An Open-label, Non-comparator, Multicenter Study to Describe the Pharmacokinetics (PK), Pharmacodynamics (PD; Viral Load) and Safety Following a Single Intravenous or Intramuscular Dose of Sotrovimab in Pediatric Participants With Mild to Moderate COVID-19 at High Risk of Disease Progression
Phase: PHASE2
Conditions: COVID-19
Sponsor: GlaxoSmithKline

                                                Protocol 
 
Study ID: 215226 
 
Official Title of Study: An open-label, non-comparator, multicenter study to describe 
                                       the pharmacokinetics (PK), pharmacodynamics (PD; viral load) 
                                       and safety following a single intravenous or intramuscular dose 
                                       of sotrovimab in pediatric participants with mild to moderate 
                                       COVID-19 at high risk of disease progression 
 
NCT number: NCT05124210 
 
Date of Document: 01-Oct-2021  
 
 
 
 
 

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GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: An open-label, non-comparator, multicenter study to describe the 
pharmacokinetics (PK), pharmacodynamics (PD; viral load) and safety following a single 
intravenous or intramuscular dose of sotrovimab in pediatric participants with mild to 
moderate COVID-19 at high risk of disease progression 
Protocol Number: GSK Study 215226/VIR-7831-5005 Amendment 1 
Compound Number 
or Name: 
Sotrovimab (also known as GSK4182136, VIR-7831) 
 
Brief Title:  
Pharmacokinetics, pharmacodynamics, and safety of single-dose sotrovimab in high-risk 
pediatric participants with mild to moderate COVID-19 
 
Study Phase: Phase 2b 
Acronym: COMET-PACE (COVID-19 Monoclonal antibody Efficacy Trial- PediAtriC 
Early treatment) 
 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited  
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
 
Regulatory Agency Identifying Number(s):  
Registry 
ID 
IND 
154430 
EudraCT 
2021-003717-18 
Approval Date: 01-OCT-2021 
©2021 the GlaxoSmithKline group of companies or its licensor. All rights reserved. 
Unauthorized copying or use of this information is prohibited.

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SPONSOR SIGNATORY: 
Protocol Title: An open-label, non-comparator, multicenter study to describe the 
pharmacokinetics (PK), pharmacodynamics (PD; viral load) and safety following a single 
intravenous or intramuscular dose of sotrovimab in pediatric participants with mild to 
moderate COVID-19 at high risk of disease progression 
Protocol Number: GSK Study 215226/VIR-7831-5005 Amendment 1 
Compound Number 
or Name: 
Sotrovimab (also known as GSK4182136, VIR-7831) 
 
 
 
 
Andrew Skingsley 
Clinical Development Lead, M.D. 
 
 
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 
Document Identifier 
Amendment 1 
01-OCT-2021 
TMF-13971114 
Original Protocol 
11-AUG-2021 
TMF-13858781 
 
Amendment 1 01-OCT-2021 
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:  
The rationale for this amendment is to 1) update the dosing scheme to use weight-based 
dosing per United States Food and Drug Administration (FDA) feedback, 2) to make 
intramuscular (IM) dosing contingent on confirmation of the efficacy of IM dosing in 
adults, 3) to include occurrence of multisystem inflammatory syndrome in children 
(MIS-C) as an objective per European Medicines Agency Pediatric Committee request 
and 4) to align blood sample collection volumes in participants <2 years to be within 
acceptable limits set out by the National Institute of Health (NIH) directives. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis; 1.2 Schema; 
4.1. Overall Design; 4.2. 
Scientific Rationale for Study 
Design; 4.3. Justification for 
Dose; 6.1. Study 
Intervention(s) Administered 
Updated dosing scheme and 
justification to include weight-
based dosing for all participants 
(Section 1.1, Section 4.3, and 
Section 6.1) and to make the 
initiation of intramuscular (IM) 
dosing dependent on efficacy of 
IM dosing in adults (Section 1.1, 
Section 1.2, Section 4.1, and 
Section 4.2). 
Changes made to address 
FDA feedback regarding 
dosing.  
1.3. Schedule of Activities 
(SoA); 3. Objectives, 
Endpoints, and Estimands; 5.2 
Exclusion Criteria; 8.5.7. 
Monitoring of Multisystem 
Inflammatory Syndrome in 
children (MIS-C) 
Added the following endpoint to 
the Other Safety endpoints: 
occurrence of multisystem 
inflammatory syndrome in 
children (MIS-C) through Day 29 
and Week 36. Specified in the 
SoA that events of MIS-C are 
collected as adverse events. 
Clarified MIS-C diagnoses 
Added endpoint at the 
request of the European 
Medicines Agency 
Pediatric Committee and 
clarified the MIS-C 
reporting and diagnosis 
criteria to be used for this 
endpoint. 

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Section # and Name 
Description of Change 
Brief Rationale 
criteria in the exclusion criteria 
and in Section 8.5.7. 
1.1. Synopsis; 1.3. Schedule of 
Activities (SoA); 4.1. Overall 
Design; 8.3.1. SARS-CoV-2 
Serology Analysis  
Created a new SoA for 
participants <2 years of age. For 
participants <2 years of age, 
removed blood samples for anti-
nucleocapsid and anti-spike 
SARS-CoV-2 antibodies and 
removed Day 8 pharmacokinetic 
sample. 
Updated procedures for 
participants <2 years of 
age to keep blood sample 
volume within acceptable 
limits set forth by NIH 
directives. 
3. Objectives, Endpoints, and 
Estimands 
Updated the objective and 
endpoint for assessment of the 
effects of sotrovimab on SARS-
CoV-2 antibodies to state that 
this will only be assessed in 
participants 2 years of age. 
To keep blood sample 
volumes within acceptable 
limits set forth by NIH 
directives, participants <2 
years of age will not have 
blood drawn for the 
purpose of SARS-CoV-2 
antibody assessment. 
1.3. Schedule of Activities 
(SoA) 
Separated coagulation studies 
from hematology and chemistry 
studies in the SoA and updated 
the study days for which 
coagulation studies will be 
performed. 
Coagulation studies are 
only clinically required at 
Screening and Day 1. 
1.1. Synopsis; 4.1. Overall 
Design; 4.3. Justification for 
Dose; 6.1. Study 
Intervention(s) Administered 
Updated cut-off for saline 
dilution. Cut-off is now 
weight-based instead of age-
based. 
Updated to keep endotoxin 
levels within acceptable 
limits for the new dosing 
scheme. 
1.1. Synopsis; 2.3.1. Risk 
Assessment; 4.1. Overall 
Design; 8.5.1. Vital Signs; 
8.6.9. Adverse Events of 
Special Interest; 9.4. Interim 
Analysis; 10.1.5.1. Joint Safety 
Review Team 
Modified the timing of JSRT 
review from two-thirds of 
participants dosed in any age 
band in either cohort to half of 
participants in either cohort 
Modified the timing of 
JSRT since larger number 
of participants can be 
dosed in a shorter period 
of time, which will be 
helpful to assess 
sotrovimab’s safety and 
tolerability profile across 
the age bands sooner. 

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Section # and Name 
Description of Change 
Brief Rationale 
8. Study Assessments and 
Procedures 
Updated blood sampling 
volumes to be within acceptable 
limits.   
Revised blood sampling 
volumes to be consistent 
with European Medicines 
Agency guidelines for 
participants 2 years of 
age and with NIH 
guidelines for participants 
<2 years of age. 
1.1. Synopsis; 1.2. Schema; 
1.3. Schedule of Activities 
(SoA); 2.3.1. Risk Assessment; 
3. Objectives, Endpoints, and 
Estimands; 4.1. Overall 
Design; 4.4. End of Study 
Definition; 5.1. Inclusion 
Criteria; 8.4.3. Phone Call for 
Subsequent COVID-19 Illness; 
8.5.6. Pregnancy Testing; 
8.6.1. Time Period and 
Frequency for Collecting AE 
and SAE Information; 8.6.6. 
Pregnancy; 8.6.9. Adverse 
Events of Special Interest; 
9.3.1. Primary Endpoint(s); 
9.4. Interim Analysis 
Changed follow-up period to 
36 weeks after dosing. In 
Section 8.4.3, the weekly phone 
call is extended to Week 35 
based on the new follow-up 
period. 
Follow-up period changed 
to be consistent with FDA 
requests for follow-up 
duration in light of new 
product half-life, which is 
also consistent with other 
clinical protocols for 
sotrovimab. 
5.2. Exclusion Criteria 
Updated exclusion criteria 
number 14 to clarify restrictions 
on receipt of authorized or 
approved SARS-CoV-2 
vaccines. 
Updated criteria based on 
CDC guidelines. 
1.3. Schedule of Activities 
(SoA); 5.1. Inclusion Criteria; 
8.5.6. Pregnancy Testing 
Updated wording for inclusion 
criteria number 5 to specify that 
contraception and pregnancy 
testing are only required for 
female participants as 
appropriate for the age and 
sexual activity of pediatric 
participants and as required by 
local regulations and added that 
Clarified that pregnancy 
testing and contraception 
are only required for 
women of child-bearing 
potential. Participants who 
are breastfeeding a child 
are not included in this 
study based on possible 

