
Liter
ln
Naperian (natural) logarithm
LLN
Lower limit of normal
MCV
Mean corpuscular volume
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
62
MedDRA
Medical Dictionary for Regulatory Activities
Mg
Milligrams
mL
Milliliter
MRT
Mean residence time
msec
Milliseconds
PD
Pharmacodynamic
PK
Pharmacokinetic
POPPK
Population Pharmacokinetics
QC
Quality control
QTcB
QT duration corrected for heart rate by Bazett’s formula
QTcF
QT duration corrected for heart rate by Fridericia’s formula
RAP
Reporting and Analysis Plan
RBC
Red blood cells
SAE
Serious adverse event(s)
SC
Subcutaneous
SD
Standard deviation
SOC
System organ class
SOP
Standard Operating Procedure
SLE
Systemic lupus erythematosus
SRM
Study Reference Manual
T
Injection duration
t
Time of last observed quantifiable concentration
t½
Terminal phase half-life
tmax
Time of occurrence of Cmax
ULN
Upper limit of normal
UK
United Kingdom
US
United States
WBC
White blood cells
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
BENLYSTA
WinNonlin
RandAll NG
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
63
11.
REFERENCES
Bosello S, Youinou P, Daridon C, Tolusso B, Bendaoud B, Pietrapertosa D, et al. 
Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and 
response to treatment in early rheumatoid arthritis. J Rheumatol 2008;35(7):1256-64.
Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator 
levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 2001; 
44:1313-9.
China FDA, 2005, Technical guidance for clinical pharmacokinetics study of chemical 
Drugs.
Emmerich F, Bal G, Barakat A, Milz J, Mühle C, Martinez-Gamboa L, et al. High-level 
serum B-cell activating factor and promoter polymorphisms in patients with idiopathic 
thrombocytopenic purpura. Br J Haematol 2007;136(2):309-14.
GlaxoSmithKline Document Number 2011N128591_05, belimumab, belimumab 
Investigator’s Brochure ,Version 15, 09-MAY-2019.
GlaxoSmithKline Document Number 2012N137242_00. CPSR. Study BEL116119.
Phase1 study of GSK1550188 An open label, randomized, parallel, single dose study to 
investigate safety and pharmacokinetics following intravenous administration and 
subcutaneous administration of GSK1550188 in healthy Japanese males-. Effective date 
14-DEC-2012.
GlaxoSmithKline Document Number 2014N216963_01. CSR BEL112341 A Phase 3, 
Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to 
Evaluate the Efficacy and Safety of Belimumab (HGS1006) Administered 
Subcutaneously (SC) to Subjects with Systemic Lupus Erythematosus (SLE) –Double-
Blind Endpoint Analysis. Effective Date 31-AUG-2017
GlaxoSmithKline Document Number 2014N216965_01. CSR. Study BEL113750. 
GSK1550188.  A 52 week study of belimumab versus placebo in the treatment of 
subjects with systemic lupus erythematosus (SLE) located in Northeast Asia – Double-
Blind Endpoint Analysis. Effective Date 01-AUG-2017.
GlaxoSmithKline Document Number 2017N342008_00. CPSR. Study 200909. A single 
dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics 
of GSK1550188 in Chinese subjects with Systemic Lupus Erythematosus (SLE). 
Effective date 28-AUG-2018.
Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, et al. Association 
of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s 
syndrome. The Journal of Clinical Investigation 2002;109(1):59-68.
Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, et al. Association of 
plasma B-Lymphocyte stimulator (BLyS) levels and disease activity in systemic lupus 
erythematosus. Arthritis Rheum 2008; 58(8):2453-9.
 
2020N435387_00

2018N385241_01
CONFIDENTIAL
209629
64
Sanders JS, Huitma MG, Kallenberg CG, Stegeman CA. Plasma levels of soluble 
interleukin 2 receptor, soluble CD30, interleukin 10 and B cell activator of the tumour 
necrosis factor family during follow-up in vasculitis associated with proteinase 3-
antineutrophil cytoplasmic antibodies: associations with disease activity and relapse. Ann 
Rheum Dis 2006;65(11):1484-9.
Schneeweis C, Rafalowicz M, Feist E, Buttgereit F, Rudolph PE, Burmester GR,et al. 
Increased levels of BLyS and sVCAM-1 in antineutrophil cytoplasmatic antibody 
(ANCA)-associated vasculitides (AAV). Clin Exp Rheumatol. 2010. 28(1 Suppl 57):62-
6.
Zhang J, Roschke V, Baker K, Wang Z, Alarcón GS, Fessler BJ, et al. Cutting edge: A 
role for B lymphocyte stimulator in systemic lupus erythematosus. J Immuno 
2001;166:6-10.
 
2020N435387_00