Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosus Belimumab Pharmacodynamics safety tolerability Pharmacokinetics Chinese subjects
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief summary:
In China, Belimumab (GSK1550188) will be developed for a dosing regimen of once-monthly intravenous (IV) infusion for the treatment of SLE. This open-label, single dose study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of belimumab in Chinese SLE subjects. A total of approximately 20 subjects will be enrolled to receive IV infusion of 10 milligrams per kilogram (mg/kg) GSK1550188 on Day 0 for the treatment of SLE. Subjects will be followed for 84 days after the administration of drug.

Detailed description:

Arms:
arm 1: In this open label study, a single dose of 10 mg/kg Belimumab will be administered intravenously in Chinese subjects with systemic lupus erythematosus.

Interventions: intervention 1: Belimumab
Intervention descriptions: intervention 1: Belimumab will be provided as white uniform lyophilized cake in vials with unit dose strength of 400 mg/vial plus excipients (citric acid/sodium citrate/sucrose/polysorbate) for reconstitution in 4.8 milliliter sterile water for injection (SWFI). Belimumab will be administered as 10 mg/kg intravenous infusion for over 1 hour on Day 0.

Protocol document:
Prot_000.pdf: 
2013N175219_01
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TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
A single dose study to evaluate the safety, tolerability, 
pharmacokinetics, and pharmacodynamics of GSK1550188 in 
Chinese subjects with Systemic Lupus Erythematosus (SLE)
Compound Number:
GSK1550188
Development Phase:
I
Effective Date:
15-MAR-2017
Protocol Amendment Number:  01
SYNOPSIS: GSK1550188 (belimumab, monoclonal anti-BLyS antibody) is a human 
IgG1monoclonal antibody that binds soluble BLyS with high affinity and inhibits its 
biological activity. Belimumab has been approved over 45 countries, including the 
United States (US), Canada, European Union, Switzerland, Brazil, and Australia for the 
treatment of adult patients with active autoantibody-positive SLE who are receiving 
standard therapy.
This is a single dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and 
pharmacodynamics (PD) of 10 mg/kg GSK1550188 administered intravenously (IV) in 
Chinese subjects with Systemic Lupus Erythematosus (SLE).
Approximately 20 subjects will be enrolled to guarantee no less than 12 subjects 
complete dosing and critical assessments. After the study has been explained to the 
subjects and they have given full informed consent, the subjects will undergo a medical 
screen within 30 days prior to the first dose, to determine their eligibility for participation 
based on the inclusion/exclusion criteria.
After screening, eligible Chinese SLE subjects will be admitted to the study center on 
Day 0. Each subject will receive the dose on Day 0 after completion of all the pre-dose 
procedure. The subjects will be kept in the study center up to 24 hours post dosing with 
subsequent outpatient visits occurring on Days1, 7, 14, 21, 28, 42, 56, and 84.
Blood samples for PK and PD analysis will be taken at regular intervals after dosing.  
Safety will be assessed by adverse events, clinical laboratory evaluations and vital signs.  
Subject: GSK1550188, belimumab, Systemic Lupus Erythematosus, safety and 
tolerability, pharmacokinetics, pharmacodynamics, Chinese subjects
Copyright 2017 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.


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Authors:
Clinical Pharmacology/ Modeling and Simulation
Clinical Research Physician, Immuno-inflammation, Infectious 
Diseases
Statistics
Data Management
Clinical Operation
Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2013N175219_00
2016-JAN-26
Original
2013N175219_01
2017-MAR-15
Amendment No. 1
Modification of Sponsor/medical monitor Information Page.
Modification of Table 1 to keep consistency with exclusion criteria and Section 6.2.1.1.
Changes to inclusion and exclusion criteria: Modification to inclusion criteria 4; 
Modification to exclusion criteria 7, 10, 14,   and addition of exclusion criteria 21 and 22.  
Modification of Section 4.2.3.1 to clarify contraceptive methods. 
Clarification of text to Section 5.7.1.
Addition of prohibited drugs within 30 days prior to Day 0 in Section 5.7.2.
Changes to Section 6: Modification of paragraph 2; Modification of Table 2: Addition of 
inclusion/exclusion check at pre-dose on Day 0; Addition of footnote 2 and footnote 10. 
Modification of footnote 3. Addition of Table 3 to Section 6. 
Addition of eligibility check at pre-dose on Day 0 to Section 6.1.2
Addition of additional IgG test required for subjects with ALT >3xULN AND 
Bilirubin >2xULN (>35% Direct Bilirubin) in Section 6.2.1.
Correct consistency errors.
PPD


PPD
PPD
PPD


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SPONSOR/MEDICAL MONITOR INFORMATION PAGE
Medical Monitor and Sponsor Contact Information:
Role
Name
Day Time 
Phone 
Number
After-hours 
Phone/Cell/
Pager 
Number
Fax 
Number
GSK Address
Primary 
Medical 
Monitor
Building 1, 917 Halei
Road Zhangjiang Hitech
Park, Pudong
Shanghai, China
Secondary 
Medical 
Monitor
Building 1, 917 Halei
Road Zhangjiang Hitech
Park, Pudong
Shanghai, China
SAE fax 
number 
Sponsor Legal Registered Address:
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline affiliate 
company (or designee). If applicable, the details of the alternative Sponsor and contact 
person in the territory will be provided to the relevant regulatory authority as part of the 
clinical trial application.
PPD
PPD


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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol 200909
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date


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TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS.............................................................................................9
1.
INTRODUCTION....................................................................................................12
1.1.
Brief Background ........................................................................................12
1.1.1.
Systemic Lupus Erythematosus and clinical management 
of the disease ..............................................................................12
1.1.2.
GSK1550188 (Belimumab) ..........................................................13
1.2.
Study Rationale ..........................................................................................14
2.
OBJECTIVES AND ENDPOINTS...........................................................................14
3.
STUDY DESIGN ....................................................................................................15
3.1.
Study Schematic.........................................................................................15
3.2.
Study Design Detail ....................................................................................15
3.3.
Discussion of Study Design ........................................................................15
3.3.1.
Design Rationale .........................................................................15
3.3.2.
Dose Rationale ............................................................................16
3.4.
Benefit-Risk Assessment............................................................................16
4.
STUDY POPULATION...........................................................................................21
4.1.
Number of Subjects ....................................................................................21
4.2.
Eligibility Criteria .........................................................................................21
4.2.1.
Inclusion Criteria..........................................................................21
4.2.2.
Exclusion Criteria.........................................................................23
4.2.3.
Contraception Requirements .......................................................25
4.2.3.1.
Female Subjects.........................................................25
4.3.
Withdrawal Criteria and Procedures............................................................26
4.4.
Subject Completion.....................................................................................27
5.
STUDY TREATMENT ............................................................................................27
5.1.
Investigational Product and Other Study Treatment....................................27
5.2.
Treatment Assignment................................................................................27
5.2.1.
Liver Chemistry Stopping Criteria ................................................27
5.2.2.
QTc Withdrawal Criteria...............................................................28
5.3.
Blinding.......................................................................................................28
5.4.
Packaging and Labeling..............................................................................28
5.5.
Preparation/Handling/Storage/Accountability..............................................28
5.5.1.
Occupational Safety.....................................................................29
5.6.
Assessment of Compliance ........................................................................30
5.7.
Concomitant Medications and Non-Drug Therapies....................................30
5.7.1.
Permitted Medications .................................................................30
5.7.2.
Prohibited Medications and Non-Drug Therapies.........................30
6.
STUDY ASSESSMENTS AND PROCEDURES .....................................................32
6.1.
Critical Baseline Assessments....................................................................35
6.1.1.
Screening Test.............................................................................35
6.1.2.
Pre-dose Examination..................................................................36
6.2.
Safety .........................................................................................................37


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6.2.1.
Liver Chemistry Follow-up Procedures ........................................37
6.2.1.1.
Additional Hepatitis B Monitoring................................40
6.2.2.
Clinical Laboratory.......................................................................40
6.2.3.
Vital Signs....................................................................................40
6.2.4.
12-Lead ECG...............................................................................41
6.3.
Pharmacokinetics .......................................................................................41
6.4.
Pharmacodynamic/Biomarkers ...................................................................41
7.
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, PREGNANCY AND 
MEDICAL DEVICE INCIDENTS.............................................................................41
7.1.
Adverse Events (AE) and Serious Adverse Events (SAEs).........................41
7.1.1.
Time period for collecting AEs and SAE information....................41
7.1.2.
Definition of Adverse Events........................................................42
7.1.3.
Definition of Serious Adverse Events...........................................43
7.1.4.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs.........................................................44
7.1.5.
Method of Detecting AEs and SAEs.............................................44
7.1.6.
Recording of AEs and SAEs ........................................................44
7.1.7.
Evaluating AEs and SAEs............................................................45
7.1.8.
Assessment of Intensity...............................................................45
7.1.9.
Assessment of Causality..............................................................45
7.1.10.
Completion and Transmission of SAEs Report ............................46
7.1.11.
Follow-Up of AEs and SAEs ........................................................46
7.1.12.
Post-study AEs and SAEs ...........................................................47
7.1.13.
Prompt Reporting of SAEs to GSK...............................................47
7.1.14.
Regulatory Reporting Requirements for SAEs .............................49
7.2.
Pregnancy ..................................................................................................49
7.3.
PML............................................................................................................50
8.
DATA MANAGEMENT ...........................................................................................50
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS...................................50
9.1.
Hypotheses and Treatment Comparisons...................................................51
9.2.
Sample Size Considerations.......................................................................51
9.2.1.
Sample Size Assumptions ...........................................................51
9.2.2.
Sample Size Sensitivity................................................................51
9.2.3.
Sample Size Re-estimation..........................................................51
9.3.
Data Analysis Considerations .....................................................................51
9.3.1.
Analysis Population .....................................................................51
9.3.2.
Analysis Data Set ........................................................................52
9.3.3.
Interim Analysis ...........................................................................52
9.3.4.
Final Analyses .............................................................................52
9.3.4.1.
Safety Analyses..........................................................52
9.3.4.1.1.
Extent of Exposure .................................52
9.3.4.1.2.
Adverse Events ......................................52
9.3.4.1.3.
Clinical Laboratory Evaluations...............52
9.3.4.1.4.
Vital Signs ..............................................53
9.3.4.1.5.
12-Lead ECG..........................................53
9.3.4.2.
Pharmacokinetic Analyses..........................................53
9.3.4.2.1.
Serum Concentrations............................53
9.3.4.2.2.
Pharmacokinetic Parameters..................53
9.3.4.3.
Pharmacodynamic/Biomarker Analyses .....................53


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10. STUDY GOVERNANCE CONSIDERATIONS........................................................54
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............54
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................54
10.3.
Quality Control (Study Monitoring) ..............................................................54
10.4.
Quality Assurance.......................................................................................55
10.5.
Study and Site Closure ...............................................................................55
10.6.
Records Retention......................................................................................55
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................56
11. REFERENCES.......................................................................................................57
12. APPENDICES........................................................................................................60
12.1.
Appendix 1: Liver Safety Process ...............................................................60
12.2.
Appendix 2: American College of Rheumatology (ACR) Criteria for 
SLE.............................................................................................................63
12.3.
Appendix 3: Adverse Event and Laboratory Value Severity Grade 
Tables.........................................................................................................65
12.4.
Appendix 4: Protocol Changes....................................................................75


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LIST OF ABBREVIATIONS
Acl
anti-cardiolipin
ACR
American College of Rheumatology
AE
Adverse Event
ALT
Alanine aminotransferase (SGPT)
ALP
Alkaline phosphatase
ANA
Anti-nuclear antibody
anti-SM
anti-Smith antigen
AST
Aspartate aminotransferase (SGOT)
AUC
Area under concentration-time curve
AUC(0-)
Area under the concentration-time curve from time zero (pre-dose) 
extrapolated to infinite time
AUC(0-t)
Area under the concentration-time curve from time zero (pre-dose) 
to last time of quantifiable concentration within a subject across all 
treatments
BILAG
British Isles Lupus Assessment Group
BlyS
B lymphocyte Stimulator
BUN
Blood urea nitrogen
CI
Confidence Interval
CL
Systemic clearance of parent drug
Cmax
Maximum observed concentration
CNS
Central Nervous System
CO2
Carbon dioxide
CPK
Creatine phosphokinase
CRF
Case Report Form
CRP
C-reactive protein
CVA
Cerebrovascular accident
DMID
Division of Microbiology and Infectious Diseases
DNA
Deoxyribonucleic acid
dsDNA
double stranded DNA
EU
European Union
ECG
Electrocardiogram
EDC
Electronic data collection
ESR
Erythrocyte Sedimentation Rate
FDA
Food and Drug Administration
FEV1
Forced expiratory volume in 1 second
GCP
Good Clinical Practice
GGT
Gamma glutamyltransferase
GSK
GlaxoSmithKline
Hb
Hemoglobin
Ht
Hematocrit
HBV
Hepatitis B virus
HbsAg
Hepatitis B surface antigen 
HbcAb
Hepatitis B core antibody
HCVAb
Hepatitis C virus antibodies


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HGS
Human Genome Sciences
HIV
Human Immunodeficiency Virus
h
Hour(s)
Ht
Hematocrit
HPLC
High-performance liquid chromatography
HR
Heart rate
IB
Investigator’s Brochure
ICH
International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use
IDSL
Integrated Data Standards Library
IEC
Independent Ethics Committee
IgG
Immunoglobulin G
IgA
Immunoglobulin A
IgM
Immunoglobulin M
IL
Interleukin
INN
International Non proprietary Name
INR
International normalised ratio
IP
Investigational product
IRB
Institutional Review Board
IU
International Unit
IUD
Intrauterine device
IUS
Intrauterine system
IV
Intravenous
IVIG
Intravenous immunoglobulin
kg
Kilogram
z
Terminal phase rate constant
L
Liter
LDH
Lactate dehydrogenase
ln
Naperian (natural) logarithm
LOQ
Limit of quantification
LLQ
Lower limit of quantification
LSLV
Last Subject Last Visit
µg
Microgram
µL
Microliter
MedDRA
Medical Dictionary for Regulatory Activities
mg
Milligrams
Ml
Milliliter
MMF
Mycophenolate mofetil
msec
Milliseconds
NSAIDs
Non-steroidal anti-inflammatory drugs
O2
Oxygen
PD
Pharmacodynamic
PGA
Physician’s Global Assessment
PK
Pharmacokinetic
PML
Progressive multifocal leukoencephalopathy
PT
Prothrombin Time


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PTT
Partial Thromboplastin Time
QC
Quality control
QTc
Corrected QT interval
QTcB
QT duration corrected for heart rate by Bazett’s formula
QTcF
QT duration corrected for heart rate by Fridericia’s formula
RA
Rheumatoid arthritis
RF
Rheumatoid factor
RAP
Reporting and Analysis Plan
RBC
Red blood cells
RNA
Ribonucleic acid
SAE
Serious adverse event(s)
SELENA
Safety of Estrogen in Lupus National Assessment trial
SLE
Systemic Lupus Erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease Activity Index
SOC
System Organ Class
SOP
Standard Operating Procedure
SPM
Study Procedures Manual
SRI
SLE responder index
SWFI
Sterile water for injection
T
Infusion duration
TACI
Transmembrane activator and calcium-modulator and cytophilin 
ligand interactor
TNF
Tumor necrosis factor
t
Time of last observed quantifiable concentration
t½
Terminal phase half-life
ULN
Upper limit of normal
UK
United Kingdom
US
United States
Vz
Volume of distribution
WBC
White blood cells
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
BENLYSTA
BlyS
Cytoxan
MedDRA
WinNonlin


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1.
INTRODUCTION
1.1.
Brief Background
1.1.1.
Systemic Lupus Erythematosus and clinical management of the 
disease
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterised by 
autoantibody production and abnormal B lymphocyte function [Pisetsky, 2001]. This 
disease is more common in women (~90% of patients) than men [NWHIC, 2003] and its 
prevalence varies with race [OMHRC, 2001; NWHIC, 2003].  SLE can lead to arthritis, 
kidney failure, heart and lung inflammation, and central nervous system (CNS) changes. 
A clinical diagnosis of SLE includes features that are thought to involve dysregulation of 
B lymphocytes [Liossis, 1996; Lipsky, 2001].  The B lymphocyte stimulator (BlyS) 
protein is a potent co-stimulator of B lymphocytes and elevated levels of BlyS are 
observed in autoimmune diseases in humans and animal models [Cheema, 2001; Gross, 
2001; Khare, 1999; Mackay, 1999; Moore, 1999; Zhang, 2001; Carter, 2003]. In SLE, the 
elevation of BlyS may contribute to the persistence of B cell subsets which produce 
pathogenic auto antibodies or promote inflammation that would otherwise be subject to 
down regulation.  Thus a therapeutic strategy which involves an antagonist to BlyS, to 
reduce B lymphocyte stimulation, reducing autoantibody production, may have 
therapeutic benefit in SLE.
Patients with SLE have about a 3-fold greater risk of mortality than the general
population.  Approximately 70% of SLE patients survive 20 years from time of diagnosis 
[Houssiau, 2004].  Standard therapies for SLE include corticosteroids (the mainstay of 
therapy), anti-malarial agents (e.g., hydroxychloroquine), non-steroidal anti-
inflammatory drugs (NSAIDs), cytotoxic agents like cyclophosphamide, and  
immunosuppressive/immunomodulatory agents (e.g., azathioprine, cyclosporine, 
mycophenolate mofetil (MMF), methotrexate, leflunomide, thalidomide, 6-
mercaptopurine) [Petri, 2001; Reveille, 2001; Ginzler, 2005; Houssiau, 2004;Ruiz-
Irastorza, 2001; Wallace, 2002; Brocard, 2005; Chatham, 2001]. Although active lupus 
nephritis and CNS vasculitis can usually be controlled over a 1 to 2 year period with 
several courses of high dose steroids and cyclophosphamide, there are trends of
progressive relapsing over time [Petri, 2001; Houssiau, 2002; Illei, 2001; Ruiz-
Irastorza, 2001]. These therapies can be associated with significant toxicity. Long-term 
use of high-dose corticosteroids can cause morbidity including osteoporosis, 
osteonecrosis, metabolic disorders (including exacerbation of diabetes), increased 
infection risk, edema, weight gain and hyperlipidemia [Chatham, 2001]. Cytotoxic agents 
like cyclophosphamide are immunosuppressive, resulting in increased risk of severe 
infections and certain carcinogenesis.
The prevalence of SLE in Hong Kong & mainland China was found to range from 
58.8/100,000 to 73.3/100,000 in two studies [Mok, 2003; Xiang, 2009]. SLE disease 
burden does not appear to be higher in China, when compared with US SLE prevalence 
estimates of 100.0/100,000 [Naleway, 2005; Chakravarty, 2007]. Conversely, SLE 


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prevalence in 5 regions (UK, Germany, France, Spain, and Italy) of European Union (EU)
was estimated at 43.0/100,000 [Govoni, 2006; Lopez, 2003; Nightingale, 2006], which is 
lower than the estimation in China. In terms of disease activity, [Boers, 2006] reported 
more severe SLE among Asian patients admitted to a medical centre in Australia.
Southeastern Asian/Chinese patients having a median Systemic Lupus Erythematosus 
Disease Activity Index (SLEDAI) of 13 at first admission, compared to a median 
SLEDAI of 8 among Caucasians.
1.1.2.
GSK1550188 (Belimumab)
GSK1550188 (International Non proprietary Name [INN]: belimumab), developed by 
Human Genome Sciences (HGS), is a recombinant, human, IgG1λ monoclonal antibody 
that binds to soluble B lymphocyte stimulator (BlyS) with high affinity and inhibits its 
biological activity. In the Phase 2 SLE (LBSL02) and Rheumatoid Arthritis (RA) 
(LBRA01) trials, belimumab reduced, but did not deplete, numbers of B lymphocyte 
subsets as well as auto antibodies. Overall, subjects with elevated levels of 
immunoglobulins at baseline experienced reductions in immunoglobulin levels or 
achieved normal levels. This observation supports the rationale that in patients with SLE, 
belimumab offers the potential to modulate B cells and specifically affect their activity by 
reducing BlyS-mediated signaling. This appears to occur in a disease-specific manner, as 
pathogenic auto antibodies are reduced. In LBRA01 rheumatoid factor (RF) and in 
LBSL02 anti-double stranded DNA (anti-dsDNA) both reduced approximately 30% with 
relative preservation of normal IgG levels. The lack of a general suppression of B cells 
across all subsets supports the hypothesis that belimumab modulates B cells and has the 
potential to preserve cells that respond to foreign or abnormal self antigens. A Phase 3, 
52-week dose ranging study (HGS1006-C1057) of IV belimumab versus placebo was 
done in sero-positive SLE patients maintained on standard therapy. A significant 
reduction in an SLE Responder Index (SRI) combined response endpoint comprising 
Safety of Estrogen in Lupus National Assessment trial (SELENA) SLEDAI score, 
Physician’s Global Assessment (PGA) score and British Isles Lupus Assessment Group 
(BILAG) organ assessment. This has been confirmed in a second longer term 76-week 
study (HGS1006-C1056) with the primary endpoint evaluated at Week 52.
Experience from open-label, long-term continuation trials of belimumab in SLE patients 
confirms prolonged treatment with belimumab is generally well tolerated. There is no 
apparent increase in the incidence rate of adverse events (AEs) or serious adverse events 
(SAEs) over time, including important events such as infections and malignancies. Long 
term belimumab treatment appears to provide sustained improvement in SLE disease 
activity and reduction of flares. The definitive assessment of the PK of belimumab is 
based on a population approach including data collected from subjects with SLE in the 
Phase 1 (LBSL01), Phase 2 (LBSL02), and Phase 3 (C1056 and C1057) studies. The PK 
of belimumab administered by IV infusion was well described by a linear 2-compartment 
model with clearance from the central compartment. After IV infusion, serum belimumab 
concentrations declined in a bi-exponential manner, with a distribution half-life of 1.1-1.8 
days.  The terminal half-life is 12.5 days for the 1 mg/kg dose and 19.4 days for the 10 
mg/kg dose.