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Section # and Name 
Description of Change 
Brief Rationale 
female participants cannot be 
breastfeeding. Updated other 
sections to be consistent with 
the inclusion criteria. 
risks of sotrovimab 
exposure. 
5.2. Exclusion Criteria 
Updated the respiratory rate by 
age for exclusion criteria 3. 
Used age-based criteria 
established by The 
Pediatric Emergency 
Medicine Resource 
(American Academy of 
Pediatrics and the 
American College of 
Emergency Physicians) 
instead of category-based 
criteria from the Pediatric 
Advanced Life Support 
(American Heart 
Association). 
1.3. Schedule of Activities 
(SoA); 8.3. Virologic 
Assessments 
Clarified that the nasal mid-
turbinate swab for virology and 
resistance analyses on Day 1 
will be collected pre-dose 
Added information to clarify 
the sampling times.  
10.2 Appendix 2: Clinical 
Laboratory Tests 
Specified that Screening 
laboratory assessments for all 
participants and all safety 
laboratory assessments for 
participants <2 years of age will 
be performed by a local 
laboratory. 
Screening laboratory 
assessment will be 
performed locally in order 
to have results of 
hematology and 
coagulation prior to 
intramuscular dosing. 
Furthermore, all laboratory 
assessments will be 
performed locally for 
participants <2 years of 
age in order to keep the 
total blood volume within 
acceptable limits based on 
guidelines for pediatric 
participants. 

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Section # and Name 
Description of Change 
Brief Rationale 
10.2 Appendix 2: Clinical 
Laboratory Tests 
Added details regarding 
urinalysis safety laboratory 
assessments.  
Added additional 
explanation on the nature 
of the analysis and 
conditions to perform 
microscopic urine analysis. 
1.1. Synopsis; 4.1. Overall 
Design; 6.1. Study 
Intervention(s) Administered 
Removed the age restriction for 
anterolateral thigh injections. 
Changed description from 
ventrolateral to anterolateral 
thigh. 
Anterolateral thigh is an 
acceptable location for IM 
injections for all ages.  
Anterolateral thigh is the 
preferred term for this 
injection location.  
9.4. Interim Analysis 
Added interim analysis of safety 
and PK data. 
Review of the data that will 
be used for determining if 
the study can proceed to 
the next recruitment step 
and whether monitoring 
time can be reduced will be 
considered as interim 
analysis. 
1.3. Schedule of Activities 
(SoA) 
Specified which visits must be 
done at the study site. 
Clarified that Screening 
and Day 1 study visits 
must be done at the site. 
8.5.5. Clinical Safety 
Laboratory Tests 
Removed bullet point that stated 
the use of heel sticks should be 
avoided.  
Heel sticks or other 
capillary draw methods 
may be necessary in order 
to keep blood sample 
volumes within acceptable 
limits for participants <2 
years of age.  
1.3 Schedule of Activities 
(SoA); 2.3.1. Risk 
Assessments; 4.2. Scientific 
Rationale for Study Design; 
7.2. Participant 
Discontinuation/Withdrawal 
from the Study; 8. Study 
Assessments and Procedures; 
Revised wording for the local 
injection site tolerability and 
pharmacokinetic footnotes in the 
SoA; corrected wording in 
Section 2.3.1 regarding the 
procedure for JSRT review of 
safety data for reduced 
monitoring time; clarified in 
Updates made for clarity 
and consistency.  

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Section # and Name 
Description of Change 
Brief Rationale 
10.1.4. Data Protection; 10.8. 
Appendix 8: World Health 
Organization (WHO) Weight-
For-Age Curves 
Section 2.3.1 the enrollment of 
participants who have 
conditions that contraindicate IM 
injections; corrected description 
of secondary endpoints in 
Section 4.2; clarified participant 
withdrawal procedures in 
Section 7.2; clarified storage of 
blood samples in Section 8; 
clarified the disclosure of 
pregnancy and contraception 
information to legal guardian in 
Section 10.1.4; provided chart 
titles for the WHO references in 
Section 10.8. 
1.1. Synopsis; 2.1. Study 
Rationale; 2.2.1 Clinical 
Experience with Sotrovimab; 
2.3.1 Risk Assessment; 2.3.2. 
Benefit Assessment 
Provided updated information. 
Updated sections to 
provide more recent 
information about 
sotrovimab. 
Title Page 
Added EudraCT number. 
The EudraCT number was 
issued for this study. 
Title Page; Sponsor Signature 
Page 
Changed order of the list of 
compound names to put 
sotrovimab first. Moved Vir 
study number to the line for 
protocol number. 
Updated for consistency 
with other sotrovimab 
protocols. 
10.10 Abbreviations and 
Trademarks 
Updated abbreviations list. 
Updated abbreviations to 
reflect in-text changes. 
11. References  
Added and removed references. 
Updated references to 
reflect in-text changes. 
All sections 
Other minor grammatical and 
typographical corrections. 
To improve readability. 

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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
TABLE OF CONTENTS .................................................................................................. 9 
1. 
PROTOCOL SUMMARY ........................................................................................ 12 
1.1. 
Synopsis ..................................................................................................... 12 
1.2. 
Schema ...................................................................................................... 21 
1.3. 
Schedule of Activities (SoA) ........................................................................ 22 
2. 
INTRODUCTION .................................................................................................... 24 
2.1. 
Study Rationale .......................................................................................... 24 
2.2. 
Background ................................................................................................ 27 
2.2.1. 
Clinical Experience with Sotrovimab ............................................ 27 
2.3. 
Benefit/Risk Assessment ............................................................................ 33 
2.3.1. 
Risk Assessment ......................................................................... 33 
2.3.2. 
Benefit Assessment ..................................................................... 39 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 39 
3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ................................................... 40 
4. 
STUDY DESIGN .................................................................................................... 43 
4.1. 
Overall Design ............................................................................................ 43 
4.2. 
Scientific Rationale for Study Design .......................................................... 44 
4.3. 
Justification for Dose .................................................................................. 46 
4.4. 
End of Study Definition ............................................................................... 47 
5. 
STUDY POPULATION ........................................................................................... 47 
5.1. 
Inclusion Criteria ......................................................................................... 47 
5.2. 
Exclusion Criteria ........................................................................................ 50 
5.3. 
Lifestyle Considerations .............................................................................. 52 
5.4. 
Screen Failures........................................................................................... 52 
5.5. 
Criteria for Temporarily Delaying Enrollment ............................................... 53 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 53 
6.1. 
Study Intervention(s) Administered ............................................................. 53 
6.2. 
Preparation, Handling, Storage, and Accountability .................................... 55 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 55 
6.4. 
Study Intervention Compliance ................................................................... 56 
6.5. 
Dose Modification ....................................................................................... 56 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 56 
6.7. 
Treatment of Overdose ............................................................................... 56 
6.8. 
Concomitant Therapy.................................................................................. 56 
6.8.1. 
Medication Not Permitted During the Study ................................. 57 
6.8.2. 
Permitted Concomitant Medication .............................................. 57 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 57 
7.1. 
Discontinuation of Study Intervention .......................................................... 57 
7.1.1. 
Temporary Discontinuation .......................................................... 57 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 57 
7.3. 
Lost to Follow Up ........................................................................................ 58 
7.4. 
Liver Chemistry Increased Monitoring Criteria ............................................ 59 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 59 
8.1. 
Efficacy ....................................................................................................... 60 
8.2. 
Screening Period ........................................................................................ 60 
8.2.1. 
Medical History ............................................................................ 60 
8.2.2. 
SARS-CoV-2 Diagnostic Testing ................................................. 61 
8.2.3. 
Secondary Contact Information .................................................... 61 
8.3. 
Virologic Assessments ................................................................................ 61 
8.3.1. 
SARS-CoV-2 Serology Analysis .................................................. 61 
8.4. 
COVID-19 Monitoring.................................................................................. 62 
8.4.1. 
Monitoring of COVID-19 Signs and Symptoms ............................ 62 
8.4.2. 
Monitoring of COVID-19 Progression ........................................... 62 
8.4.3. 
Phone Call for Subsequent COVID-19 Illness .............................. 62 
8.5. 
Safety Assessments ................................................................................... 62 
8.5.1. 
Vital Signs .................................................................................... 62 
8.5.2. 
Physical Examinations ................................................................. 63 
8.5.3. 
Electrocardiograms ...................................................................... 63 
8.5.4. 
Cardiac Monitoring ....................................................................... 64 
8.5.5. 
Clinical Safety Laboratory Tests .................................................. 64 
8.5.6. 
Pregnancy Testing ....................................................................... 65 
8.5.7. 
Monitoring of Multisystem Inflammatory Syndrome in 
Children (MIS-C) .......................................................................... 65 
8.6. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 65 
8.6.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 66 
8.6.2. 
Method of Detecting AEs and SAEs ............................................. 66 
8.6.3. 
Assessment of Severity ............................................................... 67 
8.6.4. 
Follow-up of AEs and SAEs ......................................................... 67 
8.6.5. 
Regulatory Reporting Requirements for SAEs ............................. 67 
8.6.6. 
Pregnancy ................................................................................... 67 
8.6.7. 
Cardiovascular and Death Events ................................................ 68 
8.6.8. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................... 68 
8.6.9. 
Adverse Events of Special Interest .............................................. 69 
8.7. 
Pharmacokinetics ....................................................................................... 70 
8.8. 
Resistance Analysis .................................................................................... 71 
8.9. 
Genetics ..................................................................................................... 71 
8.10. 
Biomarkers ................................................................................................. 71 
8.11. 
Immunogenicity Assessments ..................................................................... 71 
8.12. 
Health Economics ....................................................................................... 72 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 72 
9.1. 
Statistical Hypotheses................................................................................. 72 
9.2. 
Analysis Sets .............................................................................................. 72 

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9.3. 
Statistical Analyses ..................................................................................... 72 
9.3.1. 
Primary Endpoint(s) ..................................................................... 73 
9.3.2. 
Secondary Endpoints ................................................................... 73 
9.3.3. 
Other Safety Endpoints ................................................................ 73 
9.3.4. 
Exploratory Endpoints .................................................................. 74 
9.4. 
Interim Analysis .......................................................................................... 74 
9.5. 
Sample Size Determination ........................................................................ 74 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 75 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 75 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 75 
10.1.2. 
Financial Disclosure ..................................................................... 76 
10.1.3. 
Informed Consent and Assent Process ........................................ 76 
10.1.4. 
Data Protection ............................................................................ 77 
10.1.5. 
Committees Structure .................................................................. 77 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 78 
10.1.7. 
Data Quality Assurance ............................................................... 78 
10.1.8. 
Source Documents ...................................................................... 79 
10.1.9. 
Study and Site Start and Closure ................................................. 80 
10.1.10. Publication Policy ......................................................................... 80 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 82 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 84 
10.3.1. 
Definition of AE ............................................................................ 84 
10.3.2. 
Definition of SAE .......................................................................... 85 
10.3.3. 
Definition of Cardiovascular Events ............................................. 87 
10.3.4. 
Recording and Follow-Up of AE and SAE .................................... 87 
10.3.5. 
Reporting of SAE to GSK ............................................................. 89 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 90 
10.4.1. 
Definitions: ................................................................................... 90 
10.4.2. 
Contraception Guidance: ............................................................. 90 
10.5. 
Appendix 5: Management of Local Injection Site Reactions and 
Systemic Symptoms (Anaphylaxis) ............................................................. 92 
10.6. 
Appendix 6: Medical Diagnoses with Regards to Participants at 
High Risk of Disease Progression ............................................................... 94 
10.7. 
Appendix 7: CDC Weight and BMI Growth Charts ...................................... 95 
10.8. 
Appendix 8: World Health Organization (WHO) Weight-For-Age 
Curves ........................................................................................................ 96 
10.9. 
Appendix 9: Liver Event Increased Monitoring Criteria ................................ 97 
10.9.1. 
Level 1 Monitoring ....................................................................... 97 
10.9.2. 
Level 2 Monitoring ....................................................................... 97 
10.10. Appendix 10: Abbreviations and Trademarks ............................................ 100 
11. REFERENCES ..................................................................................................... 107 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: An open-label, non-comparator, multicenter study to describe the 
pharmacokinetics (PK), pharmacodynamics (PD; viral load) and safety following a single 
intravenous or intramuscular dose of sotrovimab in pediatric participants with mild to 
moderate COVID-19 at high risk of disease progression 
Brief Title: Pharmacokinetics, pharmacodynamics, and safety of single-dose sotrovimab 
in high-risk pediatric participants with mild to moderate COVID-19 
Rationale: 
There is an urgent medical need for therapeutics for the treatment of severe acute 
respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease 
2019 (COVID-19). Early treatment of mild and moderate disease in outpatients could 
prevent the more severe sequelae of COVID-19 requiring hospitalization, such as 
respiratory failure, and non-respiratory complications of COVID-19 including 
thromboembolic disease leading to pulmonary embolism and stroke, myocardial injury 
and arrhythmias, renal failure, and shock, among others. Furthermore, a potent treatment 
given early in disease could ameliorate the severity and duration of COVID-19 and 
potentially reduce transmission. 
Throughout the COVID-19 pandemic, a number of risk factors have come to be 
associated with worse clinical disease in adults: advanced age and patients with 
comorbidities such as obesity, diabetes, hypertension, chronic kidney disease, and 
congestive heart failure were more likely to have severe disease requiring hospitalization 
or die. While children are more likely than adults to have asymptomatic or mild infection, 
they account for more than 14% of total cases since the pandemic began and comprise 
19% of all new COVID-19 cases for the week ending on 10 June 2021 and significant 
morbidity and mortality can also be seen during acute infection. Between 
04 January 2021 and 20 June 2021, approximately 15.8% of 4.79 million COVID-19 
cases reported in the European Economic Area (EEA), excluding the United Kingdom 
(UK), were in children (those aged 18 years and under). Children have comprised an 
increasing proportion of weekly COVID-19 case numbers since January 2021, with the 
largest increase among those aged 5 to 11 years. This increasing proportion of weekly 
cases in children corresponds with the start of vaccination rollout in the European Union 
(EU)/EEA. Pediatric patients with COVID-19 are more likely to be hospitalized with 
severe disease or die if they are young (≤1 year) or have a history of obesity, 
gastrointestinal conditions, congenital heart disease, genetic or metabolic conditions, 
neurologic disease, diabetes mellitus, asthma or chronic lung disease, 
immunosuppression, sickle cell disease, or baseline medical complexity. Furthermore, 
multisystem inflammatory syndrome in children (MIS-C) represents a rare complication 
of SARS-CoV-2 infection observed in children and recently a similar syndrome in adults, 
multisystem inflammatory syndrome in adults (MIS-A), has also been observed. 
Multisystem inflammatory syndrome in children generally presents between 2 to 6 weeks 
following SARS-CoV-2 infection, suggesting a post-infectious complication potentially 
driven by formation of pathogenic autoantibodies. 

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Although severe COVID-19 in any age group puts strain on healthcare systems, severe 
COVID-19 in a pediatric population can be particularly problematic in the absence of 
local or regional hospitals equipped to treat severely ill children. 
For early treatment of non-hospitalized pediatric patients with mild-to-moderate 
COVID-19 at high risk of progression to severe disease, the monoclonal antibody (mAb) 
combinations of bamlanivimab/etesevimab and casirivimab/imdevimab have been 
authorized (Emergency Use Authorization [EUA]) in adolescents aged 12 to 18 years 
(≥40 kilograms [kg]) for prevention of disease progression. However, on 25 June 2021, 
the Department of Health and Human Services (HHS) halted the distribution of 
bamlanivimab/etesevimab in the United States of America (US) due to their lack of 
activity against the Gamma variant (Brazil) and the Beta variant (South Africa). 
Other treatments including remdesivir, baricitinib, remdesivir/baricitinib and 
dexamethasone (off-label use) in children are exclusively recommended for severe or 
critical COVID-19. 
There are no other treatment options approved for children, none for children below the 
age of 12 years with mild-to-moderate COVID-19, and none for children under the age of 
2 years with severe disease. Further, the route of administration for existing mAb 
combinations is intravenous (IV) with 20 to 70 minute infusion times for outpatients at a 
time when patients are still infectious and access to facilities for IV administration has 
been a rate-limiting step. Given the time required for infusion of other authorized mAbs 
and the limited outpatient availability of sites for infusion, strategies that allow for 
treatment at pharmacies, primary care clinics, and other point-of-diagnosis sites will 
unburden the healthcare system and offer the opportunity to reach more pediatric 
patients—especially in sites that do not have pediatric specialty care. 
Therefore, there is an urgent need for the development of new treatment modalities with 
an accessible administration route (intramuscular [IM]) and preserved activity against 
emerging SARS-CoV-2 variants. 
Vir Biotechnology, Inc. (Vir) has developed a human neutralizing anti-SARS-CoV-2 
antibody, VIR-7831 (GSK4182136, hereafter referred to as sotrovimab), which has an 
Fc-modification (“LS”) that is designed to improve bioavailability in the respiratory 
mucosa and increase half-life (t1/2). In humans, sotrovimab has a t1/2=48.8 days. 
Sotrovimab binds with high affinity to the receptor binding domain (RBD) of the SARS-
CoV-2 spike protein. Vir Biotechnology, Inc and GlaxoSmithKline (GSK) are 
collaborating on the development of sotrovimab for the treatment of COVID-19, 
including the use of sotrovimab via IV infusion and IM injection. 
Sotrovimab (500 mg, IV) was assessed in participants with COVID-19 in an early 
treatment study, VIR-7831-5001 (GSK Study 214367, also known as COMET-ICE 
[NCT04545060]), with the aim of preventing disease progression in non-hospitalized 
participants. For the first planned interim analysis, the Independent Data Monitoring 
Committee (IDMC) met on 10 March 2021 and reviewed data from 583 participants. The 
IDMC recommended halting enrollment in the trial due to overwhelming efficacy, with 
an 85% reduction in the risk of hospitalization or death in the sotrovimab arm versus the 
placebo arm (primary endpoint). The results of this study supported the Emergency 

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Authorization submissions. Emergency authorizations and/or marketing approvals for 
sotrovimab (Generation2 [Gen2]) for the treatment of mild-to-moderate COVID-19 have 
been received in the US on 26 May 2021 (EUA), positive opinion via Article 5(3) in the 
EU on 20 May 2021, Canada on 30 July 2021 (Interim Order), Singapore on 30 June 
2021 (Pandemic Special Access), Italy on 29 July 2021 (Temporary Authorization) and 
Australia on 20 August 2021 (Provisional Marketing Authorization). Similar emergency 
use applications have also been approved in the United Arab Emirates, Bahrain, Kuwait, 
Qatar, Oman, Switzerland, Egypt, Brazil, and a conditional marketing approval in Saudi 
Arabia.  
Sotrovimab has been formulated to allow for either IV or IM administration. 
Administration via IM dosing could allow greater access to mAb treatment without the 
requirement of facilities for IV administration. The IM administration is currently being 
evaluated in a study to evaluate safety, tolerability, pharmacokinetics (PK), and viral 
pharmacodynamics (PD) of sotrovimab administered intravenously or via IM injection in 
participants with mild to moderate COVID-19 (VIR-7831-5006/GSK Study 216912, also 
known as COMET-PEAK; NCT04779879) and in a Phase 3 study (COMET-TAIL [VIR 
7831-5008/GSK Study 217114; NCT04913675]) to assess the efficacy, safety, and 
tolerability of sotrovimab given IM versus IV for the treatment of mild/moderate 
COVID-19 in high-risk non-hospitalized participants. The COMET-TAIL study is 
evaluating the clinical efficacy of two dose levels of IM sotrovimab compared with IV 
sotrovimab for the prevention of progression of COVID-19 in a non-inferiority setting 
and includes enrollment of adolescent participants between the age of 12 to 17 years. 
Sotrovimab is a dual action mAb derived from the parent antibody S309 identified from a 
2003 SARS-CoV survivor. It targets a highly conserved epitope in the region of the 
spike RBD that does not compete with angiotensin converting enzyme 2 (ACE2) binding 
and is outside of the receptor-binding motif (RBM). Furthermore, this epitope does not 
overlap with mutations in current variants of concern and continues to be highly 
conserved; additionally, sotrovimab has a high barrier to resistance observed in vitro.  
Pseudotyped virus-like particle in vitro assessments indicate that sotrovimab retains 
activity against the UK (Alpha, B.1.1.7; 2.30-fold change in EC50 value); South Africa 
(Beta, B.1.351; 0.60-fold change in EC50 value); Brazil (Gamma, P.1; 0.35-fold change in 
EC50 value); California (Epsilon, B.1.427/B.1.429; 0.70-fold change in EC50 value); New 
York (Iota, B.1.526; 0.6-fold change in EC50 value), India (Kappa, B.1.617.1; 0.7-fold 
change in EC50 value, Delta, B.1.617.2; 1-fold changed in EC50 value, Delta Plus [AY.1; 
1.1-fold change in EC50 value and AY.2; 1.3-fold change in EC50 value]) and Peru 
(Lambda, C.37; 1.5-fold change in EC50 value) variant spike proteins. 
Microneutralization data from authentic SARS-CoV-2 variant virus also indicate that 
sotrovimab retains activity against the UK (3-fold change in EC50 value), South Africa 
(1.2-fold change in EC50 value) and Brazil (1.6-fold change in EC50 value) variants. 
This study will evaluate the PK, safety, and PD of sotrovimab administered IM or IV in 
children from birth to less than 18 years old with mild-to-moderate COVID-19 at high 
risk of disease progression. 

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Objectives, Endpoints, and Estimands: 
Objectives 
Endpointsa 
Other Estimand Attributes 
Primary 
To evaluate the pharmacokinetics by IV or 
IM administration of sotrovimab in children 
from birth to <18 years 
• Body weight-adjusted serum clearance of sotrovimab 
• Serum PK of sotrovimab administered by IM injection or IV 
infusion (PK parameters may include Cmax, Tmax, AUCinf, t1/2, 
Vz, CL, F) 
Population: PK (all participants in 
Cohort A/Cohort B who are exposed to study 
intervention and who had at least 1 non-missing 
PK assessment [non-quantifiable values will be 
considered as non-missing values]) 
Summary measure: PK model parameters 
To evaluate the safety and tolerability of 
sotrovimab by IV or IM administration 
• Incidence of adverse events (AEs), serious adverse events 
(SAEs), and adverse events of special interest (AESI) through 
Day 29 and Week 36 
Population: Safety (all participants who are 
exposed to study intervention in 
Cohort A/Cohort B) 
Summary measure: Counts and percentages 
Secondary 
To evaluate disease progression following 
IV or IM administration of sotrovimab  
• Progression of COVID-19 through Day 29 as defined by need 
for attended medical visit* or escalation to higher level of 
medical care or death 
*An attended medical visit includes visit to a hospital emergency 
room for management of illness or hospitalization for acute 
management of illness  
Population: Safety 
Summary measure: Counts and percentages 

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Objectives 
Endpointsa 
Other Estimand Attributes 
• Development of severe and/or critical respiratory COVID-19 
as manifested by requirement for supplemental oxygen 
through Day 29* 
*For participants who require oxygen or respiratory support for 
premorbid conditions, disease progression is defined as any 
sustained (>24 hours) increase in the level or method of oxygen 
support required 
Population: Safety  
Summary measure: Counts and percentages 
To characterize the effect of IV or IM 
administration of sotrovimab on 
SARS-CoV-2 viral load in respiratory tract 
samples among participants infected with 
SARS-CoV-2  
• Change from baseline in viral load in nasal secretions 
measured by qRT-PCR at Day 5, Day 8, and Day 11 
Population: Virology (all participants who are 
exposed to study intervention in 
Cohort A/Cohort B and have a quantifiable 
SARS-CoV-2 viral load measurement at 
baseline) 
Summary measure: Arithmetic mean  
Abbreviations: ADA = anti-drug antibodies; AEs = adverse events; AESI = adverse events of special interest; anti-N = anti-nucleocapsid; AUCinf = area under the serum concentration-
time curve from time zero to infinity; Cmax = maximum observed concentration; CL = clearance; ECGs =electrocardiograms; F = bioavailability; IM = intramuscular; IV = 
intravenous; PK = pharmacokinetics; SAEs = serious adverse events; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; t1/2 = terminal elimination half-life; Tmax = 
time to reach Cmax; qRT-PCR = quantitative reverse transcriptase polymerase chain reaction; Vz = apparent volume of distribution during terminal phase.  
a Endpoints will be assessed separately for IV and IM intervention. 

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Overall Design: 
This study is a Phase 2b open-label, non-comparator, multi-center study to evaluate PK, 
safety, and PD of IM or IV administration of sotrovimab in pediatric participants aged 
from birth to <18 years with mild/moderate COVID-19 at high risk of disease 
progression.  
This study includes 2 cohorts (Cohort A and Cohort B). Participants in Cohort A will 
receive IV sotrovimab and participants in Cohort B will receive sotrovimab via IM 
injections. Cohort B initiation will be contingent upon 1) acceptable PK and safety from 
adolescents aged 12 to <18 years in cohort A and 2) data from COMET-TAIL supporting 
the efficacy of IM dosing in adults. The exposure-response relationship has not yet been 
established for sotrovimab in adults following IM administration. This will be determined 
after the read-out from the COMET-TAIL study and will be used to support initiation of 
IM administration and enrollment in Cohort B.  
The decision to enroll participants in Cohort A or Cohort B will be per investigator 
discretion when both Cohorts enroll a given age group simultaneously. 
Participants will be enrolled into the following age bands for both Cohort A and 
Cohort B: 
• Adolescents aged 12 to less than 18 years  
• Children aged 6 to less than 12 years  
• Children aged 2 to less than 6 years  
• Birth to less than 2 years. 
Brief Summary: 
The purpose of this study is to assess the pharmacokinetics (PK), safety, and 
pharmacodynamics (PD) of sotrovimab administered via intravenous (IV) infusion or 
intramuscular (IM) injection in pediatric participants (aged from birth to <18 years) with 
mild/moderate COVID-19 at high risk of disease progression. Participants will be 
enrolled in one of two cohorts (Cohort A or Cohort B). Participants in Cohort A will 
receive IV sotrovimab and participants in Cohort B will receive sotrovimab via IM 
injections.  
• Study Duration: 36 weeks 
• Treatment Duration: A single dose of sotrovimab will be administered by IV 
infusion or administered intramuscularly on Day 1. 
• Visit frequency: Participants will be screened at the study site. Participants will be 
dosed at the study site on the same day as Screening or within 2 days after 
Screening. The day of dosing is referred to as Day 1. Participants will have a 
home visit or will return to the study site on Days 3, 5, 8, 11, 14, 22, and 29, as 
well as on Week 12 and Week 36, after dosing for follow-up visits. COVID-19 
disease progression will be monitored daily from Day 1 through Day 14 and on 
Day 22 and Day 29 (monitoring will be via a phone call on days when a home 
visit or clinic visit is not scheduled). Additionally, a weekly phone call will be 

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conducted starting at Week 5 on weeks when there is not a scheduled clinic/home 
visit. Participants in both Cohorts will have nasal mid-turbinate swabs for 
virology and resistance analyses and will have blood drawn for assessment of PK, 
anti-drug antibodies (ADA), and for safety assessments during the study. 
Participants 2 years of age will also have blood drawn for assessment of anti-
nucleocapsid and anti-spike SARS-CoV-2 antibodies. 
Number of Participants: 
Cohort A and Cohort B will each enroll1 approximately 36 participants; therefore, a total 
of approximately 72 participants will be enrolled in this study. The following number of 
participants will be enrolled in each age band for each Cohort:  
• Adolescents aged 12 to less than 18 years: approximately 6 participants 
• Children aged 6 to less than 12 years: approximately 12 participants  
• Children aged 2 to less than 6 years: approximately 12 participants  
• Birth to less than 2 years: approximately 6 participants 
Recruitment will start with Cohort A as follows: 
• The Cohort A 2 to <18 years age bands will be recruited simultaneously. 
• The Cohort A birth to <2 years age band will be recruited if deemed appropriate 
by the JSRT and IDMC after review of safety data once half of Cohort A 
participants 2 to <18 years (i.e., 15 participants) complete Day 29. 
Recruitment in Cohort B will occur as follows: 
• Cohort B will start recruitment if deemed appropriate after review of PK data 
through Day 29 from all adolescents in the Cohort A 12 to <18 years age band 
(i.e., 6 participants) and after the efficacy of IM dosing is confirmed in adults. 
Safety data through Day 29 from all Cohort A 12 to <18 years age band 
participants will also be reviewed by the JSRT and the IDMC prior to initiating 
Cohort B recruitment. Following favorable review,  the Cohort B 2 to <18 years 
age bands will be recruited simultaneously.  
• The Cohort B birth to <2 years age band will be recruited if deemed appropriate 
by the JSRT and IDMC after review of safety data once half of Cohort B 
participants 2 to <18 years (i.e., 15 participants) complete Day 29. 
The decision to enroll participants in Cohort A or Cohort B will be per investigator 
discretion when both Cohorts enroll a given age group simultaneously. By using the 
Interactive Response Technology (IRT) system, the dispensation will be monitored to 
                                                 
1 For this study, "enrolled" means a participant's, or their legally acceptable representative’s, agreement to 
participate in a clinical study following completion of the informed consent process and Screening. 
Potential participants who are screened for the purpose of determining eligibility for the study, but do 
not participate in the study, are not considered enrolled, unless otherwise specified by the protocol. A 
participant will be considered enrolled if the informed consent is not withdrawn prior to participating in 
any study activity after Screening. 

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ensure that the target number of participants in each Cohort and in each age band will 
receive IV infusion or IM injection. 
Intervention Groups and Duration: 
Dosing will be performed within 2 days of the Screening assessment. Dosing must occur 
7 days from onset of COVID-19 symptoms. Screening can occur on the same day as 
dosing. Eligible participants will be treated with a single IM or IV dose of sotrovimab on 
Day 1 and followed for up to 36 weeks. 
Dosing will be based on weight in each age band as follows: 
Age 
Weight Band 
Dose (mg) 
Volume (mL) 
0 to <2 years 
2 to <5 kg 
5 to <15 kg 
15 to <40 kg 
62.5 
125 
250 
1 
2 
4 
2 to <6 years 
5 to <15 kg 
15 to <40 kg 
125 
250 
2 
4 
6 to <12 years 
15 to <40 kg 
≥40 kg 
250 
500 
4 
8 
12 to <18 years 
15 to <40 kg 
≥40 kg 
250 
500 
4 
8 
Intravenous sotrovimab will be administered undiluted using a syringe pump for 
participants <15 kg, and diluted in 40 mL saline for participants 15 kg. Because 
endotoxin specification limits for sotrovimab exceeds allowable levels for infants 
weighing <1.88 kg, infants <2 kg will be excluded from the study. Intramuscular 
sotrovimab may be administered in dorsogluteal, anterolateral thigh, or deltoid muscles. 
Location of IM injections will be per participant/legally authorized representative [LAR] 
preference and the clinical discretion of the investigator.   
After IV infusion or IM injection of sotrovimab, participants will be monitored for 
2 hours. Local injection site tolerability will also be monitored during the 2 hours 
post-dose. Throughout the study, a JSRT and IDMC will review safety data from all 
participants enrolled in either Cohort. After half of participants are dosed in either Cohort 
(Cohort A or Cohort B), the JSRT will review safety data and, if there are no safety 
concerns, a recommendation may be made by the JSRT to reduce the post-dose Day 1 
monitoring and observation time to 1 hour within the same Cohort.  
All participants in Cohort A and Cohort B will be actively monitored on an outpatient 
basis for 36 weeks after dosing (i.e., Week 36). Monitoring will occur by home or clinic 
visits and phone calls throughout the 36 week period.  

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Data Monitoring/ Other Committee: 
An IDMC will review safety data throughout the conduct of the study at regular intervals 
as outlined by the IDMC charter. The roles and responsibilities of the IDMC, including 
membership, scope, frequency of meetings, and communication plan are defined in the 
IDMC charter.  
A JSRT comprised of team members from clinical research, global safety, and statistics 
from GSK and Vir, will review safety data throughout the study and will determine if a 
safety concern identified during instream data review needs to be escalated to the IDMC. 
The responsibilities of the JSRT and frequency of assessments will be outlined in the 
JSRT charter.  

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1.2. 
Schema 
 
Abbreviations: IDMC = Independent Data Monitoring Committee IM = intramuscular; IV = intravenous; JSRT = Joint Safety Review Team; n = number of participants enrolled; 
PK = pharmacokinetics; yr=years. 

T M F -1 3 9 7 1 1 1 4  
 
C O N FI D E N TI A L  
 
2 1 5 2 2 6  Pr ot o c ol A m d 1  
 
2 2  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5 d at e d 2 1 -D e c -2 0 2 0  
1. 3.  
S c h e d ul e of A cti viti e s ( S o A)  
T a bl e 1  
S o A f or P arti ci p a nt s 2 Y e ar s of A g e  
 
St u d y Vi sit D a y ±  Vi sit Wi n d o w  
S cr e e ni n g 1 
( D a y -2, -1, or 1)  
D a y 1 1 
D a y 3  
D a y 5  
D a y 8  
D a y 1 1  
D a y 1 4  
D a y 2 2  
D a y 2 9 ± 3 d  
W e e k 1 2  
( D a y 8 5 ± 7 d) 
W e e k 3 6  
( D a y 2 5 2 ± 1 4 d) 
E n d of st u d y 
( E O S) 
N ote s: i n c as e of e arly disc o nti n uati o n ( E D) or wit h dra wal ( E W), all W eek 3 6 activiti es s h o ul d b e p erf or m e d. 
1.  All Scr e e ni n g proc e d ures m ust be c o m pl et ed wit hi n 2 d ays pri or t o d osi n g. W he n p ossi bl e, Scre e ni n g a n d 
d osi n g ( D ay 1) c a n b e d o n e o n t h e s a me d ay. Co nt act i nf or m ati o n f or s ec o nd ary c o nt acts will b e c oll ect e d 
at Scr e e ni n g a n d i nf or m ati o n a b out h e a lt h c are provi d ers/f aciliti es m ay also b e c oll ect e d at Scr e eni n g.  
2.  D osi n g will b e p erf or m e d 7 d ays fro m t he o ns et of sy m pt o ms. P artici p ants will b e m o nit ore d f or 2  h ours 
aft er d osi n g. If t h e J oi nt S af ety Revi e w T e a m (J S R T) rec o m m e nds re duci n g t o 1  h o ur m o nit ori n g (s e e 
S ecti o n 1 0. 1. 5. 1 ): P artici p ants will b e m o nit ore d f or a p proxi m at ely 1 h o ur p ost -d os e.  
3.  I ncl u di n g h ei g ht, w ei g ht, a n d b o dy m ass i n dex ( B MI). T h e f ull p hysic al ex a mi n ati o n o nly n e eds t o b e 
p erf or m e d o nc e if Scre e ni n g a n d d osi n g occ ur o n t he s a m e d ay.  
4.  D aily ass ess m e nt will b e vi a a p ho ne c all wh en a cli nic or h o me visit is n ot sc h ed ul e d.  
5.  W e ekly p h o n e c all fro m W e ek 5 t o W e ek 1 1 a nd W eek 1 3  t o W e ek 3 5 t o ass ess f or t he i nci d enc e a nd 
s ev erity of s u bs e q u e nt C O VI D-1 9 ill n ess, if a ny. W eekly ass ess m e nts m ust be p erf or m e d wit hi n ± 1 d ay of 
t h e sc h e d ul e d p h o n e c all. 
6.  R ec ord D ay  1 vit al si g ns wit hi n 1  h o ur pri or t o d osi n g. Vit al si g ns  will b e m o nit or e d ev ery 1 5  mi n ut es ov er 
t h e 3 0 mi n ut e I V i nf usi o n. Vit al si g ns will als o b e m o nit ore d at ap proxi m at ely 3 0 mi n ut es, 1 h o ur, a n d 
2  h o urs (I M or I V i nf usi o n) aft er d osi n g. If t he p ost -d os e m o nit ori n g is re duc e d t o 1 h o ur p er J S R T 
rec o m m e n d ati o n: R ec or d Day 1  vit al si g ns wit hi n 1 h our pri or t o d osi n g. Vit al si g ns will b e m o nit ore d ev ery 
1 5 mi n ut es ov er t h e 3 0 mi n ut e I V i nf usi o n. Vit al si g ns will als o b e m o nit ore d at a p proxi m at ely 3 0  mi n ut es 
a n d 1 h o ur aft er d osi n g (I M or I V i nf usi o n).  
7.  At Scre e ni n g, tri plic at e  E C Gs will b e p erf or m e d. A si n gl e 1 2 -l e a d E C G will b e p erf or m e d pri or t o d osi n g o n 
D ay 1, wit hi n 3 0 mi n ut es of en d of d osi n g o n Day 1, a nd o n Day 8. If Scre e ni n g a n d d osi n g occ ur o n t h e 
s a me d ay, o nly t h e o n e s et of tri plic at e E C Gs is re quir e d pri or t o d os i n g (a n a dditi o nal pr e-d osi n g si n gl e 
E C G is n ot re q uir e d). A d diti o nal E C Gs will b e d on e as cli nic ally n e ed ed.  
8.  O n Day 1, l oc al i nj ecti o n sit e t ol era bility ass ess m e nt will b e p erf or m e d at a p proxi m at ely 1 h o ur a nd 
2  h o urs p ost -d os e. If J S R T rec o m m e n ds re duci ng m o nit ori n g ti m e , D ay 1 ass ess m e nt will b e 1 h our p ost-
d os e. All i nj ecti o n sit e re acti o ns n e ed t o b e f oll o we d by t he pri nci p al i nv esti g at or ( PI) t o r es ol uti o n.  
9.  O n Day 1, s a m pl e c oll ecti o n will occ ur pre -d os e. Scre eni n g/ Day 1 h e m at ol o gy, c o ag ul ati o n, c h e mistry, 
a n d uri n alysis o nly n e e d t o b e p erf or m e d o nc e if Scr e eni n g a n d d osi n g occ ur o n t h e s a me d ay. F or I M 
a d mi nistrati o n, t h e res ults of h e m at ol o gy a n d c o a g ul ati o n l a bor at ory res ults m ust be rec eiv e d a nd 
revi e we d pri or t o d osi n g (s e e excl usi o n crit eri a n u mb er 1 1). A list of pr ot oc ol-re quir e d s af ety l a borat ory 
t ests is provi d e d i n S ecti o n 1 0. 2 . 
1 0.  F or wo me n of c hil d -b e ari n g p ot e nti al (d efi n ed i n S ecti o n 1 0. 4. 1 ): s eru m or hi g hly s ensitiv e uri n e 
pre g n a ncy t est, as re q uire d by l oc al g ui d eli n es ( S ecti o n 8. 5. 6 ).  
1 1.  D oc u m e nt ati o n of l a b orat ory -c o nfir m e d S A R S-Co V -2 i nf ecti o n vi a a ny v ali d at e d q R T-P C R  or ot h er n ucl eic 
aci d a mplific ati o n t est ( N A A T)  fro m a ny res pir at ory s p eci m e n c oll ect e d ≤7 d ays pri or t o st u dy e ntry m ust 
b e c o nfir m e d at Scr e e ni n g. If n ot av ail a bl e, or previ o us q R T -P C R t est was n eg ativ e, a S A R S -C o V -2 q R T -
P C R or ot h er N A A T  m ust be p erf or m e d at Scre e ni n g t o c o nfir m eli gi bility.  
1 2.  D ay 1 s a m pl es will als o b e ev al u at e d f or S A R S -C o V -2 c h aract eriz ati o n (e. g., i d e ntific ati o n of v ari a nts).  
1 3.  O n Day 1, C o h ort A p artici p ants will h av e a si n gl e P K s a m pl e c oll ect e d at t h e e n d of i nf usi o n . Co h ort B 
p artici p a nts will n ot h av e a ny P K s a m pl es c oll ect e d o n Day 1.  
1 4.  D ay  1 s a mpl e c oll ecti o n is pre -d os e o nly.  
1 5.  A Es ( S ecti o n 1 0. 3 ), i ncl u di n g MI S-C, will b e c oll ect e d u ntil W eek 3 6 ( E O S) d uri n g sit e visits a nd p ho n e 
c alls.  
1 6.  All S A Es ( S ecti o n 1 0. 3 ) will b e c oll ect e d fro m d os e a d mi nistrati o n a n d o nly S A Es c o nsi d ere d rel at ed t o 
st u dy p artici p ati o n or a G S K pro duct will b e c oll ect e d fro m si g ni n g i nf or m e d c o ns e nt. S A Es will b e 
c oll ect e d d uri n g all sit e visits a nd p ho n e c alls. Not e: all S A Es m ust be re port e d wit hi n 2 4 h o urs.  
 
Cli nic ( C) or h o m e ( H) visit  
C  
C  C/ H  C/ H  C/ H  C/ H  C/ H  C/ H  C/ H  
C/ H  
C/ H  
 
I nf or m e d c o ns e nt  
X  
 
 
 
 
 
 
 
 
 
 
De mo gra phy  
X  
 
 
 
 
 
 
 
 
 
 
M e dic al hist ory (i ncl u di n g b as eli n e 
C O VI D -1 9 sy m pt o ms, c o m orbi diti es, a n d 
t o b acc o us e) 
X  
 
 
 
 
 
 
 
 
 
 
Eli gi bility crit eri a  
X  
 
 
 
 
 
 
 
 
 
 
 
St u dy i nt erv e nti o n a d mi nistrati o n  
 
X 2 
 
 
 
 
 
 
 
 
 
Ass ess m e nts  
P hysic al ex a mi n ati o n ( F =f ull, B = bri ef)  
F 3 
F 3 
 
 
B  
 
B  
B  
B  
 
 
C O VI D -1 9 si g ns/sy m pt o ms r evi e w  
X  
X  
 
 
X  
 
X  
 
X  
X  
X  
M o nit ori n g of C O VI D -1 9 dis e as e 
pro gressi o n  
 
< -----------X ( D aily) 4----------->  
X  
X  
 
 
P h o ne c all f or s u bs e q ue nt C O VI D -1 9 
m o nit ori n g  
 
W e ekly fro m 
W e ek  5 t o 
W e ek  1 1 5 
W e ekly fro m 
W e ek  1 3 t o 
W e ek  3 5 5 
Vit al si g ns (i ncl u di n g bl o od press ure, 
p uls e rat e, res pir at ory r at e, t e m p erat ure, 
a nd oxy g en s at urati o n)  
X  
X 6 X  
X  
X  
 
X  
X  
X  
X  
X  
1 2 -l e ad E C G7 
X 7 
X 7 
 
 
X  
 
 
 
 
 
 
L oc al i nj ecti o n sit e t ol era bility 
ass ess m e nt (I M o nly) 8 
 
X 8 X  
X  
X  
 
 
 
 
 
 
S a m pl e c oll ecti o n  
Uri n e st u di es  
X 9 
X 9 
 
 
X  
 
 
 
X  
 
 
He mat ol o gy a n d c h e mistry st u di es  
X 9 
X 9 
 
 
X  
 
X  
 
X  
 
 
Co ag ul ati o n st u di es  
X 9 
X 9 
 
 
 
 
 
 
 
 
 
Pre gn a ncy t est 1 0 
X  
 
 
 
 
 
 
 
 
 
X  
S A R S -C o V -2 di a g n ostic t est  
(if not previ o usly c o nfir m e d, p oi nt-of -c are 
or l oc al l a borat ory t est)  
X 1 1 
 
 
 
 
 
 
 
 
 
 
Nas al mi d -t urbi n at e s wa b f or virol o gy a n d 
resist a nc e a nalys es  
 
X 1 2 , 
1 4 
X  
X  
X  
X  
 
 
X  
 
 
Bl o od s a mpl e f or P K a nalysis  
 
X 1 3 
 
X  
X  
 
 
 
X  
X  
 
Bl o od s a mpl e f or a nti -dru g a nti b o dy  
 
X 1 4 
 
 
 
 
 
 
X  
 
X  
 
 
 
 
 
 
 
 
 
 
X 1 4 
 
 
 
 
 
 
 
 
 
 
A E revi e w 1 5 
 
< ------------------------------------ X -------------------------------------->  
 
S A E revi e w 1 6 
X 1 6 
< ------------------------------------ X -------------------------------------->  
 
Co nc o mit a nt m e dic ati o n r evi e w  
< ------------------------------------------ X ------------------------------------------->  
C CI
C CI
C CI

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Table 2 
SoA for Participant <2 Years of Age 
 
Study Visit Day ± Visit Window 
Screening1 
(Day -2, -1, or 1) 
Day 11 
Day 3` 
Day 5 
Day 8 
Day 11 
Day 14 
Day 22 
Day 29 ± 3d 
Week 12 
(Day 85 ± 7d) 
Week 36 
(Day 252 ± 14d) 
End of study 
(EOS) 
Notes: In case of early discontinuation (ED) or withdrawal (EW), all Week 36 activities should be 
performed. 
 
1. 
All Screening procedures must be completed within 2 days prior to dosing. When possible, Screening 
and dosing (Day 1) can be done on the same day. Contact information for secondary contacts will be 
collected at Screening and information about health care providers/facilities may also be collected at 
Screening.  
2. Dosing will be performed 7 days from the onset of symptoms. Participants will be monitored for 
2 hours after dosing. If the Joint Safety Review Team (JSRT) recommends reducing to 1 hour 
monitoring (see Section 10.1.5.1): Participants will be monitored for approximately 1 hour post-dose.  
3. Including height, weight, and body mass index (BMI). The full physical examination only needs to be 
performed once if Screening and dosing occur on the same day. 
4. Daily assessment will be via a phone call when a clinic or home visit is not scheduled. 
5. Weekly phone call from Week 5 to Week 11 and Week 13 to Week 35 to assess for the incidence and 
severity of subsequent COVID-19 illness, if any. Weekly assessments must be performed within ±1 day 
of the scheduled phone call. 
6. Record Day 1 vital signs within 1 hour prior to dosing. Vital signs will be monitored every 15 minutes 
over the 30 minute IV infusion. Vital signs will also be monitored at approximately 30 minutes, 1 hour, 
and 2 hours (IM or IV infusion) after dosing. If the post-dose monitoring is reduced to 1 hour per JSRT 
recommendation: Record Day 1 vital signs within 1 hour prior to dosing. Vital signs will be monitored 
every 15 minutes over the 30 minute IV infusion. Vital signs will also be monitored at approximately 
30 minutes and 1 hour after dosing (IM or IV infusion).  
7. At Screening, triplicate ECGs will be performed. A single 12-lead ECG will be performed prior to dosing 
on Day 1, within 30 minutes of end of dosing on Day 1, and on Day 8. If Screening and dosing occur on 
the same day, only the one set of triplicate ECGs is required prior to dosing (an additional pre-dosing 
single ECG is not required). Additional ECGs will be done as clinically needed. 
8. On Day 1, local injection site tolerability assessment will be performed at approximately 1 hour and 
2 hours post-dose. If JSRT recommends reducing monitoring time, Day 1 assessment will be 1 hour 
post-dose. All injection site reactions need to be followed by the principal investigator (PI) to resolution. 
9. On Day 1, sample collection will occur pre-dose. Screening/Day 1 hematology, coagulation, chemistry, 
and urinalysis only need to be performed once if Screening and dosing occur on the same day. For IM 
administration the results of hematology and coagulation laboratory results must be received and 
reviewed prior to dosing (see exclusion criteria number 11). A list of protocol-required safety laboratory 
tests is provided in Section 10.2. 
10. Documentation of laboratory-confirmed SARS-CoV-2 infection via any validated qRT-PCR or other 
nucleic acid amplification test (NAAT) from any respiratory specimen collected ≤7 days prior to study 
entry must be confirmed at Screening. If not available, or previous qRT-PCR test was negative, a 
SARS-CoV-2 qRT-PCR or other NAAT must be performed at Screening to confirm eligibility. 
11. Day 1 samples will also be evaluated for SARS-CoV-2 characterization (e.g., identification of variants). 
12. On Day 1, Cohort A participants will have a single PK sample collected at the end of infusion. Cohort B 
participants will not have any PK samples collected on Day 1. 
13. Day 1 sample collection is pre-dose only.  
14. AEs (Section 10.3) including MIS-C will be collected until Week 36 (EOS) during site visits and phone 
calls.  
15. All SAEs (Section 10.3) will be collected from dose administration and only SAEs considered related to 
study participation or a GSK product will be collected from signing informed consent. SAEs will be 
collected during all site visits and phone calls. Note: all SAEs must be reported within 24 hours.  
Clinic (C) or home (H) visit 
C 
C C/H C/H C/H C/H C/H C/H C/H 
C/H 
C/H 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical history (including baseline 
COVID-19 symptoms and 
comorbidities) 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Study intervention administration 
 
X2 
 
 
 
 
 
 
 
 
 
Assessments 
Physical examination (F=full, B=brief) 
F3 
F3 
 
 
B 
 
B 
B 
B 
 
 
COVID-19 signs/symptoms review 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
Monitoring of COVID-19 disease 
progression 
 
<-----------X (Daily)4-----------> 
X 
X 
 
 
Phone call for subsequent COVID-19 
monitoring 
 
Weekly 
from 
Week 5 to 
Week 115 
Weekly from 
Week 13 to 
Week 355 
Vital signs (including blood pressure, 
pulse rate, respiratory rate, 
temperature, and oxygen saturation) 
X 
X6 
X 
X X 
 
X 
X 
X 
X 
X 
12-lead ECG7 
X7 
X7 
 
 
X 
 
 
 
 
 
 
Local injection site tolerability 
assessment (IM only)8 
 
X8 
X 
X X 
 
 
 
 
 
 
Sample collection 
Urine studies 
X9 
X9 
 
 
X 
 
 
 
X 
 
 
Hematology and chemistry studies 
X9 
X9 
 
 
X 
 
X 
 
X 
 
 
Coagulation studies 
X9 
X9 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 diagnostic test  
(if not previously confirmed, point-of-
care or local laboratory test) 
X10 
 
 
 
 
 
 
 
 
 
 
Nasal mid-turbinate swab for virology 
and resistance analyses  
 
X11, 
13 
X 
X X 
X 
 
 
X 
 
 
Blood sample for PK analysis  
 
X12 
 
X 
 
 
 
 
X 
X 
 
Blood sample for anti-drug antibody 
 
X13 
 
 
 
 
 
 
X 
 
X 
 
AE review14 
 
<-------------------------------------- X ----------------------------------------> 
 
SAE review15 
X15 
<-------------------------------------- X ----------------------------------------> 
 
Concomitant medication review 
<-------------------------------------------- X ---------------------------------------------> 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
There is an urgent medical need for therapeutics for the treatment of severe acute 
respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease 
2019 (COVID-19). Early treatment of mild and moderate disease in outpatients could 
prevent the more severe sequelae of COVID-19 requiring hospitalization, such as 
respiratory failure, and non-respiratory complications of COVID-19 including 
thromboembolic disease leading to pulmonary embolism and stroke, myocardial injury 
and arrhythmias, renal failure, and shock, among others [Klok, 2020; Chen, 2020; CDC 
COVID-19 Response Team, 2020]. Furthermore, a potent treatment given early in 
disease could ameliorate the severity and duration of COVID-19 and potentially reduce 
transmission. 
Throughout the COVID-19 pandemic, a number of risk factors have come to be 
associated with worse clinical disease in adults: advanced age and patients with 
comorbidities such as obesity, diabetes, hypertension, chronic kidney disease, and 
congestive heart failure were more likely to have severe disease requiring hospitalization 
or die [Booth, 2021; Rosenthal, 2020; Williamson, 2020; Richardson, 2020; Garg, 2020; 
Petrilli, 2020]. While children are more likely than adults to have asymptomatic or mild 
infection, they account for more than 14% of total cases since the pandemic began and 
comprise 19% of all new COVID-19 cases for the week ending on 10 June 2021 [AAP, 
2021] and significant morbidity and mortality can also be seen during acute infection. 
Between 04 January 2021 and 20 June 2021, approximately 15.8% of 4.79 million 
COVID-19 cases reported in the European Economic Area (EEA), excluding the United 
Kingdom (UK), were in children (those aged 18 years and under) 
[ECDC, 2021]. Children have comprised an increasing proportion of weekly COVID-19 
case numbers since January 2021, with the largest increase among those aged 
5 to 11 years. This increasing proportion of weekly cases in children corresponds with the 
start of vaccination rollout in the European Union (EU)/EEA [ECDC, 2021]. Pediatric 
patients with COVID-19 are more likely to be hospitalized with severe disease or die if 
they are young (≤1 year) or have a history of obesity, gastrointestinal conditions, 
congenital heart disease, genetic or metabolic conditions, neurologic disease, diabetes 
mellitus, asthma or chronic lung disease, immunosuppression, sickle cell disease, or 
baseline medical complexity [CDC, 2021c; Graff, 2021; Kim, 2020]. Furthermore, 
multisystem inflammatory syndrome in children (MIS-C) represents a rare complication 
of SARS-CoV-2 infection observed in children and recently a similar syndrome in adults, 
multisystem inflammatory syndrome in adults (MIS-A), has also been observed 
[Feldstein, 2020; Morris, 2020]. Multisystem inflammatory syndrome in children 
generally presents between 2 to 6 weeks following SARS-CoV-2 infection, suggesting a 
post-infectious complication potentially driven by formation of pathogenic autoantibodies 
[Gottlieb, 2021; Consiglio, 2020; Gruber, 2020]. 
Although severe COVID-19 in any age group puts strain on healthcare systems, severe 
COVID-19 in a pediatric population can be particularly problematic in the absence of 
local or regional hospitals equipped to treat severely ill children [Levin, 2021]. 

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For early treatment of non-hospitalized pediatric patients with mild-to-moderate 
COVID-19 at high risk of progression to severe disease, the monoclonal antibody (mAb) 
combinations of bamlanivimab/etesevimab and casirivimab/imdevimab have been 
authorized (Emergency Use Authorization [EUA]) in adolescents aged 12 to 18 years 
(≥40 kilograms [kg]) for prevention of disease progression [EMA, 2021; FDA, 2021d; 
FDA, 2020c; Roche, 2021]. However, on 25 June 2021, the Department of Health and 
Human Services (HHS) halted the distribution of bamlanivimab/etesevimab in the United 
States of America (US) due to their lack of activity against the Gamma variant (Brazil) 
and the Beta variant (South Africa) [Eli Lilly and Company, 2021]. 
Other treatments including remdesivir, baricitinib, remdesivir/baricitinib, and 
dexamethasone (off-label use) in children are exclusively recommended for severe or 
critical COVID-19 [NIH, 2021; REACT, 2020; FDA, 2021b; RECOVERY, 2021]. 
There are no other treatment options approved for children, none for children below the 
age of 12 years with mild-to-moderate COVID-19, and none for children under the age of 
2 years with severe disease. Further, the route of administration for existing mAb 
combinations is intravenous (IV) with 20 to 70 minute infusion times for outpatients at a 
time when patients are still infectious and access to facilities for IV administration has 
been a rate-limiting step [National Academies of Sciences, Engineering, and Medicine, 
2021]. Given the time required for infusion of other authorized mAbs and the limited 
outpatient availability of sites for infusion, strategies that allow for treatment at 
pharmacies, primary care clinics, and other point-of-diagnosis sites will unburden the 
healthcare system and offer the opportunity to reach more pediatric patients—especially 
in sites that do not have pediatric specialty care. 
Therefore, there is an urgent need for the development of new treatment modalities with 
an accessible administration route (intramuscular [IM]) and preserved activity against 
emerging SARS-CoV-2 variants. 
Vir Biotechnology, Inc. (Vir) has developed a human neutralizing anti-SARS-CoV-2 
antibody, VIR-7831 (GSK4182136, hereafter referred to as sotrovimab), which has an 
Fc-modification (“LS”) that is designed to improve bioavailability in the respiratory 
mucosa and increase half-life (t1/2) [Pinto, 2020]. In humans, sotrovimab has a 
t1/2=48.8 days. Sotrovimab binds with high affinity to the receptor binding domain (RBD) 
of the SARS-CoV-2 spike protein. