A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease
Phase: PHASE2
Conditions: Severe Acute Respiratory Syndrome
Sponsor: GlaxoSmithKline

TMF-11795607 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: A randomized, double-blind, placebo-controlled, study evaluating the 
efficacy and safety of otilimab IV in patients with severe pulmonary COVID-19 related 
disease. 
Protocol Number: 214094/Amendment 03 
Compound Number 
or Name: 
GSK3196165 (otilimab) 
 
Study Name: OSCAR (Otilimab in Severe COVID-19 Related Disease). 
Brief Title: Investigating otilimab in patients with severe pulmonary COVID-19 related 
disease. 
Study Phase: Phase 2 (Part 1), Phase 3 (Part 2) 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s): 
IND: 149754 
EudraCT: 2020-001759-42 
 
 
Approval Date: 25-JAN-2021 
 
 
 
Copyright 2021 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorized copying or use of this information is prohibited. 

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SPONSOR SIGNATORY 
Protocol Title: A randomized, double-blind, placebo-controlled, study evaluating the 
efficacy and safety of otilimab IV in patients with severe pulmonary COVID-19 related 
disease. 
Protocol Number: 214094/Amendment 03 
Compound Number 
or Name: 
GSK3196165 (otilimab) 
 
 
 
 
 
 
 
 
 
 
Dr. Jatin Patel 
Clinical Development Leader 
Clinical Science (II and Fibrosis) 
 
Date 
The signed page is a separate document. 
 
 
 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 3 
25-JAN-2021 
TMF-11795607 
Amendment 2 
02-JUL-2020 
2020N436091_02 
Amendment 1 
18-MAY-2020 
2020N436091_01 
Original Protocol 
30-APR-2020 
2020N436091_00 
 
Amendment 3: 25-JAN-2021 
This amendment is considered substantial, based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union. 
Overall Rationale for the Amendment to add an additional cohort in the study.  
Before the last of 806 participants completed the study (Last Subject Last Visit, Day 60), 
an interim analysis of the primary endpoint and all-cause mortality data at Day 28 
showed that substantial clinical benefit was evident in one of the pre-defined stratification 
subgroups “Age 70 to <80 years”, with no safety concerns in any subgroup.  Given the 
ongoing pandemic and particularly high mortality of COVID-19 disease in patients over 
70 years old, together with recent publications that support the hypothesis that the 
severity of the disease is driven by a maladaptive innate immune response in which GM-
CSF plays a key role and which is more commonly elevated in older patients. GSK has 
therefore determined to urgently confirm these subgroup findings by amending the 
protocol to allow the enrolment of an additional cohort of patients aged 70 years and 
above with no upper age limit.  GSK has reviewed the results from what is now 
considered as the first part of the study (Part 1) and decided that a second part will be 
added to the study (Part 2) which has less frequent assessments to decrease the burden on 
sites.  The following changes have been made in Amendment 3 for Part 2. 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page. Study 
Phase 
Added that Part 2 is Phase 3. 
Part 2 of the study is confirmatory 
and therefore, considered Phase 3. 
1.1. Synopsis, Brief 
Summary, Number of 
Participants 
Added Part 2. 
Additional cohort required to confirm 
efficacy and safety in Part 1. 
1.1. and 3.2. 
Objectives and 
Endpoints - Part 2 
Added objectives and endpoints for 
Part 2 based on objectives and 
endpoints in Part 1, added a 
secondary endpoint “All-cause 
mortality” at Day 28, and deleted 
exploratory endpoints “Improvement 
of at least 2 points relative to baseline 
of Sequential Organ Failure 
Assessment (SOFA) score” and 
“Improvement relative to baseline in 
SpO2, FiO2, and SpO2/FiO2 ratio”. 
A pre-specified endpoint is a key 
value driver in the cost-effectiveness 
model, and the exploratory endpoints 
will not be reported. 

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Section # and Name 
Description of Change 
Brief Rationale 
1.1 and 3.2. Objectives 
and Endpoints - Part 2 
Removed ‘high-dose vasopressor’ 
from the Category 7 description for 
Part 2. 
Based on complexity to define / 
record ‘high-dose’ in Part 1. 
1.4. Schedule of 
Activities (SoA) – Part 
2 
Added SoA for Part 2. Reduced 
frequency of: COVID-19 signs and 
symptom score, vital signs, SpO2, 
FiO2 and local lab testing.  Removed 
SOFA score (except at Screening).  
Removed Day 1 ECG.  Added height 
and participant baseline and 
discharge location information.  
Revised guidance notes. 
Assessments considered non-
essential in Part 1 removed to reduce 
site burden.  Height collected for Part 
2 to allow BMI estimates to be 
calculated.  Guidance given in the 
SRM for Part 1 moved to the protocol. 
2. Introduction, 2.1. 
Study Rationale, 2.2.2. 
Scientific rationale to 
inhibit GM-CSF in 
COVID-19 patients, 
2.2.3. Timing of GM-
CSF inhibition in 
COVID patients 
Added recent and relevant changes in 
the increased understanding of the 
pathophysiology of COVID-19, 
immunosenescence, epidemiology 
and mortality risk. 
Supports the rationale for the 
additional cohort of participants 
70 years or older required to confirm 
efficacy and safety in Part 1. 
2.3.1. Risk 
Assessment 
Updated Sections on Serious 
hypersensitivity reactions (TENS 
case) and Infections (additional 
immunosuppressant therapies). 
Risk Assessment updated with 
preliminary safety data from Part 1. 
2.3.2. Benefit 
Assessment 
Added statement for Part 2. 
Supports the rationale for the 
additional cohort of participants 
70 years or older required to confirm 
efficacy in Part 1, with no safety 
concerns. 
2.3.3. Overall Benefit: 
Risk Conclusion 
Added statement for Part 2. 
Supports the rationale for the 
additional cohort of participants 
70 years or older required to confirm 
efficacy in Part 1, with no safety 
concerns. 
4.1.2. Main Cohort, 
4.1.2..2 Stratification in 
Part 2 
Added Part 2 stratification information 
and additional guidance. 
Stratification added for Part 2 to 
obtain a balanced population across 
the treatment arms with respect to the 
severity of the disease and gender, 
which are both associated with 
mortality. 
Additional guidance to increase site 
understanding. 
4.4. End of Study 
Definition 
Revised definition of End of Study for 
Part 2, and any future cohorts. 
To facilitate adding at least one extra 
cohort required to confirm efficacy 
and safety in Part 1. 

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Section # and Name 
Description of Change 
Brief Rationale 
5.2. Inclusion Criteria – 
Part 2 
Added Inclusion Criteria for Part 2 
based on Inclusion Criteria for Part 1.  
Revised age range to 70 years or 
above (#1); added footnote to indicate 
that guidance on ‘high-flow oxygen or 
equivalent’ is provided in the SRM; 
and removed text on requirement for 
contraceptive guidance for females 
(#4 Part 1). 
Additional cohort of participants 70 
years or older required to confirm 
efficacy and safety in Part 1. Upper 
age limit removed to assess potential 
benefit in an even older population.  
Contraception criterion removed 
based on age range for Part 2 (70 
years and over). 
Additional guidance to increase site 
understanding. 
5.4. Exclusion Criteria 
– Part 2 
Added Exclusion Criteria for Part 2 
based on Exclusion Criteria for Part 1: 
clarified that SOFA score is used for 
intubated ICU patients (#2), removed 
reference to ‘high-dose 
vasopressors/inotropes’ (#3), added 
the following additional medical 
conditions: severe renal dysfunction, 
severe dementia, severe disability 
(#4), clarified that patients 
demonstrating a sustained virologic 
response (SVR) for HCV are not 
excluded from participation (#8), 
clarified chemotherapy treatments 
(hormone based therapies are 
permitted) (#9), added more examples 
of immunosuppressant therapies 
(#11), reduced ANC threshold from 
<1.5 x 109/L (neutropenia  Grade 2) 
to <1.0 x 109/L (neutropenia  Grade 
3) (#19). 
Exclusion criteria modified based on 
experience in Part 1, and additional 
medical conditions added to reflect 
the recruitment of a population 70 
years and older. 
5.5. Screen Failures 
Added that participants who are 
randomized but not subsequently 
dosed, are not screen failures. 
Clarification on guidance regarding 
screen failures. 
6.1. Study 
Intervention(s) 
Administered 
Switched from sterile 0.9% (w/v) 
sodium chloride solution for placebo 
infusion in Part 1 to sterile 5% (w/v) 
dextrose solution in Part 2. 
Added text from the SRM that an in-
line filter must be used and added a 
statement that the Study Intervention 
preparation must be conducted in 
accordance with the SRM. 
Change in diluent and placebo from 
normal saline to 5% dextrose, based 
on new compatibility information. 
Clarifications of information 
previously in the SRM only. 
6.6. Concomitant 
Therapy 
Added requirement to record COVID-
19 current vaccination status in Part 
2., Removed requirement to monitor 
or caution in respect of CYP3A4 
substrate drugs. 
COVID-19 vaccines were not 
available during Part 1. 
Guidance on the caution of CYP3A4 
substrate drugs considered 
unnecessary for this single dose 
study, so removed for Part 2. 

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Section # and Name 
Description of Change 
Brief Rationale 
6.6.1. Medication NOT 
Permitted During the 
Study 
Clarified that the medications listed in 
Section 6.6.1 cannot be planned to be 
administered during the study. 
Added more examples of 
immunosuppressant therapies. 
Clarification and extra examples 
added to assist site understanding. 
6.6.2. 
Medication/Treatment 
PERMITTED During 
the Study 
Added more examples of COVID-19 
medications and clarified the guidance 
on the permitted use of these 
medications. 
Clarification and extra examples 
added to assist site understanding. 
7.1.1. Demography 
and Medical History 
Clarification added that medical 
history includes COVID-19 signs and 
symptoms on admission, and that 
COVID-19 vaccination status will be 
recorded at Screening. 
Extra guidance provided. 
COVID-19 vaccines were not 
available during Part 1. 
7.2.1.Clinical features 
of COVID-19 
Reduced frequency of collecting 
COVID-19 Signs and Symptoms from 
daily to key timepoints only. 
To reduce site burden. 
7.2.2. SpO2 (for 
participants not on 
invasive mechanical 
ventilation) 
Reduced frequency of assessment 
and clarified guidance. 
To reduce site burden and improve 
guidance. 
7.2.3. Concentration of 
inspired oxygen (FiO2) 
Reduced frequency of assessment 
and clarified guidance. 
To reduce site burden and improve 
guidance. 
7.2.6. Ordinal Scale 
Removed ‘high-dose vasopressor’ 
from the Category 7 description for 
Part 2. 
Based on complexity to define / 
record ‘high-dose’ in Part 1 
7.2.7. Participant 
baseline and discharge 
location information 
Added guidance on collecting 
participant location information (at 
baseline and discharge). 
Guidance given in the SRM for Part 1 
moved to the protocol. 
7.2.8. Sequential 
Organ Failure 
Assessment (SOFA) 
Scores 
Clarified guidance on collecting SOFA 
score. 
Clarified the text. 
To reduce site burden and improve 
guidance. 
7.3.2. Vital Signs 
Added that temperature location 
(rather than method) is collected.  
Added that height will be collected at 
Screening for Part 2. 
To improve guidance. 
Height collected for Part 2 to allow 
BMI estimates to be calculated. 
7.3.5. Pregnancy 
Testing (Part 1 only) 
Removed requirement for pregnancy 
testing in Part 2. 
Based on age range for Part 2 (70 
years and over). 
7.4.5. Pregnancy (Part 
1 only) 
Removed requirement for pregnancy 
testing in Part 2. 
Based on age range for Part 2 (70 
years and over). 
7.4.7. Adverse Events 
of Special Interest 
Clarified that CRS is an AESI if not 
related to COVID-19. 
Added reference to extra guidance in 
the protocol and SRM. 
To improve guidance. 

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Section # and Name 
Description of Change 
Brief Rationale 
7.4.7.1. Cytokine 
Release Syndrome 
Added clarification that CRS (possibly 
related to study drug, rather than 
progression of hyperinflammation in 
COVID-19 disease) is defined as a 
worsening of the CRS Grading 
System within 6 hours after start of 
study drug infusion. 
Added clarification that ‘unexpected 
oxygen requirement΄ in Grades 2 and 
3 equates to FiO2. 
To improve guidance on when to 
report CRS events. 
7.5. Pharmacokinetics 
Added clarification to Part 2 that if 
central laboratory kits are not 
available at a site, participants can be 
randomised and dosed, and the PK 
samples not collected. 
To ensure that the operational 
aspects of an exploratory endpoint 
does not prevent participant 
enrolment. 
7.7. 
Pharmacodynamics 
Added clarification to Part 2 that if 
central laboratory kits are not 
available at a site, participants can be 
randomised and dosed, and the PD 
samples not collected. 
To ensure that the operational 
aspects of an exploratory endpoint 
does not prevent participant 
enrolment. 
8.1. Statistical 
Hypothesis 
Clarification that the null hypothesis 
being tested applies to all parts of the 
study. 
To accommodate addition of Part 2. 
8.2. Sample Size 
Determination 
Added sample size for Part 2. 
Required for Part 2. 
8.4. Statistical 
Analyses 
Added clarification that each part of 
the study will be analysed separately, 
and separate analysis plans will be 
produced. 
Clarification of statistical analysis plan 
with the addition of Part 2. 
8.4.1. General 
Considerations 
Added Part 2 general considerations 
for stratification assignment. 
Required for Part 2. 
8.4.2. Primary 
Endpoint(s) 
Revised text that the primary endpoint 
was analysed when all participants in 
Part 1 had completed Day 28.  
Added text for Part 2, and details of 
how the corresponding difference in 
proportion and confidence interval will 
be calculated from the model. 
Clarification for Part 1 and required 
for Part 2. 
8.5. Interim Analysis 
Added text to confirm no interim 
analyses to assess futility and efficacy 
in Part 2, and that the IDMC will only 
review safety data. 
Information for Part 2. 
9.1.5. Committees 
Structure 
Added text to confirm that the IDMC 
will only review safety data in Part 2. 
Information for Part 2.  IDMC will 
review only safety data, because 
there are no interim analyses planned 
for Part 2. 

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Section # and Name 
Description of Change 
Brief Rationale 
Table 4. Protocol-
Required Safety 
Laboratory Tests – 
Part 2 
Changes in Part 2: removed lactate, 
procalcitonin, pregnancy testing, 
requirement for fasting glucose, and 
ALP fractionation.  Stated that PT or 
INR can be collected. 
Removed the Day 2 timepoint. 
Removed local lab tests from Part 2, 
which were considered unnecessary 
from Part 1 data. 
Removed pregnancy testing based 
on age range for Part 2 (70 years and 
over). 
9.4. Appendix 4: 
Contraceptive and 
Barrier Guidance 
Removed contraception guidance in 
Part 2. 
Based on age range for Part 2 (70 
years and over). 
9.5. Appendix 5: 
Abbreviations and 
Trademarks 
Added new abbreviations. 
Site understanding. 
9.6. Appendix 6: 
Protocol Amendment 
History 
Amendment 2 changes moved from 
the front of the protocol to this 
appendix. 
Because Amendment 3 is the current 
version. 
9.7.Appendix 7: 
Country-Specific 
Protocol Addendums 
Added country-specific protocol 
addendums for The Netherlands, 
South Africa, India and Japan. 
Added country-specific protocol 
addendums that were not included in 
previous versions of the protocol, in 
error. 
9.10. References. 
Added references and deleted 
references not cited in the main body 
of the protocol. 
New references required for the 
recent and relevant changes in the 
increased understanding of the 
pathophysiology of COVID-19, 
immunosenescence, epidemiology 
and mortality risk. 
All sections 
Other minor, grammatical and typographical corrections to improve 
readability. 
 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE .................................... 3 
1. 
PROTOCOL SUMMARY ...................................................................................... 12 
1.1. 
Synopsis .................................................................................................. 12 
1.2. 
Schema .................................................................................................... 16 
1.3. 
Schedule of Activities (SoA) – Part 1 ......................................................... 17 
1.4. 
Schedule of Activities (SoA) – Part 2 ......................................................... 20 
2. 
INTRODUCTION ................................................................................................. 23 
2.1. 
Study Rationale ........................................................................................ 23 
2.2. 
Background .............................................................................................. 25 
2.2.1. 
Role of GM-CSF in inflammation ................................................ 25 
2.2.2. 
Scientific rationale to inhibit GM-CSF in COVID-19 
patients ...................................................................................... 26 
2.2.3. 
Timing of GM-CSF inhibition in COVID patients .......................... 28 
2.3. 
Benefit/Risk Assessment .......................................................................... 31 
2.3.1. 
Risk Assessment........................................................................ 31 
2.3.2. 
Benefit Assessment ................................................................... 36 
2.3.3. 
Overall Benefit: Risk Conclusion ................................................. 36 
3. 
OBJECTIVES AND ENDPOINTS ......................................................................... 37 
3.1. 
Part 1 ....................................................................................................... 37 
3.2. 
Part 2 ....................................................................................................... 38 
4. 
STUDY DESIGN .................................................................................................. 40 
4.1. 
Overall Design .......................................................................................... 40 
4.1.1. 
Initial Safety Cohort (first 20 participants) .................................... 41 
4.1.2. 
Main Cohort (after 20 participants).............................................. 41 
4.1.2.1. 
Stratification in Part 1 ................................................ 42 
4.1.2.2. 
Stratification in Part 2 ................................................ 42 
4.2. 
Scientific Rationale for Study Design ......................................................... 43 
4.3. 
Justification for Dose ................................................................................ 43 
4.3.1. 
Otilimab ..................................................................................... 43 
4.3.2. 
Placebo ..................................................................................... 44 
4.4. 
End of Study Definition ............................................................................. 44 
5. 
STUDY POPULATION ......................................................................................... 45 
5.1. 
Inclusion Criteria – Part 1 .......................................................................... 45 
5.2. 
Inclusion Criteria – Part 2 .......................................................................... 46 
5.3. 
Exclusion Criteria – Part 1......................................................................... 47 
5.4. 
Exclusion Criteria – Part 2......................................................................... 48 
5.5. 
Screen Failures ........................................................................................ 49 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ............................. 50 
6.1. 
Study Intervention(s) Administered............................................................ 50 
6.2. 
Preparation/Handling/Storage/Accountability ............................................. 51 
6.3. 
Measures to Minimize Bias: Randomization and Blinding........................... 52 
6.4. 
Study Intervention Compliance.................................................................. 53 
6.5. 
Treatment of Overdose ............................................................................. 53 
6.6. 
Concomitant Therapy................................................................................ 53 

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6.6.1. 
Medication NOT Permitted During the Study ............................... 54 
6.6.2. 
Medication/Treatment PERMITTED During the Study ................. 54 
6.7. 
Participant Discontinuation/Withdrawal from the Study .............................. 55 
6.8. 
Lost to Follow Up ...................................................................................... 55 
7. 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 55 
7.1. 
Entry/Screening Assessments................................................................... 56 
7.1.1. 
Demography & Medical History .................................................. 56 
7.1.2. 
Chest X-ray or CT Scan ............................................................. 57 
7.2. 
Efficacy Assessments ............................................................................... 57 
7.2.1. 
Clinical features of COVID-19 ..................................................... 57 
7.2.2. 
SpO2 (for participants not on invasive mechanical 
ventilation) ................................................................................. 57 
7.2.3. 
Concentration of inspired oxygen (FiO2)...................................... 58 
7.2.4. 
Ventilation status........................................................................ 58 
7.2.5. 
ICU Supportive Care .................................................................. 58 
7.2.6. 
Ordinal Scale ............................................................................. 58 
7.2.7. 
Participant baseline and discharge location information............... 59 
7.2.8. 
Sequential Organ Failure Assessment (SOFA) Scores................ 59 
7.3. 
Safety Assessments ................................................................................. 60 
7.3.1. 
Physical Examinations ............................................................... 60 
7.3.2. 
Vital Signs.................................................................................. 60 
7.3.3. 
Electrocardiograms .................................................................... 60 
7.3.4. 
Clinical Safety Laboratory Assessments ..................................... 60 
7.3.5. 
Pregnancy Testing (Part 1 only).................................................. 61 
7.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ....................................................................................... 61 
7.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information................................................................................. 61 
7.4.2. 
Method of Detecting AEs and SAEs............................................ 62 
7.4.3. 
Follow-up of AEs and SAEs........................................................ 62 
7.4.4. 
Regulatory Reporting Requirements for SAEs............................. 62 
7.4.5. 
Pregnancy (Part 1 only) .............................................................. 62 
7.4.6. 
Cardiovascular and Death Events............................................... 63 
7.4.7. 
Adverse Events of Special Interest ............................................. 63 
7.4.7.1. 
Cytokine Release Syndrome ..................................... 64 
7.5. 
Pharmacokinetics ..................................................................................... 65 
7.6. 
Genetics ................................................................................................... 65 
7.7. 
Pharmacodynamics .................................................................................. 66 
7.8. 
Immunogenicity Assessments ................................................................... 66 
7.9. 
Health Economics/Medical Resource Utilization and Health 
Economics................................................................................................ 66 
8. 
STATISTICAL CONSIDERATIONS ...................................................................... 66 
8.1. 
Statistical Hypotheses............................................................................... 66 
8.2. 
Sample Size Determination....................................................................... 67 
8.3. 
Analysis Sets............................................................................................ 67 
8.4. 
Statistical Analyses ................................................................................... 67 
8.4.1. 
General Considerations .............................................................. 68 
8.4.2. 
Primary Endpoint(s).................................................................... 68 
8.4.3. 
Secondary Endpoint(s) ............................................................... 69 
8.4.4. 
Exploratory Endpoint(s) .............................................................. 69 
8.4.5. 
Safety Analysis .......................................................................... 69 
8.5. 
Interim Analysis ........................................................................................ 69 

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9. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS............................................................................................. 71 
9.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ......................................................................................... 71 
9.1.1. 
Regulatory and Ethical Considerations ....................................... 71 
9.1.2. 
Financial Disclosure ................................................................... 71 
9.1.3. 
Informed Consent Process ......................................................... 72 
9.1.4. 
Data Protection .......................................................................... 74 
9.1.5. 
Committees Structure................................................................. 74 
9.1.6. 
Dissemination of Clinical Study Data .......................................... 75 
9.1.7. 
Data Quality Assurance .............................................................. 76 
9.1.8. 
Source Documents..................................................................... 77 
9.1.9. 
Study and Site Start and Closure ................................................ 77 
9.1.10. Publication Policy ....................................................................... 78 
9.2. 
Appendix 2: Clinical Laboratory Tests ....................................................... 79 
9.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ...................................... 81 
9.3.1. 
Definition of AE .......................................................................... 81 
9.3.2. 
Definition of SAE ........................................................................ 82 
9.3.3. 
Definition of Cardiovascular Events ............................................ 83 
9.3.4. 
Recording and Follow-Up of AE and SAE ................................... 83 
9.3.5. 
Reporting of SAE to GSK ........................................................... 85 
9.4. 
Appendix 4: Contraceptive and Barrier Guidance (Part 1 only)................... 86 
9.4.1. 
Definitions: ................................................................................. 86 
9.4.2. 
Contraception Guidance: ............................................................ 86 
9.5. 
Appendix 5: Abbreviations and Trademarks .............................................. 88 
9.6. 
Appendix 6: Protocol Amendment History.................................................. 91 
9.7. 
Appendix 7: Country-Specific Protocol Addendums ................................... 94 
9.7.1. 
The Netherlands (27-MAY-2020) ................................................ 94 
9.7.2. 
South Africa (28-MAY-2020)....................................................... 94 
9.7.3. 
India (31-JUL-2020)_IND_01...................................................... 95 
9.7.4. 
Japan (22-JAN-2021)_JPN_04 ................................................... 96 
10. REFERENCES .................................................................................................. 103 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety 
of otilimab IV in patients with severe pulmonary COVID-19 related disease. 
Brief Title: 
Investigating otilimab in patients with severe pulmonary COVID-19 related disease. 
Rationale: 
The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the 
treatment of patients with severe pulmonary COVID-19 related disease.  
Objectives and Endpoints - Part 1: 
Objectives 
Endpoints 
Primary 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
 Participants alive and free of respiratory failure at Day 
28 
Secondary 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
 All-cause mortality at Day 60 
 Time to all-cause mortality up to Day 60 
 Participants alive and free of respiratory failure at Day 
7, 14, 42, and 60 
 Time to recovery from respiratory failure up to Day 28 
 Participants alive and independent of supplementary 
oxygen at Day 7, 14, 28, 42, and 60 
 Time to last dependence on supplementary oxygen up 
to Day 28 
 Admission to ICU up to Day 28 
 Time to final ICU discharge up to Day 28 
 Time to final hospital discharge up to Day 28 
 To compare the safety and tolerability 
of otilimab 90 mg IV versus placebo 
 Occurrence of adverse events (AEs) [up to Day 60] 
 Occurrence of serious adverse events (SAEs) [up to 
Day 60] 
Exploratory 
 To compare the efficacy of otilimab 
90 mg IV versus placebo 
Other endpoints up to Day 28 
 Invasive mechanical ventilation (if not previously 
initiated) 
 Time to invasive mechanical ventilation (if not 
previously initiated) 
 Alive and not invasively mechanically-ventilated 
 Time to definitive extubation 
 Improvement of at least 2 points relative to baseline of 
Sequential Organ Failure Assessment (SOFA) score 
 Improvement relative to baseline in SpO2, FiO2, and 
SpO2/FiO2 ratio 