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Further information is provided in the Investigator Brochure (IB) (Belimumab
Investigator’s Brochure ).
1.2.
Study Rationale
In China, GSK1550188 will be developed for a dosing regimen of once-monthly 
intravenous infusion for the treatment of SLE. The study described in this protocol will 
assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single 
intravenous 10 mg/kg GSK1550188 in Chinese subjects with SLE and to support the 
registration of GSK1550188 in China.
2.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To investigate the pharmacokinetics (PK) of 
intravenously (IV) administered GSK1550188 10 
mg/kg in Chinese subjects with SLE.
Maximum observed concentration (Cmax), 
Area under the concentration-time curve from 
time zero (pre-dose) to last time of 
quantifiable concentration within a subject 
across all treatments (AUC [0-t]), Area under 
the concentration-time curve from time zero 
(pre-dose) extrapolated to infinite time (AUC 
[0-]), Terminal phase half-life (t1/2), 
Terminal phase rate constant (λz), Systemic 
clearance of parent drug (CL), and Volume of 
distribution (Vz)
Secondary
To evaluate the safety and tolerability of 
GSK1550188 in Chinese subjects with SLE.
Safety and tolerability endpoints: adverse 
events, vital sign, 12-lead electrocardiogram 
(ECG), and clinical laboratory safety tests.
To investigate the effect of GSK1550188 on  
pharmacodynamics (PD) of B cell subsets
B cell subsets (CD20+, CD20+/27+ memory, 
CD20+/27–naïve, CD20+/69+ activated, 
CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and 
CD20-/138+ plasma cells).


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3.
STUDY DESIGN
3.1.
Study Schematic
3.2.
Study Design Detail
This will be a multicenter, single dose study of intravenous GSK1550188 at a dose of 10 
mg/kg in Chinese subjects with SLE.
After the study has been explained to the subjects and they have given full informed 
consent, the subjects will undergo a medical screen within 30 days prior to the first dose, 
to determine their eligibility for participation based on the inclusion/exclusion criteria.
After screening, eligible Chinese SLE subjects will be admitted to the study center on 
Day 0. Each subject will receive the dose on Day 0 after completion of all the pre-dose 
procedure. The subjects will be kept in the study center up to 24 hours post dosing with 
subsequent outpatient visits occurring on Days1, 7, 14, 21, 28, 42, 56, and 84.
3.3.
Discussion of Study Design
3.3.1.
Design Rationale
This study is designed to assess the pharmacokinetics, safety, tolerability, and 
pharmacodynamics of a single intravenous 10mg/kg GSK1550188 dose in Chinese subjects 
with SLE. The study is open-label as the primary endpoint (pharmacokinetic parameters) 
will not be influenced by subjects knowing that they are receiving active treatment. The 


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subjects will have pharmacokinetic samples collected for 84 days (more than five half-
lives) after dosing to enable a comprehensive pharmacokinetic profile to be generated.
The pharmacokinetics of a single intravenous 10mg/kg GSK1550188 dose has never 
been assessed in healthy subjects, but has been assessed in Japanese (Study BEL114243) 
and Western subjects (Study LBSL01) with SLE. Therefore, Chinese subjects with SLE 
instead of Chinese healthy subjects will be recruited for this study to allow unbiased 
comparison between Chinese and non-Chinese subjects, if necessary.
3.3.2.
Dose Rationale
The clinical studies of GSK1550188 in SLE subjects have shown GSK1550188 to be safe 
and well-tolerated when single doses of up to 20 mg/kg, or repeat doses at 1 mg/kg and 
10 mg/kg for more than 76 weeks were administered. The 10 mg/kg GSK1550188 dose 
has been approved in the United States (US), Canada and European Union for the 
treatment of adult patients with active autoantibody-positive SLE who are receiving 
standard therapy. It is also the dose used in the on-going Phase III study BEL113750, 
which evaluates the efficacy and safety of 10 mg/kg belimumab in Northeast Asian 
(including China) subjects with SLE. Therefore, this study will use 10 mg/kg of 
GSK1550188 as the study dose.
3.4.
Benefit-Risk Assessment
Belimumab administered by IV infusion is indicated for reducing disease activity in adult 
patients with active autoantibody positive SLE who are receiving standard therapy. The 
benefit/risk profile of belimumab for systemic lupus erythematosus remains favorable. 
Identified risks include hypersensitivity/infusion reactions and non-opportunistic 
infections. Potential risks (i.e., based on pharmacology but no association identified to 
date) include progressive multifocal leukoencephalopathy (PML) and other opportunistic 
infections; malignancies; immunogenicity; effects on immunizations (including 
interactions with live vaccine); and psychiatric events including depression and 
suicidality.  The most common AEs reported in the primary safety population of adults 
with SLE were associated with hypersensitivity/infusion-related reactions, non-
opportunistic infections, and symptoms consistent with SLE.  The majority of reports of 
infusion-related and hypersensitivity reactions were non-serious and include symptoms 
such as nausea, vomiting, diarrhea, chills, fever, rash, urticaria, pruritus, headache, 
dizziness, and dyspnoea.  However, infusion and hypersensitivity reactions can be severe 
and fatal.  Most clinical trial and spontaneous cases of serious hypersensitivity occurred 
during or within the first hour after the completion of the infusion, although some cases 
report delayed acute onset (>4 hours but <4 days) or a delayed non-acute onset (4-21 
days) hypersensitivity reactions.  
Infections have been reported with administration of belimumab and are also associated 
with both SLE and immunosuppressant medication used to treat SLE. The mechanism of 
action of belimumab may increase the potential risk for the development of infections.  In 
the phase 2 and 3 clinical trials, there was a slight increase in the overall rate of infections 
in the belimumab group compared with the placebo group. There was no difference in the 
rate of serious infections, infections leading to discontinuation, or infections of special 
interest. Out to 10 years in the Phase 2 and 3 continuation studies, the incidence rate of 
serious infections has remained stable or declined over time.  No association between 


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belimumab and the risk of opportunistic infections, including PML, has been indentified 
to date, but data are limited. Progressive multifocal leukoencephalopathy resulting in 
neurological deficits, including fatal cases, has been reported in SLE patients receiving 
immunosuppressant pharmacotherapy, including belimumab. (See Table 1)
The primary data supporting efficacy of belimumab were the Phase 3 trials (C1056 and 
C1057) in which 1,684 subjects were treated for up to 52 weeks (C1057) or 76 weeks 
(C1056) (Belimumab IB, Section 5.3.1.2). Belimumab produced significant 
improvements in the SLE Responder Index as well as in individual component SELENA-
SLEDAI score in both studies. Pooled analyses demonstrated steroid sparing, delay in 
median time to first flare, and decreased risk of severe flares over 52 weeks. Clinical trial 
data for belimumab since approval continue to show efficacy in the treatment of SLE 
through decreased SLE flares and decreased disease activity across multiple organ 
systems (Belimumab IB, Section 5.3.1.3).  The safety profile of belimumab remains 
consistent with that known at approval and is consistent with expected events based on 
the mechanism of action and the disease under study.
In the post-marketing setting with IV belimumab, delayed onset of symptoms of acute 
hypersensitivity reactions as well as recurrence of clinically significant reactions after 
initial appropriate treatment has been observed.  Belimumab should be administered by a 
healthcare professional prepared to treat hypersensitivity reactions including anaphylaxis.  
(See Table 1)
Table 1
Summary of key issues, their impact, and strategy to mitigate risk in 
this study.
Potential risk 
Summary of data
Impact- eligibility 
criteria
Strategy-monitoring 
Post-injection 
systemic reactions
and Hypersensitivity 
Administration of belimumab 
may result in infusion and 
hypersensitivity reactions, 
which can be severe and can 
be fatal.  Non-serious infusion 
reactions and hypersensitivity 
reactions are common in SLE 
clinical trials with IV 
belimumab.  Serious infusion 
and hypersensitivity reactions 
affected less than 1% of 
patients and included: 
anaphylactic reaction, 
bradycardia, hypotension, 
angioedema, and dyspnea. 
Delays in the onset of 
hypersensitivity reactions have 
been observed. Infusion 
reactions following 
administration of belimumab 
Exclusion of 
subjects with a 
history of an 
anaphylactic 
reaction to 
parenteral 
administration of 
contrast agents, 
human or murine 
proteins or 
monoclonal 
antibodies. 
Subjects should 
remain under clinical 
supervision for 3 
hours after 
completion of the 
infusion. Should 
symptoms of acute 
hypersensitivity 
occur, an extended 
period of monitoring 
may be appropriate, 
based on clinical 
judgment. This may 
include, but is not 
limited to, monitoring
vital signs and 
observing for any 
untoward reactions.
Subjects should be 
made aware of the 


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Potential risk 
Summary of data
Impact- eligibility 
criteria
Strategy-monitoring 
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.
potential risk, the 
signs and symptoms 
of such reactions, 
and the importance 
of immediately 
seeking medical 
attention.  
Belimumab should 
be administered by a 
healthcare 
professional 
prepared to treat 
hypersensitivity 
reactions including 
anaphylaxis.
Infections
Infections occurred in a slightly 
greater proportion of subjects 
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 viral 
gastroenteritis.  Serious 
infections occurred in 5% of 
patients receiving either 
belimumab or placebo. 
Exclude patients 
with a history of 
any infection 
requiring 
hospitalization, 
antivirals or 
antibiotics within 
4 weeks prior to 
Day 0., a history 
of or positive test 
at screening for 
HIV, Grade 3 or 
4 lymphopenia, 
Grade 3 or 4 IgG 
or IgA 
deficiency.  
Patients should 
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 
should be 
Monitor patients for 
signs and symptoms 
of infection, monitor 
laboratory values, 
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 DNA. If the 
quantitative hepatitis 
B virus DNA result 
shows detectable 
viral loads, then the 
subject must be 
treated immediately 
and appropriately.


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Potential risk 
Summary of data
Impact- eligibility 
criteria
Strategy-monitoring 
excluded.  
Patients who are 
anti-HbcAb 
positive should 
be tested for 
HBV DNA.  If 
DNA test is 
negative, the 
patient is eligible 
for inclusion
Progressive multifocal 
leukoencephalopathy
PML resulting in neurological 
deficits, including fatal cases, 
has been reported in SLE 
patients receiving 
immunosuppressant 
pharmacotherapy, including 
belimumab.
A diagnosis of PML 
should be 
considered in any 
subject presenting 
with new-onset or 
deteriorating 
neurological signs 
and symptoms. The 
subject should be 
referred to a 
neurologist or other 
appropriate 
specialist for 
evaluation. If PML is 
confirmed, 
consideration should 
be given to stopping 
immunosuppressant 
therapy. If PML is 
suspected, this 
should be 
immediately 
reported to the 
Medical Monitor.  
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 
Monitor patients for 
signs and symptoms 
of malignancy, 
monitor laboratory 
values, request that 
patients report signs 
and symptoms.  
Treat appropriately.


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Potential risk 
Summary of data
Impact- eligibility 
criteria
Strategy-monitoring 
of the uterine 
cervix.
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 
immunisations. The efficacy of 
concurrent vaccination in 
patients receiving belimumab 
is under investigation.  Limited 
data suggest that belimumab 
does not significantly affect the 
ability to maintain a protective 
immune response to 
immunisations received prior to 
administration of belimumab. 
Exclude patients 
who have 
received a live 
vaccine within 
30 days of Day 
0.
Do not administer 
live vaccines 
concurrently.
Potential psychiatric 
events – Depression 
and suicidality
There have been reports of 
depression and suicidality in 
patients receiving belimumab.    
The estimated rates of 
suicidality for belimumab 
remain consistent with the 
rates of the background SLE 
population.  The background 
rate for completed suicide 
identified in the literature 
ranged from 0.02 to 2.18 per 
100 PY and varied by study 
type (clinical trial or 
observational study) [Li-Yu,
2007; Cervera, 2003; Cervera,
2006; Cervera, 2009].  The 
background rate for suicidal 
behavior (completed suicide 
and attempts) is 0.12 (95% CI 
0.05, 0.24)/100 patient years 
[Karassa, 2003].  
Exclude patients 
who have 
evidence of 
serious suicide 
risk including 
any history of 
suicidal behavior
in the last 6 
months or who 
in the 
investigator’s 
judgment, pose 
a significant 
suicide risk.
Request that 
patients report signs 
and symptoms of 
psychiatric events 
including depression 
and suicidality.  
Treat appropriately


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4.
STUDY POPULATION
4.1.
Number of Subjects
Approximately 20 subjects will be enrolled to guarantee no less than 12 subjects 
complete dosing and critical assessments.
4.2.
Eligibility Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the GlaxoSmithKline (GSK) investigational product 
(IP) or other study treatment that may impact subject eligibility is provided in the IB/IB 
supplement(s), product label, add other pertinent documents.
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
4.2.1.
Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1.
Subjects who give consent to this study participation and sign informed consent 
form.
2.
Subjects at least 18 years of age inclusive at screening visit.
3.
SLE Classification: Have a clinical diagnosis of SLE according to the American 
College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 
ACR criteria present, serially or simultaneously during any interval or observation. 
[Tan, 1982; Hochberg, 1997] (See Appendix 2).
4.
SLE Treatment: Be on either no SLE medication or a stable SLE treatment regimen 
of any medication (alone or in combination) for a period of at least 2 months prior to 
Day 0.

Corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day)

Immunosuppressive or immunomodulatory agents including methotrexate, 
azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, 
mycophenolate mofetil hydrochloride, and mycophenolate sodium), 
mizoribine, calcineurin inhibitors (e.g., tacrolimus, cyclosporine), sirolimus, 
oral cyclophosphamide, 6-mercaptopurine, or thalidomide.

Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine).

Non-steroidal anti-inflammatory drugs (NSAIDs)


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NOTE: 
- For those subjects on alternating day doses of steroids, use the average of 2 
daily doses to calculate the average daily steroid dose.
-Low dose prednisone (≤15mg prednisone or equivalent) regular tapering will be 
acceptable as stable SLE treatment. 
5.
The subjects with positive test for anti-nuclear antibody (ANA) or anti-dsDNA 
serum antibody.
6.
Males and females. A female subject is eligible to enter the study if at least one of 
the following conditions apply:
Not pregnant or nursing;  
Of non-childbearing potential (i.e., women who had a hysterectomy, are 
postmenopausal which is defined as 1 year without menses, have both ovaries 
surgically removed or have current documented tubal ligation); or 
Of childbearing potential (i.e., women with functional ovaries and no documented 
impairment of oviductal or uterine function that would cause sterility). This 
category includes women with oligomenorrhoea [even severe], women who are 
perimenopausal or have just begun to menstruate. These women must have a 
negative serum pregnancy test at screening, and agree to 1 of the following: 
o Complete abstinence from penile-vaginal intercourse, when this is the 
female’s preferred and usual lifestyle, from 2 weeks prior to 
administration of the 1st dose of IP until study complete; or
o Consistent and correct use of 1 of the following acceptable methods of 
birth control for 1 month prior to the start of the IP and for 16 weeks after 
the last dose of IP:
Any intrauterine device (IUD) or intrauterine system (IUS) with a 
documented failure rate of less than 1% per year.
Oral contraceptives.
Double barrier method with vaginal spermicidal agent: Condom 
and an occlusive cap (cervical cap/vault or diaphragm) with a 
vaginal spermicidal agent (foam/gel/film/cream/suppository).
Implants of etonogestrel or levonorgestrel;
Estrogenic vaginal ring; 
Injectable progesterone; 
Percutaneous contraceptive patch; 
Male partner who is sterile prior to the female subject’s entry into 
the study and is the sole sexual partner for the female subject.
Note: MMF and other forms of mycophenolate affect the metabolism of oral 
contraceptives and may reduce their effectiveness. As such, women receiving 
mycophenolate who are using oral contraceptives for birth control should employ an 
additional method (e.g., barrier method).


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7.
Based on single or averaged QTc values of triplicate ECGs obtained over a brief 
recording period:

[QTcB or QTcF] <450 msec; or 

QTcB or QTcF <480 msec in subjects with Bundle Branch Block.
4.2.2.
Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. B-cell Therapy: Have received treatment with any B cell targeted therapy (e.g., 
rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 
[alemtuzumab], BlyS-receptor fusion protein [BR3], Transmembrane activator 
and calcium-modulator and cytophilin ligand interactor [TACI] Fc, or 
belimumab) at any time.
2. The subject has received a biologic investigational or non-investigational agent 
within 12 months prior to Day 0.
3. Received intravenous immunoglobulin (IVIG), plasmapheresis, hemodialysis, 
intravenous cyclophosphamide, or high dose prednisone and its equivalents 
(>60mg/day) within 6 months prior to Day 0.
4. The subject has received a non-biologic investigational agent within 2 months 
prior to Day 0.
5. The subject is currently participating in another clinical study or post-marketing 
study in which the subject is or will be exposed to an investigational agent.
6. The subject has severe lupus kidney disease (defined by proteinuria >6g/24h) 
within 6 months prior to the Screening visit.
7. History of a major organ transplant (eg. heart, lung, renal, liver) or hematopoietic 
stem cell/marrow transplant.
8. Active CNS lupus [including seizures, psychosis, organic brain syndrome, 
cerebrovascular accident (CVA), motor neuropathy, vasculitis] requiring medical 
intervention within 6 months prior to Screening visit.
9. Infections: Have required management of acute or chronic infections, as follows:

Currently on any suppressive therapy for a chronic infection (such as 
tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes 
zoster and atypical mycobacteria).

Hospitalisation for treatment of infection within 2 months prior to Day 0.


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
Use of parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, 
antivirals, anti-fungals, or anti parasitic agents) within 2 months prior to Day 
0.
10. The subject has IgA deficiency (IgA level <10 mg/Dl).
11. Have a history of an anaphylactic reaction to parenteral administration of contrast 
agents, human or murine proteins or monoclonal antibodies.
12. Uncontrolled other diseases: History or clinical evidence of active significant 
acute or chronic diseases (i.e., cardiovascular, pulmonary, untreated hypertension, 
anemia, gastrointestinal, hepatic, renal, neurological, cancer, or infectious 
diseases) which, in the opinion of the investigator, could confound the results of 
the study or put the subject at undue risk.
13. Have a planned surgical procedure, or a history of any other medical disease, or
laboratory abnormalities, or conditions which would make the subject (in the 
opinion of the Investigator) unsuitable for the study.
14. The subject has an abnormality on 12-lead ECG at screening which is clinically 
significant in the opinion of the investigator, and which could confound the 
results of the study. Inclusion may put the subject at undue risk.
15. Have evidence of current drug or alcohol abuse or dependence.
16. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2x upper 
limit of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated 
bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin 
<35%).
17. Have a historically positive human immunodeficiency virus (HIV) test or test 
positive at screening for HIV.
18. History of or positive test at screening visit for any of Hepatitis B surface antigen 
(HbsAg), anti- Hepatitis B core antibody (HbcAb) or anti-hepatitis C virus 
antibodies (HCVAb). If only anti-HbcAb result is positive, HBV-DNA test will 
be performed. If hepatitis B virus (HBV)-DNA results in negative, the patient is 
eligible.
NOTE: For those subjects included, additional ongoing assessment is required 
(see Section 6.2.1.1).
19. Laboratory Abnormalities: Have a Grade 3 or greater laboratory abnormality 
based on the protocol toxicity scale [Appendix 3] except for the following that are 
allowed:
Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.


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Stable Grade 3/4 proteinuria (6 g/24 hour equivalent by spot urine protein to 
creatinine ratio allowed).
Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver 
disease or malnutrition.
Stable Grade 3 neutropenia or stable Grade 3 white blood cell count. 
20. Subjects who have evidence of serious suicide risk including any history of 
suicidal behavior in the last 6 months or who, in the investigator’s opinion, pose a 
significant suicide risk.
21. Received a live vaccine within 30 days of baseline (Day 0).
22. Have a history of malignant neoplasm within the last 5 years, except for
adequately treated cancers of the skin (basal or squamous cell) or carcinoma in
situ of the uterine cervix.
4.2.3.
Contraception Requirements
4.2.3.1.
Female Subjects
Female subjects of childbearing potential must not become pregnant and so must be 
sexually inactive by abstinence or use contraceptive methods with a failure rate of <1%.  
Female subjects of childbearing potential with same sex partners (when this is their 
preferred and usual lifestyle) are not required to be abstinent or to use contraception.
Abstinence
Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle 
of the subject.  Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception. 
Contraceptive Methods with a Failure Rate of <1%

Oral contraceptive, either combined or progestogen alone

Injectable progestogen 

Implants of etonogestrel or levonorgestrel

Estrogenic vaginal ring

Percutaneous contraceptive patches

Intrauterine device (IUD) or intrauterine system (IUS) that meets the <1% failure 
rate as stated in the product label

Documented male partner sterilization prior to the female subject’s entry into the 
study, and this male is the sole partner for that subject. For this definition, 
“documented” refers to the outcome of the investigator’s/designee’s review of the 


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subject’s medical history for study eligibility, as obtained via a verbal interview with 
the subject or from the subject’s medical records.

Male condom combined with one of the contraceptive options below:

Contraceptive subdermal implant

Intrauterine device or intrauterine system

Combined estrogen and progestogen oral contraceptive

Injectable progestogen

Contraceptive vaginal ring Percutaneous contraceptive patches 
NOTE: These allowed methods of contraception are only effective when used 
consistently, correctly and in accordance with the product label. The investigator is 
responsible for ensuring subjects understand how to properly use these methods of 
contraception.

MMF and other forms of mycophenolate affect the metabolism of oral 
contraceptives and may reduce their effectiveness. As such, women receiving 
mycophenolate who are using oral contraceptives for birth control should 
employ an additional method (e.g., barrier method).
4.3.
Withdrawal Criteria and Procedures
A subject may withdraw from study treatment at any time at his/her own request, or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral or 
administrative reasons.
Should a subject fail to attend the clinic for a required study visit, the site should attempt 
to contact the subject and re-schedule the missed visit as soon as possible. The site should 
also counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to and/or should continue in the study based 
on previous non-compliance. In cases where the subject does not return for the 
rescheduled visit or cannot be reached to reschedule the missed visit, the site should 
make every effort to regain contact with the subject (3 telephone calls and if necessary a 
certified letter to the subject’s last known mailing address) so that they can appropriately 
be withdrawn from the study.
These contact attempts should be documented in the subject’s medical record. Should the 
subject continue to be unreachable, then and only then will he/she be considered to have 
withdrawn from the study with a primary reason of “Lost to Follow-up”. For all other 
subjects withdrawing from the study, an alternative reason for discontinuation should be 
recorded in the Case Report Form (CRF). If a subject prematurely withdraws from 
participation in the study for any reason, the investigator/sub-investigator must make 
every effort to assess the items specified on discontinuation test.
Refer to Section 5.2.1 for Liver Chemistry stopping criteria, Section 5.2.2 for QTc 
withdrawal and Section 7.2 for Pregnancy.


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Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event etiology (in alignment with the Food and Drug Administration
[FDA] premarketing clinical liver safety guidance). See Section 5.2.1 for details.
4.4.
Subject Completion
A subject who participates in all study sessions (including screening, treatment and 
follow-up) will be considered as having completed the study.
5.
STUDY TREATMENT
5.1.
Investigational Product and Other Study Treatment
Study Treatment
Product name:
GSK1550188
Formulation 
description:
GSK1550188 400 mg per vial plus excipients (citric acid/sodium 
citrate/sucrose/polysorbate)
Dosage form:
Reconstituted solution
Unit dose 
strength(s)/Dosag
e level(s):
400 mg per vial (to contain 80 mg/Ml when reconstituted with 4.8 Ml sterile 
water for injection [SWFI])
Route/
Administration/
Duration:
Intravenous infusion for over an hour
Physical 
description:
White uniform lyophilised cake in a 20 Ml vial
Manufacturer/
source of 
procurement:
Human Genome Sciences, Inc.
5.2.
Treatment Assignment
Subjects will be assigned to GSK1550188 10 mg/kg treatment in an open label fashion.
5.2.1.
Liver Chemistry Stopping Criteria
Liver chemistry threshold stopping criteria have been designed to assure subject safety 
and to evaluate liver event etiology (in alignment with the FDA premarketing clinical 
liver safety guidance).
Study treatment will be stopped for a subject if the following liver chemistry stopping 
criteria is met: 

ALT 3xULN
NOTE: Refer to Appendix 1 for details of the required assessments if a subject meets the 
above criteria.


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5.2.2.
QTc Withdrawal Criteria
A subject that meets any of the criteria below will be withdrawn from the study. The 
same QT correction formula (e.g., QT duration corrected for heart rate by Bazett’s 
formula [QTcB], QT duration corrected for heart rate by Fridericia’s formula [QTcF]) 
should be used to determine inclusion and discontinuation for any individual subject 
throughout the study.
[QTcB or QTcF] >500 msec,
[Change from baseline: QTcB or QTcF >60 msec]
uncorrected QT >600 msec
If a subject has underlying bundle branch block the following withdrawal criteria should 
be used instead:
Baseline QTc value (with 
underlying bundle branch block)
QTc withdrawal criteria
<450 msec
>500 msec
450-480 msec
>530 msec
Withdrawal of subjects is to be based on an average corrected QT interval (QTc) value of 
triplicate ECGs. If an ECG demonstrates a prolonged QT interval, obtain 2 more ECGs 
over a brief period of time and then use the averaged QTc values of the 3 ECGs to 
determine whether the subject should be discontinued from the study.
5.3.
Blinding
This will be an open label study.
5.4.
Packaging and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements. Label on each vial and box includes study protocol number, name of 
investigational drug, serial number, storage condition and study sponsor.
5.5.
Preparation/Handling/Storage/Accountability
The 400 mg single use vial of active IP will be reconstituted with 4.8 Ml SWFI, to yield a 
final concentration of 80 mg/Ml of GSK1550188.  After reconstitution the material is 
stable for up to 8 hours at 2-8°C, or at room temperature.
All IPs must be stored in a secure area with access limited to the investigator and 
authorized site staff and under physical conditions that are consistent with IP-specific 
requirements.  All treatment packs will be stored refrigerated at 2-8oC.  Maintenance of a 
temperature log (manual or automated) is required. Only authorized site staff may supply 
or administer IP. IP must be dispensed or administered according to procedures described 


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herein. Only subjects enrolled in the study may receive IP, in accordance with all 
applicable regulatory requirements.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance. 
The investigator or the head of the medical institution (where applicable), or designated 
site staff (e.g., storage manager, where applicable) 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 supplied and/or administered to and/or returned by subjects. Discrepancies are to 
be reconciled or resolved. Procedures for final disposition of unused study treatment are 
listed in the study procedures manual (SPM).
In the post-marketing setting, delayed onset of symptoms of acute hypersensitivity 
reactions has been observed. Subjects should remain under clinical supervision for 3
hours after completion of the infusion. Should symptoms of acute hypersensitivity occur, 
an extended period of monitoring may be appropriate, based on clinical judgement. 
Otherwise, subjects will be monitored during and after each infusion according to study 
sites’ guidelines or standard operating procedure for IV infusions. This may include, but 
is not limited to, monitoring vital signs and observing for any untoward reactions.
Subjects should be made aware of the potential risk, the signs and symptoms of such 
reactions, and the importance of immediately seeking medical attention. Trained rescue 
personnel and rescue medications/equipment should be available for the infusion.
For subjects who have previously received IVIG or subjects with a history of allergies 
(allergic responses to food, drugs, insects, or a history of urticaria), diphenhydramine 
(12.5 to 50 mg based on clinical judgment) or equivalent and paracetamol 
(acetaminophen), should be administered prophylactically, prior to dosing. Antihistamine 
H2-receptor antagonists (e.g., ranitidine) are also permitted. Sites are encouraged to 
follow their standard practices to manage any untoward infusion reactions noted during 
the infusion period.
5.5.1.
Occupational Safety
Under normal conditions of handling and administration, the IP is not expected to pose 
significant safety risks to site staff.
Adequate precautions must be taken to avoid direct eye or skin contact and to avoid the 
generation of aerosols or mists. The monitor must be notified of any unintentional 
occupational exposure.
The Procedures for Handling Ips describing the occupational hazards and recommended 
handling precautions will be provided to site staff.


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5.6.
Assessment of Compliance
When the individual dose for a subject is prepared from a bulk supply, the preparation of 
the dose will be confirmed by a second member of the study site staff. 
When subjects are dosed at the study site, they will receive study treatment directly from 
the investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents. The dose of study 
treatment 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 treatment.
5.7.
Concomitant Medications and Non-Drug Therapies
5.7.1.
Permitted Medications
Use of the medications may be continued if they have been used before the screening 
visit. Their dosage and administration, however, should be unchanged during the 
screening period.
Once the subject is enrolled and receives belimumab on Day 0, the investigator may 
adjust concurrent medications (add, eliminate, change dose level/frequency) as clinically 
required. For subjects with a history of allergies, allergic responses to food, drugs or 
insects, or a history of urticaria, antihistamine and acetaminophen may be administered 
prophylactically.
All prescription and over-the-counter medications (including herbal medicines) that have 
been taken within 60 days prior to the first infusion of study treatment and all 
concomitant medications taken during the study will be recorded in the CRF.
5.7.2.
Prohibited Medications and Non-Drug Therapies
The following medications and therapies are prohibited: 
From 12 months prior to Day 0:

Biologic investigational and non-investigational agent
From 6 months prior to Day 0:

Hemodialysis

Intravenous cyclophosphamide (Cytoxan)

High-dose prednisone (>60 mg/day)

IVIG

Plasmapheresis


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From 2 months prior to Day 0:

Non-biologic investigational agent.

Corticosteroids (prednisone or prednisone equivalent, >40 mg/day)

Parenteral antibiotics
From 30 days prior to Day 0

Live vaccine
During the study period: 

Other investigational agents (biologic or non-biologic). Investigational applies 
to any drug not approved for sale in the country in which it is being used.

Co-enrolment into another study of an investigational agent or non-drug 
therapy that may interfere with the conduct of this protocol.

Anti- tumour necrosis factor (TNF) or anti-interleukin-6 (IL-6) therapy (e.g., 
adalimumab, etanercept, infliximab).

Other biologics (e.g., rituximab, abatacept, interleukin-1 receptor antagonist 
[anakinra]).

Intravenous immunoglobulin (IVIG).

IV cyclophosphamide.

Plasmapheresis, leukapheresis.

Live vaccine.


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6.
STUDY ASSESSMENTS AND PROCEDURES
A schedule of study assessments and tests is shown in Table 2. The details of study 
assessments are shown in “Study Procedures Manual” that sponsor prepared separately. 
The time assessment window of the each PK blood sample collection is shown in Table 3. 
The end time of the infusion will be designated Time 0, and subsequent PK sampling and 
safety assessments will be performed relative to this time. It is essential that the exact time 
of blood sampling, however, should still be accurately recorded. The safety assessments 
are recommended to be conducted close to PK sample collection; however, when several 
procedures are scheduled at the same nominal time point, PK blood sampling should be given 
priority.


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Table 2
Time and Events Table
Visit
1
2
3
4
5
6
7
8
9
10
Day
Screening
Day -30 to -1
Day 0
Day 
1
Day 
7
Day 
14
Day 
21
Day 
28
Day 
42
Day 
56
Day 
84
Discontinuation11
Pre
0
5m
1h
6h
24h
Informed consent1
X
Medical History
X
X
Demography
X
Inclusion/Exclusion 
criteria
X
X2
Complete physical 
examination, 
including Height
X
Body weight
X
Vital signs3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Record 
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical Laboratory 
test4
X
X4
X
X
X
X
X
X
Spot urine (protein 
to creatinine ratio)
X
Urine drug/alcohol 
screen
X
HIV, Hepatitis B, 
C5
X
Pregnancy test 
(women)6
X
X4
X
X
X
Chest X ray
X
12 lead ECG
X
X4
X
X
X
Biological 
Markers7
X8
X
X
X
X
X
X
Blood PK sampling
X
X
X
X
X
X
X
X
X
X
X
X
X


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Visit
1
2
3
4
5
6
7
8
9
10
Day
Screening
Day -30 to -1
Day 0
Day 
1
Day 
7
Day 
14
Day 
21
Day 
28
Day 
42
Day 
56
Day 
84
Discontinuation11
Pre
0
5m
1h
6h
24h
AE/SAE Review9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Admission to Unit 
X10
Dosing
X
Discharge 
X10
Outpatient Visit 
X
X
X
X
X
X
X
X
X
X
1.
Each subject must sign an informed consent form prior to undergoing any Screening assessments.
2.
Clinical laboratory test at screening visit will be used for inclusion/exclusion criteria check.
3.
Vital signs include temperature, sitting blood pressure and heart rate. Pulse rate could be used to replace heart rate monitoring if subject has regular sinus 
rhythm.
4.
Clinical Laboratory test include hematology, chemistry and urinalysis (including C-reactive protein [CRP] and Erythrocyte Sedimentation Rate on screening). ALT 
and/or AST elevations of greater than 2.5 x ULN will require additional Hepatitis B assessment, see Section 6.2.1.1. For pre-dose safety lab monitoring including 
urine pregnancy test and 12 lead ECG, it’s recommended to be done on day 0 or within 48 hours prior to day 0 if site logistic management are limited on day 0 for 
drug dosing and intensive PK sample collection. 
5.
HIV antibody, Hepatitis B surface antigen, anti-HBc and Hepatitis C antibody.
6.
Pregnancy should be assessed with a blood test at Screening and with a urine test during the treatment period. Pregnancy beyond Day 84 and within 16 weeks 
after last dose of IP will be assessed with a homekit and subjects can report the results via phone to site.
7.
Biomarkers include immunoglobulins, B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells).
8.
Only immunoglobulins (IgG, IgM and IgA) and auto antibodies (anti-dsDNA, ANA).
9.
Includes subject history to be reported on CRF regarding any general signs or symptoms of infection.
10. The recommended date of “Admission to the Unit” and “Discharge” is only a suggestion. The subject can be admitted to unit from Day -2 to Day 0 and/or 
discharged on Day 1 based on site flexibility and resource allocation.
11. If a subject prematurely withdraws for any reason, the investigator must make every effort to assess the items specified on discontinuation test.


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Table 3
Time assessment window of the each PK sample collection
Study Day
Hrs relative to dose
Blood sampling for PK
Day 0: pre-dose
Day 0 pre-dose
-60 minutes
Day 0: 5min
5min after dose completion
± 1 minutes
Day 0: 1hour
1 hour after dose completion
± 10 minutes
Day 0: 6 hour
6 hour after dose completion
± 15 minutes
Day 0: 24 hour
24 hour after dose completion
± 1 Hrs
Day 1
48 hour after dose completion
± 2 Hrs
Day 7
192 hour after dose completion
-48Hrs to +2 Hrs
Day 14
360 Hrs after dose completion
-48Hrs to +2 Hrs
Day 21
528 Hrs after dose completion
-48Hrs to +2 Hrs
Day 28
696 Hrs after dose completion
-48Hrs to +2 Hrs
Day 42
1032 Hrs after dose completion
-48Hrs to +2 Hrs
Day 56
1368 Hrs after dose completion
-48Hrs to +2 Hrs
Day 84
2040 Hrs after dose completion
-48Hrs to +2 Hrs
6.1.
Critical Baseline Assessments
A signed written informed consent form must be obtained prior to Screening assessments, 
and before any study-specific assessments for Baseline assessments are initiated.
Baseline level is the basal value required for comparing examination/observation data 
after the infusion of investigational drug. Therefore, the examination at pre-dose is 
normally performed. If the data are not examined at Day 0, values at screening will be 
used as baseline levels.
6.1.1.
Screening Test
During the screening visit, each subject will have the following evaluations to determine 
eligibility for enrollment: 

Demographic information including gender, ethnic origin, race, date of birth.

Medical history, including cardiovascular history and risk factors.

Complete physical examination, including height.

Vital signs including temperature, sitting blood pressure, and heart rate.

Confirm classification of SLE disease (based on ACR criteria) by reviewing 
previously documented clinical records.

Clinical laboratory tests:
o
Hematology: White blood cells (WBC), Red blood cells (RBC), 
Hemoglobin (Hb), Hematocrit (Ht), platelet count and WBC-differential 


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o
Chemistry: AST, ALT, Alkaline phosphatase ( ALP),  Gamma 
glutamyltransferase (GGT), Lactate dehydrogenase (LDH), creatinine, 
Blood urea nitrogen (BUN), total bilirubin, total protein, albumin, uric 
acid, Prothrombin time (PT), Partial Thromboplastin Time (PTT), 
Erythrocyte Sedimentation Rate (ESR), CRP, glucose, sodium, potassium, 
magnesium, chloride, carbon dioxide (CO2), calcium, phosphate 
o
Urinalysis: protein, glucose, ketones, occult blood, microscopic examination
o
Spot urine for proteinuria assessment

Urine drug/alcohol screen.

HIV antibody, Hepatitis B surface antigen, anti-HBc, HBV DNA and Hepatitis C 
antibody.( NOTE: if anti-HBc result is reactive, the sample drawn for HBV DNA 
will be tested for viral DNA; otherwise, the sample will be destroyed).

Serum Pregnancy test.

Chest X ray.

12-lead ECG.

Immunoglobulins (IgG, IgM and IgA) and auto antibodies (anti-dsDNA, ANA).

Adverse events.
6.1.2.
Pre-dose Examination
Pre-dose examination will be conducted before the dose: 

Adverse events.

Body weight.

Vital signs including temperature, sitting blood pressure, and heart rate.

Current medical history.

Clinical laboratory tests: hematology, chemistry and urinalysis.

Urinary pregnancy test (for female only).

12-lead ECG.

Inclusion/exclusion criteria check

PK blood sampling.


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
B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–naïve, CD20+/69+ 
activated, CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE 
subset and CD20-/138+ plasma cells)
6.2.
Safety
The following will be made as the safety assessments.

Adverse events.

Clinical laboratory tests: hematology, chemistry and urinalysis.

Vital signs (blood pressure, heart rate and body temperature).

12-lead ECG.
6.2.1.
Liver Chemistry Follow-up Procedures
Liver chemistry withdrawal criteria have been designed to assure subject safety and 
evaluate liver event etiology. 
Liver chemistry stopping criteria 1-3 are defined below: 
1
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) (or ALT 3xULN
and international normalised ratio (INR) >1.5, if INR measure).
NOTE: if serum bilirubin fractionation is not immediately available, study drug should be 
discontinued if ALT ≥ 3xULN and bilirubin ≥ 2xULN. Serum bilirubin fractionation 
should be performed if testing is available. If testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.
2
ALT 5xULN.
3
ALT 3xULN if associated with the appearance or worsening of symptoms of 
hepatitis or hypersensitivity such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash or eosinophilia.
When any of the liver chemistry withdrawal criteria is met, do the following:

Report the event to GSK within 24 hours of learning its occurrence 

Complete the liver event CRF and SAE data collection tool if the event also meets 
the criteria for an SAE. All events of ALT 3xULN and bilirubin 2xULN
(>35% direct bilirubin) (or ALT 3xULN and INR >1.5, if INR measured; INR 
measurement is not required and the threshold value stated will not apply to 
patients receiving anticoagulants), termed ‘Hy’s Law’, must be reported as an 
SAE (excluding studies of hepatic impairment or cirrhosis). 


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NOTE: if serum bilirubin fractionation is not immediately available, study drug    
should be discontinued if ALT 3xULN and bilirubin 2xULN. Serum bilirubin 
fractionation should be performed if testing is available. If testing is unavailable, 
record presence of detectable urinary bilirubin on dipstick, indicating direct 
bilirubin elevations and suggesting liver injury.

Complete the liver imaging and/or liver biopsy CRFs if these tests are performed 

Perform liver event follow up assessments, and monitor the subject until liver 
chemistries resolve, stabilize, or return to baseline values as described below. 

Withdraw the subject from the study (unless further safety follow up is required) 
after completion of the liver chemistry monitoring as described below. 
In addition, for criterion 1:  

Make every reasonable attempt to have subjects return to clinic within 24 hours
for repeat liver chemistries, liver event follow up assessments (see below), and 
close monitoring 

A specialist or hepatology consultation is recommended 

Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline
phosphatase , bilirubin) resolve, stabilize or return to within baseline values 
For criteria 2 and 3: 

Make every reasonable attempt to have subjects return to clinic within 24-72 hrs
for repeat liver chemistries and liver event follow up assessments (see below) 

Monitor subjects weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within baseline values; criterion 5 subjects 
should be monitored as frequently as possible.

Subjects with ALT 3xULN but <5xULN and bilirubin <2xULN, without 
hepatitis symptoms or rash, and who can be monitored weekly for 4 weeks 

Notify the GSK medical monitor within 24 hours of learning of the abnormality to 
discuss subject safety. 

Must return weekly for repeat liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to within baseline 

If at any time these subjects meet the liver chemistry stopping criteria, proceed as 
described above 

If, after 4 weeks of monitoring, ALT <3xULN and bilirubin <2xULN, monitor 
subjects twice monthly until liver chemistries normalize or return to within 
baseline values. 


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For criteria 1-3, make every attempt to carry out the liver event follow up assessments 
described below: 

Viral hepatitis serology including: 

Hepatitis A IgM antibody; 

Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM);  

Hepatitis C ribonucleic acid (RNA); 

Cytomegalovirus IgM antibody;  

Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); 

Hepatitis E IgM antibody

Blood sample for pharmacokinetic (PK) analysis, obtained within one to two
weeks after the liver event.  Record the date/time of the PK blood sample draw 
and the date/time of the last dose of IP prior to blood sample draw on the CRF. If 
the date or time of the last dose is unclear, provide the subject’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK 
sample. Instructions for sample handling and shipping are in the SPM. 

Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). 

Fractionate bilirubin, if total bilirubin 2xULN

Obtain complete blood count with differential to assess eosinophilia 

Record the appearance or worsening of clinical symptoms of hepatitis, or 
hypersensitivity, such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever rash or eosinophilia as relevant on the AE report form 

Record use of concomitant medications, acetaminophen, herbal remedies, other 
over the counter medications, or putative hepatotoxins, on the concomitant 
medications report form. 

Record alcohol use on the liver event alcohol intake case report form 
The following are required for subjects with ALT 3xULN and bilirubin 2xULN (>35% 
direct) but are optional for other abnormal liver chemistries: 

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies, total IgG.


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
Liver imaging (ultrasound, magnetic resonance, or computerized tomography) to 
evaluate liver disease.
6.2.1.1.
Additional Hepatitis B Monitoring
Safety assessment for Hepatitis B during the trial will be as follows:

ALT and/or AST elevations of greater than 2.5 x ULN will require:

Sites to review screening laboratory results for anti-HBc:
o
If screening anti-HBc result was reactive, then obtain HBV DNA.
If HBV DNA returns reactive, investigator will determine the extent of 
required attention for proper follow up of potential hepatitis B re-
activation.
o
If screening anti-HBc result was negative, then repeating hepatitis B testing is 
optional per investigator upon investigating for other causes.
Refer to the SPM for guidance on documenting the suspected reason for ALT 
and/or AST elevations of greater than 2.5 x ULN.
6.2.2.
Clinical Laboratory
Blood and urine will be taken for clinical laboratory test at screening and at pre-dose, and 
Days 0, 1, 14, 28, 56 and 84 post-dose. 

Hematology: WBC, RBC, Hb, Ht, PT, PTT, platelet count and WBC-differential 
(including ESR on screening) 

Chemistry: AST, ALT, ALP, GGT, LDH, creatinine, BUN, total bilirubin, total 
protein, albumin, uric acid, glucose, sodium, potassium, magnesium, chloride, 
carbon dioxide, calcium, phosphate (including CRP on screening) 

Urinalysis: protein, glucose, ketones, occult blood, microscopic examination

Spot urine for proteinuria assessment
Note: ALT and/or AST elevations of greater than 2.5 x ULN will require Hepatitis B
assessment, see Section 6.2.1.1
All clinical laboratory blood samples will be sent to a central laboratory for analysis (details 
provided in the SPM). The central laboratory will fax laboratory results to the Investigator 
and will transmit the results electronically to GlaxoSmithKline.
6.2.3.
Vital Signs
Systolic and diastolic blood pressure (sitting), heart rate, and body temperature will be 
measured. Measurements of vital signs will be taken at screening and at pre-dose, and at 
5 minutes, 1, 6 and 24 hours, and Days 1, 7, 14, 21, 28, 42, 56 and 84 post-dose. 


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At the discretion of the Investigator, vital signs may be assessed at unscheduled visits. 
6.2.4.
12-Lead ECG
Measurements of 12-Lead ECG will be taken at screening and at pre-dose, and 24 hours
and Day 84 post-dose. The ECG parameters are HR, PR, QRS, QT and QTc.
6.3.
Pharmacokinetics
Blood samples will be collected for PK at pre-dose, and at 5 minutes, 1, 6 and 24 hours, 
and Days 1, 7, 14, 21, 28, 42, 56 and 84 post-dose. The actual date and time of sampling 
will be recorded in the CRF.  Serum will be harvested within one hour of blood sample
collection. PK samples will be sent to a local bioanalytical laboratory and analyzed using 
a validated method (details provided in the SPM).
6.4.
Pharmacodynamic/Biomarkers
Blood samples will be collected at screening and at pre-dose, Days 14, 28, 42, 56 and 84 
post-dose. The actual date and time of sampling will be recorded in the CRF. All blood 
samples will be sent to a central laboratory for analysis (details provided in the SPM).  
The central laboratory will fax the results to the Investigator and will transmit the results 
electronically to GlaxoSmithKline.

B cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, 
CD20+/69+activated, CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE 
subset and CD20-/138+ plasma cells).
7.
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, 
PREGNANCY AND MEDICAL DEVICE INCIDENTS
7.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)
The investigator or site staff is responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.
7.1.1.
Time period for collecting AEs and SAE information
AEs will be collected from the start of Study Treatment and until the Day 84 or study 
discontinuation. Medical occurrences that begin prior to the start of study treatment but 
after obtaining informed consent may be recorded on the Medical History/Current 
Medical Conditions CRF.
Serious AEs will be recorded from the time the consent form is signed until the follow-up 
contact. All SAEs will be recorded and reported to GSK within 24 hours.


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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 
subject has been discharged from the study, and he/she considers the event reasonably 
related to the study treatment or study participation, the investigator would promptly 
notify GSK.
7.1.2.
Definition of Adverse Events
An AE is any untoward medical occurrence in a patient or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product.  
Events meeting the definition of an AE include:

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgement of the investigator.

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae.).
Events that do not meet the definition of an AE include:

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that is associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’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 subject’s 
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure are an AE.

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).


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
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.
7.1.3.
Definition of Serious Adverse Events
If an event is not an AE per Section 7.1.2, 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, etc).
An SAE is any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
NOTE:  The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event.  It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:  In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or out-patient setting.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in disability/incapacity, or
NOTE:  The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect
f.
Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious.  Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.


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g.
Is associated with liver injury and impaired liver function defined as:

ALT 3xULN and total bilirubin* 2xULN (>35% direct), or

ALT 3xULN and INR** >1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable 
and ALT 3xULN and total bilirubin 2xULN, then the event is still to be reported 
as an SAE.
** INR testing not required per protocol and the threshold value does not apply to 
subjects receiving anticoagulants.  If INR measurement is obtained, the value is to be 
recorded on the SAE form.
7.1.4.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 
including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgement of the investigator are to be recorded as Aes or SAEs.
However, any clinically significant safety assessments that are associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the subject’s 
condition, are not to be reported as Aes or SAEs.
7.1.5.
Method of Detecting AEs and SAEs
The investigator (or sub-investigators) will do the medical examination following the 
schedule with nondirective interview such as the following sentences.

“How are you feeling?”

“Have you had any (other) medical problems since your last visit/contact?”

“Have you taken any new medicines, other than those provided in this study, 
since your last visit/contact?”
7.1.6.
Recording of AEs and SAEs
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE on the CRF. It is not acceptable for the investigator to send photocopies of the 
subject’s medical records to GSK in lieu of completion of the appropriate AE/SAE CRF 
pages. However, there may be instances when copies of medical records for certain cases 
are requested by GSK. In this instance, all subject identifiers will be blinded on the 
copies of the medical records prior to submission to GSK.


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The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
7.1.7.
Evaluating AEs and SAEs
The definition of an AE and a SAE is provided in Section 7.1.2 and Section 7.1.3.
7.1.8.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study. The assessment will be based on Division of Microbiology and 
Infectious Diseases (DMID) Adverse Event Severity Grade Tables (see Appendix 3),
where possible:
SEVERITY:
Mild – An event that is easily tolerated by the subject, causing minimal discomfort and
not interfering with everyday activities (Grade 1 DMID)
Moderate – An event that is sufficiently discomforting to interfere with normal everyday
activities (Grade 2 DMID)
Severe – An event that prevents normal everyday activities (Grade 3 or 4 DMID)
An AE that is assessed as severe is not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both Aes and SAEs can be assessed as 
severe. An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
7.1.9.
Assessment of Causality
The investigator (or sub-investigator) is obligated to assess the relationship between IP 
and the occurrence of each AE/SAE. A “reasonable possibility” is meant to convey that 
there are facts/evidence or arguments to suggest a causal relationship, rather than a 
relationship cannot be ruled out. The investigator (or sub-investigator) will use clinical 
judgement to determine the relationship. Alternative causes, such as natural history of the 
underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the event to the IP will be considered and investigated. The investigator 
(or sub-investigator) will also consult the IB and/or Product Information, in the 
determination of 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 when an SAE has occurred and the investigator (or sub-
investigator) has minimal information to include in the initial report to GSK. However, it 
is very important that the investigator (or sub-investigator) always make an 
assessment of causality for every event prior to the initial transmission of the SAE 


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data to GSK. The investigator (or sub-investigator) may change his/her opinion of 
causality in light of follow-up information, amending the SAE data collection tool 
accordingly. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
The investigator (or sub-investigator) will provide the assessment of causality as per the 
instructions for completion of the AE/SAE data collection tool.
7.1.10.
Completion and Transmission of SAEs Report
Once an investigator (or sub-investigator) becomes aware that an SAE has occurred in a 
study subject, she/he will report the information to GSK within 24 hours or as outlined in 
the protocol in the section titled, “Prompt Reporting of Serious Adverse Events and Other 
Events to GSK”. The SAE data collection tool will always be completed as thoroughly as 
possible with all available details of the event, and submitted to GSK within the 
designated time frames. If the investigator (or sub-investigator) does not have all 
information regarding an SAE, he/she will not wait to receive additional information 
before notifying GSK of the event and completing the appropriate data collection tool. 
The appropriate data collection tool will be updated when additional information is 
received. 
The investigator (or sub-investigator) will always provide an assessment of causality at 
the time of the initial report as described in the section of this document titled, 
“Assessment of Causality”. 
The primary mechanism for reporting SAEs to GSK will be the electronic data collection 
(EDC) tool (e.g., InForm system). If the electronic system is unavailable for greater than 
24 hours, the site will use the paper SAE data collection tool and fax it to GSK. The site 
will then enter the serious adverse event data into the electronic system as soon as it 
becomes available. 
GSK will provide a separate list of contact details for reporting SAEs, including fax 
numbers and telephone numbers. 
7.1.11.
Follow-Up of AEs and SAEs
After the initial AE/SAE report, the investigator (or sub-investigator) is required to 
proactively follow each subject and provide further information to GSK on the subject’s 
condition. All Aes and SAEs documented at a previous visit/contact and that are 
designated as ongoing, will be reviewed at subsequent visits/contacts. 
All Aes and SAEs will be followed until resolution, until the condition stabilizes, until 
the event is otherwise explained, or until the subject is lost to follow-up. This applies to 
all subjects, including those withdrawn prematurely. The investigator (or sub-
investigator) will ensure that follow-up includes any supplemental investigations as may 
be indicated to elucidate the nature and/or causality of the AE or SAE.  This may include 
additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 


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GSK may request that the investigator perform or arrange for the conduct of 
supplemental measurements and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator (or sub-investigator) is obligated to 
assist. If a subject 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 (may not be required for studies where death is an endpoint). 
New or updated information will be recorded in the originally completed SAE data 
collection tool.  The investigator (or sub-investigator) will submit the updated SAE data 
to GSK within the designated reporting time frames.
7.1.12.
Post-study AEs and SAEs
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
detection period as defined in the protocol. 
Investigators (or sub-investigator) are not obligated to actively seek AEs or SAEs in 
former subjects. However, if the investigator (or sub-investigator) learns of any SAE, 
including a death, at any time after a subject has been discharged from the study, and 
considers the event reasonably related to the IP or study participation, the investigator (or 
sub-investigator) will promptly notify GSK. 
After the study is completed at a given site, the EDC tool will be taken off-line to prevent 
the entry of new data or changes to existing data. If the site is notified of a new SAE from 
a subject or receives updated data on a previously reported SAE after the EDC tool has 
been taken off-line, the site can report this information on the paper SAE data collection 
tool or to their GSK protocol contact by telephone. 
7.1.13.
Prompt Reporting of SAEs to GSK
SAEs, pregnancies, medical device incidents, and liver function abnormalities meeting 
pre-defined criteria will be reported promptly by the investigator to GSK as described in 
the following table once the investigator determines that the event meets the protocol 
definition for that event.

Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool

If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the SAE contactor.

Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available.

The investigator will be required to confirm review of the SAE causality by ticking 
the ‘reviewed’ box at the bottom of the eCRF page within 72 hours of submission of 
the SAE.


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
After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) 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 subject or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, the site can report this information on a paper SAE form or to SAE 
contactor by telephone.

Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page.
Table 4
Reporting of SAE and Other Events to GSK
Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
“SAE” data 
collection tool
24 hours
Updated “SAE” 
data collection tool 
Pregnancy
2 Weeks
Pregnancy 
Notification Form
2 Weeks
Pregnancy Follow 
up Form
Liver chemistry 
abnormalities Phase 
III-IV:
ALT3xULN and 
Bilirubin2xULN
(>35% direct) (or 
ALT3xULN and 
INR>1.5, if INR 
measured)***
24 hours*
SAE data 
collection tool.
**Liver Event CRF 
and liver imaging 
and/or biopsy 
CRFs if applicable
24 hours
Updated SAE data 
collection tool. 
**Updated Liver 
Event CRF
ALT8xULN; 
ALT3xULN with 
hepatitis or rash or 
3xULN and <5xULN
that persists 4 
weeks
24 hours*
**Liver event CRF 24 hours 
**Updated Liver 
Event CRF
ALT5xULN plus 
bilirubin <2xULN
24 hours*
**Liver event CRF 
does not need 
completing unless 
elevations persist 
for 2 weeks or 
subject cannot be 
monitored weekly 
for 2 weeks
24 hours
ALT5xULN and 
bilirubin <2xULN that 
persists 2 weeks
24 hours*
**Liver event CRF 
24 hours
Updated liver event 
CRF


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Initial Reports
Follow-up Information on a Previous 
Report
ALT3xULN and <5x 
ULN and bilirubin 
<2xULN
24 hours*
**Liver event CRF 
does not need 
completing unless 
elevations persist 
for 4 weeks or 
subject cannot be 
monitored weekly 
for 4 weeks
*GSK to be notified at onset of liver chemistry elevations to discuss subject safety.
** Liver event documents should be completed as soon as possible.
*** INR measurement is not required; if measured, the threshold value stated will not apply to 
patients receiving anticoagulants.
The method of recording, evaluating and follow-up of Aes and SAEs plus procedures for 
completing and transmitting SAE reports to GSK are provided in the SPM.  Procedures 
for post-study Aes/SAEs are provided in the SPM.
7.1.14.
Regulatory Reporting Requirements for SAEs
Prompt notification of SAEs by the investigator to GSK is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation. GSK will 
comply with country specific regulatory requirements relating to safety reporting to 
regulatory authorities, IRBs/IECs and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.  An investigator who receives an investigator safety report 
describing an SAE(s) or other specific safety information (e.g., summary or listing of 
SAEs) from GSK will file it with the IB and will notify the Institutional Review Board
(IRB)/ Independent Ethics Committee (IEC), if appropriate according to local 
requirements.
7.2.
Pregnancy
Any pregnancy that occurs during study participation and for 16 weeks following last 
dose must be reported using a clinical trial pregnancy form. For pregnancy occurring 
after the last visit but within 16 weeks after last dose, it can be reported by subjects using 
a phone call. To ensure subject safety, each pregnancy must be reported to GSK within 2 
weeks of learning of its occurrence.
The pregnancy must be followed up to determine outcome (including premature 
termination) and status of mother and child.


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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 subject 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 subject has a positive pregnancy test during study participation, complete a 
Pregnancy Notification Form and fax it to GSK. Follow the subject to determine the 
outcome of the pregnancy and forward the outcome information using a Pregnancy 
Follow-up Form to GSK no later than 6 to 8 weeks following the estimated delivery date.
7.3.
PML
Progressive multifocal leukoencephalopathy (PML) resulting in neurological deficits, 
including fatal cases, has been reported in SLE patients receiving immunosuppressant 
pharmacotherapy, including belimumab. A diagnosis of PML should be considered in 
any subject presenting with new-onset or deteriorating neurological signs and symptoms. 
The subject should be referred to a neurologist or other appropriate specialist for 
evaluation. If PML is confirmed, consideration should be given to stopping 
immunosuppressant therapy.  If PML is suspected, this should be immediately 
reported to the Medical Monitor.
8.
DATA MANAGEMENT
For this study subject data will be collected using GSK defined case report forms and 
combined with data provided from other sources in a validated data system.
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
errors and inconsistencies in the data.  Adverse events and concomitant medications 
terms will be coded using MedDRA (Medical Dictionary for Regulatory Activities) and 
an internal validated medication dictionary, GSK Drug.  Original CRFs will be retained 
by GSK, while the investigator will retain a copy.  Subject initials will not be collected or 
transmitted to GSK according to GSK policy.
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
Full details of tabulation/analyses will be described in the “Reporting Analysis Plan” 
(RAP). 
Any changes form analyses described within this protocol will be stated in “RAP” and 
“Final Clinical Study Report” 
If the study is prematurely discontinued, all available data will be listed and a review will 
be carried out to assess which statistical analyses are still considered appropriate.


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Data obtained for this study and used for statistical analysis will be examined for outliers, 
and their accuracy will be verified or queried. Values verified as accurate will be 
included in the analysis.
All categorical data will be summarized by reporting the frequency and percentage of 
subjects in each cohort.
All continuous data will be summarized using mean, standard deviation, median, ranges, 
and 95% confidence interval (CI) where applicable.
9.1.
Hypotheses and Treatment Comparisons
The primary objective of this study is to evaluate the pharmacokinetics of single dose 
GSK1550188 in Chinese subjects with SLE. No formal statistical hypothesis testing will 
be conducted; however, summaries of safety parameters, PK, and PD will be provided. 
9.2.
Sample Size Considerations
9.2.1.
Sample Size Assumptions
There are no formal calculations of power or sample size for this study. The sample size 
of 20 to obtain 12 evaluable subjects has been chosen based on feasibility, as well as to 
meet requirement of China FDA, 2005 (CFDA Guidance). 
With 12 evaluable subjects in this study, assuming that the CV% of Cmax and AUC(0-
inf) is 20.0% and 32.1% respectively (from study C1105), it is estimated that the lower 
and upper bounds of the 95% confidence interval would lie within 13.4% of the point 
estimate for Cmax and 22.0% of the point estimate for AUC(0-inf). This is narrower than 
the Japan study BEL114243, in which the 95% confidence interval lied within 15.0% of 
the point estimate for Cmax and 33.7% of the point estimate for AUC (0-inf).
9.2.2.
Sample Size Sensitivity
No sample size sensitivity analysis will be performed.
9.2.3.
Sample Size Re-estimation
No sample size re-estimation will be performed.
9.3.
Data Analysis Considerations
9.3.1.
Analysis Population
All subjects who receive the study medication will be included in the safety population.
All subjects who receive the study medication and for whom a pharmacokinetic sample is 
obtained will be included in the pharmacokinetic concentration population. 


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All subjects who receive a dose of GSK1550188 and for whom pharmacokinetic 
parameters can be calculated will be included in the pharmacokinetic parameter 
population. 
All subjects who receive the study medication and for whom pharmacodynamic data is 
available will be included in the pharmacodynamic population.
If any subject is excluded from analyses, the details and reason will be described in the 
final study report.
9.3.2.
Analysis Data Set
All available data will be included in the data sets.
9.3.3.
Interim Analysis
No formal interim analysis is planned.
9.3.4.
Final Analyses
9.3.4.1.
Safety Analyses
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively according to GSK’s Integrated Data Standards Library (IDSL) standards. 
Summaries of safety data (adverse events and the results of examinations) will include 
adverse events, serious adverse events, vital signs, ECG and laboratory parameters.
9.3.4.1.1.
Extent of Exposure
The date and time of study drug administration will be listed.
9.3.4.1.2.
Adverse Events
Adverse events will be coded using (MedDRA) and summarized by System Organ 
Classes (SOCs) and Preferred Term. A summary of the number and percentage of 
subjects with Aes occurring on or after the treatment start date will be displayed.
9.3.4.1.3.
Clinical Laboratory Evaluations
For clinical laboratory data, summary statistics will be provided for each laboratory 
parameter and listings showing time courses will be prepared. Change from baseline data 
will also be summarized.
Data exceeding the reference values will be listed.


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9.3.4.1.4.
Vital Signs
For systolic and diastolic blood pressure and heart rate, summary statistics will be 
provided and listings showing time courses will be prepared. Change from baseline data 
will also be summarized.
9.3.4.1.5.
12-Lead ECG
All 12-lead ECG data will be listed and summarised in the same manner as described 
above for blood pressure and heart rate.  The ECG parameters, HR, PR, QRS, QT and 
QTc, will be presented in the summary table. 
9.3.4.2.
Pharmacokinetic Analyses
Pharmacokinetic analysis will be the responsibility of the Clinical Pharmacokinetics 
Modeling & Simulation department within GlaxoSmithKline.  
9.3.4.2.1.
Serum Concentrations
Serum concentrations of GSK1550188 at each assessment point will be listed to prepare 
figures showing individual concentration-time profiles on both linear and semi-log scales. 
In addition, the mean and median serum concentrations at each assessment point will be 
calculated from concentration data of individual subjects to prepare figures showing 
mean and median serum concentration-time profiles on both linear and semi-log scales.
9.3.4.2.2.
Pharmacokinetic Parameters
Serum concentration-time data for GSK1550188 will be analyzed by non-compartmental 
methods using WinNonlin 5.2 or above. Calculations will be based on the actual dose and 
sampling dates and times recorded during the study. From the concentration-time data for 
GSK1550188, the following pharmacokinetic parameters will be determined: maximum 
concentration (Cmax), area under the plasma concentration-time curve [AUC(0-t) and 
AUC(0-∞)], and apparent terminal phase half-life (t1/2), terminal phase elimination rate 
(λz), systemic clearance (CL), and volume of distribution (Vz). Summary statistics for 
the above parameters will be calculated.
For each of the derived serum GSK1550188 pharmacokinetic parameters, the following 
summary statistics will be calculated: median, minimum, maximum, arithmetic mean, 
standard deviation, coefficient of variation, geometric mean, 95% confidence interval for 
the geometric mean and standard deviation of logarithmically transformed data.
9.3.4.3.
Pharmacodynamic/Biomarker Analyses
Estimates of percent change from baseline for B cell subsets will be performed in the PD 
population. Full details of analyses of PD will be outlined in the “RAP”. The data of the 
PD population will be summarised. All derived parameters will be listed and 
summarized.


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10.
STUDY GOVERNANCE CONSIDERATIONS
10.1.
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will also be conducted in accordance with International Conference on 
Harmonization of Technical Requirements for Registration of Pharmaceuticals for 
Human Use (ICH) Good Clinical Practice (GCP), all applicable subject privacy 
requirements, and, the guiding principles of the 2008 Declaration of Helsinki. This 
includes, but is not limited to, the following:

IRB/IEC review and favorable opinion/approval to conduct the study and of any 
subsequent relevant amended documents

Written informed consent (and any amendments) to be obtained for each subject 
before participation in the study

Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol deviations 
to IRB/IEC)
Written informed consent must be obtained from each subject prior to participation in the 
study.
10.3.
Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK 
monitors will contact the site prior to the start of the study to review with the site staff the 
protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and 
GSK requirements. When reviewing data collection procedures, the discussion will also 
include identification, agreement and documentation of data items for which the CRF
will serve as the source document.
GSK will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements.


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The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents
10.4.
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of 
the study. In the event of an assessment, audit or inspection, the investigator (and 
institution) must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to 
all relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective and/or 
preventative actions to address any findings/issues identified.
10.5.
Study and Site Closure
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations including GCP, and GSK procedures.
In addition, GSK reserves the right to temporarily suspend or prematurely discontinue 
this study at any time for reasons including, but not limited to, safety or ethical issues or 
severe non-compliance. For multicenter studies, this can occur at one or more or at all 
sites. If GSK determines such action is needed, GSK will discuss this with the 
investigator or the head of the medical institution (where applicable), including the 
reasons for taking such action. When feasible, GSK will provide advance notification to 
the investigator or the head of the medical institution, where applicable, of the impending 
action prior to it taking effect.
If the study is suspended or prematurely discontinued for safety reasons, GSK will 
promptly inform investigators or the head of the medical institution (where applicable) 
and the regulatory authorities of the suspension or premature discontinuation of the study 
and the reason(s) for the action. If required by applicable regulations, the investigator or 
the head of the medical institution (where applicable) must inform the IRB/IEC promptly 
and provide the reason for the suspension or premature discontinuation.
10.6.
Records Retention
Following closure of the study, the investigator or the head of the medical institution 
(where applicable) must maintain all site study records, except for those required by local 
regulations to be maintained by someone else, in a safe and secure location.  The records 
must be maintained to allow easy and timely retrieval, when needed (e.g., audit or 
inspection), and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and staff.  Where 
permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken.  The 


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investigator must assure that all reproductions are legible and are a true and accurate copy 
of the original, and meet accessibility and retrieval standards, including re-generating a 
hard copy, if required.  Furthermore, the investigator must ensure there is an acceptable 
back-up of these reproductions and that an acceptable quality control process exists for 
making these reproductions.
GSK will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the 
strictest standard applicable to that site for the study, as dictated by any institutional 
requirements or local laws or regulations, or GSK standards/procedures; otherwise, the 
retention period will default to 25 years.
The investigator must notify GSK of any changes in the archival arrangements, including, 
but not limited to, archival at an off-site facility or transfer of ownership of the records in 
the event the investigator leaves the site.
10.7.
Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK will also provide the 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 results summary will be posted to the Clinical Study Register no later than eight 
months after the final primary completion date, the date that the final subject was 
examined or received an intervention for the purposes of final collection of data for the 
primary outcome. In addition, a manuscript will be submitted to a peer reviewed journal 
for publication no later than 18 months after the last subject’s last visit (LSLV).  When 
manuscript publication in a peer reviewed journal is not feasible, a statement will be 
added to the register to explain the reason for not publishing.


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11.
REFERENCES
Boers A, Li Q, Wong M, Miller M, Littlejohn G. Differences in SLE disease activity 
between patients of Caucasian and South-East Asian/Chinese background in an 
Australian hospital. APLAR Journal of Rheumatology. 2006;9:43-48. 
Brocard A, Barbarot S, Milpied B, Stalder JF. Thalidomide in the treatment of chronic 
discoid lupus erythematosus. Ann Dermatol Venereol. 2005;132(11 Pt 1):853-6. 
Carter RH. A role for BlyS in tissue inflammation?. Arthritis Rheum. 2003;48(4):882-5. 
Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus
erythematosus during a 10-year period: a comparison of early and late manifestations in a
cohort of 1,000 patients. Medicine 2003;82(5):299-308.
Cervera R, Khamashta MA, Hughes GRV. The Euro-lupus project: epidemiology of 
systemic lupus erythematosus in Europe. Lupus 2009;18:869-74.
Cervera R. Systemic lupus erythematosus in Europe at the change of the millennium: 
Lessons from the “Euro-Lupus Project”. Autoimmun Rev 2006;5:180-6.
Chakravarty EF, Bush TM, Manzi S, Clarke AE, Ward MM. Prevalence of adult systemic 
lupus erythematosus in California and Pennsylvania in 2000: estimates obtained using 
hospitalization data. Arthritis Rheum. 2007;56:2092-4. 
Chatham WW, Kimberly RP. Treatment of lupus with corticosteroids. Lupus. 
2001;10(3):140-7. 
Cheema DS, Roschke V, Hilbert DM, Stohl W. Elevated serum B-lymphocyte stimulator 
levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 
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Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Tables, May 
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Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, P et al. 
Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J 
Med. 2005;353(21):2219-28. 
GlaxoSmithKline Document Numbers 2011N128591_01, Belimumab Investigator’s 
Brochure , 20-JUN-2013,version 11
Govoni M, Castellino G, Bosi S, Napoli N, Trotta F. Incidence and prevalence of 
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Gross J, Dillon S, Mudri S, Johnston J, Littau A, Roque R, et al, TACI-Ig neutralizes 
molecules critical for B cell development and autoimmune disease. Impaired B-cell 
maturation in mice lacking BlyS. Immunity. 2001;15(2):289-302.
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classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. 
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Early Response to Immunosuppressive therapy predicts good renal outcome in lupus 
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randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis 
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therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term 
renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 
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tumor necrosis family and B lymphocyte stimulator. Science. 1999;285(5425):260-3. 
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12.
APPENDICES
12.1.
Appendix 1: Liver Safety Process
The procedures listed below are to be followed if a subject meets the liver chemistry 
stopping criteria defined in Section 5.2.1:

Notify the GSK medical monitor within 24 hours of learning of the abnormality to 
confirm the subject’s study treatment cessation and follow-up.

Complete the “Safety Follow-Up Procedures” listed below.

Complete the liver event case report forms.  If the event also meets the criteria of an 
SAE (see Section 7.1.3), the SAE data collection tool will be completed separately 
with the relevant details.

Upon completion of the safety follow-up withdraw the subject from the study unless 
further safety follow up is required  

Do not restart study treatment 

Refer to the Flow chart for a visual presentation of the procedures listed below.
Safety Follow-Up Procedures for subjects with ALT 3xULN:

Monitor subjects weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within baseline values.
Safety Follow-Up Procedures for subjects with ALT 3xULN and total bilirubin 
2xULN (>35% direct bilirubin); or ALT 3xULN and INR1 >1.5

This event is considered an SAE (see Section 7.1.3).  Serum bilirubin fractionation 
should be performed if testing is available. If fractionation is unavailable, urinary 
bilirubin is to be measured via dipstick (a measurement of direct bilirubin, which 
would suggest liver injury).

Make every reasonable attempt to have subjects return to the clinic within 24 hours 
for repeat liver chemistries, additional testing, and close monitoring (with specialist 
or hepatology consultation recommended).

Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within baseline values.
In addition, for all subjects with ALT 3xULN, every attempt must be made to also 
obtain the following:

Viral hepatitis serology including:
Hepatitis A IgM antibody.
                                                
1 INR testing not required per protocol and the threshold value does not apply to subjects receiving 
anticoagulants.


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Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM). 
Hepatitis C RNA. 
Cytomegalovirus IgM antibody.
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing).
Hepatitis E IgM antibody.

Blood sample for pharmacokinetic (PK) analysis, obtained as per the Time and 
Events Table (Table 2) of last dose. Record the date/time of the PK blood sample 
draw and the date/time of the last dose of study treatment prior to blood sample draw 
on the CRF.  If the date or time of the last dose is unclear, provide the subject’s best 
approximation.  If the date/time of the last dose cannot be approximated OR a PK 
sample cannot be collected in the time period indicated above, do not obtain a PK 
sample.  Instructions for sample handling and shipping are included in the SPM.

Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH).

Fractionate bilirubin, if total bilirubin 2xULN.

Assess eosinophilia

Record the appearance or worsening of clinical symptoms of hepatitis (fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash or eosinophilia) 
on the AE CRF.

Record use of concomitant medications, acetaminophen, herbal remedies, other over 
the counter medications, or putative hepatotoxins on the Concomitant Medications 
CRF.

Record alcohol use on the Liver Events CRF.
The following are required for subjects with ALT 3xULN and bilirubin 2xULN
(>35% direct) but are optional for other abnormal liver chemistries:

Anti-nuclear antibody, anti-smooth muscle antibody, and Type 1 anti-liver kidney 
microsomal antibodies, total IgG.

Serum acetaminophen adduct high-performance liquid chromatography (HPLC) 
assay (quantifies potential acetaminophen contribution to liver injury in subjects with 
definite or likely acetaminophen use in the preceding week).

Liver imaging (ultrasound, magnetic resonance, or computerized tomography) to 
evaluate liver disease.

The Liver Imaging and/or Liver Biopsy CRFs are also to be completed if these tests 
are performed.


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Refer to the diagram below for a visual presentation of the procedures listed above.


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12.2.
Appendix 2: American College of Rheumatology (ACR) 
Criteria for SLE
The ACR Criteria for the Classification of Systemic Lupus Erythematosus* [Tan, 
1982; Hochberg, 1997]
Criterion 
Definition 
1. Malar “butterfly” rash
Fixed erythema, flat or raised, over the malar eminences, 
tending to spare the nasolabial folds.
2. Discoid rash
Erythematosus raised patches with adherent keratotic 
scaling and follicular plugging; atrophic scarring may occur 
in older lesions.
3. Photosensitivity
Skin rash as a result of unusual reaction to sunlight, by 
patient history or physician observation.
4. Oral ulcers
Oral or nasopharyngeal ulceration usually painless.
5. Arthritis
Nonerosive arthritis involving 2 or more peripheral joints 
characterized by tenderness.
6. Serositis
a. Pleuritis (convincing history or pleuritic pain or rub 
heard by physician or evidence of pleural effusion), OR 
b. Pericarditis (documented by ECG, rub, or evidence or 
pericardial effusion).
7. Renal disorder 
a. Persistent proteinuria (>0.5 grams/day or >3 + if 
quantitation not performed) OR 
b. Cellular casts (may be red cell, hemoglobin, granular, 
tubular, or mixed).
8. Neurologic disorder 
a. Seizures (in the absence of offending drugs or known 
metabolic derangements; ie, uremia, ketoacidosis, or 
electrolyte imbalance) OR 
b. Psychosis (in the absence of offending drugs or known 
metabolic derangements; ie, uremia, ketoacidosis, or 
electrolyte imbalance.
9. Hematologic disorder 
a. Hemolytic anemia (with reticulocytosis) OR
b. Leukopenia (<4000/Ml total on 2 or more occasions), OR
c. Lymphopenia (<1500/Ml on 2 or more occasions), OR 
d. Thrombocytopenia (<100,000/Ml in the absence of 
offending drugs).
10. Immunologic disorder 
a. Anti-DNA (antibody to native DNA in abnormal titer), 
OR b. Anti-Sm (presence of antibody to Sm nuclear 
antigen), OR c. Positive-finding of antiphospholipid 
antibodies based on 1) an abnormal serum level of IgG or 
IgM anticardiolipin antibodies, 2) a positive test result for 
lupus anticoagulant using a standard method, or 3) a false-


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Criterion 
Definition 
positive serologic test for syphilis known to be positive for 
at least 6 months and confirmed by Treponema pallidum 
immobilization (TPI) or fluorescent treponemal antibody 
(FTA) absorption test.
11. Antinuclear antibody 
(ANA) 
Abnormal titer of ANA by immunofluorescence or an 
equivalent assay at any point in time and in the absence of 
drugs known to be associated with “drug-induced lupus”
syndrome.
* The proposed classification is based on 11 criteria.  For the purpose of identifying 
patients in clinical studies, a person shall be said to have systemic lupus erythematosus if 
any 4 or more of the 11 criteria are present, serially or simultaneously, during any 
interval or observation.
References
Hochberg MC. Updating the American College of Rheumatology revised criteria for the 
classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal 
N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus 
erythematosus. Arthritis Rheum. 1982;25(11):1271-7. 


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12.3.
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables
HEMATOLOGY
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Hemoglobin
>9.5 – 11.0 g/Dl
>8.0 – 9.5 g/Dl
6.5 – 8.0 g/Dl
<6.5 g/Dl
Leukocytes
3000-3999/mm3
2000-2999/mm3
1000-1999/mm3
<1000/mm3
Absolute Neutrophil Count
1500-1999/mm3
1000-1499/mm3
500-999/mm3
<500/mm3
Platelets
75,000 – 99,999/mm3 50,000 – 74,999/mm3
25,000 – 49,999/mm3
<25,000/mm3
Prothrombin Time (PT)
>1.0-1.25 x ULN*
>1.25-1.5 x ULN
>1.5-3.0 x ULN
>3.0 x ULN
Partial Thromboplastin Time (PTT)
>1.0-1.66 x ULN
>1.66-2.33 x ULN
>2.33-3.0 x ULN
>3.0 x ULN
Methemoglobin
5.0-10.0 %
10.1-15.0 %
15.1-20.0 %
>20%
(continued)
*ULN = Upper Limit of Normal.                                                                                                                Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CARDIOVASCULAR
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Cardiac Arrhythmia
-
Asymptomatic/transient; 
dysrhythmia; no treatment req
Recurrent/persistent 
dysrhythmia. 
Symptomatic; treatment 
req
Unstable dysrhythmia hospitalization
and treatment required
Hypotension
Transient orthostatic 
hypotension, no 
treatment
Symptoms correctable 
with oral fluid treatment
IV fluid req,
no hospitalization req
Hospitalization req
Hypertension
Transient, increase
>20 mm/Hg; no 
treatment
Recurrent; chronic increase
>20 mm/Hg, treatment req
Acute treatment req; out 
patient hospitalization 
possible
Hospitalization req
Pericarditis
Minimal effusion
Mild/moderate asymptomatic 
effusion, no treatment
Symptomatic effusion,
pain, ECG changes
Tamponade OR pericardiocentesis 
OR surgery req
Hemorrhage, Blood Loss
-
Mildly symptomatic; 
no treatment required
Gross blood loss OR
1-2 units transfused
Massive blood loss OR
>2 units transfused
(continued)
Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CHEMISTRIES
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Sodium
  Hyponatremia
130-135 meq/L
123-129 meq/L
116-122 meq/L
<116 meq/L
  Hypernatremia
146-150 meq/L
151-157 meq/L
158-165 meq/L
>165 meq/L
Potassium
  Hypokalemia
3.0-3.4 meq/L
2.5-2.9 meq/L
2.0-2.4 meq/L
<2.0 meq/L
  Hyperkalemia
5.6-6.0 meq/L
6.1-6.5 meq/L
6.6-7.0 meq/L
>7.0 meq/L
Phosphate
  Hypophosphatemia
2.0-2.4 mg/Dl
1.5-1.9 mg/Dl
1.0-1.4 mg/Dl
<1.0 mg/Dl
Calcium- (Corrected For Albumin)
  Hypocalcemia
7.8-8.4 mg/Dl
7.0-7.7 mg/Dl
6.1-6.9 mg/Dl
<6.1 mg/Dl
  Hypercalcemia
10.6-11.5 mg/Dl
11.6-12.5 mg/Dl
12.6-13.5 mg/Dl
>13.5 mg/Dl
Magnesium
  Hypomagnesemia
1.2-1.4 meq/L
0.9-1.1 meq/L
0.6-0.8 meq/L
<0.6 meq/L
Albumin
  Hypoalbuminemia
3.00-3.49 g/Dl
2.50-2.99 g/Dl
2.00-2.49 g/Dl
<2.00 g/Dl
Bilirubin (Total)
  Hyperbilirubinemia (Total)
>1.0-1.5 x ULN
>1.5-2.5 x ULN
>2.5-5 x ULN
>5 x ULN
Glucose
  Hypoglycemia
55-64 mg/Dl
40-54 mg/Dl
30-39 mg/Dl
<30 mg/Dl
  Hyperglycemia 
116-160 mg/Dl
161-250 mg/Dl
251-500 mg/Dl
>500 mg/Dl
  (non fasting & no prior diabetes)
  Triglycerides
151-399 mg/Dl
400-750 mg/Dl
751-1200 mg/Dl
>1200 mg/Dl
Creatinine
>1.0-1.5 x ULN
>1.5-3.0 x ULN
>3.0-6.0 x ULN
>6.0 x ULN
(continued)
Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
CHEMISTRIES (continued)
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Uric Acid
  Hyperuricemia
7.5-10.0 mg/Dl
10.1-12.0 mg/Dl
12.1-15.0 mg/Dl
>15.0 mg/Dl
Liver Transferases  (AST, ALT, 
and GGT)
1.25-2.5 x ULN
>2.5-5.0 x ULN
>5.0-10.0 x ULN
>10.0 x ULN
Alkaline Phosphatase
1.25-2.5 x ULN
>2.5-5.0 x ULN
>5.0-10.0 x ULN
>10.0 x ULN
Pancreatic Enzymes
Amylase
>1.0-1.5 x ULN
>1.5-2.0 x ULN
>2.0-5.0 x ULN
>5.0 x ULN
Pancreatic amylase
>1.0-1.5 x ULN
>1.5-2.0 x ULN
>2.0-5.0 x ULN
>5.0 x ULN
Lipase
>1.0-1.5 x ULN
>1.5-2.0 x ULN
>2.0-5.0 x ULN
>5.0 x ULN
Hypoglobulinemia (IgG)*
550-700 mg/Dl
400-549 mg/Dl
250-399 mg/Dl
<250 mg/Dl
(continued)
*[Eibl, 1995; Goldfarb, 2001; Yamini, 2001].                                                                                        Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
GASTROINTESTINAL
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Nausea
Mild OR transient; 
reasonable intake 
maintained
Mod discomfort 
OR intake decreased 
for <3 days
Severe discomfort OR 
minimal intake 
for 3 days
Hospitalization required
Vomiting
Mild OR transient; 
2-3 episodes/day OR 
mild vomiting lasting 
<1 week
Mod OR persistent; 
4-5 episodes per day; 
OR vomiting lasting 
1 week
Severe vomiting of all 
foods/fluids in 24 hours 
OR orthostatic 
hypotension
OR IV treatment req
Hypotensive shock OR hospitalization 
required for IV treatment req
Diarrhea
Mild or transient; 
3-4 loose stools per 
day 
OR mild diarrhea 
lasting 
<1 week
Mod OR persistent; 
5-7 loose stools per day 
or diarrhea lasting 
1 week
Bloody diarrhea; 
OR orthostatic 
hypotension 
OR >7 loose stools/day 
OR IV treatment req
Hypotensive shock 
OR hospitalization req
Oral Discomfort/Dysphagia
Mild discomfort, no 
difficulty swallowing
Difficulty swallowing but 
able to eat and drink
Unable to swallow solids
Unable to drink fluids; 
IV fluids req
Constipation
Mild
Moderate
Severe
Distention with vomiting
(continued)
Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
RESPIRATORY
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Cough 
(for aerosol studies) 
Transient; no 
treatment
Treatment associated 
cough; inhaled bronchodilator
Uncontrolled cough; 
systemic treatment req
Bronchospasm Acute
Transient; no 
treatment; 
Forced expiratory 
volume in 1 second 
(FEV1) 70% to 
<80% 
(or peak flow)
treatment req; normalizes with 
bronchodilator; 
FEV1 50% to <70% 
(or peak flow)
No Normalization 
with bronchodilator; 
FEV 25% to <50% 
(or peak flow), retractions
Cyanosis; FEV1 <25% 
(or peak flow) OR intubated
Dyspnea
Dyspnea on exertion
Dyspnea with 
normal activity
Dyspnea at rest
Dyspnea requiring oxygen (O2) therapy


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
URINALYSIS
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Proteinuria
  Dipstick
  Protein
1 +
2-3 +
4 +
Nephrotic syndrome
  Spot Urine:     
Protein:Creatinine 
   Ratio mg/mg
0.2-1.0
>1.0-2.0
>2.0-3.5
>3.5
  24 Hour Urine:
   Protein
200 mg – 1g loss/day
>1-2 g loss/day
>2-3.5 g loss/day
Nephrotic syndrome
OR >3.5 g loss/day
Hematuria
Microscopic only
>3 to <10 RBC/hpf
Gross, No clots
10 RBC/hpf
Gross plus clots OR 
RBC casts
Obstructive OR transfusion required
(continued)
RBC = red blood cell; hpf = high power field.
Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
MISCELLANEOUS
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Fever (oral >12 hours)
37.7-38.5C or
100.0-101.5F
38.6-39.5C OR
101.6-102.9F
39.6-40.5C OR
103-105F
>40.5C OR >105F
Headache
Mild; No treatment req
Mod; or non-narcotic 
analgesia treatment
Severe; OR responds to 
initial narcotic treatment
Intractable; OR requiring 
repeated narcotic treatment
Allergic Reaction
Pruritus without rash
Localized urticaria
Generalized urticaria 
angioedema
Anaphylaxis
Cutaneous/Rash/ Dermatitis
Erythema, pruritus rash 
OR dry desquamation
Diffuse maculopapular 
OR dry desquamation
Vesiculation OR moist 
desquamation ulceration
ANY ONE: mucous membrane 
involvement, suspected 
Stevens-Johnson (TEN), erythema 
multiforme, necrosis req surgery, 
exfoliative dermatitis
Local Reaction (secondary 
to parenteral treatment- not 
vaccination or skin test)
Erythema
Induration <10 mm 
OR inflammation 
OR phlebitis
Induration >10 mm 
OR ulceration
Necrosis of skin
Fatigue
Normal activity 
Reduced <25%
Normal activity 
Reduced 25-50%
Normal activity 
reduced >50%; 
cannot work
Unable to care for self
(continued)
Modified from DMID Adult Toxicity Tables, 2001


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12.3
Appendix 3: Adverse Event and Laboratory Value Severity Grade Tables (continued)
NEUROLOGIC
GRADE 1
GRADE 2
GRADE 3
GRADE 4
MILD
MODERATE
SEVERE
POTENTIALLY LIFE-THREATENING
Neuro-cerebellar
Slight incoordination 
OR 
dysdiadochokinesia
Intention tremor OR 
dysmetria OR slurred speech 
OR nystagmus
Ataxia requiring assistance 
to walk or arm incoordination 
interfering with ADLs
Unable to stand
Neuro-psych/ mood
none
Severe mood changes 
requires medical intervention
Acute psychosis requiring 
hospitalization
Paresthesia 
(burning, tingling, etc)
Mild discomfort; 
no treatment needed
Mod discomfort 
non-narcotic analgesia req
Severe discomfort; OR 
narcotic analgesia req with 
symptomatic improvement
Incapacitating; OR not responsive 
to narcotic analgesia
Neuro-motor
Mild weakness in 
muscle of feet but 
able to walk and/or 
mild increase or 
decrease in reflexes
Mod weakness in feet (unable to 
walk on heels and/or toes), mild 
weakness in hands, still able to do 
most hand tasks and/or loss of 
previously present reflex or 
development of hyperreflexia 
and/or unable to do deep knee 
bends due to weakness
Marked distal weakness 
(unable to dorsiflex toes or 
foot drop), and mod proximal 
weakness i.e., in hands 
interfering with ADLs and/or 
requiring assistance to walk 
and/or unable to rise from 
chair unassisted
Confined to bed or wheelchair 
because of muscle weakness
Neuro-sensory
Mild impairment 
sensations, 
(i.e., vibratory, 
pinprick, hot/cold in 
great toes) in focal 
area or symmetrical 
distribution
Mod impairment mod de-
sensation, 
(i.e., of vibratory, pinprick, 
hot/cold to ankles) and/or joint 
position or mild impairment that is 
not symmetrical.
Severe impairment (dec or 
loss of sensation to knees or 
wrists) or loss of sensation of 
at least mod degree in 
multiple different body areas 
(i.e., upper and lower 
extremities)
Sensory loss involves limbs 
and trunk
(concluded)
Modified from DMID Adult Toxicity Tables, 2001


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References
Eibl MM, Rosen FS. Intravenous gamma globulin and plasmapheresis. In: Frank MM, 
editor. Samter’s Immunologic Diseases (5th ed.). Boston:Little, Brown, 1995:1529-36. 
Goldfarb NS, Avery RK, Goormastic M, Mehta AC, Schilz R, Smedira N, Pien L, Haug 
MT, Gordon SM, Hague LK, Dresing JM, Evans-Walker T, Maurer JR. 
Hypogammaglobulinemia in lung transplant recipients. Transplantation. 2001;71(2):242-
6. 
Yamini MH, Avery RK, Mawhorter SD, Young JB, Ratliff NB, Hobbs RE, McCarthy 
PM,  Smedira NG,  Goormastic M,  Pelegrin D, Starling RC. Hypogammaglobulinemia 
following cardiac transplantation: a link between rejection and infection. J Heart Lung 
Transplant. 2001;20(4):425-30. 


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12.4.
Appendix 4: Protocol Changes
Protocol amendment 01 applies to all sites.
Section
Previous Text
Revised Text
Rationale
Sponsor/medical 
monitor 
Information 
Page
Deletion of 
 from 
medial monitor contact information. 
Change of Medical Monitor 
contact information
Section 3.4 
Benefit-Risk 
Assessment
Table 1-Column “Strategy-monitoring ”
for infection
Monitor patients for signs and symptoms of 
infection, monitor laboratory values, 
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 >2.0 x ULN, obtain quantitative 
hepatitis B virus DNA. If the quantitative 
hepatitis B virus DNA result shows 
detectable viral loads, then the subject must 
be treated immediately and appropriately.
Monitor patients for signs and symptoms 
of infection, monitor laboratory values, 
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 >2.0 2.5 x ULN, obtain 
quantitative hepatitis B virus DNA. If the 
quantitative hepatitis B virus DNA result 
shows detectable viral loads, then the 
subject must be treated immediately and 
appropriately.
To keep consistency among 
Table 1 and Section 6.2.1.1
PPD


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Section
Previous Text
Revised Text
Rationale
Section 4.2.1 
Inclusion 
Criteria
4. SLE treatment:
NOTE:
-For those subjects on alternating day doses 
of steroids, use the average of 2 daily doses 
to calculate the average daily steroid dose.
Add:
NOTE:
-For those subjects on alternating day 
doses of steroids, use the average of 2 
daily doses to calculate the average daily 
steroid dose.
-Low dose prednisone (≤15mg 
prednisone or equivalent)) regular 
tapering will be accepted as stable 
SLE treatment. 
Clarify the regular tapering 
of low dose prednisone is 
acceptable for enrolment. 
Section 4.2.2 
Exclusion 
Criteria
7. History of renal transplant.
7. History of a major organ transplant
(eg. heart, lung, renal, liver) or
hematopoietic stem cell/marrow 
transplant.
Clarify subjects with 
different transplant history 
need to be excluded
Section 4.2.2 
Exclusion 
Criteria
10. The subject has 
hypogammaglobulinemia or IgA 
deficiency (IgA level <10 mg/Dl).
10. The subject has 
hypogammaglobulinemia or IgA 
deficiency (IgA level <10 mg/Dl).
Delete 
hypogammaglobulinemia 
because it is duplicate with 
IgA deficiency and 
exclusion criteria 19.
Section 4.2.2 
Exclusion 
14. The subject has an abnormality on 
12-lead ECG at screening which is 
14. The subject has an abnormality on 
12-lead ECG at screening which is 
Clarification the exclusion 


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Section
Previous Text
Revised Text
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Criteria
clinically significant in the opinion of 
the investigator
clinically significant in the opinion of the 
investigator, and which could confound 
the results of the study. Inclusion may 
put the subject at undue risk.
criteria of abnormal ECG. 
Section 4.2.2 
Exclusion 
Criteria
Add :
21. Received a live vaccine within 30 
days of baseline (Day 0).
Considering the mechanism 
of action of belimumab, it 
may impact the 
immunization, so exclude 
subjects who received live 
vaccine within 30 days of 
baseline.
Section 4.2.2 
Exclusion 
Criteria
Add :
22. Have a history of malignant 
neoplasm within the last 5 years, 
except for adequately treated 
cancers of the skin (basal or 
squamous cell) or carcinoma in
situ of the uterine cervix.
To keep consistence among 
Section3.2.4 Benefit-Risk 
Assessment and Exclusion 
Criteria.
Section 4.2.3.1

Male condom combined with:a female 
diaphragm, either with or without a 
vaginal spermicide (foam, gel, cream 
or suppository).

Male condom combined with one of 
the contraceptive options below:a 
female diaphragm, either with or 
without a vaginal spermicide (foam, 
gel, cream or suppository).
Provide detail descriptions 
on pregnancy requirements


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Section
Previous Text
Revised Text
Rationale

Contraceptive subdermal 
implant

Intrauterine device or 
intrauterine system

Combined estrogen and 
progestogen oral 
contraceptive Injectable 
progestogen 

Contraceptive vaginal ring 
Percutaneous contraceptive 
patches 
5.7.1. Permitted 
Medications
For subjects with a history of allergies, 
allergic responses to food, drugs or insects, 
or a history of urticaria, antihistamine and 
acetaminophen should be administered 
prophylactically.
For subjects with a history of allergies, 
allergic responses to food, drugs or 
insects, or a history of urticaria, 
antihistamine and acetaminophen may 
be should be administered 
prophylactically.
Clarify “should be” is a 
recommendation; it helps 
reduce the risk of a reaction 
for those patients who have 
a history of allergies. 
Section 5.7.2 
Prohibited 
Medications and 
Non-drug 
Therapies
Add:
From 30 days prior to Day 0
•
Live vaccine
To keep consistency with 
the new addition of 
exclusion criteria 21.


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Section
Previous Text
Revised Text
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Section 6 
STUDY 
ASSESSMENTS 
AND 
PROCEDURES
Paragraph2:
The end time of the infusion will be 
designated Time 0, and subsequent PK 
sampling and safety assessments will be 
performed relative to this time.When several 
procedures are scheduled at the same nominal 
time point, PK blood sampling should be 
given priority.
Add: 
The time assessment window of the 
each PK blood sample collection is 
shown in Table 3.The end time of the 
infusion will be designated Time 0, and 
subsequent PK sampling and safety 
assessments will be performed relative to 
this time. It is essential that the exact 
time of blood sampling, however, 
should still be accurately recorded.
The safety assessments are 
recommended to be conducted close to 
PK sample collection; however, when 
several procedures are scheduled at the 
same nominal time point, PK blood 
sampling should be given priority.
Add:
Table 3 Time assessment window of 
the each PK sample collection
Add Table 3 to clarify the 
allowed time-window for 
PK sample collection. 
Section 6 Study 
assessments and 
Procedures
In Table 2, Add:
Inclusion/Exclusion criteria check at 
pre-dose on Day 0
To allow using pulse rate 
monitoring to replace heart 
rate monitoring if subject 
has sinus rhythm which is 


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Section
Previous Text
Revised Text
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Notes for Table 2:
1.
Each subject must sign an informed 
consent form prior to undergoing any 
Screening assessments.
2.
Vital signs include temperature, sitting 
blood pressure and heart rate.
3.
Clinical Laboratory test include 
hematology, chemistry and urinalysis 
(including C-reactive protein [CRP] 
and Erythrocyte Sedimentation Rate on 
screening). ALT and/or AST elevations 
of greater than 2.5 x ULN will require
additional Hepatitis B assessment, see 
Section 6.2.1.1
4.
HIV antibody, Hepatitis B surface 
antigen, anti-HBc and Hepatitis C 
antibody.
5.
Pregnancy should be assessed with a 
blood test at Screening and with a urine 
test during the treatment period.
Pregnancy beyond Day 84 and within 
16 weeks after last dose of IP will be 
assessed with a homekit and subjects 
can report the results via phone to site.
6.
Biomarkers include immunoglobulins 
B cell subsets (CD20+, CD20+/27+ 
memory, CD20+/27–naïve, 
CD20+/69+ activated, CD20+/138+ 
In Table 2, update table footnotes:
1.
Each subject must sign an informed 
consent form prior to undergoing 
any Screening assessments.
2.
Clinical laboratory test at 
screening visit will be used for 
inclusion/exclusion criteria check. 
3.
Vital signs include temperature, 
sitting blood pressure and heart rate. 
Pulse rate could be used to replace 
heart rate monitoring if subject 
has sinus rhythm. 
4.
Clinical Laboratory test include 
hematology, chemistry and 
urinalysis (including C-reactive 
protein [CRP] and Erythrocyte 
Sedimentation Rate on screening).
ALT and/or AST elevations of 
greater than 2.5 x ULN will require
additional Hepatitis B assessment, 
see Section 6.2.1.1. For pre-dose 
safety lab monitoring including 
urine pregnancy test and 12 lead 
ECG, it’s recommended to be 
done on day 0 or within 48 hours 
prior to day 0 if site logistic 
management are limited on day 0
for drug dosing and intensive PK 
matching clinic practice. 
To exclude subjects who 
violate inclusion/exclusion 
criteria before dosing on 
Day 0.
To increase flexibility 
based on site real situation.


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Section
Previous Text
Revised Text
Rationale
plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE 
subset and CD20-/138+ plasma cells).
7.
Only immunoglobulins (IgG, IgM and 
IgA) and auto antibodies (anti-dsDNA, 
ANA).
8.
Includes subject history to be reported 
on CRF regarding any general signs or 
symptoms of infection.
9.
If a subject prematurely withdraws for 
any reason, the investigator must make 
every effort to assess the items 
specified on discontinuation test.
sample collection. 
5.
HIV antibody, Hepatitis B surface 
antigen, anti-HBc and Hepatitis C 
antibody.
6.
Pregnancy should be assessed with a 
blood test at Screening and with a 
urine test during the treatment 
period. Pregnancy beyond Day 84 
and within 16 weeks after last dose 
of IP will be assessed with a homekit 
and subjects can report the results 
via phone to site..
7.
Biomarkers include 
immunoglobulins, B cell subsets 
(CD20+, CD20+/27+ memory, 
CD20+/27–naïve, CD20+/69+ 
activated, CD20+/138+ 
plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT 
SLE subset and CD20-/138+ plasma 
cells).
8.
Only immunoglobulins (IgG, IgM 
and IgA) and auto antibodies (anti-
dsDNA, ANA).
9.
Includes subject history to be 
reported on CRF regarding any 
general signs or symptoms of 
infection.
10. The recommended date of


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Section
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“Admission to the Unit” and 
“Discharge” is only a suggestion. 
The subject can be admitted to 
unit from Day -2 to Day 0 and/or 
discharged on Day 1 based on site 
flexibility and resource allocation.
11. If a subject prematurely withdraws 
for any reason, the investigator must 
make every effort to assess the items 
specified on discontinuation test.
Section 6.1.2 
Pre-dose 
examination
Add:
Inclusion/Exclusion criteria check
To exclude subjects who 
violate inclusion/exclusion 
criteria before dosing on 
Day 0.
Section 6.2.1 
Liver Chemistry 
Follow-up 
Procedures
The following are required for subjects with 
ALT 3xULN and bilirubin 2xULN 
(>35% direct) but are optional for other 
abnormal liver chemistries: 

Anti-nuclear antibody, anti-smooth 
muscle antibody, and Type 1 anti-
liver kidney microsomal antibodies.
The following are required for subjects 
with ALT 3xULN and bilirubin 
2xULN (>35% direct) but are optional 
for other abnormal liver chemistries: 

Anti-nuclear antibody, anti-smooth 
muscle antibody, and Type 1 anti-
liver kidney microsomal antibodies,
total IgG.
Total IgG was added 
according to the latest 
global safety requirement.

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
200909
1
Division
:
Worldwide Development
Information Type
:
Clinical Pharmacology Reporting and Analysis Plan (RAP)
Title
:  Reporting and analysis plan for a single dose study to 
evaluate the safety, tolerability, pharmacokinetics and 
pharmacodynamics of GSK1550188 in Chinese subjects with 
Systemic Lupus Erythematosus (SLE)
Compound Number 
:
GSK1550188
Effective Date 
:
02-MAY-2017
Description :

The purpose of this reporting and analysis plan (RAP) is to describe the planned 
analyses and output to be included in the Clinical Pharmacology Study Report for 
Protocol 200909.

This RAP is intended to describe some of the pharmacokinetic-pharmacodynamic 
analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the 
final Statistical Analysis Complete (SAC) deliverable.
Subject: Belimumab, intravenous, Systemic Lupus Erythematosus, Pharmacokinetics, 
Pharmacodynamics, Chinese subject.
Author’s Name and Functional Area: 
28-APR-2017
(eSignature)
Statistics, China Medical
Approved by:
02-MAY-2017
(eSignature)
Statistics, China Medical
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD


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TABLE OF CONTENTS
1.
INTRODUCTION......................................................................................................4
2.
REPORTING & ANALYSIS PLAN SYNPOSIS.........................................................4
3.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................6
3.1.
Changes to the Protocol Defined Statistical Analysis Plan............................6
3.2.
Study Objective(s) and Endpoint(s)...............................................................6
3.3.
Study Design ................................................................................................7
3.4.
Statistical Hypotheses...................................................................................7
4.
PLANNED ANALYSES ............................................................................................7
4.1.
Interim Analyses ...........................................................................................7
4.2.
Final Analyses ..............................................................................................7
5.
ANALYSIS POPULATIONS .....................................................................................8
5.1.
Protocol Deviations.......................................................................................8
6.
GENERAL CONSIDERATIONS FOR DATA ANALYSES AND HANDLING
CONVENTIONS.......................................................................................................8
7.
STUDY POPULATION ANALYSES .........................................................................9
7.1.
Overview of Planned Analyses .....................................................................9
8.
PRIMARY STATISTICAL ANALYSES....................................................................10
8.1.
Pharmacokinetic Analyses..........................................................................10
8.1.1.
Overview of Planned Pharmacokinetic Analyses .........................10
8.1.2.
Drug Concentration Measures .....................................................10
8.1.3.
Pharmacokinetic Parameters.......................................................10
8.1.4.
Statistical Analyses......................................................................11
9.
SECONDARY STATISTICAL ANALYSES .............................................................12
9.1.
Safety Analyses..........................................................................................12
9.1.1.
Overview of Adverse Events........................................................12
9.1.2.
Overview of Planned Safety Analyses .........................................12
9.2.
Pharmacodynamic Analyses.......................................................................14
9.2.1.
Overview of Planned Pharmacodynamic Analyses ......................14
9.2.2.
Pharmacokinetic-Pharmacodynamic Modelling Analyses ............14
10. REFERENCES.......................................................................................................15
11. APPENDICES........................................................................................................16
11.1.
Appendix 1: Time & Events.........................................................................17
11.1.1.
Protocol Defined Time & Events ..................................................17
11.2.
Appendix 2: Treatment States.....................................................................20
11.2.1.
Treatment States for Concomitant Medications Data ...................20
11.2.2.
Treatment States for AE Data......................................................20
11.3.
Appendix 3: Data Display Standards & Handling Conventions....................21
11.3.1.
Study Treatment & Sub-group Display Descriptors......................21
11.3.2.
Baseline Definition & Derivations .................................................21
11.3.2.1.
Baseline Definitions....................................................21


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11.3.2.2.
Derivations and Handling of Missing Baseline 
Data ...........................................................................21
11.3.3.
Reporting Process & Standards...................................................22
11.4.
Appendix 4: Derived and Transformed Data ...............................................25
11.4.1.
General........................................................................................25
11.4.2.
Study Population..........................................................................25
11.4.3.
Safety ..........................................................................................25
11.4.4.
Pharmacokinetic ..........................................................................26
11.4.5.
Pharmacodynamic or Biomarker..................................................26
11.4.6.
Pharmacokinetic/Pharmacodynamic............................................27
11.5.
Appendix 5: Premature Withdrawals & Handling of Missing Data ...............28
11.5.1.
Premature Withdrawals................................................................28
11.5.2.
Handling of Missing Data.............................................................28
11.5.2.1.
Handling of Missing Dates..........................................29
11.5.2.2.
Handling of Partial Dates............................................29
11.6.
Appendix 6: Clinical Laboratory Evaluations ...............................................30
11.7.
Appendix 7: Abbreviations & Trade Marks ..................................................31
11.7.1.
Abbreviations...............................................................................31
11.7.2.
Trademarks .................................................................................32
11.8.
Appendix 8: List of Data Displays ...............................................................33
11.8.1.
Data Display Numbering..............................................................33
11.8.2.
Mock Example Referencing .........................................................33
11.8.3.
Deliverable [Priority].....................................................................33
11.8.4.
Study Population Tables..............................................................34
11.8.5.
Safety Tables...............................................................................35
11.8.6.
Pharmacokinetic Tables...............................................................38
11.8.7.
Pharmacodynamic Tables ...........................................................39
11.8.8.
Safety Figures .............................................................................39
11.8.9.
Pharmacokinetic Figures .............................................................40
11.8.10. Pharmacodynamic Figures ..........................................................41
11.8.11. ICH Listings .................................................................................41
11.8.12. Non-ICH Listings..........................................................................45
11.9.
Appendix 9: Example Mock Shells for Data Displays ..................................46


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1.
INTRODUCTION
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Pharmacology Study Report for Protocol:
All decisions regarding key analysis, as defined in this RAP document, have been made 
prior to first subject first visit (FSFV).
2.
REPORTING & ANALYSIS PLAN SYNPOSIS
Overview
Key Elements of the Reporting and Analysis Plan 
Purpose
The purpose of this Reporting and Analysis Plan (RAP) is to describe:

All planned analyses and outputs required for the final Clinical 
Pharmacology Study Report (CPSR) of study 200909
Protocol

This RAP is based on the protocol (Dated: 26/JAN/2016) of study 
200909 (GSK Document Number 2013N175219_00).
Primary 
Objective

To investigate the pharmacokinetics (PK) of intravenously (IV) 
administered GSK1550188 10 mg/kg in Chinese subjects with SLE.
Secondary 
Objective

To evaluate the safety and tolerability of GSK1550188 in Chinese 
subjects with SLE.

To investigate the effect of GSK1550188 on pharmacodynamics (PD)
of B cell subsets.
Primary 
Endpoint

Serum concentrations and the derived pharmacokinetic parameters of 
GSK1550188: Cmax, t1/2, AUC(0-t), AUC(0-), λz , CL and Vz.
Secondary 
Endpoint

Safety and tolerability endpoints: adverse events, vital sign, 12-lead 
ECG, and clinical laboratory safety tests

B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–naïve, 
CD20+/69+ 
activated, 
CD20+/138+ 
plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells)
Study 
Design

Multicenter, single dose study of intravenous GSK1550188 at a dose 
of 10 mg/kg Chinese subjects with SLE.

A medical screen within 30 days prior to the first dose.

Subjects will receive the dose on Day 0 and be kept in the study center 
up to 24 hours post dosing with subsequent outpatient visits occurring 
on Days 1, 7, 14, 21, 28, 42, 56, and 84.
Planned 
Analyses

No interim analyses are planned.

The final planned analyses will be performed after all subjects have 
completed the study and after database freeze (both the CRF data and 
PK data).
Analysis 

The ‘Safety’ Population (Comprised of subjects who receive at least 


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Overview
Key Elements of the Reporting and Analysis Plan 
Population
one dose of study medication) will be used to evaluate Study 
Population and Safety.

The ‘Pharmacokinetic Concentration Population’ (Comprised of 
subjects who receive the study medication and for whom a 
pharmacokinetic sample is obtained and analysed). 

The ‘Pharmacokinetic Parameter Population’ is defined as all subjects 
who receive a dose of GSK1550188 and for whom pharmacokinetic 
parameters can be calculated.

The ‘Pharmacodynamic Population’ is defined as all subjects who 
receive the study medication and for whom pharmacodynamic data is 
available.
Hypothesis

There is no formal hypothesis being tested in this study.
Primary 
Analyses

Pharmacokinetics: Pharmacokinetic data will be presented in graphical 
and/or tabular form and will be summarized descriptively.
Secondary 
Analyses

Safety data will be presented in tabular and/or graphical format and 
summarized descriptively according to GSK’s Integrated Data 
Standards Library (IDSL) standards.

Pharmacodynamics data of B cell subsets will be listed and 
summarized.

Other exploratory PK-PD analyses will be considered, when 
appropriate. These include exposure (PK parameters and 
concentrations)-response (B-cell subsets) analyses using linear and 
nonlinear mixed effect modelling methods. The results may be 
summarized in a report, separate from the main CPSR.


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3.
SUMMARY OF KEY PROTOCOL INFORMATION
3.1.
Changes to the Protocol Defined Statistical Analysis Plan
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol (Dated: 26/JAN/2016).
3.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary 
Primary 

To investigate the pharmacokinetics 
(PK) of intravenously (IV) 
administered GSK1550188 10 mg/kg 
in Chinese subjects with SLE

Serum concentrations and the derived 
pharmacokinetic parameters of 
GSK1550188: Cmax, t1/2, AUC(0-t), 
AUC(0-), λz , CL and Vz.
Secondary Objectives 
Secondary Endpoints 

To evaluate the safety and tolerability 
of GSK1550188 in Chinese subjects 
with SLE.

To investigate the effect of 
GSK1550188 on the 
pharmacodynamics (PD) of B cell 
subsets.

Safety and tolerability endpoints: adverse 
events, vital sign, 12-lead ECG, and 
clinical laboratory safety tests.

B cell subsets (CD20+, CD20+/27+ 
memory, CD20+/27–naïve, CD20+/69+ 
activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE 
subset and CD20-/138+ plasma cells).


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3.3.
Study Design
Overview of Study Design and Key Features
Design Features

Multicenter, single dose study of intravenous 
GSK1550188 in Chinese subjects with SLE.
Dosing

Each subject will receive a dose of 10 mg/kg on Day 0 
after completion of all pre-dose procedures.
Treatment Assignment

The subjects will be kept in the study center up to 24 
hours post dosing with subsequent outpatient visits 
occurring on Days 1, 7, 14, 21, 28, 42, 56, and 84.
Interim Analysis

No interim analysis is planned.
3.4.
Statistical Hypotheses
No formal hypothesis is being tested in the study.
4.
PLANNED ANALYSES
4.1.
Interim Analyses
No interim analyses are planned.
4.2.
Final Analyses
The final planned analyses will be performed after all subjects have completed the study 
and after database freeze (both the CRF data and PK data). 


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5.
ANALYSIS POPULATIONS
Population
Definition / Criteria
Analyses Evaluated
Safety

Subjects who receive at least one dose 
of study medication.

Study Population

Safety
Pharmacokinetic  
Concentration 
Population

Subjects who receive the study 
medication and for whom a 
pharmacokinetic sample is obtained
and analysed.

PK Analyses
Pharmacokinetic 
Parameter 
Population

Subjects who receive a dose of 
GSK1550188 and for whom 
pharmacokinetic parameters can be 
calculated.

PK Analyses
Pharmacodynamic
Population

Subjects who receive the study 
medication and for whom 
pharmacodynamic data are available.

PD Analyses
5.1.
Protocol Deviations

A listing of the inclusion/exclusion criteria deviation record for all subjects with 
deviations will be provided. 

Important 
protocol 
deviations 
(including 
deviations 
related 
to 
study 
inclusion/exclusion criteria, conduct of the trial, patient management or patient 
assessment) will be summarized and listed.

Other deviations will be noted as applicable, including use of prohibited concomitant 
medications during the study, incorrect study drug administration, and any other 
deviations deemed to have the potential for notably influencing the study results. 

Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Management Plan.
o
Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset. 
o
This dataset will be the basis for listing of protocol deviations.
For details of important protocol deviations criteria please refer to protocol deviation 
management plan.
6.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
AND HANDLING CONVENTIONS
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions. 


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Table 1
Overview of Appendices
Section
Component
Section 11.1
Appendix 1: Time & Events
Section 11.2
Appendix 2: Treatment States 
Section 11.3
Appendix 3: Data Display Standards & Handling Conventions
Section 11.4
Appendix 4: Derived and Transformed Data
Section 11.5
Appendix 5: Premature Withdrawals & Handling of Missing Data
Section 11.6
Appendix 6: Clinical Laboratory Evaluations
7.
STUDY POPULATION ANALYSES
7.1.
Overview of Planned Analyses
The Safety Analyses will be based on the Safety population, unless otherwise specified.
Screen failures will be listed and summarized for all ‘Screened’ subjects. .
The Pharmacokinetic Analyses will be based on the Pharmacokinetic concentration
population and Pharmacokinetic parameter population.
The Pharmacodynamic Analyses will be based on the Pharmacodynamic population.
Table 2 provides an overview of the planned study population analyses, with full details 
of data displays being presented in Appendix 8 (Section 11.8): List of Data Displays.
Table 2
Overview of Planned Study Population Analyses
Display Type
Data Display’s Generated
Figure
Table
Listing
Subject Disposition
Subject Disposition
Y
Reasons for Screening Failures
Y
Y
Reasons for Withdrawals
Y
Study Analysis Populations
Y
Y
Inclusion and Exclusion Criteria Deviations
Y
Important Protocol Deviations
Y
Y
Other Protocol Deviations
Y
Y
Demography
Demographics Characteristics
Y
Y
Race and Racial Combinations
Y


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Display Type
Data Display’s Generated
Figure
Table
Listing
Medical Condition & Concomitant  Medications
Concomitant Medication
Y
Medical Conditions (Current/Past)
Y
NOTES :

Y = Yes display generated.
8.
PRIMARY STATISTICAL ANALYSES
8.1.
Pharmacokinetic Analyses
8.1.1.
Overview of Planned Pharmacokinetic Analyses
The pharmacokinetic (PK) concentration and parameter analyses will be based on the PK 
concentration and parameter population, unless otherwise specified.
Table 3 provides an overview of the planned analyses, with full details being presented in 
Appendix 8: List of Data Displays. 
Table 3
Overview of Planned Pharmacokinetic Analyses
[Endpoint / 
Parameter/ Display 
Type]
Untransformed
Log-Transformed
Summary
Individual
Summary
Individual
T
F
F
L
T
F
F
L
PK Concentration Data
Plasma Drug 
Concentrations
Y
Y
Y
Y
Y
Y
PK Parameter Data
Parameters
Y
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listings, Y = Display generated.

Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
8.1.2.
Drug Concentration Measures
Refer to Appendix 3: Data Display Standards & Handling Conventions (Section 11.3.3
Reporting Process & Standards).
8.1.3.
Pharmacokinetic Parameters

Refer to Appendix 3: Data Display Standards & Handling Conventions
(Section 11.3.3 Reporting Process & Standards).


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
The pharmacokinetic parameters will be calculated by standard non-
compartmental analysis according to current working practices and 
usingWinNonlin6.3 or above.

All calculations of non-compartmental parameters will be based on actual 
sampling times.

If data permits, population PK modelling will be conducted and independent PK 
modelling plan document may be provided.

Pharmacokinetic parameters described as following and in Table 4 will be 
determined from intravenously (IV) administered GSK1550188, as data permits.
Table 4
Derived Pharmacokinetic Parameters
Parameter
Parameter Description
AUC(0–)
Area under the concentration-time curve from time zero 
(pre-dose) extrapolated to infinite time
AUC(0–t)
Area under the concentration-time curve from time zero 
(pre-dose) to last time of quantifiable concentration
CL
Clearance
Cmax
Maximum observed concentration
λz
Terminal phase rate constant
t½
Terminal phase half-life
Vz
Volume of distribution after intravenous administration
8.1.4.
Statistical Analyses
Pharmacokinetic concentration and parameter data will be summarized descriptively and 
presented in tabular and/or graphic formats per GSK IDSL standard.
All derived pharmacokinetic parameters described above will be summarised and listed 
according to the Pharmacokinetic Parameter Population defined in Section 5. For each of 
these parameters the following summary statistics will be calculated: arithmetic mean, 
95% confidence interval for the arithmetic mean, standard deviation, median, minimum, 
maximum, between coefficient of variation, geometric mean, 95% confidence interval for 
the geometric mean and standard deviation of log-transformed data. 
For the purposes of calculating summary statistics and for statistical analysis, all PK 
parameters will be log-transformed.
Between subjects coefficient of variation (%CVb) for log-transformed data will be 
calculated according to the following methods:
%CVb = SQRT(exp(SD2)-1) * 100 


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where SD is the standard deviation of the log-transformed data.
Between subjects coefficient of variation (%CVb) for untransformed data will be 
calculated according to the following methods:
%CVb = (SD/Mean) * 100
9.
SECONDARY STATISTICAL ANALYSES
9.1.
Safety Analyses
9.1.1.
Overview of Adverse Events
The CRF texts for adverse events (AEs) will be coded using MedDRA version 19.0 or 
above, and will be reported using the System Organ Class (SOC) and Preferred Term 
(PT). In the summary of AEs, the incidence of AEs will be the number of subjects 
reporting AEs and not the number of AEs reported. Multiple occurrences of the same AE 
in one individual will be counted only once when calculating the number and percentage 
of subjects.
The following AEs will be summarized and listed:

All AEs;

All AEs by maximum intensity

All drug-related AEs

All drug-related AEs by maximum intensity

All Serious AEs

All AEs leading to study withdrawals
More details can be found in Section 9.1.2.
9.1.2.
Overview of Planned Safety Analyses
The safety analyses will be based on the “Safety population”, unless otherwise specified.
Table 5 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 8: List of Data Displays.


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Table 5
Overview of Planned Safety Analyses
[Endpoint / Parameter/ 
Display Type]
Absolute
Change from Baseline
Summary
Individual
Summary
Individual
T
F
F
L
T
F
F
L
Exposure
Exposure
Y
Adverse Events
All AEs [1]
Y
Y
AEs – Max Intensity
Y
Y
Drug Related AEs
Y
Y
Drug Related AEs – Max 
Intensity
Y
Y
Serious AEs
Y
AEs leading to study 
Withdrawal
Y
Laboratory Values
Clinical Chemistry
Y
Y
Y
Hematology
Y
Y
Y
Urinalysis
Y
Y
Immunoglobulin
Y
Y
Y
Toxicity  Grade[2]: 
Chemistry
Y
Y
Toxicity  Grade: 
Hematology
Y
Y
Toxicity  Grade: Urinalysis
Y
Y
Toxicity Grade:
Immunoglobulin
Y
Y
ECG
ECG Parameters
Y
ECG Values
Y
Y
Abnormal ECG
Y
Y
Vital Signs
Vital Values
Y
Y
Y
Liver Events
Liver Events
Y
NOTES :

T = Table, F = Figure, L = Listing, Y = Yes display generated, PCI=Potential Clinical Importance

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
1.  Listing will include subject’s numbers for individual AE’s & the table includes AE system organ classes and preferred 
terms. 
2.  Toxicity grades are defined in Appendix 3 of the protocol.


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9.2.
Pharmacodynamic Analyses
9.2.1.
Overview of Planned Pharmacodynamic Analyses
The pharmacodynamic analyses will be based on the “pharmacodynamic population”, 
unless otherwise specified. Table 6 provides an overview of the planned analyses, with 
further details of data displays being presented in Appendix 8: List of Data Displays.
Table 6
Overview of Planned Pharmacodynamic Analyses
[Endpoint / 
Parameter/ Display 
Type]
Absolute
Change from Baseline
Figure
Table
Listing
Figure
Table
Listing
B Cell Subsets
Y
Y
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listings, Y = Display generated.
9.2.2.
Pharmacokinetic-Pharmacodynamic Modelling Analyses
Supplemental compartmental PK modelling and additional PK/PD modelling analyses 
may be conducted to characterize the relationship between Belimumab exposure and the 
B cell subsets profile. These supplemental analyses, as feasible, will be outlined and 
reported in a separate document.


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10.
REFERENCES
Human Genome Sciences Clinical Pharmacokinetics Report HGS1006-POPPK.  
Population pharmacokinetics of belimumab (monoclonal anti-BLyS antibody) following 
intravenous administration in patients with systemic lupus erythematosus.  March, 2010.


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11.
APPENDICES
Section
Appendix
RAP Section 6 : General Considerations for Data Analyses & Data Handling Conventions
Section 11.1
Appendix 1: Time and Events
Section 11.2
Appendix 2: Treatment States 
Section 11.3
Appendix 3: Data Display Standards & Handling Conventions

Study Treatment & Sub-group Display Descriptors

Baseline Definitions & Derivations

Reporting Process & Standards
Section 11.4
Appendix 4: Derived and Transformed Data

General, Study Population & Safety

Pharmacokinetic

Pharmacodynamic or Biomarkers

Pharmacokinectic/Pharmacodynamic
Section 11.5
Appendix 5: Premature Withdrawals & Handling of Missing Data

Premature Withdrawals

Handling of Missing Data
Section 11.6
Appendix 6: Clinical Laboratory Evaluations
Other RAP Appendices
Section 11.7
Appendix 7: Abbreviations & Trade Marks
Section 11.8
Appendix 8: List of Data Displays


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11.1.
Appendix 1: Time & Events
11.1.1.
Protocol Defined Time & Events
Visit
1
2
3
4
5
6
7
8
9
10
Day
Screening
Day -30 to -1
Day 0
Day 
1
Day 
7
Day 
14
Day 
21
Day 
28
Day 
42
Day 
56
Day 
84
Discontinuation9
Pre
0
5m
1h
6h
24h
Informed consent1
X
Medical History
X
X
Demography
X
Complete physical 
examination, including
Height
X
Inclusion/Exclusion 
criteria
x
Body weight
X
Vital signs2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Record Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical Laboratory 
test3
X
X
X
X
X
X
X
X
Spot urine (protein to
X


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Visit
1
2
3
4
5
6
7
8
9
10
Day
Screening
Day -30 to -1
Day 0
Day 
1
Day 
7
Day 
14
Day 
21
Day 
28
Day 
42
Day 
56
Day 
84
Discontinuation9
Pre
0
5m
1h
6h
24h
creatinine ratio)
Urine drug/alcohol 
screen
X
HIV, Hepatitis B, C4
X
Pregnancy test 
(women)5
X
X
X
X
X
Chest X ray
X
12 lead ECG
X
X
X
X
X
Biological Markers6
X7
X
X
X
X
X
X
Blood PK sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
AE/SAE Review8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Admission to Unit 
X
Dosing
X
Discharge 
X
Outpatient Visit 
X
X
X
X
X
X
X
X
X
X


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1.
Each subject must sign an informed consent form prior to undergoing any Screening assessments.
2.
Vital signs include temperature, sitting blood pressure and heart rate.
3.
Clinical Laboratory test include hematology, chemistry and urinalysis (including CRP and Erythrocyte Sedimentation Rate on screening). ALT and/or AST elevations of 
greater than 2.5 x ULN will require additional Hepatitis B assessment, see Section 6.2.1.1 in protocol.
4.
HIV antibody, Hepatitis B surface antigen, anti-HBc and Hepatitis C antibody.
5.
Pregnancy should be assessed with a blood test at Screening and with a urine test during the treatment period.
6.
Biomarkers include immunoglobulins B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–naïve, CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma cells).
7.
Only immunoglobulins (IgG, IgM and IgA) and autoantibodies (anti-dsDNA, ANA).
8.
Includes subject history to be reported on CRF regarding any general signs or symptoms of infection.
9.
If a subject prematurely withdraws for any reason, the investigator must make every effort to assess the items specified on discontinuation test.


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11.2.
Appendix 2: Treatment States
Assessments and events will be classified according to time of occurrence relative to the 
start and/or stop date of the study treatment.
11.2.1.
Treatment States for Concomitant Medications Data
No definition of treatment states for concomitant medications in this study.
11.2.2.
Treatment States for AE Data
Treatment State
Definition
Onset Time Since 
start time of 
dosing
AE Onset Date – Dosing Start Date + 1
Duration (Days) 
AE Resolution Date – AE Onset Date + 1
Drug-related
If relationship is marked ‘YES’ on Inform/CRF OR value is missing.
NOTES: 

If the study treatment stop date is missing then the AE will be considered to be On-Treatment.


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11.3.
Appendix 3: Data Display Standards & Handling 
Conventions
11.3.1.
Study Treatment & Sub-group Display Descriptors
Treatment Group Descriptions
Description
Data Displays for Reporting 
Belimumab 10 mg/kg
Belimumab 10 mg/kg
11.3.2.
Baseline Definition & Derivations
11.3.2.1.
Baseline Definitions
For all endpoints (expect as noted in the table) the baseline value will be the last pre-dose 
assessment. The change from baseline will be calculated by subtracting the baseline 
values from the individual post-baseline values.  If either the baseline or post-baseline
value is missing, the change from baseline is set to missing as well.
Table 7
Baseline Definitions
Parameter
Study Assessments Considered 
As Baseline
Baseline Used in 
Data Display
Screening
Day -1
Day 0       
(Pre-Dose)
Safety
LAB
X
X
Day 0(Pre Dose)[1]
Vital Signs
X
X
Day 0 (Pre Dose)
12 Lead ECG
X
X
Day 0 (Pre Dose)
NOTES: 

Unless otherwise stated, the mean of replicate assessments at any given time point will be used as the value for 
that time point.
1.  For baseline value, if it is missing at baseline visit, then the latest non-missing value of screening will be used to 
replace. 
11.3.2.2.
Derivations and Handling of Missing Baseline Data
Definition
Reporting Details
Change from Baseline
= Post-Dose Visit Value – Baseline
% Change from Baseline
= 100 x [(Post-Dose Visit Value – Baseline) / Baseline]
NOTES :

Unless otherwise specified, the baseline definitions specified in Section 11.3.2.1. Baseline Definitions will be used 
for derivations for endpoints / parameters and indicated on summaries and listings.

Unless otherwise stated, if baseline data is missing no derivation will be performed and will be set to missing.

The baseline definition will be footnoted on all change from baseline displays.


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11.3.3.
Reporting Process & Standards
Reporting Process
Software

The currently supported versions of SAS software will be used.
Reporting Area
HARP Server
US
HARP Area
: \ARPROD\GSK1550188\200909\Final
QC Spreadsheet
: \ARWORK\GSK1550188\200909\Final\Documents
Analysis Datasets 

Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.1.3 & 
AdaM IG Version 1.0).

For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will be 
implemented for conversion from SI to SDTM.
Generation of RTF Files

RTF files will be generated.
Reporting Standards
General

The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated:
o
4.03 to 4.23: General Principles
o
5.01 to 5.08: Principles Related to Data Listings
o
6.01 to 6.11: Principles Related to Summary Tables
o
7.01 to 7.13: Principles Related to Graphics 
Formats

All data will be reported according to the actual treatment the subject received unless 
otherwise stated.

GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected.

Numeric data will be reported at the precision collected on the eCRF.

The reported precision from non eCRF sources will follow the IDSL statistical principles but 
may be adjusted to a clinically interpretable number of DP’s.
Planned and Actual Time

Reporting for tables, figures and formal statistical analyses :
o
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated.
o
The impact of any major deviation from the planned assessment times and/or scheduled 
visit days on the analyses and interpretation of the results will be assessed as appropriate.


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Reporting Standards

Reporting for Data Listings: 
o
Planned and actual time relative to study drug dosing will be shown in listings (Refer to 
IDSL Statistical Principle 5.05.1).
o
Unscheduled or unplanned readings will be presented within the subject’s listings. 
o
Visits outside the protocol defined time-windows (i.e. recorded as protocol deviations) will 
be included in listings but omitted from figures, summaries and statistical analyses.
Unscheduled Visits

Unscheduled visits will not be included in summary tables.

Unscheduled visits will not be included in figures.

All unscheduled visits will be included in listings.
Descriptive Summary Statistics
Continuous Data
Refer to IDSL Statistical Principle 6.06.1
Categorical Data
N, n, frequency, %
Reporting of Pharmacokinetic Concentration Data
Descriptive Summary 
Statistics
Refer to IDSL Statistical Principle 6.06.1
Refer to GUI_51487
Any plasma concentrations below the assay lower limit of quantification
(NQ) will be imputed using the following rules:
NQs at the beginning of a subject profile (i.e. before the first
  incidence of a measurable concentration) are deemed to be  zero 
as it is assumed that in this circumstance no drug is yet 
measurable in the plasma.
For NQs at the end of the subject profile (i.e. after the last 
incidence of a measurable concentration):
(1)
for individual plots and pharmacokinetic analyses these  are 
dropped (set to missing) as they do not provide any useful 
information (and can erroneously indicate that absolutely no 
drug is present)
(2)
for summary statistics these are set to 0 (to avoid skewing 
of the summary statistics)
Individual NQs which fall between two measurable 
concentrations are set to missing (individual values of this nature 
are assumed to be an anomaly)
More than one consecutive NQ between measurable 
concentrations are set to 0. 
Measurable concentrations after more than one consecutive mid-
profile NQ (a mid-profile NQ is defined as any NQ where 
measurable concentrations exist both before and after that NQ in 
the profile): 
For summary, these will be set to missing. 
For individual plot, no action will be done. 
All NQs will remain as “NQ” in listings.


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Reporting Standards
Reporting of Pharmacokinetic Parameters
Descriptive Summary 
Statistics.                       
(Log Transformed)   
N, n, arithmetic mean, median, min, max, SD, 95% CI of arithmetic mean 
will be provided for non-logged data.
For logged data, N, n, geometric mean, 95% CI of geometric mean, 
standard deviation (SD) of logged data and between geometric 
coefficient of variation (CVb (%)) will be reported.
[1] CVb (%) = √ (exp(SD2) - 1) * 100 [NOTE: SD = SD of log transformed 
data]
Reporting of Pharmacodynamic Data
Descriptive Summary 
Statistics. (Not Being 
Log Transformed)
B cell subsets (CD20+, CD20+/27+ memory, CD20+/27–naïve, 
CD20+/69+ activated, CD20+/138+ plasmacytoid, 
CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ plasma 
cells)
Graphical Displays

Refer to IDSL Statistical Principals 7.01 to 7.13.


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11.4.
Appendix 4: Derived and Transformed Data
11.4.1.
General
Multiple Measurements at One Time Point

Where multiple measurements are recorded for a particular time point, the mean of the 
measurements will be calculated and used in any derivation of summary statistics.  However 
all available data will be listed.

Where more than the specified number of measurements has been taken, the recorded 
values nearest to the scheduled time will be used in the derivation of the appropriate 
summary measure (i.e. mean or maximum).
Study Day

The Study day will be provided on the listings to show the relative date to a reference date. In 
this study, the reference date will be defined as the date of visit on Day 0 (i.e. start date of 
dosing). The study day will be calculated by:
o
Date of interest ≥Date of visit on Day 0
Study Day = Date of interest –Date of visit on Day 0+1
o
Date of interest < Date of visit on Day 0
Study Day = Date of interest –Date of visit on Day 0
11.4.2.
Study Population
Demographics
Age

GSK standard IDSL algorithms will be used for calculating age where birth date will be imputed 
as follows:
o
Any subject with a missing day will have this imputed as day ‘15’. 
o
Any subject with a missing date and month will have this imputed as ‘30th June’.

Birth date will be presented in listings as ‘YYYY’.

Use informed consent date as Reference for age calculation.
Body Mass Index (BMI)

Calculated as Weight (kg) / [Height (m)]2
11.4.3.
Safety
Laboratory Parameters

If a laboratory value which is expected to have a numeric value for summary purposes, has a
non-detectable level reported in the database, where the numeric value is missing, but typically 
a character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 
determine how much to add or subtract in order to impute the corresponding numeric value. 
o
Example 1: 2 Significant Digits =  ‘< x ‘ becomes x – 0.01
o
Example 2: 1 Significant Digit   =  ‘> x’ becomes x + 0.1
o
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1    


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11.4.4.
Pharmacokinetic
PK
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be used to summarize 
the concentration values of belimumab in plasma at each sampling time point / collection interval for 
each profile day. Individual subject concentration data will be listed.
Individual plasma concentration-time profiles and median/mean profiles will be plotted. Each of the 
figures will contain one plot on the untransformed scale (i.e. a linear plot) and one plot on the log 
transformed scale (i.e. log-linear plot). 
The concentration data described above will be summarised, listed and plotted based on
Pharmacokinetic Concentration Population defined in Section 5. 
The pharmacokinetic parameters (AUC(0-∞), AUC(0-t), Cmax, t½, z, CL, Vz) will be determined 
from the plasmaconcentration-time data for belimumab. The pharmacokinetic parameters will be 
calculated by standard non-compartmental analysis according to current working practices and 
using WinNonlin6.3 or above. All calculations of non-compartmental parameters will be based on 
actual sampling times.
All the derived parameters described above will be summarised and listed. For each of these 
parameters the following summary statistics will be calculated: arithmetic mean, 95% confidence 
interval for the arithmetic mean, standard deviation, median, minimum, maximum, between 
coefficient of variation, geometric mean, 95% confidence interval for the geometric mean and 
standard deviation of log-transformed data. 
All derived pharmacokinetic parameters described above will be summarised and listed according to 
the Pharmacokinetic Parameter Population defined in Section 5. 
11.4.5.
Pharmacodynamic or Biomarker
PD
The central laboratory will transmit the following results electronically to GlaxoSmithKline:

B cell subsets (CD20+, CD20+/27+ memory, CD20+/27– naïve, CD20+/69+activated, 
CD20+/138+ plasmacytoid, CD19+/27BRIGHT/38BRIGHT SLE subset and CD20-/138+ 
plasma cells).
Estimates of percent change from baseline for B cell subsets will be performed in the PD 
population. The 6-point summary, n, mean, median, standard deviation, minimum and maximum will 
be used for analysis. All derived parameters will be listed and summarized.
The mean and median profile of raw data of B cell subsets will be figured using line plots by 
treatment. The plots with the level of B cell subsets on y-axis and the planned time on x-axis will be 
prepared.


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11.4.6.
Pharmacokinetic/Pharmacodynamic
PK/PD
Other exploratory PK-PD analyses will be considered, when appropriate. These include exposure 
(PK parameters and concentrations)-response (B-cell subsets) analyses using linear and nonlinear 
mixed effect modelling methods. The results may be summarized in a report, separate from the 
main CPSR.


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11.5.1.
Premature Withdrawals
Element
Reporting Detail
General

Subject study completion (i.e. as specified in the protocol) was defined as 
completion of all the phases of the study including the follow up visit.

Withdrawn subjects were not replaced in the study.

All subjects who withdraw prematurely from the study will be documented and 
the reason for their withdrawal recorded in the final Clinical Pharmacology Study 
Report (CPSR).

All available data from subjects who were withdrawn from the study will be listed 
and all available planned data will be included in summary, tables and figures, 
unless otherwise specified.

In the event that the study is prematurely discontinued, all available data will be 
listed and a review carried out by the study team to assess which statistical 
analyses are still considered appropriate and population approach may be used 
to deal with such situations as appropriate.
11.5.2.
Handling of Missing Data
Element
Reporting Detail
General

Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument :
o
These data will be indicated by the use of a “blank” in subject listing 
displays. Unless all data for a specific visit are missing in which case the 
data is excluded from the table. 
o
Answers such as “Not applicable” and “Not evaluable” are not considered to 
be missing data and should be displayed as such.
Outliers

Any subjects excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report.
11.5.
Appendix 5: Premature Withdrawals & Handling of Missing 
Data


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11.5.2.1.
Handling of Missing Dates
Element
Reporting Detail
General
Partial dates will be displayed as captured in subject listing displays.
Adverse 
Events

Completely missing start or end dates will remain missing, with no imputation 
applied. Consequently, time to onset and duration of such events will be 
missing.
11.5.2.2.
Handling of Partial Dates
Element
Reporting Detail
General
Partial dates will be displayed as captured in subject listing displays.
Concomitant 
Medications

Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention:
o
If the partial date is a start date, a '01' will be used for the day If the partial 
date is a stop date, a '28/29/30/31' will be used for the day (dependent on 
the month and year).

The recorded partial date will be displayed in listings.
Adverse 
Events

Any partial dates for adverse events will be raised to data management. If the 
full date cannot be ascertained, the following assumptions will be made:
o
If the partial date is a start date, a '01' will be used for the day. 
o
However, if these results in a date prior to start date of study treatment and 
the event could possibly have occurred on treatment from the partial 
information, then the start date of study treatment will be assumed to be the 
start date. 
o
The AE will then be considered to start on-treatment (worst case).
o
If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year).

The recorded partial date will be displayed in listings.


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11.6.
Appendix 6: Clinical Laboratory Evaluations
Character Values
For laboratory values that are above or below the lower limit of quantification, having 
only character values starting with “<” or “>,” numeric values will be derived using the 
following rules, where LRESSI is the character result in standard units, and LNRES is 
the numeric version of the result:

If LRESSI > x then LNRES = x + 1, where x is an integer >= 1.
If LRESSI > x.y then LNRES = x.y +0.1, where x, y are integers.
If LRESSI > x.yz then LNRES = x.yz + 0.01, where x, y, z are integers.
Etc.

If LRESSI “< x” then LNRES = x - 1, where x is an integer >= 1.
If LRESSI “< x.y” then LNRES = x.y - 0.1, where x, y are integers.
If LRESSI “< x.yz” then LNRES = x.yz - 0.01, where x, y, z are integers.
Etc.
Severity Grade
The laboratory value severity grade tables are showed in Appendix 3 of protocol. 
Laboratory toxicity will be graded using Adverse Event Severity Grading Tables when 
possible.  Note that four analytes, potassium, glucose, calcium, and sodium, have 
toxicities in both the high and low directions, and both will be presented in toxicity 
displays by the name of the toxicity.  For example, calcium will have two toxicity 
sections, one for hypocalcaemia and one for hypercalcaemia. These toxicities will be 
mapped to their high or low form by using the following formulae:
RESULT < (LLN+ULN)/2 = “Hypo” toxicity
RESULT > (LLN+ULN)/2 = “Hyper” toxicity
where LLN is Lower Limit of Normal and ULN is Upper Limit of Normal.


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11.7.
Appendix 7: Abbreviations & Trade Marks
11.7.1.
Abbreviations
AE
Adverse event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
AUC
Area under concentration-time curve
AUC(0–)
Area under the concentration-time curve from time zero (pre-dose) 
extrapolated to infinite time
AUC(0–t)
Area under the concentration-time curve from time zero (pre-dose) to 
last time of quantifiable concentration
BMI
Body mass index
BP
Blood pressure
CL
Clearance
Cmax
Maximum observed concentration
CRF
Case report form
%CV
Coefficient of variation
ECG
Electrocardiogram
GSK
GlaxoSmithKline
HBsAg
Hepatitis B surface antigen
hr
hour
IV
Intravenous
kg
Kilogram
mg
Milligram
mL
Millilitre
msec
Millisecond
ng
Nanogram
PK
Pharmacokinetics
RBC
Red blood cell
SAE
Serious adverse event(s)
SD
Standard deviation
λz
Terminal phase rate constant
t½
Terminal phase half-life
ULN
Upper limit of normal
WBC
White blood cell
Vz
Volume of distribution after intravenous administration
Vss
Volume of distribution after intravenous administration at steady state


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11.7.2.
Trademarks
Trademarks of the GlaxoSmithKline 
Group of Companies
Trademarks not owned by the 
GlaxoSmithKline Group of Companies
BELIMUMAB
SAS
WinNonlin


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11.8.
Appendix 8: List of Data Displays
11.8.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.01 to 1.07
N/A
Safety
2.01 to 2.26
2.2 to 2.4
Pharmacokinetic
3.1 to 3.3
3.1 to 3.3
Pharmacodynamics
4.1 to 4.2
4.1 to 4.4
Section
Listings
ICH Listings
1 to 30
Other Listings
31 to 33
11.8.2.
Mock Example Referencing
Non IDSL specifications will be referenced as indicated and if required an example 
mock-up displays provided in Appendix 9: Example Mock Shells for Data Displays.
Section
Figure
Table
Listing
Study Population
POP_Fn
POP_Tn
POP_Ln
Safety
SAFE_Fn
SAFE_Tn
SAFE_Ln
Pharmacokinetic
PK_Fn
PK_Tn
PK_Ln
Pharmacodynamics
PD_Fn
PD_Tn
PD_Ln
NOTES: 

Non-Standard displays are indicated in the ‘IDSL / TST ID / Example Shell’ or ‘Programming Notes’ column as
‘[Non-Standard] + Reference.’
11.8.3.
Deliverable [Priority]
Delivery [Priority] [1]
Description
SAC[1]
Final Statistical Analysis Complete
NOTES: 
1.
Indicates priority (i.e. order) in which displays will be generated for the reporting effort.


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11.8.4.
Study Population Tables
Study Population Tables
No.
Population
IDSL / TST ID / Example 
Shell
Title
Programming Notes
Deliverable [Priority]
Subject Disposition 
1.01
Safety
ES1
Summary of Subject Disposition 
SAC [1]
1.02
Screened
ES6
Summary of Screening Failures
SAC [1]
1.03
Screened
POP_T1 
Summary of Study Analysis Populations
SAC [1]
1.04
Safety
DV1A
Summary of Important Protocol Deviations
SAC [1]
1.05
Safety
DV1A
Summary of Other Protocol Deviation
SAC [1]
Demographics
1.06
Safety
DM1
Summary of Demographic Characteristics 
Include BMI
SAC [1]
1.07
Safety
DM5
Summary of Race and Racial Combinations
SAC [1]


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11.8.5.
Safety Tables
Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
Adverse Events
2.01
Safety
CP_AE1p
Summary of All Adverse Events   
SAC [1]
2.02
Safety
CP_AE1p
Summary of all adverse events by maximum 
intensity
SAC [1]
2.03
Safety
CP_AE1p
Summary of Drug-Related Adverse Events
SAC [1]
2.04
Safety
CP_AE1p
Summary of all drug-related adverse events 
by maximum intensity
SAC [1]
2.05
Safety
CP_AE1p
Summary of Serious Adverse Events
SAC [1]
2.06
Safety
CP_AE1p
Summary of Adverse Events Leading to 
Withdrawals from Study
SAC [1]
Labs
2.07
Safety
LB1
Summary of Chemistry Laboratory Values
SAC [1]
2.08
Safety
LB1
Summary of Hematology Laboratory Values
SAC [1]
2.09
Safety
UR3
Summary of Urinalysis Dipstick Results
SAC [1]
2.10
Safety
LB1
Summary of Immonoglobulin
SAC [1]
2.11
Safety
LB1
Summary of Change from Baseline in 
Chemistry Laboratory Values
SAC [1]


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Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
2.12
Safety
LB1
Summary of Change from Baseline in 
Hematology Laboratory Values
SAC [1]
2.13
Safety
LB1
Summary of Percent Change from Baseline in 
Immonoglobulin
Including the mean of baseline 
value
SAC [1]
2.14
Safety
SAFE_T1
Worst Laboratory Toxicity Grade: Chemistry
SAC [1]
2.15
Safety
SAFE_T1
Worst Laboratory Toxicity Grade: Hematology
SAC [1]
2.16
Safety
SAFE_T1
Worst Laboratory Toxicity Grade: Urinalysis
SAC [1]
2.17
Safety
SAFE_T1
Worst Laboratory Toxicity Grade: 
Immonoglobulin
SAC [1]
2.18
Safety
SAFE_T2
Laboratory Toxicity Grade Worsening of at 
Least 2 Grades from Baseline: Chemistry
SAC [1]
2.19
Safety
SAFE_T2
Laboratory Toxicity Grade Worsening of at 
Least 2 Grades from Baseline: Hematology
SAC [1]
2.20
Safety
SAFE_T2
Laboratory Toxicity Grade Worsening of at 
Least 2 Grades from Baseline: Urinalysis
SAC [1]
2.21
Safety
SAFE_T2
Laboratory Toxicity Grade Worsening of at 
Least 2 Grades from Baseline: 
Immunoglobulin
SAC [1]


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Safety Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
ECG
2.22
Safety
EG2
Summary of ECG Parameter
Use latest assessment in case of 
multiple assessments at any 
given time point
SAC [1]
2.23
Safety
EG2
Summary of Mean Change from Baseline in 
ECG Values
SAC [1]
2.24
Safety
EG1
Summary of the Number and Percentage of 
Subjects Who Had Abnormal ECG Findings
Including ‘Clinically Significant’
and ‘Not Clinically Significant’
SAC [1]
Vital Signs
2.25
Safety
VS1
Summary of Vital Signs  
Including systolic blood pressure, 
diastolic blood pressure and 
pulse, respiratory Rate, 
temperature
SAC [1]
2.26
Safety
VS1
Summary of Change from Baseline in Vital 
Signs
SAC [1]


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11.8.6.
Pharmacokinetic Tables
Pharmacokinetic : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
PK Concentration Data
3.1
PK
Concentration
PKCT1/PK01
Summary of Belimumab Plasma Pharmacokinetic 
Concentration-Time Data 
SAC [1]
PK Parameter Data
3.2
PK Parameter
PKPT1/PK03
Summary of Derived Belimumab Plasma 
Pharmacokinetic Parameters
Including: arithmetic mean, 95% 
confidence interval for the 
arithmetic mean, standard 
deviation, median, minimum, 
maximum, between coefficient of 
variation, geometric mean and 
95% confidence interval
SAC [1]
3.3
PK Parameter
PKPT3/PK05
Summary of Derived Belimumab Plasma 
Pharmacokinetic Parameters Based on Log-
Transformation
SAC [1]


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11.8.7.
Pharmacodynamic Tables
Pharmacodynamic : Tables
No.
Population
IDSL / TST ID 
/ Example 
Shell
Title
Programming Notes
Deliverable [Priority]
PD Parameter Data
4.1
PD
PKPT1/PK03
Summary of B Cell Subsets
SAC [1]
4.2
PD
PKPT1/PK03
Summary of Percent Change from Baseline in B Cell 
Subsets
Including the mean of baseline 
value
SAC [1]
11.8.8.
Safety Figures
Safety: Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Responsibility
Deliverable [Priority]
Labs
2.1
Safety
SAFE_F1
Mean Profile of Immunoglobulin
SAC [1]
2.2
Safety
SAFE_F1
Median Profile of Immunoglobulin
SAC [1]
2.3
Safety
SAFE_F2
Mean Profile of Percent Change from Baseline in 
Immunoglobulin
SAC [1]
2.4
Safety
SAFE_F2
Median Profile of Percent Change from Baseline in 
Immunoglobulin
SAC [1]
Note: Use consistent colour for treatments in all figures


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11.8.9.
Pharmacokinetic Figures
Pharmacokinetic : Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Responsibility
Deliverable [Priority]
Individual Concentration Plots
3.1
PK
Concentration
PKCF1P/ 
PK16a
Individual Belimumab Plasma Concentration-Time 
Plot (Linear and Semi-Log) 
SAC [1]
Mean Concentration Plots
3.2
PK
Concentration
PKCF2/ PK17
Mean (+SD) Belimumab Plasma Concentration-Time 
Plot (Linear and Semi-Log) 
SAC [1]
Median Concentration Plots
3.3
PK
Concentration
PKCF3/ PK18
Median (Range) Belimumab Plasma Concentration-
Time Plot (Linear and Semi-Log) 
SAC [1]
Note: Use consistent colour for treatments in all figures


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11.8.10.
Pharmacodynamic Figures
Pharmacodynamic : Figures
No.
Population
IDSL / TST ID 
/ Example 
Shell
Title
Programming Notes
Deliverable [Priority]
PD Parameter Data
4.1
PD
PD_F1
Mean Profile of B Cell Subsets
SAC [1]
4.2
PD
PD_F1
Median Profile of B Cell Subsets
SAC [1]
4.3
PD
PD_F2
Mean Profile of Percent Change from Baseline in B Cell Subsets
SAC [1]
4.4
PD
PD_F2
Median Profile of Percent Change from Baseline in B Cell Subsets
SAC [1]
11.8.11.
ICH Listings
ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
Subject Disposition
1
Screened
ES7
Listing of Reasons for Screening Failure
SAC [1]
2
Safety
ES2
Listing of Reasons for Study Withdrawal
SAC [1]
3
Safety
DV2
Listing of Important Protocol Deviations
SAC [1]
4
Safety
IE3
Listing of Subjects with Inclusion/Exclusion 
Criteria Deviations
SAC [1]
5
Safety
DV2
Listing of Other Protocol Deviations
SAC [1]


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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
Demographics
6
Safety
DM2
Listing of Demographic Characteristics
SAC [1]
7
Safety
DM9
Listing of Race and Racial Combinations
SAC [1]
Medical Conditions & Concomitant Medications
8
Safety
CM3
Listing of Concomitant Medications by 
Generic Term
SAC [1]
9
Safety
MH2
Listing of Medical Conditions
SAC [1]
Exposure
10
Safety
EX3
Listing of Exposure
SAC [1]
Adverse Events
11
Safety
AE7
Listings of Subject Numbers for Individual 
Adverse Events
SAC [1]
12
Safety
AE2
Relationship between System Organ Class 
and Verbatim Text
SAC [1]
13
Safety
CP_AE8
Listing of All Adverse Events
SAC [1]
14
Safety
CP_AE8
Listing of All Adverse Events by Maximum 
Intensity
SAC [1]
15
Safety
CP_AE8
Listing of Drug-Related Adverse Events
SAC [1]


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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
16
Safety
CP_AE8
Listing of Drug-Related Adverse Events by 
Maximum Intensity
SAC [1]
17
Safety
CP_AE8a
Listing of Serious Adverse Events
The listing will be provided by fatal and 
non-fatal outcomes
SAC [1]
18
Safety
CP_AE8
Listing of Adverse Events Leading to 
Withdrawal from Study
.
SAC [1]
LABS
19
Safety
SAFE_L1
Laboratory Results: Chemistry
SAC [1]
20
Safety
SAFE_L1
Laboratory Results: Hematology
SAC [1]
21
Safety
SAFE_L1
Laboratory Results: Urinalysis
SAC [1]
22
Safety
SAFE_L1
Laboratory Results: Immunoglobulin
SAC [1]
ECG
23
Safety
CP_EG3
Listing of ECG Values for All Subjects
SAC [1]
24
Safety
CP_EG3
Listing of All ECG Findings for Subjects with 
An Abnormal Finding
Including ‘Clinically Significant’ and ‘Not 
Clinically Significant’
SAC [1]


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ICH Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
Vital Signs
25
Safety
CP_VS4
Listing of Vital Signs for All Subjects 
SAC [1]
Liver Event
26
Safety
LIVER5
Listing of Liver Monitoring/Stopping Event 
Reporting
SAC [1]
27
Safety
LIVER6
Listing of Liver Stopping Event Information 
for RUCAM Score
SAC [1]
28
Safety
SAFE_L2
Listing of Medical Conditions at Onset of 
Liver Event
SAC [1]
29
Safety
LIVER7
Listing of Liver Biopsy Details
SAC [1]
30
Safety
LIVER8
Listing of Liver Imaging Details
SAC [1]


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11.8.12.
Non-ICH Listings
Non-ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable [Priority]
PK
31
PK
Concentration
PK08
Listing of Individual Subject Concentration
IA (SAC)
32
PK Parameter
PK13
Listing of Derived Pharmacokinetic 
Parameters
IA (SAC)
PD
33
PD
PD_L1
Listing of  B Cell Subset
IA (SAC)


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46
11.9.
Appendix 9: Example Mock Shells for Data Displays
Data Display Specification will be made available on Request.