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
1 3  
O bj e cti v e s  
E n d p oi nts  
 Oxy gen -fr ee days 
 Ventilator -fr e e days 
 Ti m e to r es olution of pyr exia (for at least 48h)  
Ot h er e n d p oi nt s u p t o Day 60  
 Clinic al status ass ess ed using an or dinal sc ale 1 
ass ess ed at Days 4, 7, 14, 28, 42, and 60  
 Ti m e to i m pr ov e m ent of at least 2 c ategories r elativ e to 
bas eline on an or dinal sc ale 1 
 Change in C O VI D -19 signs and sy m pto ms  
 T o deter mine the  phar m ac okinetics 
( P K) pr ofile of otili m ab 
P K E n d p oi nt s u p t o Day 14 
 Otili m ab clear anc e ( CL) and other P K par a m eters as 
appr opriate using s pars e P K s a m pling  
 T o deter mine:  
 Ex pos ur e -r es pons e. 
 P har m ac ody na mic ( P D) 
bio m ark ers  
 Changes in k ey m ark ers of 
infla m m atio n 
P D E n d p oi nt s u p t o Day 28 
 Ex pos ur e -r es pons e r elations hi p for k ey effic acy, s afety 
and P D endpoints  
 K ey m ark ers of infla m m ati on including, but not li mited 
to C R P, s er u m ferritin and infla m m atory cytokines as 
appr opriate 
 
1Or di n al S cale ( G S K mo difie d versi o n, a d a pt e d fr o m W H O , 2020 versi o n) 
 
 
O bje cti v e s a n d E n d p oi nts - P art 2  
O bj e cti v e s  
E n d p oi nts  
Pri m ar y  
 T o c o m par e the effic acy of otili m ab 90 
m g I V v ers us plac ebo  
 P articipants aliv e and fr ee of r es pir atory failur e at Day 
28 
Se c o n d ar y  
 T o c o m par e the effic acy of otili m ab 90 
m g I V v ers us plac ebo  
 All -c aus e m ortality at Day 28 
 All -c aus e m ortality at Day 60 
 Ti m e to all -c aus e m ortality up to Day 60 
 P articipants aliv e and fr ee of r es pir atory failur e at Day 
7, 14, 42, and 60 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e 
pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
1 4  
O bj e cti v e s  
E n d p oi nts  
 Ti m e to r ec ov ery fr o m r es pir atory failur e up to Day 28  
 P articipants aliv e and independe nt of s upple m entary 
oxy gen at Day 7, 14, 28, 42, and 60  
 Ti m e to last dependenc e  on s upple m entary oxy gen up 
to Day 28 
 Ti m e to final I C U disc har ge up to Day 28 
 Ti m e to first disc h arg e fro m i nvesti g ator site u p to 
D ay 6 0  
 Ti m e to first disc h arg e to n o n -h ospitalise d resi d e nc e 
u p to D ay 6 0  
 T o c o m par e the s afety and toler ability 
of otili m ab 90 m g I V v ers us plac ebo  
 Occ urr enc e of adv ers e ev ents ( A Es) [up to Day 60]  
 Occ urr enc e of s erious adv ers e ev ents ( S A Es) [up to 
Day 60]  
Expl or at or y  
 T o c o m par e the effic acy of otili m ab 
90 m g I V v ers us  plac ebo 
Ot h er e n d p oi nt s u p t o Day 28  
 Inv asiv e m ec hanic al v entilati o n (if not pr eviously 
initiate d) 
 Ti m e to inv asiv e m ec hanic al v entilati on (if not 
pr eviously initiate d)  
 Aliv e and not inv asiv ely m ec hanic ally -v entil ated 
 Ti m e to definitiv e extubatio n  
 Oxy gen -fr ee days 
 Ventilator -fr e e days 
 A d mission to I C U up to Day 28 
Ot h er e n d p oi nt s u p t o Day 60  
 Ti m e to i m pr ov e m ent of at least 2 c ategories r elativ e to 
bas eline on an or dinal sc ale 1 
 Change in C O VI D -19 signs and sy m pto ms  
 T o deter mine the phar m ac okinetics 
( P K) pr ofile of otili m ab 
P K E n d p oi nt s  u p t o Day 14  
 Otili m ab clear anc e ( CL) and other P K par a m eters as 
appr opriate using s pars e P K s a m pling  
 T o deter mine:  
 Ex pos ur e -r es pons e. 
 P har m ac ody na mic ( P D) 
bio m ark ers  
 Changes in k ey m ark ers of 
infla m m atio n 
P D E n d p oi nt s u p t o Day 28 
 Ex pos ur e -r es pons e r elations hi p for k ey effic acy, s afety 
and P D endpoints  
 K ey m ark ers of infla m m ati on including, but not li mited 
to C R P, s er u m ferritin and infla m m atory cytokines as 
appr opriate 
 
1Or di n al S cale ( G S K mo difie d versi o n, a d a pt e d fr o m W H O , 2020 versi o n) 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
1 5  
 
O v e r all D e si g n:  
T his st u d y is a m ulti -c e nter, ra n d o mize d, d o u ble -blin d, pla c e b o -c o ntr olle d trial t o ass ess 
t he effic a c y a n d s afet y of otili ma b f or t he tre at me nt of s e vere p ul m o nar y C OVI D -1 9 
relate d dis e as e.  T he st u d y p o p ulatio n c o nsists of h os pitalize d participa nts wit h ne w o ns et 
h y p o xia re q uirin g sig nific a nt o x y ge n s u p p ort  or re q uirin g in vasive me c ha nic al ve ntilatio n 
(4 8 h o urs  bef ore d osin g ).  All participa nts will re c eive sta n dar d of c are as per 
instit utio nal pr ot oc ols, in a d ditio n t o st u d y tre at me nt. 
B rief S u m m ar y:  
P articipa nts will be re cr uite d fr o m t w o m ut ually -e xcl usive  c ate g ories wit hin t he or dinal 
s c ale: 
 
P art 1  
T he first 2 0 participa nts (initial s afet y c o h ort) will be fr o m c ate g or y 5 a b o ve 
(
).  
Sinc e t his is t he first ti me t hat otili ma b has be e n teste d in participa nts wit h s e vere 
p ul m o nar y C O VI D -1 9 relate d dis e as e, initial d osin g will be sta g gere d, a n d s afet y data 
re vie w e d.  U nless a s af et y sig nal is ide ntifie d d urin g t he o n g oin g s afet y re vie w b y t he 
G S K s afet y re vie w te a m (S R T ) a n d perio dic re vie w b y t he I n de pe n de nt D ata M o nit orin g 
C o m mitte e ( I D M C), e nr ol me nt of t he main c o h ort of participa nts will be initiate d, a n d 
t he e nr ol me nt rate will be c a p pe d t o c o ntr ol ra n d o mizatio n . 
P art 2  
After e valuatio n of t he pri mar y e n d p oint in P art 1, t he ne xt a p pr o xi mately 3 5 0 
participa nts will be a ge 7 0 ye ars o r a b o ve. 
N u m be r of P artici p a nts:  
P art 1  
A ma xi m u m of a p pr o xi mately 8 0 0 participa nts will be ra n d o mly assig ne d t o st u d y 
inter ve ntio n.  A n y participa nt w h o re c eives st u d y inter ve ntio n will be c o nsidere d  
e valua ble.  
P art 2  
A ma xi m u m of a p pr o xi mately 
3 5 0 participa nts will be ra n d o mly assig ne d t o st u d y 
inter ve ntio n.  A n y participa nt w h o re c eives st u d y inter ve ntio n will be c o nsidere d 
e valua ble .  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e 
pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

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Intervention Groups and Duration: 
Participants will be randomized 1:1 by interactive response technology (IRT) in a blinded 
manner to receive either a blinded 1-hour infusion of otilimab 90 mg or placebo IV in 
addition to standard of care.  Participants will be assessed daily until Discharge (or 
Day 28, whichever is sooner), and followed up at Days 42 and 60 after randomization. 
Independent Data Monitoring Committee: Yes 
1.2. 
Schema 
 
 

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1.3. 
Schedule of Activities (SoA) – Part 1 
See Section 7 for further details of study procedures listed in the SoA. 
Assessments 
Screening2 
Day 1 Days 2-7 Day 144 Day 285 
Discharge / 
Early 
Withdrawal7  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)6, 7 
Notes 
Informed consent3 
X 
 
 
 
 
 
 
 
Eligibility assessment 
X 
 
 
 
 
 
 
 
Thoracic CT scan or chest X-ray 
X 
 
 
 
 
 
 
Chest X-ray or CT scan must be available 
at Screening to confirm a diagnosis of 
pneumonia and eligibility.  Record in the 
eCRF if a CT scan or chest X-ray is done 
between Screening and Discharge. 
Demography 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
At Screening, record the signs and 
symptoms of COVID-19 at admission, as 
detailed in the eCRF. 
Daily clinical features of COVID-19 (for 
non-mechanically ventilated participants) 
 
=============== Daily1 =============== 
X 
Daily review of COVID-19 signs and 
symptoms, as detailed in the eCRF. 
Full physical examination 
X 
 
 
 
 
X 
 
 
12-lead ECG 
X 
X 
 
 
 
X 
 
Day 1 - record before dosing. 
Weight 
X 
 
 
 
 
 
 
 
Vital Signs:  blood pressure, pulse, 
respiratory rate and temperature 
X 
=============== Daily1 =============== 
 
Day 1 – measure pre-infusion and 
approximately 1 hour post-infusion.  
Measure daily AM (at about same time 
daily), as per standard of care (SoC). 
SpO2 (for participants not on invasive 
mechanical ventilation) 
X 
=============== Daily1 =============== 
 
Day 1 - record before dosing.  Measure 
daily AM and PM (at about same times 
daily), as per SoC. 
Concentration of inspired oxygen (FiO2) 
and / or oxygen flow rate (L/min) 
X 
=============== Daily1 =============== 
 
Day 1 - record before dosing.  Measure 
daily AM and PM (at about same times 
daily), as per SoC. 
Ventilation status, ICU admission and 
discharge, and ICU supportive care 
X 
=============== Daily1 ===============
X 
Includes ventilation status (method of non-
invasive ventilation or mechanical 
ventilation).  Record participant admission 
or discharge from the ICU.  Record 
oxygen treatment if used at home. 

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Assessments 
Screening2 
Day 1 Days 2-7 Day 144 Day 285 
Discharge / 
Early 
Withdrawal7  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)6, 7 
Notes 
Ordinal scale 
X 
=============== Daily1 =============== 
X 
Day 1 - record category before 
randomization (for stratification).   
Record daily AM (at about same time 
daily). 
SOFA score (ICU participants ONLY) 
X 
=============== Daily1 =============== 
 
Day 1 - record before dosing.  Record 
daily AM (at about same time daily), as per 
SoC. 
SAE/AE review 
X 
=============== Daily1 =============== 
X 
At Screening, only SAEs related to study 
participation or GSK concomitant 
medication will be recorded. 
Concomitant medication review 
X8 
=============== Daily1 =============== 
X 
 
Survival follow-up 
 
 
 
 
 
X 
X 
 
Laboratory Assessments 
Local Laboratory tests9 
X 
X 
X11 
X 
X 
X 
 
Day 1 - collect before dosing. 
Only if not discharged.  Refer to Table 3 
for the list of laboratory assessments 
required.  Collected at any time during the 
day, as convenient. 
Pregnancy test 
X 
 
 
 
 
X 
(verbal confirmation  
on Day 60) 
Local urine or serum test at Screening and 
Discharge.  Verbal confirmation of 
pregnancy status will be obtained at 
follow-up phone call. 
PD sample (cytokines)9 
X10 
 
X11 
 
 
 
 
Only if not discharged.  Collected at any 
time during the day, as convenient.  
Sample collection time must be recorded. 
PK sample 
 
X12 
X13 
X 
 
 
 
Only if not discharged.  Samples after Day 
1 can be collected at any time during the 
day, as convenient.  Sample collection 
time must be recorded. 

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Assessments 
Screening2 
Day 1 Days 2-7 Day 144 Day 285 
Discharge / 
Early 
Withdrawal7  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)6, 7 
Notes 
Treatment Administration 
Randomization 
 
X 
 
 
 
 
 
 
IV dosing with otilimab or placebo 
 
X 
 
 
 
 
 
1-hour IV infusion.  Record start and end 
times of the infusion.  Randomization and 
Dosing should be as close as possible. 
1. 
Assessment to be conducted every day from Day 1 until Discharge (or until Day 28 if the participant remains hospitalized). 
2. 
Up to 48 h before randomization.  If Screening and Randomization are within 24h, there is no need to repeat Day 1 pre-dose assessments (except Ordinal Scale and pre-infusion 
vital signs). 
3. 
Consent may be collected before the 48h screening window if the investigator considers that the participant is likely to become eligible, and wants to ensure that consent is given 
by the participant (rather than an LAR). 
4. 
If the participant is discharged before Day 13, the Day 14 and Day 28 visits will be replaced with a phone call (±2 days).  If the participant is discharged on Day 13, the Day 14 visit 
is not required, and the Day 28 visit will be a phone call (±2 days).  When visits are replaced with a phone call, complete the same assessments as the Day 42 or 60 phone call. 
5. 
If the participant is discharged between Day 15 and Day 27, the Day 28 visit will be replaced with a phone call (±2 days).  When visits are replaced with a phone call, complete the 
same assessments as the Day 42 or Day 60 phone call. 
6. 
Follow-up phone calls at Day 42 (±2 days) and Day 60 (±2 days).  If the participant has not been discharged, these will be visits. 
7. 
See Section 6.7 for information on Early Withdrawal. 
8. 
At Screening, prior medications will be recorded from the 14 days before Screening. 
9. 
If a cytokine release syndrome (CRS) is suspected (see Section 7.4.7.1), the following samples should be taken as soon as possible after suspected CRS onset and again 24 h 
later: Hematology, CRP, D-dimer, ferritin, PD sample (cytokines). 
10. Sample can be collected anytime from Screening up to start of infusion. 
11. Days 2, 4 and 7 only. 
12. Immediately after infusion. 
13. Days 2 and 7 only. 
 

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1.4. 
Schedule of Activities (SoA) – Part 2 
See Section 7 for further details of study procedures listed in the SoA. 
Assessments 
Screening3 
Day 1 Days 2-7 Day 145 Day 286 
Discharge / 
Early 
Withdrawal8  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)7, 8 
Notes 
Informed consent4 
X 
 
 
 
 
 
 
 
Eligibility assessment 
X 
 
 
 
 
 
 
 
Thoracic CT scan or chest X-ray 
X 
 
 
 
 
 
 
Chest X-ray or CT scan must be available 
at Screening to confirm a diagnosis of 
pneumonia and eligibility. Record in the 
eCRF if a CT scan or chest X-ray is done 
between Screening and Discharge. 
Demography 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
At Screening, record the signs and 
symptoms of COVID-19 at admission, as 
detailed in the eCRF. 
SOFA score (intubated patients only) 
X 
 
 
 
 
 
 
 
Clinical features of COVID-19 (for non-
mechanically ventilated participants) 
 
X 
X1 
X 
X 
X 
X 
Review of COVID-19 signs and 
symptoms, as detailed in the eCRF. 
Full physical examination 
X 
 
 
 
 
X 
 
 
12-lead ECG 
X 
 
 
 
 
X 
 
Screening ECG can be taken any time 
before dosing to confirm eligibility. 
Weight and height 
X 
 
 
 
 
 
 
Weight and height can be estimated, refer 
to Section 7.3.2. 
Vital Signs: blood pressure, pulse, 
respiratory rate and temperature 
X 
X 
X1 
X 
X 
X 
 
Day 1 – measure pre-infusion and 
approximately 1 hour post-infusion. 
Measure AM (at about same time), as per 
standard of care (SoC). 
SpO2 (for participants not on invasive 
mechanical ventilation) 
X 
=============== Daily2 =============== 
 
Day 1 - record before dosing. Measure 
daily AM (at about same time), as per 
SoC. 
Concentration of inspired oxygen (FiO2) 
and / or oxygen flow rate (L/min) 
X 
=============== Daily2 =============== 
 
Day 1 - record before dosing. Measure 
daily AM (at about same time), as per 
SoC. 
Ventilation status, ICU admission and 
discharge, and ICU supportive care 
X 
=============== Daily2 ===============
X 
Includes ventilation status (method of non-
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Assessments 
Screening3 
Day 1 Days 2-7 Day 145 Day 286 
Discharge / 
Early 
Withdrawal8  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)7, 8 
Notes 
ventilation). Record participant admission 
or discharge from the ICU. Record oxygen 
treatment if used at home. 
Ordinal scale 
X 
=============== Daily2 =============== 
X 
Day 1 - record category before 
randomization (for stratification). 
Record daily AM (at about same time). 
SAE/AE review 
X 
=============== Daily2 =============== 
X 
At Screening, only SAEs related to study 
participation or GSK concomitant 
medication will be recorded. 
Concomitant medication review 
X9 
=============== Daily2 =============== 
X 
 
Survival follow-up 
 
 
 
 
 
X 
X 
 
Participant baseline and discharge 
location information 
X 
 
 
 
 
X 
X 
Refer to Section 7.2.7. At baseline, record 
the participant’s residence status before 
contracting COVID-19 and before initial 
hospital admission. 
Laboratory Assessments 
Local Laboratory tests10 
X 
X 
X1 
X 
X 
X 
 
Day 1 - collect before dosing. No need 
to collect after discharge.  Refer to Table 4 
for the list of laboratory assessments 
required. Collected at any time during the 
day, as convenient. 
PD sample (cytokines)10, 15 
X11 
 
X12 
 
 
 
 
No need to collect after discharge. 
Collected at any time during the day, as 
convenient.  Sample collection time must 
be recorded. If participants are discharged 
on a day when a PD sample is scheduled, 
the sample should be collected prior to 
discharge. 
PK sample15 
 
X13 
X14 
X 
 
 
 
No need to collect after discharge. After 
Day 1, samples can be collected at any 
time during the day, as convenient.  
Sample collection time must be recorded. 
If participants are discharged on a day 
when a PK sample is scheduled, the 

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Assessments 
Screening3 
Day 1 Days 2-7 Day 145 Day 286 
Discharge / 
Early 
Withdrawal8  
Follow-up 
Phone call (D42 & 60 / 
Early Withdrawal)7, 8 
Notes 
sample should be collected prior to 
discharge. 
Treatment Administration 
Randomization 
 
X 
 
 
 
 
 
 
IV dosing with otilimab or placebo 
 
X 
 
 
 
 
 
Approximately 1-hour IV infusion. Record 
start and end times of the infusion. 
Randomization and Dosing should be as 
close as possible on the same day. 
1. Assessment to be conducted on Days 4 and 7 (if not discharged). 
2. Assessment to be conducted every day from Day 1 until Discharge (or until Day 28 if the participant remains hospitalized). 
3. Up to 48 h before randomization.  If Screening and Randomization are within 24h, there is no need to repeat Day 1 pre-dose assessments (except Ordinal Scale and pre-infusion 
vital signs). 
4. Consent may be collected before the 48h screening window if the investigator considers that the participant is likely to become eligible, and wants to ensure that consent is given 
by the participant (rather than an LAR). 
5. If the participant is discharged before Day 13, the Day 14 and Day 28 visits will be replaced with a phone call (±2 days).  If the participant is discharged on Day 13, the Day 14 visit 
is not required, and the Day 28 visit will be a phone call (±2 days).  When visits are replaced with a phone call, complete the same assessments as the Day 42 or 60 phone call. 
6. If the participant is discharged between Day 15 and Day 27, the Day 28 visit will be replaced with a phone call (±2 days).  When visits are replaced with a phone call, complete the 
same assessments as the Day 42 or Day 60 phone call. 
7. Follow-up phone calls at Day 42 (±2 days) and Day 60 (±2 days).  If the participant has not been discharged, these will be visits. 
8. See Section 6.7 for information on Early Withdrawal. 
9. At Screening, record COVID-19 current vaccination status, and any other prior medications within 14 days before Screening. 
10. If a cytokine release syndrome (CRS) related to drug is suspected (see Section 7.4.7.1), the following samples should be taken as soon as possible after suspected CRS onset 
and again 24 h later: Hematology, CRP, D-dimer, ferritin, PD sample (cytokines). 
11. Sample can be collected anytime from Screening up to start of infusion. 
12. Days 2, 4 and 7 only. 
13. Immediately after infusion. 
14. Days 2 and 7 only. 
15. If central laboratory kits for PK/PD sampling are not available at a site (for operational reasons), participants can be randomised and dosed, and the PK or PD samples not 
collected (refer to Section 7.5 and Section 7.7. 
  

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2. 
INTRODUCTION 
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hemopoietic growth 
factor and a key mediator of tissue inflammation, that signals through the GM-CSFα/β 
receptor complex.  GM-CSF has multiple cellular sources, including monocytes, 
macrophages, T cells, B cells, neutrophils and tissue resident cells [Wicks, 2016].  GM-
CSF exerts multiple pro-inflammatory effects on myeloid cells including macrophages, 
monocytes and neutrophils.  Pre-clinical models and human clinical trials have 
demonstrated that neutralizing GM-CSF or blocking the GM-CSFRα subunit can be 
efficacious in inflammatory diseases such as rheumatoid arthritis.  Otilimab is a fully 
human anti-GM-CSF monoclonal antibody (mAb) that has been well tolerated by 
subjects and demonstrates anti-inflammatory activity in RA patients (phase 3 clinical 
trials ongoing). 
Emerging data from COVID-19 patients indicate that GM-CSF may play an important 
role in the acute hyper-inflammatory state associated with severe stages of illness.  
Treatment with an anti-GM-CSF receptor (anti-GM-CSFR) mAb (mavrilimumab) was 
well tolerated, reduced fever and improved oxygenation in 6 patients experiencing a steep 
decline of pulmonary status due to COVID-19 pneumonia.  All patients were reported to 
respond to treatment, and 3 out of the 6 patients were discharged within 5 days [Kiniksa, 
2020], further supporting the scientific rationale to evaluate the efficacy of otilimab in 
these patients. 
Update for Part 2 
New literature data has associated raised levels of GM-CSF in the circulation of COVID-
19 patients with age, disease severity and mortality [Hue, 2020; Thwaites, 2020].  
Furthermore, dysregulation of the circulating myeloid cell compartment involving 
inflammatory / dysfunctional / maladapted monocytes and neutrophils is being 
increasingly recognised as a key driver of severe COVID-19 disease.  GM-CSF targets 
monocytes, macrophages and neutrophils and GM-CSF as a key driver of severe COVID-
19 disease has been widely proposed [Bonaventura, 2020; Lang, 2020; Mehta, 2020a].  
The scientific rationale supporting targeting GM-CSF in severe COVID-19 disease is 
also supported by use of an anti-GM-CSF receptor (anti-GM-CSFR) mAb 
(mavrilimumab) in the clinic.  Mavrilimumab was shown to be well tolerated and clinical 
outcomes compared with standard care in 17 non-mechanically ventilated patients with 
severe COVID-19 pneumonia and systemic hyperinflammation (17 patients, single-centre 
prospective cohort study [De Luca, 2020]. 
2.1. 
Study Rationale 
A subset of patients with SARS-CoV-2 infection develop pulmonary complications and 
may transition to a form of acute respiratory distress syndrome (ARDS) and the most 
severe stage of illness, which manifests as an extra-pulmonary, systemic hyper-
inflammation syndrome [Siddiqi, 2020].  Markers of systemic inflammation appear to be 
elevated at this disease stage and have shown that inflammatory cytokines such as IL-2, 
IL-7, G-CSF, MCP-1, MIP-1α and TNFα were significantly elevated, particularly in 
COVID-19 patients requiring ICU treatment compared with those not requiring ICU 

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treatment [Huang, 2020].  Elevated levels of IL-6 have also been detected in COVID-19 
patients and have been correlated with adverse patient outcomes [Coomes, 2020]. 
In healthy subjects, GM-CSF is not detectable in the circulation, however, GM-CSF was 
detectable in plasma of some COVID-19 patients whether they received ICU care or not 
[Huang, 2020].  In a separate study, numbers of GM-CSF-expressing monocytes, T -
cells, B cells and NK cells were found in the blood of COVID-19 ICU and non-ICU 
patients compared with healthy controls.  The COVID-19 ICU patient group also had 
increased numbers of CD4+ T cells co-expressing GM-CSF and IFNγ, as well as 
increased numbers of GM-CSF+ CD8+ T cells compared with non-ICU patients [Zhou, 
2020]. 
GM-CSF is well known to drive monocytes/macrophages into proinflammatory 
phenotypes that are primed to produce inflammatory cytokines including TNFα, IL-1β 
and IL-6 [Hamilton, 2019; Wicks, 2016].  The observation that GM-CSF neutralization 
prevented IL-6, IL-8 and MCP-1 cytokine release by monocytes in a co-culture CAR T-
cell assay [Sachdeva, 2019], and cytokine release in a humanized CAR T-cell xenograft 
mouse model [Sterner, 2019], suggests a role for GM-CSF as a driver of hyper-
inflammation and cytokine release syndrome (CRS). 
Therefore, by blocking GM-CSF signaling, an anti-GM-CSF mAb such as otilimab is 
hypothesized to work “upstream” of IL-6 in the hyper-inflammatory processes triggered 
by SARS-CoV-2 infection and will directly inhibit proinflammatory activities of 
monocytes/macrophages (e.g. by reducing TNFα, IL-1β and IL-6 production) that 
perpetuate inflammation and cause tissue damage. 
Otilimab, an anti-GM-CSF mAb, is currently in phase 3 development (ContRAst 
program) for rheumatoid arthritis (RA) following phase 2 results, which showed a 
positive efficacy and safety profile based on a large clinically-driven response for joint 
improvement and pain. 
In addition, lenzilumab (KB003), another anti-GM-CSF mAb dosed IV over 20 weeks 
was generally well tolerated in a placebo-controlled study in inadequately controlled 
asthma patients, with no safety signals of concern and no increase in infection rate 
[Molfino, 2016].  Moreover, there were no dose limiting toxicities identified and no 
treatment emergent, study drug-related, grade 3 or 4 toxicities reported in a phase 1 study 
of lenzilumab dosed in 15 patients with chronic myelomonocytic leukemia [Patnaik, 
2020]. 
Otilimab has not previously been tested in patients with severe pulmonary COVID-19 
related disease.  This study aims to show that otilimab improves the respiratory status of 
patients with severe pulmonary COVID-19 related disease compared with standard of 
care.  In order to understand risk and benefit in a stepwise fashion, the study has a leading 
cohort with detailed safety assessments to provide early evidence of safety prior to the 
larger cohort of patients to provide further confirmatory efficacy and safety data that may 
facilitate early access to patients. 

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Update for Part 2 
Recent literature data have shown GM-CSF to be particularly elevated in hospitalised 
COVID-19 patients 70 years not requiring oxygen, and in all patient ages with severe 
disease [Thwaites, 2020] and was associated with mortality [Hue, 2020; Thwaites, 2020].  
Age is widely recognised as the most significant risk factor for severe COVID-19 disease 
and immune cell changes in severe COVID-19 disease bear resemblance to those 
observed in the aging immune system [Hazeldine, 2020; Pietrobon, 2020; Salimi, 2020].  
The ageing immune system is characterized by an expansion of inflammatory / 
dysfunctional monocytes, reduced lymphocyte function, reduced naïve T cell numbers 
and dysregulated myeloid cell responses [Aiello, 2019; Hazeldine, 2020; Pietrobon, 
2020; Salimi, 2020].  These changes result in a reduced ability of older individuals to 
respond to novel antigens and increased levels of circulating inflammatory mediators.  
This may predispose older patients to the development of severe COVID-19 disease with 
resultant increased viral load, increasing immune cell accumulation and further 
dysregulating monocytes, macrophage and neutrophil activities (in the circulation and the 
lung) [Pence, 2020; Pietrobon, 2020].  Post-mortem findings in fatal COVID-19 disease 
have shown the inflammatory infiltrate in lungs and other organs consists of high levels 
of macrophages and neutrophils [Carsana 2020; Nienhold, 2020; Schurink, 2020]. 
Therefore, targeting GM-CSF may prove more beneficial in severe COVID-19 patients 
aged 70 years. 
Otilimab has been tested in patients with severe pulmonary COVID-19 related disease in 
Part 1 of this study, with evidence of efficacy in the pre-defined stratification group of 
participants 70 to <80 years old, with no safety concerns.  The second part of this study 
aims to confirm that otilimab improves the recovery of patients 70 years old with severe 
pulmonary COVID-19 related disease. 
2.2. 
Background 
2.2.1. 
Role of GM-CSF in inflammation 
Originally identified as a hematopoietic growth factor, GM-CSF is now recognized as a 
key driver of tissue inflammation that exerts multiple pro-inflammatory effects on 
myeloid cells.  The cellular sources of GM-CSF include T cells, B cells, monocytes, 
macrophages, neutrophils and tissue resident cells [Wicks, 2016] and GM-CSF signals 
via the GM-CSFα/β receptor complex which is expressed on myeloid cells.  GM-CSF 
promotes survival and polarizes monocytes/macrophages into pro-inflammatory 
phenotypes that are primed to produce pro-inflammatory cytokines including TNFα, 
IL-1β and IL-6 [Hamilton, 2019].  GM-CSF also extends neutrophil survival, primes the 
neutrophil oxidative burst, enhances phagocytosis and promotes neutrophil adhesion to 
endothelial cells and promotes neutrophil trafficking to sites of inflammation [Wicks, 
2016]. 
Therapeutic inhibition of GM-CSF signaling by mavrilimumab in RA subjects has been 
shown to reduce circulating serum IL-6 levels and indirectly suppress T-cell activation 
[Guo, 2018].  Efficacy and safety data from clinical trials in rheumatoid arthritis (RA) 

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patients indicate that inhibition of GM-CSF or its receptor is anti-inflammatory and well 
tolerated with long-term dosing [Burmester, 2018; Taylor, 2019]. 
2.2.2. 
Scientific rationale to inhibit GM-CSF in COVID-19 patients 
Some patients with severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) 
infection develop pulmonary complications and may transition to acute respiratory 
distress syndrome (ARDS) and the most severe stage of illness, which manifests as an 
extra-pulmonary, systemic hyper-inflammation syndrome.  It is widely proposed that 
intervention with immunomodulatory therapies to reduce this hyper-inflammatory state 
could be beneficial, particularly in the later and more severe stages of COVID-19 disease 
[Mehta, 2020b; Siddiqi, 2020]. 
COVID-19 pneumonia patients have serological markers associated with macrophage 
activation syndrome and the limited COVID-19 post-mortem data available shows 
prominent alveolar edema, hyalinosis (intra-alveolar proteinosis) and fibrin deposition 
with pneumocytes viral cytopathic change and immune cell infiltration [McGonagle, 
2020].  Pulmonary post-mortem findings from 38 COVID-19 cases from Italy have 
shown that inflammatory infiltrate was composed by macrophages in alveolar lumens and 
lymphocytes mainly in the interstice [Carsana, 2020].  Therefore, in later stages of severe 
disease suppressing hyper-inflammatory processes (“cytokine storm syndrome” [Mehta, 
2020b]) with an immunomodulator would be important to limit further lung damage, 
prevent respiratory failure, shock, and multi-organ failure. 
In health, GM-CSF is not detectable in the circulation, however, GM-CSF was detectable 
in plasma of some COVID-19 patients whether they received ICU care or not [Huang, 
2020].  In a separate study, increased numbers of GM-CSF-expressing monocytes, T-
cells, B cells and NK cells were found in the blood of COVID-19 ICU and non-ICU 
patients compared with healthy controls.  The COVID-19 ICU patient group also had 
increased numbers of CD4+ T cells co-expressing GM-CSF and IFNγ, as well as 
increased numbers of GM-CSF+ CD8+ T cells compared with non-ICU patients [Zhou, 
2020]. 
COVID-19 patients have increased numbers of circulating GM-CSF+ monocytes 
compared to healthy controls.  ICU treated patients also have increased numbers of IL-6+ 
monocytes and CD14+CD16+ monocytes compared with non-ICU patients [Zhou, 2020]. 
A small study has also shown that pro-inflammatory monocyte-derived macrophages 
dominate over resident alveolar macrophages in the lungs of patients with severe 
COVID-19, whereas resident alveolar macrophages predominated in the lungs of 
mild/recovering COVID-19 patients [Liao, 2020].  The existence of these monocyte-
derived macrophages suggests that activated monocytes infiltrate the injured lung from 
the blood, release inflammatory cytokines and may differentiate into activated 
macrophages.  It has been proposed that in severe or critical COVID-19 cases, since the 
lung barrier integrity is interrupted, monocytes and neutrophils are chemotactic to the 
infection site to clear exudates with virus particles and infected cells, resulting in 
uncontrolled inflammation.  In this process, because of the substantial reduction and 
dysfunction of lymphocytes, the adaptive immune response cannot be effectively 
initiated, and the uncontrolled virus infection leads to more macrophage infiltration and a 

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further worsening of lung injury [Li, 2020].  GM-CSF is well known to drive 
monocytes/macrophages into proinflammatory phenotypes that are primed to produce 
inflammatory cytokines including IL-6, TNF and IL-1β [Hamilton, 2019; Wicks, 2016]. 
The observation that GM-CSF neutralization prevented IL-6, IL-8 and MCP-1 cytokine 
release by monocytes in a co-culture CAR T-cell assay [Sachdeva, 2019], and that GM-
CSF neutralization prevented human VEGF, IP10 and IL-1R cytokine release and 
murine IP10 and MCP-1 chemokine release in a humanized CAR T-cell xenograft mouse 
model [Sterner, 2019], suggests a role for GM-CSF as a driver of hyper-inflammation 
and cytokine release syndrome (CRS). 
As well as GM-CSF, other markers of systemic inflammation are elevated in hospitalized 
COVID-19 patients [Huang, 2020].  Plasma levels of IL-1β, IL-1Rα, IL-6, IL-8, IL-9, IL-
10, IFNγ, IP-10, MIP-1β, PDGF, and VEGF concentrations were higher in both ICU 
patients and non-ICU COVID-19 patients than in healthy controls.  Plasma levels of IL-2, 
IL-7, G-CSF, MCP-1, MIP-1α and TNFα were significantly elevated in COVID-19 
patients requiring ICU treatment compared with those not requiring ICU treatment 
[Huang, 2020].  Elevated levels of IL-6 are reported in COVID-19 patients and have been 
correlated with adverse patient outcomes [Coomes, 2020]. 
These observations support the hypothesis that hyper-inflammation leads to poor 
outcome in hospitalized patients, transition to ICU/ventilator and death due to cytokine 
storm and organ damage.  In these patients there is a strong rationale that inhibiting 
hyper-inflammatory processes with targeted immunomodulatory approaches would be 
beneficial [Mehta, 2020b; McGonagle, 2020]. 
Update for Part 2 
More recent studies have reported that levels of some inflammatory mediators, including 
IL-6, are elevated in COVID-19 [Kox, 2020; Sinha, 2020], but are typically ten times 
lower than those reported in acute respiratory distress syndrome (ARDS) and sepsis 
[Damas, 1992] suggesting that other factors may play a major role in COVID-19 severity. 
The latest data from the CDC show the increases in risk of death for COVID-19 patients 
were 10x, 30x, 90x, 220x, and 630x higher for patients in the 40-49, 50-64, 65-74, 75-84, 
and 85+ year age groups, respectively, than those in the 18-29 age group [CDC, 2020].  
In addition, it is clear that mortality increases significantly with age for COVID-19 
patients in US intensive care units (ICUs) with 17.1%, 25.5%, 36.3%, 45.1%, and 48.9% 
in the 40-49, 50-59, 60-69, 70-79, and 80+ year old groups dying (GSK analysis, data on 
file).  Similar trends have been reported in the UK, with 17%, 24%, 42%, 55%, and 65% 
of COVID-19 patients in the 40-49, 50-59, 60-69, 70-79, and 80+ year old groups dying 
within 28 days; and patients aged 70 accounted for 27% of all patients recently admitted 
to ICUs [ICNARC, 2021]. 
Emerging analyses of circulating immune cells have revealed that severe COVID-19 is 
marked by a dysregulated myeloid cell compartment involving emergency myelopoiesis 
with both dysfunctional/maladapted and immature monocytes and neutrophils [Mann, 
2020; Schulte-Schrepping, 2020].  Changes in COVID-19 monocyte function and 
phenotype have been proposed to resemble those that occur with age and have been 

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hypothesised to be a potential mechanism predisposing older patients to increased 
morbidity and mortality due to SARS-CoV-2 infection [Pence, 2020; Pietrobon, 2020].  
In addition, single-cell studies of bronchoalveolar lavage samples suggest dysregulated 
pulmonary immune responses, resulting in pro-inflammatory monocyte-derived 
macrophages dominating over resident alveolar macrophages in the lungs of severe 
COVID-19 patients [Liao, 2020].  Moreover, post-mortem findings in fatal COVID-19 
disease have shown the inflammatory infiltrate in lungs and other organs consists of high 
levels of neutrophils and macrophages as well as neutrophilic plugs [Carsana 2020; 
Nienhold, 2020; Schurink, 2020]. 
SARS-CoV-2 infection has been shown to cause increased expression of pulmonary 
epithelial GM-CSF [Blanco-Melo, 2020; Chandrashekar, 2020], and persistent activation 
of GM-CSF has been proposed to contribute to injurious lung inflammation preclinically 
[Halstead, 2015].  Intranasal administration of an anti-GM-CSFRα or anti-GM-CSF 
monoclonal antibody inhibited cell influx and inflammation in the lungs of mice 
challenged with LPS [Alessandris, 2019; Bozinovski, 2002].  Neutralization of GM-CSF 
was shown to dose-dependently suppress neutrophilic inflammation, inhibit TNF mRNA 
expression, reduce macrophage replication and suppress matrix metalloprotease 9 (MMP-
9) levels and activity [Bozinovski, 2002; Bozinovski, 2004].  MMP-9 is a protease that 
degrades extracellular matrix proteins and an early increase in circulating MMP-9 has 
been observed in COVID-19 patients with respiratory failure [Ueland, 2020]. 
Therefore, by blocking GM-CSF signalling, an anti-GM-CSF mAb is hypothesized to 
have beneficial effects on the hyperinflammatory state associated with severe COVID-19 
disease and poor patient outcomes in patients aged 70 for a number of reasons.  Firstly, 
elevated circulating GM-CSF levels have been associated with disease severity and 
mortality in COVID-19 patients [Hue, 2020; Thwaites, 2020] and raised GM-CSF levels 
are already evident in hospitalised 70 year old COVID-19 patients not requiring oxygen 
[Thwaites, 2020].  Secondly, changes in COVID-19 monocyte function and phenotype 
have been proposed to resemble those that occur with age and have been hypothesised to 
be a potential mechanism predisposing older patients to severe COVID-19 disease 
[Pence, 2020].  Thirdly, as the main target for GM-CSF is myeloid cells and 
dysfunctional/inflammatory/maladapted monocytes and macrophages are associated with 
severe COVID-19 disease, blocking GM-CSF may have broad immunomodulatory 
effects.  For example, it could affect monocyte/macrophage production of multiple pro-
inflammatory cytokines, chemokines and other mediators that lead to hyperinflammation, 
tissue damage, end organ failure and drive severe COVID-19 pathogenesis [Bonaventura, 
2020; Lang, 2020; Mehta, 2020a]. 
2.2.3. 
Timing of GM-CSF inhibition in COVID patients 
GM-CSF is not produced in most healthy tissues, but local alveolar production of GM-
CSF is necessary for mature alveolar macrophage differentiation and lung homeostasis 
function over the long term.  Complete genetic or auto-antibody ablation of GM-CSF (or 
its receptor) eventually results in pulmonary alveolar proteinosis (PAP), however this is 
likely not to be a concern in severe pulmonary COVID-19 related disease since PAP 
takes many months/years to develop [Sakagami, 2010; Trapnell, 2019], and has not been 

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observed following long-term inhibition of GM-CSF signaling with an anti-GM-CSF 
mAb (mavrilimumab) treatment in RA patients [Burmester, 2018]. 
Increased levels of GM-CSF in bronchoalveolar lavage (BAL) fluids on Day 1 and 3 of 
diagnosis with ARDS was associated with improved survival [Matute-Bello, 2000], and a 
second study of 29 critically-ill patients within 24 hours of diagnosis with ventilator-
associated pneumonia (VAP) demonstrated that higher GM-CSF/TGFβ1 BAL ratios 
correlated with increased patient survival [Overgaard, 2015].  However, administration of 
recombinant GM-CSF by intravenous (IV) infusion daily for 14 days evaluated in a 
randomized phase II trial in 130 patients with acute lung injury (ALI)/ARDS had no 
effect on ventilator-free days, mortality or organ failure [Paine, 2012]. 
Intranasal administration of an anti-GM-CSFR or anti-GM-CSF monoclonal antibody 
inhibited cell influx and inflammation in the lungs of mice challenged with LPS 
[Alessandris, 2019; Bozinovski, 2002].  Neutralization of GM-CSF was shown to dose-
dependently suppress neutrophilic inflammation, inhibit TNF mRNA expression, 
suppress matrix metalloprotease 9 (MMP9) levels and activity, and reduce macrophage 
replication [Bozinovski, 2002; Bozinovski, 2004]. 
Conversely, preclinical studies assessing influenza A infection in mice deficient in GM-
CSF or its receptor have demonstrated a more severe viral infection in the absence of 
pulmonary GM-CSF signaling; whereas intranasal administration of GM-CSF to 
wildtype mice or GM-CSF overexpression in the airways of GM-CSF knockout mice 
reduced mortality following influenza A infection [Halstead, 2015; Halstead, 2018; 
Huang, 2011].  However, it has been speculated that at high influenza viral titer, 
persistent activation of GM-CSF as induced by highly pathogenic influenza strains, GM-
CSF may contribute to injurious inflammation [Halstead, 2015]. 
Thus, local lung expression of GM-CSF in the early stages of COVID-19 related 
pulmonary disease in patients may help control viral titer and to maintain the epithelial 
lung barrier.  As the disease progresses to hypoxia, controlling the viral load is thought to 
be less important, whereas suppressing the systemic hyper-inflammatory process 
(“cytokine storm syndrome” [Mehta, 2020b]) is much more important to limit further 
lung damage, prevent respiratory failure, shock, and multi-organ failure.  Therefore, once 
hypoxia occurs in COVID-19 patients, it is reasonable to propose that reducing systemic 
hyper-inflammatory processes with targeted immunomodulatory approaches may be most 
beneficial [Mehta, 2020b]. 
To support this, there have been several reports of anti-IL-6 mAbs having some benefit in 
small studies of patients with severe pulmonary COVID-19 related disease where 
beneficial clinical response has been inferred by outcomes such as reduction in fever, 
oxygen requirements, C-reactive protein (CRP), radiological pulmonary abnormalities 
[Roche, 2020; Xu, 2020], or need for ventilation [Hermine, 2020].  Moreover, review of 
interim data from an ongoing large phase 3 study of sarilumab led to a recommendation 
by the IDMC to continue only in the more advanced “critical” group whose outcomes had 
improved and discontinuing the less advanced “severe” group, without any new safety 
findings [Sanofi, 2020].   

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By blocking GM-CSF signaling, an anti-GM-CSF mAb such as otilimab is hypothesized 
to work “upstream” of IL-6 in the hyper-inflammatory processes triggered by SARS-
CoV-2 infection and will directly inhibit proinflammatory activities of 
monocytes/macrophages (e.g. by reducing IL-6, TNF and IL-1 production) that 
perpetuate inflammation and cause tissue damage.  In addition, as described previously, 
early experience in treating COVID-19 patients with severe pulmonary disease with an 
anti-GM-CSF receptor mAb (mavrilimumab) has been well tolerated and demonstrated 
clinical benefit through fever reduction and improved oxygenation. 
Update for Part 2 
As discussed above, recent publications suggest that the severity of COVID-19 disease is 
driven by a maladaptive innate immune response in which GM-CSF plays a key role and 
where an aging immune system may predispose older patients to the worst outcomes.  
Therefore, targeting GM-CSF may prove more beneficial in severe COVID-19 patients 
aged 70 years.  This hypothesis is supported by the preliminary clinical efficacy 
findings with otilimab in Part 1.  The second part of this study aims to confirm that 
otilimab facilitates the recovery of patients 70 years old with severe pulmonary COVID-
19 related disease.   
As of the date of approval of this protocol amendment, no targeted immunomodulatory 
therapy has been demonstrated to improve oxygen requirements, recovery from 
respiratory failure, or reduce mortality in a patient population with severe COVID-19-
related pulmonary disease. 
 

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2.3. 
Benefit/Risk Assessment 
The potential risk assessment and mitigation strategy for the administration of otilimab in this protocol is outlined below. 
2.3.1. 
Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably expected adverse events of otilimab may be 
found in the Investigator’s Brochure (IB).  The assessment of potential risks and mitigation strategy for the administration of otilimab in 
this protocol is outlined below. 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention(s) Otilimab 
Cytokine release syndrome (CRS) 
CRS is a systemic inflammatory response caused by 
the release of inflammatory cytokines, such as IL-6, 
tumor necrosis factor alpha (TNFα), by lymphocytes 
(B cells, T cells, and/or natural killer cells) and/or 
myeloid cells (macrophages, dendritic cells, and 
monocytes).  This can lead to a constellation of 
clinical symptoms including fever, flu-like symptoms, 
hypotension, to severe inflammatory syndrome 
leading to widespread organ dysfunction, even 
death.  It is not expected that the inhibition of GM-
CSF signaling, by administration of otilimab, would 
carry the risk of directly inducing CRS. 
Pre-Clinical Data 
GM-CSF neutralization in CAR T-cell assays or in 
vivo models  inhibited cytokine release [Sachdeva, 
2019; Sterner, 2019].  In vitro otilimab showed 
variable results, with evidence of cytokine elevation 
at elevated levels of otilimab (50 and 100 µg/mL). 
Primate toxicology studies demonstrated no 
evidence of CRS with concentrations at Cmax of 
2,690 µg/mL (54x higher than anticipated human 
levels) and substantial safety margin for AUCs. 
Mitigation: 
Part 1:  
 To mitigate the uncertainty around safety and 
tolerability of otilimab IV, dosing will occur in an 
initial safety cohort of 20 non-mechanically 
ventilated participants, and these participants will 
be closely monitored and dosed in a staggered 
manner (see Section 4.1). 
 Unless a safety signal is identified during the 
ongoing safety review by the GSK SRT and 
periodic review by the IDMC, enrolment of the 
main cohort of participants will be initiated. 
Part 1 and Part 2 
 Careful dose selection. 
 Exclusion of participants who do not require 
oxygen therapy, and estimated GFR 
30 mL/min/1.73m2 (Section 5.3 and Section 
5.4, Exclusion Criteria). 
Monitoring: 
Part 1 
 All participants will be hospitalized during 
infusion and will be closely monitored for signs 
and symptoms of CRS (defined as a worsening 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Clinical Data: 
There has been no evidence of cytokine release or 
symptoms suggestive of CRS in any human study 
with otilimab or in Part 1 of the study.  PK data from 
IV administration of absolute doses of otilimab 90 
mg or higher is available from a total of 46 HVs and 
patients, with a maximum concentration of 56 µg/mL 
in one HV. 
of the CTCAE CRS Grade, Section 7.4.7.1.  
Cytokine Release Syndrome) within 6 hours of 
infusion. 
 CRS (considered not related to COVID-19) is 
categorized as an AESI. 
 Evidence of CRS that occurs within 6 hours of 
infusion and demonstrated as worsening of CRS. 
 In the event of CRS (considered not related to 
COVID-19), investigators should follow 
institutional guidelines for symptom 
management. 
 In the event that new onset of CRS (considered 
not related to COVID-19) is suspected, the 
medical monitor must be notified immediately 
and under no circumstance can this exceed 
24 hours, and the event must also be reported 
within 24 hours as an AE or an SAE. 
Part 2 
 All participants will be hospitalized during 
infusion and will be closely monitored for signs 
and symptoms of CRS (Section 7.4.7.1) within 
6 hours of the start of infusion. 
 CRS (considered not related to COVID-19) of 
new onset or worsening of CRS grade, and 
occurring within 6 hours from the start of infusion 
is categorized as an AESI and must be reported 
as an AE or SAE. 
 If CRS (considered not related to COVID-19) 
does occur, the medical monitor must be notified 
immediately (within 24 hours). 
Serious hypersensitivity reactions 
There is a potential risk of hypersensitivity reactions, 
including anaphylaxis, during and following the 
administration of protein-based products, such as 
otilimab. 
Mitigation: 
 Exclusion of participants with a history of allergic 
reaction, including anaphylaxis to any previous 
treatment with an anti-GM-CSF therapy (Section 
5.3 and Section 5.4 Exclusion Criteria) 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Clinical Data: 
No serious allergic or acute systemic reactions have 
been observed in completed clinical trials with 
otilimab. 
In Part 1 of Study 214094, a participant developed 
toxic epidermal necrolysis 32 days after a single 
dose of otilimab 90 mg administered intravenously 
with a fatal outcome. The participant received 
confounding concomitant medications, including 
sertraline, lansoprazole, piperacillin/tazobactam, 
cefotaxime and rovamycine. 
Monitoring: 
 Serious hypersensitivity reactions are 
categorized as AESIs. 
 Hypersensitivity to be managed appropriately per 
local guidelines/medical judgement 
 All participants hospitalized during infusion and 
will undergo monitoring for hypersensitivity 
reactions 
Infusion site reactions 
Infusions may be associated with local reactions 
(e.g. swelling, induration, pain). 
Non-clinical Data: 
No macroscopic or microscopic changes indicative 
of local injection site reactions were observed 
following SC administration in cynomolgus monkeys. 
Clinical Data: 
Injection/infusion site reactions have been reported 
in completed Phase II studies with otilimab and were 
non-serious and of mild to moderate intensity. 
Monitoring: 
 Infusion site reactions are categorized as AESIs 
 Monitor for infusion site reactions throughout 
study. 
Neutropenia  Grade 3 (<1.0 x 109/L) 
Although there is a perceived theoretical risk that 
GM-CSF blockade may affect maturation of 
leukocytes and their precursors, mice lacking GM-
CSF do not develop neutropenia or show any major 
perturbation of hematopoiesis [Stanley, 1994]. 
Clinical Data: 
Neutropenia has been observed in completed 
studies of otilimab; however, no clinically significant 
cases have been observed. 
Mitigation: 
Part 1  
Exclusion of participants with ANC <1.5 x 109/L 
(neutropenia  Grade 2) (Section 5.3 Exclusion 
Criteria) 
Part 2  
Exclusion of participants with ANC <1.0 x 109/L 
(neutropenia  Grade 3) (Section 5.4 Exclusion 
Criteria) 
Monitoring: 
 Neutropenia Grade 3 (<1.0 x 109/L) is 
categorized as an AESI. 
 Full blood count (with differential) performed 
throughout hospitalization. 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Infections 
Immune-modulating biologic drugs are associated 
with an increased risk of serious and opportunistic 
infections.  Because of the role of GM-CSF in anti-
infective immunity, otilimab also has the potential to 
increase the risk of infection.  GM-CSF has been 
noted to play a role in helping the lung fight infection 
and recover from any injury.  Therefore, it is possible 
that otilimab, by blocking GM-CSF, may affect the 
ability of the lungs to fight lung infection or properly 
recover from infection 
Non-clinical Data: 
Studies in knock-out mice showed that GM-CSF 
deficiency affects the ability of mice to control 
infection when infected with M. tuberculosis or 
pulmonary group B streptococcus [Paine, 2001; 
LeVine, 1999]. 
No changes in peripheral blood populations 
(lymphocytes, neutrophils, monocytes, eosinophils 
or basophils), phagocytic activity of peripheral blood 
polymorphonuclear cells (investigational endpoint in 
the 26 week study), T-cell dependent B-cell primary 
or secondary response, or circulating cytokine levels 
(26 week study) were observed. 
Clinical Data: 
Based on the mechanism of action of otilimab an 
increased risk of infection including TB, fungal and 
opportunistic infections could be expected for anti-
GM-CSF treatment, because of the role of GM-CSF 
in anti-infective immunity. 
One healthy subject in study MSC-1000 experienced 
septic shock secondary to pneumonia 29 days after 
receiving a single dose of 1.5 mg/kg but recovered 
after treatment with antibiotics. 
In Phase II completed studies, no significant 
infections or opportunistic infections were reported. 
Eligibility Criteria  
Exclusion of participants with: 
 Untreated systemic bacterial, fungal, viral, or 
other infection (other than SARS-CoV-2). 
 Known active tuberculosis (TB), history of 
untreated or incompletely treated active or latent 
TB, suspected or known extrapulmonary TB 
 Known HIV regardless of immunological status 
 Known HBsAg and/or anti-HCV positive 
 Part 1: Absolute neutrophil count (ANC) <1.5 x 
109/L (neutropenia  Grade 2) 
 Part 2: ANC <1.0 x 109/L (neutropenia  Grade 
3) 
 Received monoclonal antibody therapy (e.g. 
tocilizumab, sarilumab) within the past 3 months 
prior to randomization, including intravenous 
immunoglobulin, or planned to be received 
during the study 
 Part 1: Received immunosuppressant therapy 
including but not limited to cyclosporin, 
azathioprine, tacrolimus, mycophenolate, janus 
kinase (JAK) inhibitors (e.g. baricitinib, tofacitinib, 
upadacitinib) within the last 3 months prior to 
randomization or planned to be received during 
the study. 
 Part 2:  Received immunosuppressant therapy 
including but not limited to cyclosporin, 
azathioprine, tacrolimus, mycophenolate, JAK 
inhibitors (e.g. baricitinib, tofacitinib, 
upadacitinib), nintedanib, disease-modifying 
antirheumatic drugs (DMARDs, e.g. 
methotrexate) within the last 3 months prior to 
randomization or planned to be received during 
the study. 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
 Currently receiving chronic oral corticosteroids 
for a non-COVID-19 related condition in a dose 
higher than prednisone 10 mg or equivalent per 
day. 
Monitoring: 
 Serious infections are categorized as AESIs. 
Note: An infection is considered serious if it 
meets any of the regulatory definitions of serious 
which include fatal, life-threatening, prolongation 
of existing hospitalization (since subjects are 
already hospitalized) or re-hospitalization, and if 
in the opinion of the investigator the infection 
meets other serious criteria.  
 Participants will be hospitalized under direct 
medical supervision and closely monitored for 
signs of infection as part of SoC with appropriate 
diagnostic tests and antibiotic treatment, as 
necessary. 
 Routine laboratory assessments will be obtained 
throughout hospitalization. 
AESI=Adverse Event of Special Interest, ANC= Absolute Neutrophil Concentration, AUC=Area Under the Curve, CAR=Chimeric Antigen Receptor, Cmax=Maximum Concentration, 
CRS=Cytokine Release Syndrome, CTCAE=Common Terminology Criteria for Adverse Events, DMARDs=Disease Modifying Antirheumatic Drugs, HV=Healthy Volunteer, 
GFR=Glomerular Filtration Rate, IDMC=Independent Data Monitoring Committee, SC=Subcutaneous. 
 

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2.3.2. 
Benefit Assessment 
Otilimab is currently in Phase 3 clinical development for the treatment of RA, at weekly 
doses of 90 and 150 mg SC for up to 12 months in pivotal studies and thereafter eligible 
for treatment in a long-term extension study. 
In completed studies (IV and SC), cumulatively 447 patients and healthy volunteers (HV) 
have received otilimab (326 RA patients, 25 multiple sclerosis (MS) patients, 22 hand 
osteoarthritis patients, and 74 HVs). 
Although otilimab has not been studied before in this acutely ill population, there is 
biologic rationale which supports the use of otilimab in the treatment of COVID-19 
patients with pulmonary complications. 
GM-CSF can act as a proinflammatory cytokine that promotes myeloid cell survival and 
polarizes monocytes/macrophages into pro-inflammatory phenotypes that are primed to 
produce pro-inflammatory cytokines including TNFα, IL-1β and IL-6.  GM-CSF also 
extends neutrophil survival, primes the oxidative burst, enhances phagocytosis and 
promotes neutrophil adhesion to endothelial cells and neutrophil trafficking to sites of 
inflammation. 
COVID-19 ICU patients have increased circulating numbers of IL-6+ monocytes, 
CD14+CD16+ monocytes and GM-CSF+IFNγ+ helper T cells compared with non-ICU 
COVID-19 patients.  Once hypoxia occurs, stopping the systemic hyper-inflammatory 
processes to limit further damage to lung and other organs would the most important 
therapeutic approach.  Preclinical data suggest that elevated levels of GM-CSF in the 
lung could be more beneficial in the early stages of disease and may play a role in disease 
resolution by helping control viral titer, restore or maintain the lung barrier function, and 
return to tissue homeostasis.  As the disease progresses, suppressing the systemic hyper-
inflammatory processes would be a priority and where otilimab could be beneficial.  
Therefore, a single dose of otilimab in patients with pneumonia and oxygenation 
impairment, would be expected to inhibit inflammation and still allow sufficient GM-
CSF levels in the lung during the recovery phase. 
Update for Part 2 
Otilimab has been tested in patients with severe pulmonary COVID-19 related disease in 
Part 1 of this study, with substantial clinical benefit in the pre-defined stratification group 
of participants 70 to <80 years old, with no safety concerns identified (including all 
AESIs) in either the overall study population or the pre-defined stratification group of 
participants 70 to <80 years old. 
2.3.3. 
Overall Benefit: Risk Conclusion 
The overall benefit-risk assessment takes into account the potential benefit of otilimab 
treatment through GM-CSF blockade and mitigation of the hyper-inflammatory response. 
This hyper-inflammatory response associated with severe SARS-CoV-2 infection can 
result in severe or fatal pulmonary disease and multi-organ failure. 

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With the planned safety monitoring measures around the expected low risk of CRS and 
overall favorable safety profile to date, the overall benefit-risk assessment for the patient 
population proposed for this study is considered positive. 
Part 2 
With the planned safety monitoring measures around the expected very low risk of CRS 
and overall favorable safety profile to date, the overall benefit-risk assessment for the 
patient population included in Part 1 and proposed for Part 2 of this study is considered 
positive. 
3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Part 1 
Objectives 
Endpoints 
Primary 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
 Participants alive and free of respiratory failure at Day 
28 
Secondary 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
 All-cause mortality at Day 60 
 Time to all-cause mortality up to Day 60 
 Participants alive and free of respiratory failure at Day 
7, 14, 42, and 60 
 Time to recovery from respiratory failure up to Day 28 
 Participants alive and independent of supplementary 
oxygen at Day 7, 14, 28, 42, and 60 
 Time to last dependence on supplementary oxygen up 
to Day 28 
 Admission to ICU up to Day 28 
 Time to final ICU discharge up to Day 28 
 Time to final hospital discharge up to Day 28 
 To compare the safety and tolerability 
of otilimab 90 mg IV versus placebo 
 Occurrence of adverse events (AEs) [up to Day 60] 
 Occurrence of serious adverse events (SAEs) [up to 
Day 60] 
Exploratory 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
Other endpoints up to Day 28 
 Invasive mechanical ventilation (if not previously 
initiated) 
 Time to invasive mechanical ventilation (if not 
previously initiated) 
 Alive and not invasively mechanically-ventilated 
 Time to definitive extubation 
 Improvement of at least 2 points relative to baseline of 
Sequential Organ Failure Assessment (SOFA) score 
 Improvement relative to baseline in SpO2, FiO2, and 
SpO2/FiO2 ratio 
 Oxygen-free days 

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
3 8  
 
O bj e cti v e s  
E n d p oi nts  
 Ventilator -fr e e days 
 Ti m e to r es olution of pyr exia (for at least 48h)  
Ot h er e n d p oi nt s u p t o Day 60  
 Clinic al status ass ess ed using an or dinal sc ale 1 
ass ess ed at Days 4, 7, 14, 28, 42, and 60  
 Ti m e to i m pr ov e m ent of at least 2 c ategories r elativ e to 
bas eline on an or dinal sc ale 1 
 Change  in C O VI D -19 signs and sy m pto ms  
 T o deter mine the phar m ac okinetics 
( P K) pr ofile of otili m ab 
P K E n d p oi nt s u p t o Day 14  
 Otili m ab clear anc e ( CL) and other P K par a m eters as 
appr opriate using s pars e P K s a m pling  
 T o deter mine:  
 Ex pos ur e -r es pons e. 
 P har m ac ody na mic ( P D) 
bio m ark ers  
 Changes in k ey m ark ers of 
infla m m atio n 
P D E n d p oi nt s u p t o Day 28 
 Ex pos ur e -r es pons e r elations hi p for k ey effic acy, s afety 
and P D endpoints  
 K ey m ark ers of infla m m ati on including, but not li mited 
to C R P, s er u m ferritin and infla m m atory cytokines as 
appr opriate 
 
1Or di n al Sc al e ( G S K m o difi e d v er si o n, a d a pte d fr o m  W H O , 2 0 2 0 v er si o n)  
 
T he pri mar y esti ma n d is t he o d ds ratio bet w e e n otili ma b vers us pla c e b o in t he p r o p ortio n 
of participa nts alive a n d fre e of res pirat or y failure  at D a y 2 8 in participa nts wit h s e vere 
p ul m o nar y C O VI D -1 9 relate d dis e as e re gar dless of us e of a d ditio nal 
me dic atio ns or 
c ha n ges t o sta n dar d of c are.  
3. 2.  
P art 2  
O bj e cti v e s  
E n d p oi nts  
Pri m ar y  
 T o c o m par e the effic acy of otili m ab 90 
m g I V v ers us plac ebo  
 P articipants aliv e and fr ee of r es pir atory failur e at Day 
28 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

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Objectives 
Endpoints 
Secondary 
 To compare the efficacy of otilimab 90 
mg IV versus placebo 
 All-cause mortality at Day 28 
 All-cause mortality at Day 60 
 Time to all-cause mortality up to Day 60 
 Participants alive and free of respiratory failure at Day 
7, 14, 42, and 60 
 Time to recovery from respiratory failure up to Day 28 
 Participants alive and independent of supplementary 
oxygen at Day 7, 14, 28, 42, and 60 
 Time to last dependence on supplementary oxygen up 
to Day 28 
 Time to final ICU discharge up to Day 28 
 Time to first discharge from investigator site up to 
Day 60  
 Time to first discharge to non-hospitalised residence 
up to Day 60 
 To compare the safety and tolerability 
of otilimab 90 mg IV versus placebo 
 Occurrence of adverse events (AEs) [up to Day 60] 
 Occurrence of serious adverse events (SAEs) [up to 
Day 60] 
Exploratory 
 To compare the efficacy of otilimab 
90 mg IV versus placebo 
Other endpoints up to Day 28 
 Invasive mechanical ventilation (if not previously 
initiated) 
 Time to invasive mechanical ventilation (if not 
previously initiated) 
 Alive and not invasively mechanically-ventilated 
 Time to definitive extubation 
 Oxygen-free days 
 Ventilator-free days 
 Admission to ICU up to Day 28 
Other endpoints up to Day 60 
 Time to improvement of at least 2 categories relative to 
baseline on an ordinal scale1 
 Change in COVID-19 signs and symptoms 
 To determine the pharmacokinetics 
(PK) profile of otilimab 
PK Endpoints up to Day 14 
 Otilimab clearance (CL) and other PK parameters as 
appropriate using sparse PK sampling 
 To determine: 
 Exposure-response. 
 Pharmacodynamic (PD) 
biomarkers 
 Changes in key markers of 
inflammation 
PD Endpoints up to Day 28 
 Exposure-response relationship for key efficacy, safety 
and PD endpoints 
 Key markers of inflammation including, but not limited 
to CRP, serum ferritin and inflammatory cytokines as 
appropriate 
 

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
4 0  
 
1Or di n al Sc al e ( G S K m o difi e d v er si o n, a d a pte d fr o m  W H O , 2 0 2 0 v er si o n)  
T he pri mar y esti ma n d is t he o d ds ratio bet w e e n otili ma b vers us pla c e b o in t he p r o p ortio n 
of participa nts alive a n d fre e of res p irat or y failure at D a y 2 8 in participa nts wit h s e vere 
p ul m o nar y C O VI D -1 9 relate d dis e as e re gar dless of us e of a d ditio nal 
me dic atio ns or 
c ha n ges t o sta n dar d of c are.  
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
T his st u d y is a m ulti -c e nter, ra n d o mize d, d o u ble -blin d,  pla c e b o -c o ntr olle d trial t o ass ess 
t he effic a c y a n d s afet y of otili ma b f or t he tre at me nt of s e vere p ul m o nar y C O VI D-1 9 
relate d dis e as e.  T he st u d y p o p ulatio n c o nsists of h os pitalize d  participa nts  wit h ne w o ns et 
h y p o xia re q uirin g sig nific a nt o x y ge n s u p p ort  or  re q uirin g in vasive me c ha nic al ve ntilatio n 
(4 8 h o urs  bef ore d osin g ).  All participa nts will re c eive sta n dar d of c are as per 
instit utio nal pr ot oc ols, in a d ditio n t o st u d y tre at me nt.  Us e of  dr u gs  or tre at me nts 
s pe cific ally inte n de d f or C O VI D -1 9 relate d dis e as e are per mitte d o nly if a c c or din g t o 
loc al h os pital/instit uti o nal p olicies, a n d if n ot e xclu de d in Se ctio n  5. 3  a n d Se ctio n 5. 4  
E xclusio n C riteria Prior/ C o nc o mita nt t hera pies.  A n y c o nc er ns relate d t o eligibilit y in 
res pe ct of me dic atio ns or tre at me nts ta ke n f or C O VI D-1 9 relate d dis e as e s h o uld be 
dis c uss e d wit h t he G S K me dic al m o nit or (s).  Se e Se ctio n  6. 6 . 
After c o m pletio n of s cre e nin g ass ess me nts, participa nts will be tre ate d wit h a sin gle I V 
d os e of otili ma b 9 0 m g o n D a y 1, ass ess e d daily  w hile in h os pital u ntil D is c har ge ( or 
D a y  2 8, w hic he ver is s o o ner) , a n d f ollo w e d u p at D a y s 4 2  a n d 6 0 after ra n d o mizatio n. 
P articipa nts will be re cr uite d fr o m t w o m ut ually -e xcl usive  c ate g ories  wit hin t he or dinal 
s c ale: 
 
P articipa nts will initially be ra n d o mize d 1:1 b y intera ctive res p o ns e te c h n olo g y (I R T) in a 
blin de d ma n ner t o re c eive eit her a 1-h o ur inf usio n of  otili ma b 9 0 m g or pla c e b o I V  in 
a d ditio n t o sta n dar d of c are . 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e 
pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
4 1  
 
4. 1. 1.  
I niti al S af et y C o h ort (fir st 2 0 p arti ci p a nt s)  
P art 1  
 
T he first 2 0 participa nts will be fr o m c ate g or y  5  a b o ve (
 
).  Sinc e t his is t he first ti me t hat 
otili ma b has be e n teste d in participa nts wit h s e vere p ul m o nar y C O VI D -1 9  relate d 
dis e as e , initial d osin g will be sta g gere d, a n d s afet y data re vie w e d as f ollo ws: 
 
T he first t w o participa nts t o be d os e d will be ra n d o mize d 1:1 ( otili ma b: pla c e b o) a n d 
m o nit ore d clos ely.  After a p pr o xi mately 2 4 h o urs, t he clinic al stat us of b ot h 
participa nts will be ass ess e d b y t he in vestigat or(s) a n d t he n dis c uss e d wit h t he G S K 
me dic al m o nit or.  If n o s afet y iss ues are ide ntifie d, a n d t he G S K  me dic al m o nit or 
a n d in vestigat or(s) a gre e, t w o f urt her participa nts will be allo w e d t o be d os e d.  
 
T he t hir d a n d f o urt h participa nts will als o be ra n d o mize d 1:1 ( otili ma b: pla c e b o ) a n d 
m o nit ore d clos ely.  After a p pr o xi mately 2 4 h o urs, t he clinic al stat us of all f o ur 
participa nts will be ass ess e d b y t he in vestigat or(s) a n d t he n dis c uss e d wit h t he G S K 
me dic al m o nit or.  If n o s afet y iss ues are ide ntifie d, a n d t he G S K me dic al m o nit or 
a n d in vestigat or(s) a gre e, re cr uit me nt a n d d osin g of f urt her participa nts will start. 
 
T he G S K Safet y Re vie w Te a m ( S R T) wil l re vie w a vaila ble blin de d s afet y data o n a 
w e e kly basis f or t he a d ditio nal 1 6 participa nts  in t he initial s afet y c o h ort. 
 
S afet y data will  be re vie w e d b y t he I n de pe n de nt D ata M o nit orin g C o m mitte e 
(I D M C), as o utline d in t he I D M C c harter  (refer t o Se ctio n 9. 1. 5  f or m ore 
inf or matio n a b o ut t he I D M C). 
U nless a s afet y sig nal is ide ntifie d d urin g t he o n g oin g s afet y re vie w b y t he G S K S R T  a n d 
e valuatio n b y t he I D M C, e nr ol me nt of t he mai n c o h ort  of participa nts ( b ot h c ate g ories 5 
a n d 6) will be  initiate d. 
4. 1. 2.  
M ai n  C o h ort ( aft er 2 0 p arti ci p a nt s)  
P art 1  
After t he initial s afet y c o h ort, e nr ol me nt rate will initiall y be c a p pe d t o c o ntr ol 
ra n d o mizatio n.  F or t he first 2 0 0 participa nts, a w e e kly ma xi m u m ra n d o mizatio n c a p will 
be s et usin g t he st u d y I R T s yste m, as f ollo ws:  
 
P articipa nt 2 1 t o 1 0 0 –  ra n d o mizati o n c a p of 2 0 participa nts / w e e k  
 
P articipa nt 1 0 1 t o 2 0 0 –  ra n d o mizatio n c a p of 5 0 participa nts / w e e k  
After 2 0 0 participa nts, it is pla n ne d t hat t he ra n d o mi zatio n c a p will be re m o ve d.  T he 
ra n d o mizatio n c a ps will be s u bje ct t o re visio n b y t he I D M C at t he s c he d ule d data re vie w 
me etin gs ( as o utline d in t he I D M C C harter). 
 
P art 2  
After e valuatio n of t he pri mar y e n d p oint  a n d all-c a us e m ortalit y data  at D a y 2 8 in P art 1, 
t he ne xt a p pr o xi mate ly 3 5 0 participa nts will be at le as t 7 0 ye ars old  wit h n o u p per li mit .  
C CI

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
4 2  
 
4. 1. 2. 1.  
Str atifi c ati o n i n P art 1  
B as e d o n t he st u d y eligibilit y criteria, t he clinic al stat us of t he participa nts e nterin g t he 
main c o h ort (i. e. after t he 2 0t h participa nt) of t he st u d y will be wit hin t he t w o or dinal 
s c ale c ate g ories 5 a n d 6  a n d als o a ge gr o u ps, as f ollo ws: 
 
 
.  A ge < 6 0  ye ars  
 
 
  A ge 6 0 t o < 7 0  ye ars  
 
 
.  A ge 7 0 t o < 8 0  ye ars  
 
 A ge < 6 0  ye ars  
 
 A ge 6 0 t o < 7 0  ye ars  
 
 A ge 7 0 t o < 8 0  ye ars  
T he ratio nale f or t h e se  stratific atio n fa ct ors is t o o btain a bala nc e d p o p ulatio n a cr oss t he 
tre at me nt ar ms wit h res pe ct t o t he s e verit y of t he dis e as e a n d a ge gr o u p w hic h are b ot h 
ass ociate d wit h incre as e d m ortalit y [Grass elli , 2 0 2 0 ; W u , 2 0 2 0].  
F urt her , t he tar get perc e nta ge of participa nt s in c ate g or y 6 (
 
) will be n o m ore t ha n 6 0 % of t he st u d y p o p ulatio n .  Ho w e ver , t his 
tar get ma y be re vis e d bas e d o n o n g oin g I D M C re vie ws  (s e e Se ctio n 9. 1. 5 ). 
4. 1. 2. 2.  
Str atifi c ati o n i n P art 2  
B as e d o n t he st u d y eligibilit y criteria, t he clinic al stat us of t he participa nts e nterin g P art 2  
of t he st u d y will be wit hin t he t w o or dinal s c ale c ate g ories 5 a n d 6 a n d als o ge n der , as 
f ollo ws: 
 
 
  Male  
 
 
.  Fe male  
 
 Male  
 
 Fe male  
F urt her, t he tar get perc e nta ge of participa nts in c ate g or y 6 (
 
) will be n o m ore t ha n a p pr o xi mately 4 0 % of t he st u d y p o p ulatio n.  
T he ratio nale f or t hes e stratific atio n fa ct ors is t o o btain a bala nc e d p o p ulatio n a cr oss t he 
tre at me nt ar ms wit h res pe ct t o t he s e verit y of t he dis e as e a n d ge n der  w hic h are ass ociate d 
wit h incre as e d m ortalit y [I C N A R C, 2 0 21 ]. Stratific atio n  t o eit her Cate g or y 5 or 6 will be 
c o n d ucte d at ra n d o mizatio n.   F ollo win g ra n d o mizatio n usin g t he I R T s yste m, it is n ot 
p ossible t o c ha n ge a participa nt’s strata –  t heref ore, e ver y eff ort m ust be ma de t o e nter 
t he strata inf or matio n c orre ctly.   If a participa nt’s stat us c ha n ges bet w e e n ra n d o mizatio n 
a n d d osin g, t he y c a n still be d os e d (if de e me d a p pr o priate b y t he in vestigat or).  F or this 
re as o n, ra n d o mizatio n a n d d osin g s h o uld be as clos e as p ossible o n t he s a me da y . 
C CI
C CI
C CI
C CI
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a 
c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y 
c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a 
c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d p art y 
c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
4 3  
 
4. 2.  
S ci e ntifi c R ati o n al e f or St u d y D e si g n  
A m ultic e nt er, ra n d o mize d, d o u ble-bli n d, pla c e b o -c o ntr olle d trial is a w ell-esta blis he d 
strate g y t o e valuate effic a c y a n d s afet y of in vestigatio nal 
me dicinal pr o d ucts. 
T he st u d y will utili ze a gr o u p s e q ue ntial desig n wit h interi m a nalys es  t hat inte n ds t o 
ide ntif y e arly sig ns of clinic al effic a c y if res p o ns es are hig her t ha n e x pe cte d a n d t o a v oid 
t he us e of ineffe ctive t hera pe utics in se verely or critic ally ill participa nts wit h s e vere 
p ul m o nar y C O VI D -1 9 relate d dis e as e.  I n a d ditio n, fre q ue nt in-stre a m re vie ws of s afet y 
data will be perf or me d t o ide ntif y e arly sig ns of har m  a n d st o p t he st u d y if t hes e are 
ide ntifie d.  T his desig n allo ws  f or t he ass ess me nt of effic a c y a n d s afet y as w ell as 
e valuatin g t he be nefit:ris k.  
4. 3.  
J u stifi c ati o n f or D o s e  
4. 3. 1.  
Otili m a b  
C CI

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
4 4  
 
4. 3. 2.  
Pl a c e b o  
T here is n o esta blis he d tre at me nt f or s e vere p ul m o nar y C O VI D -1 9 relate d dis e as e, he nc e 
a pla c e b o c o ntr ol is re q uire d t o distin g uis h t he s afet y a n d t olera bilit y of otili ma b fr o m t he 
ba c k gr o u n d sig ns a n d s y m pt o ms of s e vere p ul m o nar y C O VI D -1 9 relat e d dis e as e a n d t o 
e valuate its p ote ntial be nefit o n clinic al o utc o mes.  
4. 4.  
E n d of St u d y D efi niti o n  
P art 1  
 
A participa nt is c o nsidere d t o ha ve c o m plete d t he st u d y if he/s he has c o m plete d all visits 
of t he st u d y t hr o u g h t o D a y 6 0  or has die d  pr ior t o D a y 6 0.  T he e n d of t he st u d y is 
define d as t he date of t he last c o nta ct of t he last participa nt in P art 2 of  t he st u d y. 
P art 2  
 
A participa nt is c o nsidere d t o ha ve c o m plete d t he st u d y if he/s he has c o m plete d all visits 
of t he st u d y t hr o u g h t o D a y 6 0 or has die d  prior t o D a y 6 0.  T he e n d of t he st u d y is 
define d as t he date of t he last c o nta ct of t he last participa nt in  t his a d ditio nal c o h ort  in 
P art 2 ( or a n y f ut ure a d ditio nal c o h orts) in t he st u d y. 
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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria – Part 1 
Participants are eligible to be included in Part 1 of the study only if all of the following 
criteria apply: 
AGE 
1. Age 18 years and 79 years at the time of obtaining informed consent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
2. Participants must: 
a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed 
on an appropriate specimen; e.g. respiratory tract sample]) 
b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or 
computerized tomography [CT] scan consistent with COVID-19) 
c. AND be developing new onset of oxygenation impairment requiring any of the 
following: 
1. high-flow oxygen (15L/min) 
2. non-invasive ventilation (e.g. CPAP, BiPAP) 
3. mechanical ventilation 48h prior to dose 
d. AND have increased biological markers of systemic inflammation (either CRP 
>ULN1 or serum ferritin >ULN1). 
1According to local reference range.  Repeat CRP or ferritin tests are permitted. 
 
SEX 
3. No gender restriction. 
4. Female participants must meet and agree to abide by the contraceptive criteria 
detailed in Appendix 4.  Contraceptive use by women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies. 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 
9.4: Contraceptive and Barrier Guidance. 
OR 
o Is a woman of childbearing potential (WOCBP) and using a contraceptive 
method that is highly effective, with a failure rate of <1%, as described in 
Section 9.4 during the study intervention period and for at least 60 days after 
the last dose of study intervention (sexual abstinence is acceptable if it is the 
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o If not consistently on a highly effective method of contraception (Section 
9.4) during hospitalization, the participant must agree to a highly effective 
contraception plan if discharged before Day 60. 
o The investigator should evaluate potential for contraceptive method failure (e.g. 
noncompliance, recently initiated) in relation to the first dose of study 
intervention. 
o A WOCBP must have a negative highly sensitive pregnancy test (urine or 
serum as required by local regulations) at hospital admission or before the first 
dose of study intervention.  See Section 7.3.5 Pregnancy Testing (additional 
requirements for pregnancy testing during and after study intervention). 
o The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an 
early undetected pregnancy. 
 
INFORMED CONSENT 
5. Capable of giving written informed consent as described in Section 9.1.3.  If 
participants are not capable of giving written informed consent, alternative consent 
procedures will be followed as detailed in Section 9.1.3. 
 
5.2. 
Inclusion Criteria – Part 2 
Participants are eligible to be included in Part 2 of the study only if all of the following 
criteria apply: 
AGE 
1. Age 70 years or above at the time of obtaining informed consent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
2. Participants must: 
a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed 
on an appropriate specimen; e.g. respiratory tract sample]) 
b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or 
computerized tomography [CT] scan consistent with COVID-19) 
c. AND be developing new onset of oxygenation impairment requiring any of the 
following: 
1. high-flow oxygen (15L/min)1 
2. non-invasive ventilation (e.g. CPAP, BiPAP) 
3. mechanical ventilation 48h prior to dose 
d. AND have increased biological markers of systemic inflammation (either CRP 
>ULN2 or serum ferritin >ULN2). 
1or equivalent as detailed in the study reference manual (SRM). 
2According to local reference range.  Repeat CRP or ferritin tests are permitted. 
 
SEX 
3. No gender restriction. 

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INFORMED CONSENT 
4. Capable of giving written informed consent as described in Section 9.1.3.  If 
participants are not capable of giving written informed consent, alternative consent 
procedures will be followed as detailed in Section 9.1.3. 
 
5.3. 
Exclusion Criteria – Part 1 
Participants are excluded from Part 1 of the study if any of the following criteria apply: 
RELATED TO SEVERE PULMONARY COVID-19 RELATED DISEASE 
1. Progression to death is imminent and inevitable within the next 48 hours, 
irrespective of the provision of treatments, in the opinion of the investigator. 
2. Multiple organ failure according to the investigator’s judgement or a Sequential 
Organ Failure assessment (SOFA score) >10 if in the ICU. 
3. Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or high-
dose (>0.15g/kg/min) noradrenaline (or equivalent) or more than one vasopressor. 
 
CONCOMITANT MEDICAL CONDITIONS 
4. Current serious or uncontrolled medical condition (e.g. significant pulmonary 
disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class 
III or higher], renal dysfunction, acute myocardial infarction or acute 
cerebrovascular accident within the last 3 months), or abnormality of clinical 
laboratory tests that, in the investigator's judgment, precludes the participant's safe 
participation in and completion of the study. 
5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-
CoV-2). 
6. Known active tuberculosis (TB), history of untreated or incompletely treated active 
or latent TB, suspected or known extrapulmonary TB. 
7. Known HIV regardless of immunological status. 
8. Known HBsAg and/or anti-HCV positive. 
9. Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy. 
 
PRIOR MEDICATIONS/TREATMENTS 
10. Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the 
past 3 months prior to randomization, including intravenous immunoglobulin, or 
planned to be received during the study. 
11. Received immunosuppressant therapy including but not limited to cyclosporin, 
azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, 
tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned 
to be received during the study. 
Note: Participants with an organ transplant are therefore excluded (except patients 
with corneal transplants not requiring immunosuppression). 
12. History of allergic reaction, including anaphylaxis to any previous treatment with 
an anti-GM-CSF therapy. 
13. Received COVID-19 convalescent plasma within 48 hours of randomization. 

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Note: Participants who have received COVID-19 convalescent plasma but continue 
to worsen in the 48 hours after infusion of the convalescent plasma, in the opinion 
of the investigator, will become eligible for the study. 
 
PROHIBITED MEDICATIONS 
14. Currently receiving chronic oral corticosteroids for a non-COVID-19 related 
condition in a dose higher than prednisone 10 mg or equivalent per day. 
15. Treatment with an investigational drug within 30 days of randomization. 
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
16. Participating in other drug clinical trials, including for COVID-19. 
 
DIAGNOSTIC ASSESSMENTS 
17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper 
limit of normal (ULN). 
18. Platelets <50,000/mm3. 
19. Hemoglobin 9 g/dL. 
20. Absolute neutrophil count (ANC) <1.5 x 109/L (neutropenia  Grade 2). 
21. Estimated GFR 30 mL/min/1.73m2. 
 
OTHER CRITERIA 
22. Pregnant or breastfeeding females.  
 
5.4. 
Exclusion Criteria – Part 2 
Participants are excluded from Part 2 of the study if any of the following criteria apply: 
RELATED TO SEVERE PULMONARY COVID-19 RELATED DISEASE 
1. Progression to death is imminent and inevitable within the next 48 hours, 
irrespective of the provision of treatments, in the opinion of the investigator. 
2. Multiple organ failure according to the investigator’s judgement or a Sequential 
Organ Failure assessment (SOFA score) >10 if intubated in the ICU. 
3. Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or more 
than one inotrope/vasopressor of any class. 
 
CONCOMITANT MEDICAL CONDITIONS 
4. Current serious or uncontrolled medical condition (e.g. significant pulmonary 
disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class 
III or higher], severe renal dysfunction, acute myocardial infarction or acute 
cerebrovascular accident within the last 3 months), severe dementia, severe 
disability, or abnormality of clinical laboratory tests that, in the investigator's 
judgment, precludes the participant's safe participation in and completion of the 
study. 
5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-
CoV-2). 
6. Known active tuberculosis (TB), history of untreated or incompletely treated active 
or latent TB, suspected or known extrapulmonary TB. 

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7. Known HIV regardless of immunological status. 
8. Known HBsAg and/or anti-HCV positive (patients demonstrating a sustained 
virologic response (SVR) are not excluded from participation). 
9. Currently receiving radiotherapy, chemotherapy (hormone based therapies are 
permitted) or immunotherapy for malignancy. 
 
PRIOR MEDICATIONS/TREATMENTS 
10. Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the 
past 3 months prior to randomization, including intravenous immunoglobulin, or 
planned to be received during the study. 
11. Received immunosuppressant therapy including but not limited to cyclosporin, 
azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, 
tofacitinib, upadacitinib), nintedanib, DMARDs (e.g. methotrexate) within the last 
3 months prior to randomization or planned to be received during the study. 
Note: Participants with an organ transplant are therefore excluded (except patients 
with corneal transplants not requiring immunosuppression). 
12. History of allergic reaction, including anaphylaxis to any previous treatment with 
an anti-GM-CSF therapy. 
13. Received COVID-19 convalescent plasma within 48 hours of randomization. 
Note: In order to become eligible for the study, participants who have received 
COVID-19 convalescent plasma must, in the opinion of the Investigator, continue 
to worsen clinically for at least 48 hours after infusion of the convalescent plasma.  
 
PROHIBITED MEDICATIONS 
14. Currently receiving chronic oral corticosteroids for a non-COVID-19 related 
condition at a dose higher than prednisone 10 mg or equivalent per day. 
15. Treatment with an investigational drug or substance within 30 days of 
randomization unless approved by the Medical Monitor. 
 
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE 
16. Participating in other drug clinical trials, including for COVID-19. 
 
DIAGNOSTIC ASSESSMENTS 
17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper 
limit of normal (ULN). 
18. Platelets <50,000/mm3. 
19. Hemoglobin 9 g/dL. 
20. Absolute neutrophil count (ANC) <1.0 x 109/L (neutropenia  Grade 3). 
21. Estimated GFR 30 mL/min/1.73 m2. 
 
5.5. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized.  Participants who are randomized but not 
subsequently dosed, are not screen failures.  A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
5 0  
 
res p o n d t o q ueries fr o m re g ulat or y a ut h orities.  Mini mal inf or matio n inclu des 
de m o gra p h y, s cre e n failure details, eligibilit y criteria,  a n y pr ot oc ol de viatio ns  a n d a n y 
pr ot oc ol de viatio ns a n d a n y s erio us a d vers e e ve nts ( S A Es).  
I n divid uals w h o d o n ot me et t he criteria f or participatio n in t his st u d y ma y be res cre e ne d 
o nc e.   Res cre e ne d participa nts s h o uld be assig ne d a ne w participa nt n u m ber f or e a c h 
s cre e nin g/res cre e nin g e ve nt. 
6.  
S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T 
T H E R A P Y  
St u d y inter ve ntio n is define d as a ny in vestigatio nal inter ve ntio n(s) or pla c e b o inte n de d t o 
be a d ministere d t o a st u d y participa nt a c c or din g t o t he st u d y pr ot oc ol.  
6. 1.  
St u d y I nt er v e nti o n(s ) A d mi ni st er e d  
C CI

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
5 1  
 
6. 2.  
Pr e p ar ati o n/ H a n dli n g/ St or a g e/ A c c o u nt a bilit y  
 T he site u n blin de d p har ma cist m ust c o nfir m a p pr o priate te m perat ure c o n ditio ns 
ha ve be e n maintaine d d urin g tra nsit f or all st u d y inter ve ntio n re c eive d a n d a n y 
dis cre pa ncies are re p orte d a n d res olve d bef ore us e of  t he st u d y inter ve ntio n. 
 O nly participa nts e nr olle d in t he st u d y ma y re c eive st u d y inter ve ntio n.  All st u d y 
inter ve ntio ns m ust be st ore d in a s e c ure, e n vir o n me ntally c o ntr olle d, a n d 
m o nit ore d ( ma n ual or a ut o mate d) are a in a c c or da nc e wit h t he la belle d st orage 
c o n ditio ns wit h a c c ess li mite d t o t he in vestigat or a n d a ut h orize d site staff. 
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 The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study intervention accountability, reconciliation, and 
record maintenance (i.e. receipt, reconciliation, and final disposition records). 
 Further guidance and information for the final disposition of unused study 
intervention are provided in the SRM. 
 Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff.  Take adequate precautions 
to avoid direct eye or skin contact and the generation of aerosols or mists.  In the 
case of unintentional occupational exposure notify the monitor, Medical Monitor 
and/or GSK study contact. 
 A Material Safety Data Sheet (MSDS)/equivalent document describing 
occupational hazards and recommended handling precautions either will be 
provided to the investigator, where this is required by local laws, or is available 
upon request from GSK. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally randomized using IRT.  Before the study is initiated, the 
log in information and directions for the IRT will be provided to each site.  Study 
intervention will be administered at the time-point detailed in the SoA (Section 1.3 and 
Section Returned study intervention must not be re-dispensed. 
The IRT will be programmed with blind-breaking instructions.  In case of an emergency, 
the investigator has the sole responsibility for determining if unblinding of a participant’s 
intervention assignment is warranted.  Participant safety must always be the first 
consideration in making such a determination.  If a participant’s intervention assignment 
is unblinded GSK must be notified within 24 hours after breaking the blind.  The date and 
reason that the blind was broken must be recorded in the source documentation and case 
report form, as applicable. 
Participants will be randomized in a ratio of 1:1 to receive study intervention (Section 
1.2, Section 4.1 and Section 6.1).  Investigators will remain blinded to each participant’s 
assigned study intervention throughout the course of the study.  To maintain this blind, all 
participants will receive a single IV infusion.  An unblinded pharmacist (or unblinded 
designee) will be responsible for the dispensation of the study intervention and will 
endeavor to ensure that there are no differences in time taken to dispense between the 
different intervention arms.  The IV bag should be prepared away from view of the 
blinded site staff and the participant.  Every IV infusion must be labelled to maintain the 
blind (refer to SRM). 
Unblinded monitors and in the event of a Quality Assurance audit, the auditor(s) will be 
allowed access to unblinded study intervention records at the site(s) to verify that 
randomization/dispensing has been done accurately. 
A participant may continue in the study if that participant’s intervention assignment is 
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GSK’s Pharma Safety staff may unblind the intervention assignment for any participant 
with an SAE.  If the SAE requires that an expedited regulatory report be sent to one or 
more regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to investigators in accordance with local regulations and/or GSK 
policy. 
6.4. 
Study Intervention Compliance 
Participants will receive study intervention directly from the investigator or designee, 
under medical supervision.  The date and time of the dose administered will be recorded 
in the source documents.  The dose of study intervention and study participant 
identification will be confirmed at the time of dosing by a member of the study site staff 
other than the person administering the study intervention. 
6.5. 
Treatment of Overdose 
For this study, any dose of otilimab greater than the 90 mg dose indicated in this study or 
used more frequently than permitted (otilimab 90 mg single IV infusion) will be 
considered an overdose. 
No specific treatment is recommended for an overdose of otilimab, and the investigator 
should treat as clinically indicated. 
In the event of a potential overdose, the investigator should: 
 Contact the Medical Monitor immediately. 
 Closely monitor the participant for adverse event (AE)/serious adverse event 
(SAE) and laboratory abnormalities. 
 Contact the unblinded monitor with the quantity and duration of the overdose to 
be documented. 
6.6. 
Concomitant Therapy 
At Screening, information will be collected on any medications the participant has taken 
in the 14 days before screening.  In Part 2, current COVID-19 vaccination status will also 
be recorded. 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded along with: 
 reason for use 
 dates of administration including start and end dates 
 dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
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A participant who has received COVID-19 convalescent plasma will be eligible for the 
study if, in the opinion of the Investigator, they continue to worsen clinically for at least 
48 hours after infusion of the convalescent plasma. 
Part 1 only - Due to the effect of cytokines on the CYP450 enzymes (Section 2.3) 
initiation or discontinuation of study intervention may have a clinically relevant effect for 
CYP substrates with a narrow therapeutic index e.g. warfarin and theophylline should be 
monitored. 
Part 1 only - Investigators should exercise caution when study intervention is co-
administered with CYP3A4 substrate drugs where decrease in effectiveness is 
undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. 
Aside from those medications specified in Exclusion Criteria (Section 5.3 and Section 
5.4) or Section 6.6.1, all regular medications that are required by the participant will be 
allowed.  All concomitant medications (and treatments, such as convalescent plasma) 
should be recorded in the eCRF. 
6.6.1. 
Medication NOT Permitted During the Study 
The following medications cannot be planned to be administered during the study (see 
the note in Section 6.6.2, which provides guidance on the use of treatments for COVID-
19 that might benefit the patient or be considered lifesaving): 
 Any monoclonal antibody therapy (e.g. tocilizumab, sarilumab), including 
intravenous immunoglobulin 
 Immunosuppressant therapy including but not limited to cyclosporin, 
azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, 
tofacitinib, upadacitinib), nintedanib, DMARDs (e.g. methotrexate). 
 Chronic oral corticosteroids (for a non-COVID-19 related condition) in a dose 
higher than prednisone 10 mg or equivalent per day, are not permitted. 
6.6.2. 
Medication/Treatment PERMITTED During the Study 
The following medications are permitted during the study: 
 The participant’s regular medication. 
 Treatment required for standard of care (e.g. analgesia, antipyretic, sedation). 
 Medications/treatments required for ICU care. 
 Additional medications/treatments of COVID-19 related disease (e.g. remdesivir, 
favipiravir, convalescent plasma, tocilizumab, sarilumab) are permitted only if 
according to local hospital/institutional policies, and not part of a clinical trial if it 
is felt that the participant might benefit or it might be considered life-saving.  Any 
concerns regarding the acceptability of potential treatments should be discussed 
with the GSK medical monitor(s). 

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6.7. 
Participant Discontinuation/Withdrawal from the Study 
 A participant may withdraw from the study at any time at his/her own request, at 
the request of their legally authorized representative (LAR) or may be withdrawn 
at any time at the discretion of the investigator for safety, behavioral, or 
compliance reasons.  This is expected to be uncommon. 
 At the time of discontinuing from the study, if possible, a Withdrawal visit (same 
as Discharge visit) should be conducted (for hospitalized participants) or a 
Withdrawal phone call (same as Follow-up phone call) should be conducted (for 
non-hospitalized participants), as shown in the SoA. 
 If the participant withdraws consent or the LAR requests that the participant is 
withdrawn for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
 If a participant withdraws from the study or the LAR requests that the participant 
is withdrawn, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records. 
6.8. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she is unable to be contacted by 
the study site after discharge from hospital.  Every effort must be made to reduce missing 
data.   
 The site must attempt to contact the participant as soon as possible and counsel 
the participant on the importance of maintaining the assigned study schedule and 
ascertain whether or not the participant wishes to and/or should continue in the 
study. 
 Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods).  These contact attempts should be 
documented in the participant’s medical record. 
 Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is described in Section 9.1.9. 
7. 
STUDY ASSESSMENTS AND PROCEDURES 
This section lists the parameters of each planned study assessment.  Participants will 
mainly be evaluated using standard of care investigations.  In addition to standard care, 
data will be collected for the Ordinal Scale and the Clinical Features of COVID-19, and 
blood samples will be collected for PK and PD analysis (collected as detailed in the SoA, 
Section 1.3 and Section 1.4). 

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 Study procedures and their timing are summarized in the SoA (Section 1.3 and 
Section 1.4). 
 As detailed in the SoA (Section 1.3 and Section 1.4), follow-up phone calls must 
be made within ±2 days of the scheduled time-point, but every effort must be 
made to complete the phone call on the scheduled day.  This is particularly 
important if the Day 28 time-point is a phone call, because this is the study 
primary endpoint. 
 Every effort must be made to reduce missing data throughout the study. 
 Protocol waivers or exemptions are not allowed. 
 Urgent study-related safety concerns should be discussed with the GSK medical 
monitor immediately upon occurrence or awareness to determine if the participant 
should continue or in exceptional circumstances withdraw from the study. 
 Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3 and Section 1.4), is essential and required for study conduct. 
 All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria.  The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable. 
 Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and taken before obtaining consent may be utilized for 
screening or baseline purposes provided the procedure met the protocol-specified 
criteria and was performed within the time frame defined in the SoA. 
 The maximum amount of blood collected from each participant over the duration 
of the study for the purpose of meeting the objectives will not exceed 200 mL.  
This does not include any standard of care assessments. 
 Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
7.1. 
Entry/Screening Assessments 
7.1.1. 
Demography & Medical History 
The following demographic parameters will be captured: year of birth, gender and 
ethnicity/race.  If it is not possible to collect at Screening, demography can be collected at 
any point during the study. 
We are collecting details of race and ethnicity in this study since there have been reports 
from several counties that ethnic minority groups have been disproportionately affected 
by either the incidence or outcomes of COVID-19 related disease.  In line with ICH E5 
principles, this information is therefore paramount to the assessment of the ethnic 
sensitivity of otilimab in this patient population. 

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To the extent practical given the participant’s condition, a full medical history, including 
cardiovascular risk, will be taken during Screening or as information becomes available 
at any point during the study.  This should record concurrent medical conditions and 
concomitant medications. 
Medical history will include a detailed list of signs and symptoms of COVID-19 recorded 
at admission (see Section 7.2.1) 
Part 1- At Screening, information will be collected on any medications the participant 
has taken in the 14 days before Screening. 
Part 2 - At Screening, COVID-19 vaccination status will be recorded, as well as any 
prior medications within 14 days before Screening. 
7.1.2. 
Chest X-ray or CT Scan 
A chest X-ray or computerized tomography (CT) scan must be available at Screening to 
confirm a diagnosis of pneumonia and eligibility.  If another chest X-ray or CT scan is 
done after Screening and before Discharge, this status should be recorded in the eCRF. 
7.2. 
Efficacy Assessments 
General Note: Research staff are asked to liaise with clinical staff managing the 
participant to ensure that all study relevant data is collected efficiently and accurately and 
that study related assessments are not performed soon after or before those required for 
participant clinical management.  Hence, all study mandated physical examination 
assessments, measurements of vital signs and obtaining blood for laboratory tests / point 
of care tests should be performed in coordination with the clinical staff looking after the 
participant. 
7.2.1. 
Clinical features of COVID-19 
Signs and symptoms of COVID-19 will be collected for non-mechanically ventilated 
participants.  A detailed list of signs and symptoms of COVID-19 at admission will be 
recorded at Screening, and an abbreviated list of signs and symptoms of COVID-19 will 
be recorded at the timepoints defined in the SoA (Section 1.3 and Section 1.4; list of 
signs and symptoms outlined in the eCRF). 
7.2.2. 
SpO2 (for participants not on invasive mechanical ventilation) 
SpO2 should be measured at the timepoints defined in the SoA (Section 1.3 and Section 
1.4).  Where possible, SpO2 should be measured “at rest” i.e. not having undergone a 
procedure for at least 5 minutes.  When a participant is mechanically ventilated, no SpO2 
value is expected in the eCRF. 
Part 2:  SpO2 should be measured once daily in the morning (up to discharge) at 
approximately the same time as the Ordinal Scale categorisation.   

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
5 8  
 
7. 2. 3.  
C o n c e ntr ati o n of i n s pir e d o x y g e n ( Fi O 2 ) 
C o nc e ntratio n of ins pire d o x y ge n ( Fi O 2) a n d/ or o x y ge n flo w rate ( L/ min) s h o uld be 
me as ure d at t he ti me p oints define d in t he S o A ( Se ctio n 1. 3  a n d Se ctio n 1. 4 ). 
P art 2:   Fi O 2 a n d/ or o x y ge n flo w rate s h o uld be me as ure d o nc e daily in t he m or nin g ( u p 
t o dis c har ge) at a p pr o xi mately t he s a me ti me as t he Or dinal Sc ale c ate g oris atio n.  
7. 2. 4.  
V e ntil ati o n st at u s  
V e ntilatio n stat us (in vasive  or n o n -in vasive ve ntilatio n), 
mas k or nas al cat heter  o x y ge n 
will be c olle cte d at ti mes o utline d in t he S o A  ( Se ctio n 1. 3  a n d Se ctio n 1. 4 ).  F or 
me c ha nic ally ve ntilate d participa nts, in dic ate if t he participa nt w as in t he pr o ne or s e mi-
pr o ne p ositio n  at a n y ti me  w hilst me c ha nic ally ve ntilate d .  If t he participa nt is dis c har ge d 
fr o m h os pital wit h o x y ge n s u p p ort, re c or d o x y ge n tre at me nt at s u bs e q ue nt p h o ne c all 
f ollo w-u ps (at ti mes o utline d in t he S o A ( Se ctio n 1. 3  a n d Se ctio n 1. 4 ). 
7. 2. 5.  
I C U S u p p orti v e C ar e  
F or participa nts in I C U, a d ditio nal inf or matio n will be c olle cte d o n t he us e of s u p p ortive 
c are:  in otr o pes/ vas o press ors, re nal re pla c e me nt t hera p y (R R T ) a n d e xtra c or p ore al 
me m bra ne o x y ge natio n ( E C M O ) s h o uld be re c or de d at t he ti me p oints define d in t he S o A 
( Se ctio n 1. 3  a n d Se ctio n  1. 4 ). 
7. 2. 6.  
Or di n al S c al e  
T he m ut ually e xclusive or dinal s c ale pres e nte d in  Ta ble 2 , a da pte d fr o m t he W H O  s c ale 
2 0 2 0, will be us e d t o ass ess clinic al i m pr o ve me nt at t he ti me p oints in dic ate d in t he S o A 
( Se ctio n 1. 3  a n d Se ctio n  1. 4 ). 
T a bl e 2  
Or di n al S c al e ( G S K m o difi e d v er si o n, a d a pt e d fr o m  W H O , 2 0 2 0 
v e r si o n)  
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e 
pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y 
t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

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7.2.7. 
Participant baseline and discharge location information 
At Discharge, the location of where a participant is discharged to must be recorded in the 
eCRF.  There are 2 categories of location (each with sub-categories): 
1. Non-hospitalized residence / facility 
2. Hospitalized residence / facility 
A detailed description is provided in the SRM for the sub-categories for 1 and 2 above. 
In order to relate the above discharge information to the participant’s residence status 
before contracting COVID-19, information must be collected at Screening about the 
participant’s residence before initial hospital admission for COVID-19 (refer to the SRM 
for more information). 
7.2.8. 
Sequential Organ Failure Assessment (SOFA) Scores 
The SOFA score is a tool for grading organ dysfunction in critically ill participants - 
usually those who are in ICU and intubated and mechanically ventilated.  Scores range 
from 0 to 4 for each component and represent the extent of dysfunction or failure 
[Vincent, 1996]. 
The SOFA score is made up of the following components: 
 The Respiratory System component of the SOFA score will be assessed using 
PaO2/FiO2 (mmHg) and will require an arterial blood gas (ABG) measurement.  If 
an ABG is not available, it is acceptable to estimate PaO2/FiO2 (mmHg) from 
SpO2/FiO2. 
 The Nervous System component of the SOFA score will be determined using the 
Glasgow Coma Scale (GCS).  If possible, GCS is assessed  during a sedation 
holiday.  If a participant is intubated and ventilated (and there is no sedation 
holiday in the previous 24 hours), the Glasgow Coma Score (GCS) assessment 
can be omitted, and a score of +4 used. 
 The Cardiovascular System component of the SOFA score can be determined by 
Mean Arterial Pressure (MAP) measurement or administration of vasopressors. 
 The Liver, Renal, and Coagulation components of the SOFA score will be 
determined by measurement of total bilirubin, serum creatinine, and platelet count 
respectively.  The highest score of the last 24-hour period for each measurement 
should be used. 
Part 1:  SOFA scores will be determined at the time points stipulated in SoA (Section 
1.3). 
Part 2:  SOFA score will be used only for eligibility assessment in patients who are 
intubated and mechanically ventilated (Section 1.4). 

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7.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3 and 
Section 1.4) – where possible, these should be aligned with standard of care. 
7.3.1. 
Physical Examinations 
 A full physical examination will include, at a minimum, assessments of the 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.  Results 
will not be recorded in the eCRF. 
7.3.2. 
Vital Signs 
 Temperature, pulse rate, respiratory rate, blood pressure will be assessed.  Single 
measurements will be used at all timepoints as detailed in the SoA. 
 The location used to measure temperature will be as per standard of care but must 
be recorded in the eCRF. 
 At Screening only, body weight should either be measured, established from the 
medical records e.g. last 3 months, or reported/estimated at the bedside.   
 Part 2 only: at Screening only, height should be measured, established from the 
medical records, or reported by the participant or LAR. 
7.3.3. 
Electrocardiograms 
 Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3 and 
Section 1.4). 
 Each ECG report must be reviewed by the Principal Investigator (PI) or his 
qualified designee.  Each ECG must be initialled and dated by the PI or his/her 
qualified designee reviewing the report. 
7.3.4. 
Clinical Safety Laboratory Assessments 
 See Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency. 
 The investigator must review the laboratory report, document this review, and 
record any clinically significant changes occurring during the study as an AE.  
The laboratory reports must be filed with the source documents. 
 Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
 All laboratory tests with values considered clinically significantly abnormal 
(during participation in the study until the follow up visit) should be repeated until 
the values return to normal or baseline or are no longer considered significantly 
abnormal by the investigator or medical monitor.  If clinically significant values 

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do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified. 
 If laboratory values from non-protocol specified laboratory tests are performed 
and require a change in participant management or are considered clinically 
significant by the investigator (e.g. SAE), then the results must be recorded. 
7.3.5. 
Pregnancy Testing (Part 1 only) 
 Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at Screening to confirm eligibility as per Section 5.1. 
 Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at Discharge.  If the participant has been discharged before Day 60, the 
Day 60 phone call will include a verbal confirmation about pregnancy status. 
 Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant’s time in the study. 
7.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of AEs or SAEs can be found in Section 9.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 9.3. 
7.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
 All AEs and SAEs will be collected from the start of intervention until the follow-up 
visit at the time points specified in the SoA (Section 1.3 and Section 1.4).  However, 
any SAEs assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to a 
GSK product will be recorded from the time a participant consents to participate in 
the study. 
 Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as Medical History/Current Medical 
Conditions not as AEs. 

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 All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3.  The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
 Investigators are not obligated to actively seek information on AEs or SAEs after the 
conclusion of the study participation.  However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, 
and he/she considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor. 
7.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE.  Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence. 
7.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts.  All SAEs, and non-serious AEs of special 
interest (as defined in Section 7.4.7), will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up (as defined in 
Section 6.8).  Further information on follow-up procedures is given in Appendix 3. 
7.4.4. 
Regulatory Reporting Requirements for SAEs 
 Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
 The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation.  The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
 An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
7.4.5. 
Pregnancy (Part 1 only) 
 Details of all pregnancies in female participants will be collected after the start of 
study intervention and until follow-up visit (Day 60). 
 If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the pregnancy 
in a female participant.  While pregnancy itself is not considered to be an AE or SAE, 

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any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
 Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
 The participant will be followed to determine the outcome of the pregnancy.  The 
investigator will collect follow-up information on the participant and the neonate, and 
the information will be forwarded to the sponsor. 
 Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in Section 
7.4.4.  While the investigator is not obligated to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting. 
7.4.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Appendix 3 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the eCRF will 
be required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death. 
The CV eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the eCRF within one week of receipt of a CV Event data query prompting its completion. 
The Death eCRF is provided immediately after the occurrence or outcome of death is 
reported.  Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
7.4.7. 
Adverse Events of Special Interest 
The potential risks of otilimab are discussed in Section 2.3. 
Adverse events of special interest (AESI) include: 
 Cytokine release syndrome (CRS) (not related to COVID-19 [see Section 7.4.7.1]) 
 Serious hypersensitivity reactions 
 Infusion site reactions 
 Neutropenia  Grade 3 (<1.0 x 109/L) 
 Serious infections 
 
AESIs should be reported as AEs or SAEs, as appropriate.  Please refer to Section 9.3 
(Appendix 3) and the SRM.   

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7.4.7.1. 
Cytokine Release Syndrome 
Cytokine-associated toxicity, also known as cytokine release syndrome (CRS), is a non–
antigen-specific toxicity that occurs as a result of strong immune activation.  The 
magnitude of immune activation typically required to mediate clinical benefit using 
modern immunotherapies exceeds levels of immune activation that occurs in more 
natural settings.  As immune-based therapies have become more potent, CRS is becoming 
increasingly recognized. 
Symptomatology associated with CRS and the severity of symptoms varies greatly but 
may be quite mild, and management can be complicated by inter-current conditions in 
these participants.  This may be particularly the case in patients with severe pulmonary 
COVID-19 related disease. 
Potentially life-threatening severe complications of CRS include cardiac dysfunction, 
acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and 
disseminated intravascular coagulation.  Of particular concern is cardiac dysfunction, 
which can be rapid onset and severe, but is typically reversible. 
In the event of CRS, investigators should follow institutional guidelines for symptom 
management.  Additional guidance can be found in the published literature [Lee, 2014]. 
 
For this study, CRS (possibly related to study drug, rather than progression of 
hyperinflammation in COVID-19 disease) is defined as a worsening of the CRS Grading 
System (below) within 6 hours after start of study drug infusion. 
 
In the event that CRS is suspected (defined as a worsening of the CRS Grading System 
within 6 hours of drug administration) and is thought to be caused by otilimab by the 
investigator, additional blood samples should be taken (see Section 1.3 and Section 1.4, 
and Section 9.2).  These blood samples should be taken as soon as possible after 
suspected CRS onset and then again 24 hours later.  The following blood samples should 
be taken: 
 PD (cytokine) sample 
 Hematology 
 CRP 
 D-dimer 
 Ferritin 
In the event that new onset of CRS is suspected, the medical monitor must be notified 
immediately and under no circumstance can this exceed 24 hours, and the event must 
also be reported within 24 hours as an AE or an SAE.  The investigator will submit any 
updated data related to the CRS event (including completion of any AE or SAE CRF 
forms) to the sponsor within 24 hours of it being available. Additional CRF forms related 
to the CRS event should then be completed as soon as possible. 

T M F -1 1 7 9 5 6 0 7  
C O N FI D E N TI A L  
 
 
 
2 1 4 0 9 4  
 
6 5  
 
C R S Gr a di n g S yste m 1 
Gr a d e  
T o xi city  
1Ad a pte d fr o m  L e e , 2 0 1 4  
2Gr a d es
r efer to C T C A E v 5. 0 gr a din g 
 
7. 5.  
P h ar m a c o ki n eti c s  
 B lo o d s a m ples (a p pr o xi mately 3. 5  m L ) will be c olle cte d f or me as ure me nt of 
s er u m c o nc e ntratio ns of otili ma b  as s pe cifie d in t he S o A  ( Se ctio n 1. 3  a n d Se ctio n 
1. 4 ). 
 T he a ct ual date a n d ti me  ( 2 4-h o ur cloc k ti me) of e a c h blo o d s a m ple c olle ctio n 
will be re c or de d.  
 C olle ctio n, pr oc essin g, st ora ge a n d s hip pin g pr oc e d ures are pr o vide d in t he 
c e ntral la b orat or y ma n ual.    
 P art 2  - If c e ntral la b orat or y kits are n ot a vaila ble at a site  (f or o peratio nal 
re as o ns), participa nts c a n be ra n d o mis e d a n d d os e d , a n d t he P K s a m ples n ot 
c olle cte d.  I n t his sit uatio n, t he missin g s a m ples w o uld n ot be a pr ot oc ol 
de viatio n.  T his is justifia ble, be c a us e P K s a m plin g is a n e x plorat or y e n d p oint.  
 I nter ve ntio n c o nc e ntratio n inf or matio n t hat ma y/ w o uld u n blin d t he st u d y will n ot 
be re p orte d t o in vestigative sites or blin de d pers o n nel u ntil t he st u d y has be e n 
u n blin de d.  
7. 6.  
G e n eti c s  
Ge net ics are n ot e valuate d in t his st u d y. 
C CI
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d 
b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.

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7.7. 
Pharmacodynamics  
 Blood samples will be collected to help understand the disease, otilimab target 
levels and response to otilimab in COVID-19 related  disease, as specified in the 
SoA (Section 1.3 and Section 1.4). 
 Biomarkers may include, but are not limited to: inflammatory cytokines, such as 
IL-6; growth factors, such as GM-CSF; and other molecules that are indicative of 
hyper-inflammation. 
 The actual date and time (24-hour clock time) of each blood sample collection 
will be recorded. 
 Collection, processing, storage and shipping procedures are provided in the 
central laboratory manual. 
 Part 2 - If central laboratory kits are not available at a site (for operational 
reasons), participants can be randomised and dosed, and the PD samples not 
collected.  In this situation, the missing samples would not be a protocol 
deviation.  This is justifiable, because PD sampling is an exploratory endpoint. 
GSK may store samples for up to 15 years after the end of the study to achieve study 
objectives.  Additionally, with participants’ consent, samples may be used for further 
research by GSK or others such as universities or other companies to contribute to the 
understanding of SARS-CoV-2 infection, associated COVID-19 disease or other 
diseases, the development of related or new treatments or research methods. 
7.8. 
Immunogenicity Assessments 
Antibodies to otilimab will not be assessed as part of this study, since this is a single dose 
study. 
7.9. 
Health Economics/Medical Resource Utilization and Health 
Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters will 
not be evaluated in this study. 
8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Statistical Hypotheses 
The primary objective of this study is to compare the efficacy of otilimab 90 mg IV 
versus placebo in participants with severe pulmonary COVID-19 related disease. 
In all parts of the study, the study will test the null hypothesis that the difference between 
otilimab 90 mg and placebo on the proportion of participants alive and free of respiratory 
failure at Day 28 is less than or equal to zero versus the alternative hypothesis that 
otilimab 90 mg increases the proportion of participants alive and free of respiratory 
failure compared with placebo at Day 28. 

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8.2. 
Sample Size Determination 
Otilimab and placebo will be randomized in a 1:1 ratio. 
Part 1 
The study will utilize a group sequential design, using a Lan-DeMets alpha-spending 
function to control the type I error with four interim analyses for futility, two early in the 
study where futility alone will be assessed, using Pocock analogue rules; and two for 
efficacy, at later times in the study and at the same time as futility, using the O’Brien-
Fleming analogue rules [Lan, 1983].  A sample size of 800 participants will provide 
approximately 90% power to detect a difference of 12% in the proportion of participants 
alive and free of respiratory failure at a one-sided 2.5% significance level and an assumed 
placebo response rate of 45%.  The minimal detectable effect for this design is 7%. 
Full details of the decision criteria and interim analysis plan will be given in the IDMC 
charter and analysis plan. 
The assumed placebo response is based on data from recent publications of studies of 
patients with severe pulmonary COVID-19 related disease [Sanofi, 2020]. 
Part 2 
A sample size of 346 participants will provide approximately 80% power to detect a 
difference of 15% in the proportion of participants alive and free of respiratory failure at 
a one-sided 2.5% significance level and an assumed placebo response rate of 45%.  The 
minimal detectable effect for this design is 10.6%. 
8.3. 
Analysis Sets 
Part 1 and Part 2 
The primary population will be the modified intent to treat (MITT) population, defined as 
all participants who were randomized and received study drug.  This population will be 
used for all data summaries and analyses.  Any participant who receives study 
intervention will be considered evaluable. 
Further details of analysis sets will be provided in the Analysis Plan. 
8.4. 
Statistical Analyses 
Full details of all analyses will be described in the Analysis Plan.  Each part of the study 
will be analysed separately, and separate analysis plans will be produced.   
This section is a summary of the planned statistical analyses for the primary endpoint. 

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8.4.1. 
General Considerations 
Part 1 
In the case of a difference between the stratification assigned at the time of randomization 
and the data collected in the eCRF, the analyses will be performed based on the 
calculated stratum at randomization.  All analyses will be adjusted for ordinal scale 
category at baseline (category 5 or 6) and age group (treated as categorical variable 
defined by the levels <60 years, 60 to <70 years, 70 to <80 years).  Confidence intervals 
will use the 95% levels unless otherwise specified. 
Part 2 
In the case of a difference between the stratification assigned at the time of randomization 
and the data collected in the eCRF, the analyses will be performed based on the 
calculated stratum at randomization.  All analyses will be adjusted for ordinal scale 
category at baseline (category 5 or 6) and gender (male or female).  Confidence intervals 
will use the 95% levels unless otherwise specified. 
8.4.2. 
Primary Endpoint(s) 
The primary endpoint is whether or not a participant is alive and free of respiratory 
failure at Day 28. 
The primary endpoint was analysed when all participants in Part 1 had completed Day 
28.  In Part 2, the primary endpoint will be analysed after all participants have completed 
Day 28. The final analysis will be conducted for each part of the study after the last 
participant has completed the study. Participants are considered alive and free of 
respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) 
modified version ordinal scale adapted from World Health Organization (WHO) scale 
2020 (Section 7.2.6. Table 2 - Ordinal Scale). 
Part 1 and Part 2 
The primary estimand is the odds ratio between otilimab versus placebo in the proportion 
of participants alive and free of respiratory failure at Day 28 in participants with severe 
pulmonary COVID-19 related disease regardless of use of additional medications or 
changes to standard of care.  No other intercurrent events are expected and the strategy 
for analysis will be to use the treatment policy strategy, with data analyzed as collected.  
It is expected missing data will be minimal and most will be lost to follow up data after 
discharge and this along with intermittent data will be imputed using multiple imputation 
under the missing at random assumption.  Every effort will be made to reduce missing 
data.  Supplemental estimand strategies and missing data sensitivities may be performed 
and further details will be provided in the analysis plan. 
The primary endpoint will be summarized using counts and proportions of the number of 
participants alive and free of respiratory failure and will be analyzed using a logistic 
regression model, adjusting for ordinal scale category at baseline and age group.  The 
outcome of the model is an odds ratio, and a confidence interval for the odds of 
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In addition, the corresponding difference in proportion and confidence interval will be 
calculated from the model [Ge, 2011]. 
The analysis of the primary endpoint at the in-stream interim analyses in Part 1 will be 
the same as that described for the primary endpoint above. 
8.4.3. 
Secondary Endpoint(s) 
Full details of all analysis methods for the secondary endpoints will be provided in the 
analysis plan. 
8.4.4. 
Exploratory Endpoint(s) 
Full details of all analysis methods for the exploratory endpoints will be provided in the 
analysis plan. 
8.4.5. 
Safety Analysis 
For safety data, no formal hypotheses will be tested.  Occurrence of AEs, SAEs, and 
AESIs, including laboratory tests, vital signs, and 12-lead ECGs will be displayed in the 
form of listings, frequencies, summary statistics, graphs, and statistical analyses where 
appropriate.  Interpretation will be aided by clinical expertise.  Full details, including 
example outputs, will be documented in the analysis plan. 
8.5. 
Interim Analysis 
Part 1 
Interim analyses will be used to assess safety, futility and efficacy.  Safety stopping rules 
will be put in place for the IDMC to stop the study if there is an excess risk of mortality.  
Full details of timing of analyses and all stopping criteria will be given in the IDMC 
charter. 
An IDMC will actively monitor in-stream interim unblinded safety and efficacy data to 
make recommendations to GSK as per IDMC charter.  The IDMC members will include 
4-6 physicians with relevant medical specialist training and one statistician.  Details 
regarding the IDMC process will be available in relevant IDMC documents prior to the 
first participant’s visit. 
A GSK Safety Review Team (SRT) will review the blinded safety data of this study at 
regular intervals through both initial safety and main cohort dosing.  Details regarding the 
SRT process will be available in relevant SRT documents.  The SRT will inform the 
IDMC if any safety signals are identified. 
Part 2 
There will be no interim analyses to assess futility and efficacy. 
An IDMC will actively monitor in-stream interim unblinded safety data to make 
recommendations to GSK as per IDMC charter for Part 2.  The IDMC members will 
include 4-6 physicians with relevant medical specialist training and one statistician.  

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Details regarding the IDMC process will be available in relevant IDMC documents prior 
to the first participant’s visit. 
A GSK Safety Review Team (SRT) will review the blinded safety data of this study at 
regular intervals through the study.  Details regarding the SRT process will be available 
in relevant SRT documents. 
 

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9. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
9.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
9.1.1. 
Regulatory and Ethical Considerations 
 This study will be conducted in accordance with the protocol and with: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o Applicable International Conference on Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines 
o Applicable laws and regulations 
 The protocol, protocol amendments, informed consent form (ICF), IB and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by the 
investigator and reviewed and approved by the IRB/IEC before the study is 
initiated. 
 Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 
 Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
 The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC 
o Notifying the IRB/IEC of SAE or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations 
9.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 

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financial certification or disclosure statements to the appropriate regulatory authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
9.1.3. 
Informed Consent Process 
Given that this trial is being conducted in participants with COVID-19, and given that 
some of the participants will be mechanically ventilated upon enrolment, alternative 
procedures to obtain informed consent will be used.  Participants may be consented in 
three ways, as described below.  The EMA Guidance on the Management of Clinical 
Trials during the COVID-19 (Coronavirus) pandemic (Version 2, 27-Mar-20) [EMA, 
2020] and the FDA Guidance on Conduct of Clinical Trials of Medical Products during 
the COVID-19 Pandemic (updated 16-Apr-20) [FDA, 2020] have been considered. 
 
1.  Participant is enrolled by signing the informed consent. 
If the participant is capable of understanding and signing the informed consent (paper or 
eConsent), the below points will apply: 
 The investigator or his/her representative will explain the nature of the study to 
the participant and answer all questions regarding the study. 
 The medical record must include a statement that written (or electronic) informed 
consent was obtained before the participant was enrolled in the study and the date 
the written consent was obtained.  The authorized person obtaining informed 
consent must also sign the informed consent form (ICF).  If paper consent is used, 
and there is an infection risk to the person obtaining consent, the trial participant 
and the person obtaining consent may sign and date separate ICFs.  All relevant 
records should be archived in the Investigator Site File.  A correctly signed and 
dated ICF should be obtained from the trial participant as soon as possible. 
 Consent may be collected before the 48h screening window if the investigator 
considers that the participant is likely to become eligible, and wants to ensure that 
consent is given by the participant rather than a legally authorized representative 
(LAR). 
 
2. Participant is enrolled by consenting orally. 
If the participant is capable of understanding, but not able to provide written consent 
(paper or eConsent), informed consent can be obtained orally, the below points will 
apply: 
 The investigator or his/her representative will explain the nature of the study to 
the participant and answer all questions regarding the study. 
 Oral consent must be given in the presence of an impartial witness.  In such cases, 
the witness is required to sign and date the ICF (paper or electronic) and the 
investigator is expected to record how the impartial witness was selected.  All 
relevant records should be archived in the Investigator Site File.  A correctly 
signed and dated ICF should be obtained from the trial participant as soon as 
possible. 
 

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3. Participant is enrolled by his/her legally authorized representative (LAR) (written 
or oral). 
If the participant is unable to provide informed consent, the investigator or delegate can 
obtain consent from an LAR.  If consent is obtained from an LAR, the following points 
will apply: 
 The investigator or his/her representative will explain the nature of the study to 
the LAR and answer all questions regarding the study. 
 Best efforts will be undertaken to obtain written consent (paper, email or 
eConsent) from an LAR.  However, if the LAR is not able to provide written or 
electronic consent for logistical reasons, informed consent can be obtained orally 
from the LAR.  As above for oral participant consent, oral LAR consent must be 
given to the investigator in the presence of an impartial witness.  In such cases, 
the witness is required to sign and date the ICF and the investigator is expected to 
record how the impartial witness was selected.  A correctly signed and dated ICF 
should be obtained from the LAR as soon as possible. 
 The investigator has responsibility for applying local laws in the matter of who 
has the capacity to consent and who qualifies as an LAR of a potential participant. 
 An LAR is defined as an individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective participant, to the 
participant’s participation in the clinical trial. 
 An LAR can be a member of the participant’s family, next-of-kin or trusted 
person previously designated by the participant. 
 As soon as is practically possible following a participant regaining capacity, 
participants will be asked to provide informed consent to remain in the study.  If 
they decline, then they will be withdrawn from the study.  The participant will 
decide if they want to allow samples already collected to be used or request for 
them to be discarded if not yet analyzed. 
 All relevant records should be archived in the Investigator Site File. 
Documentation of Informed consent process 
 
The management of the informed consent process will be documented in the medical 
source notes.  This will include which process was used to obtain consent.  The following 
should be noted in regard to the informed consent process: 
 
 If consent is provided orally by the participant or LAR in the presence of an 
impartial witness, the witness name, time and date of witnessing must be recorded 
in medical source notes.  The investigator must also document how the impartial 
witness was selected. 
 If consent is provided by LAR, name, time and date of LAR and name of the 
personnel at site that collected this information. 
 Participants/LAR must be informed that their participation is voluntary.  
Participants and/or LAR will be required to sign electronically or on paper (or 
agree orally) to a statement of informed consent that meets the requirements of 21 
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Accountability Act (HIPAA) requirements, where applicable, and the IEC or 
study center. 
A copy of all signed ICF(s) must be provided to the participant or the participant’s LAR. 
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about otilimab or about the study disease; publish the results of these research 
efforts; work with government agencies or insurers to have otilimab approved for medical 
use or approved for payment coverage. 
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research.  The investigator or authorized designee 
will inform each participant or their LAR of the possibility of further research not related 
to the study/disease.  Participants or their LAR will be told that they are free to refuse to 
participate and may withdraw their consent at any time and for any reason during the 
storage period.  A separate signature (participant or LAR) will be required to document 
agreement to allow any participant data and/or remaining leftover samples to be used for 
further research not related to the study/disease.  Participants or their LAR who decline 
further research will tick the corresponding “No” box. 
9.1.4. 
Data Protection 
 Participants will be assigned a unique identifier by the sponsor.  Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 
 The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law.  The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent. 
 The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
9.1.5. 
Committees Structure 
Part 1 
 
An Independent Data Monitoring Committee (IDMC) comprised of clinical experts 
external to GSK will review unblinded data at defined timepoints during the study.  If 
deemed appropriate by the IDMC, or upon request by GSK or investigators, additional 
timepoints for review may be added. 
Details of the structure and function of the IDMC, and analysis plan for IDMC reviews, 
are outlined in the IDMC Charter, which is available upon request. 

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In addition to the IDMC, the GSK SRT will review blinded safety data at a minimum of a 
weekly basis to ensure participant safety, which includes safety signal detection at any 
time during the study.  Details of this are included in Section 8.5. 
In the unlikely event that the IDMC cannot be convened for a scheduled meeting, the 
GSK Independent Safety Review Committee (iSRC) will review the unblinded outputs 
(as outlined in the IDMC Charter). 
Part 2 
 
An IDMC comprised of clinical experts external to GSK will review unblinded safety 
data at defined timepoints during the study.  If deemed appropriate by the IDMC, or upon 
request by GSK or investigators, additional timepoints for review may be added. 
Details of the structure and function of the IDMC, and analysis plan for IDMC reviews, 
are outlined in the IDMC Charter, which is available upon request. 
The GSK SRT will review blinded safety data at a minimum of a monthly basis to ensure 
participant safety, which includes safety signal detection at any time during the study.  
Details of this are included in Section 8.5. 
In the unlikely event that the IDMC cannot be convened for a scheduled meeting, the 
GSK Independent Safety Review Committee (iSRC) will review the unblinded outputs 
(as outlined in the IDMC Charter). 
9.1.6. 
Dissemination of Clinical Study Data 
 Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
 GSK will also provide all investigators who participated in the study with a 
summary of the study results and will tell the investigators what treatment their 
participants received.  The investigator(s) is/are encouraged to share the summary 
results with the study participants, as appropriate. 
 Under the framework of the SHARE initiative, GSK intends to make anonymized 
participant-level data from this trial available to external researchers for scientific 
analyses or to conduct further research that can help advance medical science or 
improve patient care.  This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding.  
Requests for access may be made through www.clinicalstudydatarequest.com. 
 GSK will provide the investigator with the randomization codes for their site only 
after completion of the full statistical analysis. 
 The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 

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 GSK intends to make anonymized patient-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care.  This helps ensure the data 
provided by trial participants are used to maximum effect in the creation of 
knowledge and understanding 
 A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
9.1.7. 
Data Quality Assurance 
 All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data).  The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF. 
 Guidance on completion of CRFs will be provided in the eCRF Guidelines. 
 Quality tolerance limits (QTLs) will be pre-defined in the QTL Plan to identify 
systematic issues that can impact participant safety and/or reliability of study 
results.  These pre-defined parameters will be monitored during and at the end of 
the study and all deviations from the QTLs and remedial actions taken will be 
summarized in the clinical study report. 
 The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 
 Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 
 The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
 The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
 Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period.  No records may be 
destroyed during the retention period without the written approval of the sponsor.  
No records may be transferred to another location or party without written 
notification to the sponsor. 

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9.1.8. 
Source Documents 
 Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at the 
investigator’s site. 
 Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained.  The investigator may need to request previous medical 
records or transfer records, depending on the study.  Also, current medical records 
must be available. 
 Definition of what constitutes source data and its origin can be found in the 
Source Data Acknowledgment. 
 The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
 Study monitors will perform ongoing monitoring (remote or on-site) as per the 
Monitoring Plan to confirm that data entered into the CRF by authorized site 
personnel are accurate, complete, and verifiable from source documents; that the 
safety and rights of participants are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
9.1.9. 
Study and Site Start and Closure 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
 If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements.  The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up 
 Discontinuation of further study intervention development 
 
 

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For site termination: 
 Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
 Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator 
9.1.10. 
Publication Policy 
 The results of this study may be published or presented at scientific meetings.  If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission.  This allows the sponsor to protect proprietary 
information and to provide comments. 
 The sponsor will comply with the requirements for publication of study results.  
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data.  In this case, a coordinating investigator will be designated 
by mutual agreement. 
 Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 

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9.2. 
Appendix 2: Clinical Laboratory Tests  
The tests detailed in Table 3 and Table 4 will be performed by the local laboratory. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Table 3 
Protocol-Required Safety Laboratory Tests – Part 1 
Laboratory 
Assessments1 
Parameters 
Hematology 
Hemoglobin 
RBC Indices: 
WBC count (differential) 
absolute and/or %: 
 
Hematocrit 
MCV 
Neutrophils 
 
Platelet Count 
MCH 
Lymphocytes 
 
RBC Count 
%Reticulocytes 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
Coagulation 
APTT / APTR 
PT 
INR 
Clinical 
Urea (BUN) 
Phosphate 
AST / SGOT 
Chemistry 
Creatinine 
Troponin I4 
ALT / SGPT 
 
Glucose2 
D-dimer 
Gamma-GT 
 
Potassium 
Ferritin5 
Total bilirubin 
 
Sodium 
CRP 
Direct bilirubin 
 
Calcium   
LDH 
ALP7 
 
Lactate3 
Procalcitonin5, 6  
Total protein 
 
Creatine kinase 
ESR5 
Albumin 
Pregnancy 
Highly sensitive serum or urine human chorionic gonadotropin (hCG) 
pregnancy test (as needed for women of childbearing potential) 
CRS Event 
If CRS is suspected, the following samples should be taken as soon as 
possible after suspected CRS on-set and again 24 h later: Hematology, CRP, 
D-dimer, ferritin, PD (cytokine sample – see Section 1.3) 
1. Hematology, Coagulation and Clinical Chemistry testing at the following time-points (unless 
otherwise indicated below):  Screening, Day 1, Day 2, Day 4, Day 7, Day 14, Day 28 and 
Discharge 
2. Record glucose fasting / non-fasting status 
3. Can be measured from arterial blood gas test 
4. If troponin I is not available locally, troponin T can be reported  
5. To be measured at Screening, Day 7 and Day 14 only 
6. Procalcitonin to be measured if the test is available locally 
7. If alkaline phosphatase is elevated, consider fractionating 
 

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Table 4 
Protocol-Required Safety Laboratory Tests – Part 2 
Laboratory 
Assessments1 
Parameters 
Hematology 
Hemoglobin 
RBC Indices: 
WBC count (differential) 
absolute and/or %: 
 
Hematocrit 
MCV 
Neutrophils 
 
Platelet Count 
MCH 
Lymphocytes 
 
RBC Count 
%Reticulocytes 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
Coagulation 
APTT / APTR 
PT or INR 
 
Clinical 
Urea (BUN) 
Phosphate 
AST / SGOT 
Chemistry 
Creatinine 
Troponin I2 
ALT / SGPT 
 
Glucose 
D-dimer 
Gamma-GT 
 
Potassium 
Ferritin3 
Total bilirubin 
 
Sodium 
CRP 
Direct bilirubin 
 
Calcium   
LDH 
ALP 
 
Creatine kinase 
ESR3 
Total protein 
 
 
 
Albumin 
CRS Event 
If CRS (considered possibly drug related – see Section 7.4.7.1) is suspected, 
the following samples should be taken as soon as possible after suspected 
CRS on-set and again 24 h later: Hematology, CRP, D-dimer, ferritin, PD 
(cytokine sample – see Section 1.3 and Section 1.4) 
1. Hematology, Coagulation and Clinical Chemistry testing at the following time-points (unless 
otherwise indicated below):  Screening, Day 1, Day 4, Day 7, Day 14, Day 28 and Discharge 
2. If troponin I is not available locally, troponin T can be reported  
3. To be measured at Screening, Day 7 and Day 14 only 

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9.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
9.3.1. 
Definition of AE 
AE Definition 
 An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of a study intervention, whether or not considered related to the 
study intervention. 
 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated 
with the use of a study intervention. 
 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECG, radiological scans, vital signs measurements), including 
those that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (i.e., not related to progression of underlying disease). 
 Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
 New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming intent.  
Such overdoses should be reported regardless of sequelae. 
 "Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported 
as an AE or SAE.  Such instances will be captured in the efficacy assessments.  However, 
the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported 
as AE or SAE if they fulfil the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition  
 Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the investigator to be 
more severe than expected for the participant’s condition. 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 

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 Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
 Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
 
9.3.2. 
Definition of SAE 
An SAE is defined as any serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant 
was at risk of death at the time of the event.  It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting.  
Complications that occur during hospitalization are AE.  If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event is serious.  When in doubt as to 
whether “hospitalization” occurred or was necessary, the AE should be considered serious. 
 Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
 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 with or prevent everyday life functions but 
do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
 Medical or scientific judgment should be exercised by the investigator in deciding whether 
SAE reporting is appropriate in other situations such as significant medical events that may 
jeopardize the participant or may require medical or surgical intervention to prevent one of 
the other outcomes listed in the above definition.  These events should usually be considered 
serious. 

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o Examples of such events include invasive or malignant cancers, intensive treatment for 
allergic bronchospasm, blood dyscrasias, convulsions, acute deterioration of liver 
function, or development of intervention dependency or intervention abuse. 
 
9.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the following 
AEs and SAEs: 
 Myocardial infarction/unstable angina 
 Congestive heart failure 
 Arrhythmias 
 Valvulopathy 
 Pulmonary hypertension 
 Cerebrovascular events/stroke and transient ischemic attack 
 Peripheral arterial thromboembolism 
 Deep venous thrombosis/pulmonary embolism 
 Revascularization 
 
9.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
 When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) related to 
the event. 
 The investigator will then record all relevant AE/SAE information. 
 It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to GSK in lieu of completion of the GSK required form. 
 There may be instances when copies of medical records for certain cases are requested by 
GSK.  In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to GSK. 
 The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
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 Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
 Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
 Severe: An event that prevents normal everyday activities.  An AE that is assessed as severe 
should not be confused with an SAE.  Severe is a category utilized for rating the intensity of 
an event; and both AE and SAE can be assessed as severe. 
 An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
 A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
 The investigator will use clinical judgment to determine the relationship. 
 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated. 
 The investigator will also consult the Investigator’s Brochure (IB) and/or Product Information, 
for marketed products, in his/her assessment. 
 For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK.  However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to GSK. 
 The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
 The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AE and SAE 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to elucidate 
the nature and/or causality of the AE or SAE as fully as possible.  This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
 If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide GSK with a copy of any post-mortem findings including 
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 New or updated information will be recorded in the originally submitted documents. 
 The investigator will submit any updated SAE data to GSK within 24 hours of receipt of 
the information. 
 
9.3.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
 
The primary mechanism for reporting SAE to GSK will be the electronic data collection tool. 
 If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
 The site will enter the SAE data into the electronic system as soon as it becomes available. 
 The investigator or medically-qualified sub-investigator must show evidence within the eCRF 
(e.g., check review box, signature, etc.) of review and verification of the relationship of each 
SAE to investigational product/study participation (causality) within 72 hours of SAE entry into 
the eCRF. 
 After the study is completed at a given site, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
 If a site receives a report of a new SAE from a study participant or receives updated data on 
a previously reported SAE after the electronic data collection tool has been taken off-line, 
then the site can report this information on a paper SAE form (see next section) or to the SAE 
coordinator by telephone. 
 Contacts for SAE reporting can be found in Study Reference Manual. 
 
SAE Reporting to GSK via Paper Data Collection Tool 
 
Facsimile transmission of the SAE paper data collection tool is the preferred method to 
transmit this information to the SAE coordinator. 
 In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
 Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE data collection tool within the designated reporting time frames. 
 Contacts for SAE reporting can be found in Study Reference Manual. 

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9.4. 
Appendix 4: Contraceptive and Barrier Guidance (Part 1 
only) 
9.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
 A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. 
 Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
 For individuals with permanent infertility due to an alternate medical cause other than 
the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. 
 
 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual 
cycle cannot be confirmed before first dose of study intervention, additional evaluation 
should be considered. 
9.4.2. 
Contraception Guidance: 
 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per 
year when used consistently and correctly. 
 Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
 Intrauterine device (IUD) 
 Intrauterine hormone-releasing system (IUS)c 
 Bilateral tubal occlusion 
 Azoospermic partner (vasectomized or due to a medical cause) 

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 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed.  If not, an additional highly effective method of contraception should be used.  
Spermatogenesis cycle is approximately 90 days. 
 
 
Note: documentation of azoospermia for a male participant can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history interview 
 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
 Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
o oral 
o intravaginal 
o transdermal 
o injectable 
 Progestogen-only hormone contraception associated with inhibition of ovulationc 
o oral 
o injectable 
 Sexual abstinence 
 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention 
and  is the participant’s normal practice.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
a. Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly.  Typical use failure rates 
differ from those when used consistently and correctly. 
c.  Male condoms must be used in addition to hormonal contraception.  If locally required, in 
accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of 
action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal 
(coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not 
acceptable methods of contraception.  Male condom and female condom should not be used 
together (due to risk of failure from friction). 
 

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9.5. 
Appendix 5: Abbreviations and Trademarks 
Ab 
Antibody 
ABG 
Arterial Blood Gas 
ADE 
Adverse Device Effect 
AE(s) 
Adverse event(s) 
AESI 
Adverse event of special interest 
ALI 
Acute Lung Injury 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
ANC 
Absolute Neutrophil Count 
APTT/APTR 
Activated Partial Thromboplastin Time/Activated Partial 
Thromboplastin Time Ratio 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
Aspartate transaminase 
AUC 
Area Under the Curve 
BAL 
Bronchoalveolar Lavage 
BiPAP 
Bilevel Positive Airway Pressure 
BUN 
Blood Urea Nitrogen 
CAR 
Chimeric Antigen Receptor 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
Clearance 
Cmax 
Maximum Concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus Disease 2019 
CPAP 
Continuous Positive Airway Pressure 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRS 
Cytokine Release Syndrome 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CTCAE 
Common terminology criteria for Adverse Events 
CTFG 
Clinical Trial Facilitation Group 
CV 
Cardiovascular 
DMARD 
Disease-modifying antirheumatic drug 
ECG 
Electrocardiogram 
ECMO 
Extracorporeal Membrane Oxygen 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
ESR 
Erythrocyte sedimentation rate 
FDA 
Food and Drug Administration 
FiO2 
Concentration of Inspired Oxygen 
FU 
Follow-up 
GCP 
Good Clinical Practice 
GCS 
Glasgow Coma Scale 
GFR 
Glomerular filtration rate 
GM-CSF 
Granulocyte-macrophage colony stimulating factor 

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GM-CSFR 
Granulocyte-macrophage colony stimulating factor receptor 
GSK 
GlaxoSmithKline 
h 
Hour 
HBsAg 
Hepatitis B-surface Antigen 
hCG 
Human chorionic gonadotropin 
HF 
Human Factors 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HRT 
Hormone replacement therapy 
HV 
Healthy volunteer 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
ICU 
Intensive Care Unit 
IDMC 
Independent Data Monitoring Committee 
IEC 
Institutional ethics committee 
IFN 
Interferon Gamma 
IFU 
Instructions For Use 
IL 
Interleukin 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional review board 
IRT 
Interactive Response Technology 
iSRC 
Independent Safety Review Committee 
ITT 
Intent to Treat 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
JAK 
Janus Kinase 
L 
Liter 
LAM 
Lactational amenorrhea method 
LAR 
Legally Authorized Representative 
LDH 
Lactate dehydrogenase 
mAb 
Monoclonal antibody 
MAP 
Mean Arterial Pressure 
MCP-1 
Monocyte Chemoattractant Protein-1 Alpha 
MCV 
Mean cell volume 
MCH 
Mean corpuscular hemoglobin 
MedDRA 
Medical dictionary for regulatory activities 
g 
Microgram 
m2 
Square Meters 
mg 
Milligram 
Min 
Minute 
MIP-1 
Macrophage Inflammatory Protein-1 
mL 
Milliliter 
mm3 
Cubic Millimeters 
mmHg 
Millimeters of Mercury 
MS 
Multiple sclerosis 

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MSDS 
Material safety data sheet 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NOAEL 
No observed adverse effect level 
NYHA 
New York Heart Association 
OR 
Odds Ratio 
PAP 
Pulmonary alveolar proteinosis 
PD 
Pharmacodynamic 
PFS 
Prefilled syringe 
PI 
Principal Investigator 
PT 
Prothrombin Time 
PK 
Pharmacokinetics 
RA 
Rheumatoid arthritis 
RBC 
Red Blood Cell 
RRT 
Renal replacement therapy 
RT-PCR 
Reverse Transcriptase Polymerase Chain Reaction 
SADE 
Serious Adverse Device Effect  
SARS-CoV-2 
Severe Acute Respiratory Syndrome–Coronavirus-2 
SC 
Subcutaneous 
SAE(s) 
Serious adverse event(s) 
SoA 
Schedule of Activities 
SOFA 
Sequential Organ Failure Assessment 
SpO2 
Blood Oxygen Saturation 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
SSD 
Safety Syringe Device 
TB 
Tuberculosis 
TNFα 
Tumor necrosis factor alpha 
ULN 
Upper limit of normal 
USADE 
Unanticipated Serious Adverse Device Effect 
VAP 
Ventilator-associated Pneumonia 
WBC 
White Blood Cell 
WHO 
World Health Organization 
WOCBP 
Woman of Childbearing Potential 
WONCBP 
Woman of Non-Childbearing Potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
None 
 
MedDRA 

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9.6. 
Appendix 6: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 2: 02-JUL-2020 
This amendment is considered to be non-substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment: modifications to the protocol in response to 
regulatory and ethics committee feedback, and clarifications based on investigator 
feedback.  The main changes are (1) clarification that Day 1 pre-dose assessments do not 
need to be repeated if Screening and Randomization are within 24 hours; (2) expedited 
reporting of cytokine release syndrome (CRS) as an AESI; (3) clarification that organ 
transplant patients are excluded per Exclusion Criteria #11; (4) clarification of conditions 
by which convalescent plasma is permitted or not during the study; (5) removed specific 
mention of chloroquine and hydroxychloroquine; (6) expanded the null hypothesis; (7) 
consent may be collected before the 48h screening window. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3. Schedule 
of Activities 
Revised text that if Screening and 
Randomization are within 24 hours rather 
than the same day, there is no need to 
repeat Day 1 pre-dose assessments, 
(except Ordinal Scale and pre-infusion vital 
signs), and that Randomization and Dosing 
should be as close as possible. 
Added note that consent may be collected 
before the 48h screening window. 
Investigator’s feedback. 
Section 2.3.1. Risk 
Assessment and 
Section 7.4.7.1. 
Cytokine Release 
Syndrome 
Added statement that in the event that new 
onset of CRS is suspected, the medical 
monitor should be notified immediately and 
under no circumstance should this exceed 
24 hours, and the event must also be 
reported within 24 hours as an AE or an 
SAE. 
Regulatory request. 
Section 4.4 
Definition of a participant who completes 
the study updated to include participants 
who die prior to Day 60. 
Clarification of definition. 
Section 5.2. 
Exclusion Criteria 
#11 
Added note that participants with an organ 
transplant are excluded. 
Ethics Committee request. 
Section 5.2. 
Exclusion Criteria 
#13 
Added conditions by which convalescent 
plasma is not permitted during the study. 
Investigator’s feedback. 
Section 5.2. 
Exclusion Criteria 
#19 
Hemoglobin 9 g/dL. 
Error in units. 
Section 6.6. 
Concomitant Therapy 
Added conditions by which convalescent 
plasma is permitted. 
Investigator’s feedback. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 6.6.2. 
Medication/Treatment 
PERMITTED During 
the Study 
Removed specific mention of chloroquine 
and hydroxychloroquine. 
No longer expected to be widely 
used following clinical trials 
results. 
Section 7.2.4. 
Ventilation status 
Added statement to record if the participant 
was in the prone or semi-prone position at 
any time whilst mechanically ventilated. 
Investigator’s feedback. 
Section 7.2.6. Ordinal 
Scale 
Added note for additional organ support. 
Clarification. 
Section 7.3.1. 
Physical 
Examinations 
Clarification that physical exam results will 
not be recorded in the eCRF. 
Investigator’s feedback. 
Section 8.1. 
Statistical 
Hypotheses 
Expanded the null hypothesis. 
Clarification of the null 
hypothesis. 
Section 9.1.3. 
Informed Consent 
Process 
Added note that consent may be collected 
before the 48h screening window. 
Clarification. 
All sections 
Other minor, grammatical and typographical corrections to improve readability. 
 
Amendment 1: 18-MAY-2020 
This amendment is considered to be substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment: modifications to the protocol in response to 
regulatory feedback, and clarifications based on investigator feedback.  The key change is 
revision of the primary endpoint (where definition of “free of respiratory failure” is 
participants in categories 1-4 on GSK Ordinal Scale).  Other changes are (1) to revise 
recording of blood pressure and pulse rate; (2) to add details of randomization caps; (3) to 
simplify/clarify some Inclusion and Exclusion Criteria; (4) to clarify medications 
permitted during the study. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 and 
Section 3 Objectives 
and Endpoints 
Revised “independent of 
supplementary oxygen” to “free 
of respiratory failure” for 
Primary Endpoint; added or 
revised Secondary Endpoints 
(added Time to all-cause 
mortality, Time to recovery from 
respiratory failure and Time to 
last dependence on 
supplementary oxygen); added 
or revised some Exploratory 
Endpoints (added Change in 
COVID-19 signs and 
symptoms). 
Regulatory feedback, new FDA guidance 
for the development of COVID-19 
treatments, and clarification. 
 
 
 
 
 
 
 
 
 
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
 
Removed details of organ 
support in the Ordinal Scale. 
 
Clarification based on regulatory and 
investigator feedback and to ensure 
alignment with Exclusion Criteria 3 and 
description of categories in the Ordinal 
Scale. 
Section 1.3 Schedule 
of Activities 
Revised recording of blood 
pressure and pulse rate to daily 
up to Day 28 or discharge. 
Regulatory request. 
Section 4.1.2. Main 
Cohort (after 20 
Participants) 
Acknowledgment that 
randomization caps will be 
used. 
Text added in line with the IDMC Charter 
for transparency purposes. 
Section 5.1. Inclusion 
Criteria 
Inclusion 2: Removal of SpO2 
93% on room air. 
 
Inclusion 4: Clarification of 
sexual abstinence. 
#2 Feedback from investigators based on 
clinical practice to identify participants with 
oxygenation impairment. 
#4 Regulatory feedback. 
Section 5.2. Exclusion 
Criteria 
Exclusion 3: Added use of high-
dose or multiple vasopressors 
as an exclusion. 
Clarification of Exclusion Criteria related to 
organ support. 
Section 6.6.2. 
Medication/Treatment 
Permitted During the 
Study 
Added statement that all 
treatments for participants in 
the ICU are permitted, and 
clarification of additional 
treatments of COVID-19 related 
disease. 
Clarification based on regulatory and 
investigator feedback and to ensure 
alignment with Exclusion Criteria 3 and 
description of categories on the ordinal 
scale. 
Section 7.2.6, Ordinal 
Scale 
Removed details of organ 
support in the Ordinal Scale. 
Clarification based on regulatory and 
investigator feedback and to ensure 
alignment with Exclusion Criteria 3 and 
description of categories in the Ordinal 
Scale. 
Section 8.1. Statistical 
Hypotheses 
Revised null hypothesis for 
consistency with changes to the 
Primary Endpoint and added 
alternative to the null 
hypothesis. 
Regulatory feedback for Primary Endpoint 
and clarification for alternative to null 
hypothesis. 
Section 8.4.2. Primary 
Endpoint(s) 
Revised “independent of 
supplementary oxygen” to “free 
of respiratory failure” for 
Primary Endpoint. 
Regulatory feedback. 
8.5. Interim Analysis 
Safety stopping rules have 
been put in place for the IDMC 
to stop the study if there is an 
excess risk of mortality. 
Regulatory request. 
Section 9.4.2. 
Contraception 
Guidance: 
Clarification of situations when 
sexual abstinence is 
acceptable. 
Regulatory request. 
All sections 
Other minor, grammatical and typographical corrections to improve 
readability. 

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9.7. 
Appendix 7: Country-Specific Protocol Addendums 
The addition of Part 2 has changed the section numbering of the document, which means 
that the numbering of the Country-Specific Protocol Addendums will have changed.  
This will be documented at a local level (if the impacted countries are approved for 
Part 2).  Therefore, all investigators in countries with a Country-Specific Protocol 
Addendum should refer to the locally provided Country-Specific Protocol Addendum and 
any associated documentation.  
9.7.1. 
The Netherlands (27-MAY-2020) 
A country specific addendum for the Netherlands was made to the Global Protocol (dated 
30-APR-2020) and all future versions.   
The addendum requires that in the Netherlands (hydroxy)chloroquine as a concomitant 
medication is prohibited. 
The following section of the Global Protocol was amended: 
6.6.1. Medication NOT Permitted During the Study 
…… Chloroquine and hydroxychloroquine. 
 
9.7.2. 
South Africa (28-MAY-2020) 
A country specific addendum for South Africa was made to the Global Protocol (dated 
30-APR-2020) and all future versions.   
The addendum requires that in South Africa HIV testing should be conducted at 
Screening. 
The following sections of the Global Protocol were amended: 
1.3. Schedule of Activities 
HIV test added at Screening (if HIV status unknown). 
5.2. Exclusion Criteria 
HIV positive added as an exclusion criterion – as below: 
CONCOMITANT MEDICAL CONDITIONS 
4. Current serious or uncontrolled medical condition (e.g. significant pulmonary 
disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class 
III or higher], significant renal dysfunction, acute myocardial infarction or acute 
cerebrovascular accident within the last 3 months) or abnormality of clinical 
laboratory tests that, in the investigator’s judgment, precludes the participant’s safe 
participation in and completion of the study. 
5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-
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6. Known active tuberculosis (TB), history of untreated or incompletely treated active 
or latent TB, suspected or known extrapulmonary TB. 
7. Known HIV positive regardless of immunological status. 
8. Known HBsAg and/or anti-HCV positive. 
9. Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy. 
 
9.7.3. 
India (31-JUL-2020)_IND_01 
A country specific addendum for India was made to the Global Protocol (Amendment 2, 
dated 02-JUL-2020) and all future versions.   
If India participate in Part 2 of the study, the country specific addendum for India (dated 
31-Jul-20) will be updated to reflect the changes in Protocol Amendment 3 (country 
specific addendum update not completed at the point of Protocol Amendment 3 sign off).   
A global Protocol Amendment will not be issued when the second version of the India 
country specific addendum is released.  Therefore, all investigators in India should refer 
to the locally provided country specific addendum for India. 
The addendum was made based on a recommendation from the SEC for patients with 
severe pulmonary COVID-19 related disease (29-Jul-2020). 
The following section of the Global Protocol was amended (text in bold and underlined 
indicates new text): 
5.1. Inclusion Criteria 
AGE 
1. Age 18 years and 79 years at the time of obtaining informed consent. 
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS 
2. Participants must: 
a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed 
on an appropriate specimen; e.g. respiratory tract sample]) 
b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or 
computerized tomography [CT] scan consistent with COVID-19) 
c. AND be developing new onset of oxygenation impairment defined as SpO2 
90% on room air 
d. AND requiring any of the following: 
1. high-flow oxygen (15L/min) 
2. non-invasive ventilation (e.g. CPAP, BiPAP) 
3. mechanical ventilation 48h prior to dose 
e. AND have increased biological markers of systemic inflammation (either CRP 
>ULN1 or serum ferritin >ULN1). 
1According to local reference range.  Repeat CRP or ferritin tests are permitted. 
 

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9.7.4. 
Japan (22-JAN-2021)_JPN_04 
If minor changes are made to the Country Specific Requirements for Japan (e.g. the 
Study Period dates are amended), the global protocol will not be updated, and the 
changes will be recorded in the local document only.  Therefore, all investigators in Japan 
should refer to the locally provided Country Specific Requirements Document for Japan. 
The following country specific requirements apply for Japan: 
1. Study Conduct Considerations 
1.1 Regulatory and Ethical Considerations 
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW Notification 
No.28 dated 27th March, 1997)” and Pharmaceuticals and Medical Devices Act. 
The statement “I acknowledge that I am responsible for overall the study conduct.” on the 
Investigator Protocol Agreement Page means the investigator’s responsibility defined by 
Japanese GCP. 
GSK will submit the CTN to the regulatory authorities in accordance with 
Pharmaceuticals and Medical Devices Act before conclusion of any contract for the 
conduct of the study with study sites. 
1.2 Informed Consent 
Prior to participation in the study, the investigator should fully inform the potential 
participant and/or the participant's legally acceptable representative of the study including 
the written information. The investigator should provide the participant and/or the 
participant's legally acceptable representative ample time and opportunity to inquire 
about details of the study. The participant and/or the participant’s legally acceptable 
representative should sign and personally date the consent form. If the participant is 
capable of understanding but not able to provide written consent, or if the legally 
authorized representative is not able to provide written consent, informed consent can be 
obtained orally in the presence of an impartial witness (Protocol Section 9.1.3). The 
person, who conducted the informed consent discussion and the study collaborator giving 
supplementary explanation, where applicable, should sign and personally date the consent 
form. If an impartial witness is required, the witness should sign and personally date the 
consent form. The investigator should retain this signed and dated form (and other written 
information) together with the source medical records, such as clinical charts (in 
accordance with the rules for records retention, if any, at each medical institution) and 
give a copy to the participant and/or the participant’s legally acceptable representative. If 
the participant is a minor, document informed consent will be obtained from both the 
participant and his/her legally acceptable representative. In addition, if a minor 
participant reaches an adult during the treatment period, the participant's consent to 
participate in the clinical trial will be obtained again. 
Regarding informed consent process of this study, the following is added according to 
GCP 7.3. 

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 
The study population consists of hospitalized participants with new onset hypoxia 
requiring significant oxygen support or requiring early invasive mechanical 
ventilation (48 hours before dosing). The consent by participants themselves is 
obtained whenever possible, but the study population includes participants who may 
have difficulty in giving their own consent under Article 50, Paragraphs 1 and 2. An 
application for marketing approval of otilimab is intended to be submitted so that 
otilimab will be used for emergency treatment to save lives of patients in a life-
threatening condition. 
 
There is no approved drug specifically targeting severe pulmonary COVID-19 
related disease in Japan as of 3 June 2020, although remdesivir has been approved in 
Japan for SARS-CoV-2 infection. Currently it is unknown if available treatments are 
likely to achieve sufficient therapeutic effects on severe pulmonary COVID-19 
related disease in the prospective participants. 
 
Otilimab is expected to inhibit inflammation due to SARS-CoV-2 infection. There is 
a sufficient possibility of preventing further aggravation and saving the life of the 
prospective participants by using otilimab for patients with severe COVID-19 related 
pulmonary disease (protocol Section 2). 
 
An Independent Data Monitoring Committee (IDMC) has been established for this 
study, and interim analyses will be used to assess safety, futility and efficacy 
(protocol Section 9.1.5).  
 
If the participant is unable to provide informed consent and consent is obtained from 
his/her legally authorized representative (LAR), participants will be asked to provide 
informed consent to remain in the study as soon as practically possible following the 
participant regaining capacity. If they decline, then they will be withdrawn from the 
study. Unidentified persons are excluded from the study because of the consent 
process in that consent is obtained from a his/her LAR before the study start if the 
participant is unable to provide informed consent (protocol Section 9.2.3). 
1.3 Study Period 
JUL/2020 – SEP/2021  
1.4 Study Administrative Structure 
Sponsor information is included in Exhibit 1. List of Medical Institutions and 
Investigators is included in Exhibit 2. 
2 MODIFICATION TO THE GLOBAL PROTOCOL 
2.1 Exclusion Criteria – Part 1 (Protocol Section 5.3) 
The following underlined texts are added in the relevant part of the protocol. 
No.6 of the exclusion criteria 
Known active tuberculosis (TB), history of untreated or incompletely treated active or 
latent TB, suspected or known extrapulmonary TB. 

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In addition, conduct QuantiFERON-TB Gold plus test or T-SPOT test at screening, if 
either of tests was not conducted within 4 weeks before Day 1. If either of test results is 
obtained during screening and show positive result, the participants are ineligible. If any 
test results can’t be obtained during screening because of result availability, check either 
of test results after IP dosing once the result is obtained. If it is found that either of tests 
shows positive result after IP dosing, the participants should be managed appropriately 
per local guidelines/medical judgement.  
No.8 of the exclusion criteria 
Known HBsAg and/or anti-HCV positive 
In addition, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), 
hepatitis B surface antibody (HBsAb) and HBV deoxyribonucleic acid (DNA) are tested 
about all participants in Japan at screening. Based on all results obtained during 
screening, check the below about all participants in principle.  
 
positive for hepatitis B surface antigen (HBsAg) or  
 
positive for hepatitis B core antibody (HBcAb) and positive for HBV 
deoxyribonucleic acid (DNA) or  
 
positive for hepatitis B surface antibody (HBsAb) and positive for HBV 
deoxyribonucleic acid (DNA) 
If any of the above can’t be judged during screening because of result availability, check 
the tests after IP dosing once the remaining results are obtained. If it is found that 
participants are applied any of the above after IP dosing, the participant should be 
managed appropriately per local guidelines/medical judgement. If it is found that 
participants are positive for HBcAb and/or HBsAb and negative for HBV DNA, the 
participants should be checked for HBV DNA again at Day 28 (or at Discharge if before 
Day 28).  
2.2 Exclusion Criteria – Part 2 (Protocol Section 5.4) 
The following underlined texts are added in the relevant part of the protocol. 
No.6 of the exclusion criteria 
Known active tuberculosis (TB), history of untreated or incompletely treated active or 
latent TB, suspected or known extrapulmonary TB. 
In addition, conduct QuantiFERON-TB Gold plus test or T-SPOT test at screening, if 
either of tests was not conducted within 4 weeks before Day 1. If either of test results is 
obtained during screening and show positive result, the participants are ineligible. If any 
test results can’t be obtained during screening because of result availability, check either 
of test results after IP dosing once the result is obtained. If it is found that either of tests 
shows positive result after IP dosing, the participants should be managed appropriately 
per local guidelines/medical judgement.  

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No.8 of the exclusion criteria 
Known HBsAg and/or anti-HCV positive (patients demonstrating a sustained virologic 
response (SVR) are not excluded from participation). 
In addition, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), 
hepatitis B surface antibody (HBsAb) and HBV deoxyribonucleic acid (DNA) are tested 
about all participants in Japan at screening. Based on all results obtained during 
screening, check the below about all participants in principle.  
 
positive for hepatitis B surface antigen (HBsAg) or  
 
positive for hepatitis B core antibody (HBcAb) and positive for HBV 
deoxyribonucleic acid (DNA) or  
 
positive for hepatitis B surface antibody (HBsAb) and positive for HBV 
deoxyribonucleic acid (DNA) 
If any of the above can’t be judged during screening because of result availability, check 
the tests after IP dosing once the remaining results are obtained. If it is found that 
participants are applied any of the above after IP dosing, the participant should be 
managed appropriately per local guidelines/medical judgement. If it is found that 
participants are positive for HBcAb and/or HBsAb and negative for HBV DNA, the 
participants should be checked for HBV DNA again at Day 28 (or at Discharge if before 
Day 28). 
2.3 Study Intervention(s) Administered (Protocol Section 6.1) 
The following supplementary explanation is added. 
 
In this study, only single-use vials will be used. 
 
2.4 STUDY ASSESSMENTS AND PROCEDURES (Protocol Section 7) 
The following texts are updated in the relevant part of the protocol according to the tests 
for TB and HBV. 
 
The maximum amount of blood collected from each participant over the duration of 
the study for the purpose of meeting the objectives will not exceed 200 mL 230 mL.  
This does not include any standard of care assessments. 
 
2.5 Clinical Laboratory Tests (Protocol Appendix 2) 
The following underlined texts are added in the relevant part of the protocol. 

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Table 3 
Protocol-Required Safety Laboratory Tests – Part 1  
Laboratory 
Assessments1 
Parameters 
Hematology 
Hemoglobin 
RBC Indices: 
WBC count (differential) 
absolute and/or %: 
 
Hematocrit 
MCV 
Neutrophils 
 
Platelet Count 
MCH 
Lymphocytes 
 
RBC Count 
%Reticulocytes 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
Coagulation 
APTT / APTR 
PT 
INR 
Clinical 
Urea (BUN) 
Phosphate 
AST / SGOT 
Chemistry 
Creatinine 
Troponin I4 
ALT / SGPT 
 
Glucose2 
D-dimer 
Gamma-GT 
 
Potassium 
Ferritin5 
Total bilirubin 
 
Sodium 
CRP 
Direct bilirubin 
 
Calcium   
LDH 
ALP7 
 
Lactate3 
Procalcitonin5, 6  
Total protein 
 
Creatine kinase 
ESR5 
Albumin 
Pregnancy 
Highly sensitive serum or urine human chorionic gonadotropin (hCG) 
pregnancy test (as needed for women of childbearing potential) 
CRS Event 
If CRS is suspected, the following samples should be taken as soon as 
possible after suspected CRS on-set and again 24 h later: Hematology, CRP, 
D-dimer, ferritin, PD (cytokine sample – see Section 1.3) 
Other Tests8 
Serology [hepatitis B surface antigen (HBsAg), hepatitis B core antibody 
(HBcAb), hepatitis B surface antibody (HBsAb), HBV DNA], tuberculosis 
(QuantiFERON-TB Gold plus test or T-Spot TB test) 
1. Hematology, Coagulation and Clinical Chemistry testing at the following time-points (unless 
otherwise indicated below):  Screening, Day 1, Day 2, Day 4, Day 7, Day 14, Day 28 and 
Discharge 
2. Record glucose fasting / non-fasting status 
3. Can be measured from arterial blood gas test 
4. If troponin I is not available locally, troponin T can be reported  
5. To be measured at Screening, Day 7 and Day 14 only 
6. Procalcitonin to be measured if the test is available locally 
7. If alkaline phosphatase is elevated, consider fractionating 
8. Test at screening. In addition, the participants with positive HBcAb and/or HBsAb and 
negative HBV DNA should be checked for HBV DNA again at Day 28 (or at Discharge if 
before Day 28).  
 

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Table 4 
Protocol-Required Safety Laboratory Tests – Part 2 
Laboratory 
Assessments1 
Parameters 
Hematology 
Hemoglobin 
RBC Indices: 
WBC count (differential) 
absolute and/or %: 
 
Hematocrit 
MCV 
Neutrophils 
 
Platelet Count 
MCH 
Lymphocytes 
 
RBC Count 
%Reticulocytes 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
Coagulation 
APTT / APTR 
PT or INR 
 
Clinical 
Urea (BUN) 
Phosphate 
AST / SGOT 
Chemistry 
Creatinine 
Troponin I2 
ALT / SGPT 
 
Glucose 
D-dimer 
Gamma-GT 
 
Potassium 
Ferritin3 
Total bilirubin 
 
Sodium 
CRP 
Direct bilirubin 
 
Calcium   
LDH 
ALP 
 
 
 
Total protein 
 
Creatine kinase 
ESR 3 
Albumin 
CRS Event 
If CRS (considered possibly drug related – see Section 7.4.7.1) is suspected, 
the following samples should be taken as soon as possible after suspected 
CRS on-set and again 24 h later: Hematology, CRP, D-dimer, ferritin, PD 
(cytokine sample – see Sections 1.3 and 1.4) 
Other Tests4 
Serology [hepatitis B surface antigen (HBsAg), hepatitis B core antibody 
(HBcAb), hepatitis B surface antibody (HBsAb), HBV DNA], tuberculosis 
(QuantiFERON-TB Gold plus test or T-Spot TB test) 
1. Hematology, Coagulation and Clinical Chemistry testing at the following time-points (unless 
otherwise indicated below):  Screening, Day 1, Day 4, Day 7, Day 14, Day 28 and Discharge 
2. If troponin I is not available locally, troponin T can be reported  
3. To be measured at Screening, Day 7 and Day 14 only 
4. Test at screening. In addition, the participants with positive HBcAb and/or HBsAb and 
negative HBV DNA should be checked for HBV DNA again at Day 28 (or at Discharge if 
before Day 28). 
 
2.6 CONTRACEPTIVES ALLOWED DURING THE STUDY – Part 1 only 
(Appendix 4) 
Of contraceptive methods defined in the protocol Appendix 4, Contraceptive Methods 
Approved in this Study, the following are not approved in Japan as contraceptive 
methods. 
Highly Effective Methods That Have Low User Dependency 
 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation 

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Highly Effective Methods That Are User Dependent 
 
Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation  
 
intravaginal 
 
transdermal 
 
injectable 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
 
oral 
 
injectable 
 
 

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10. 
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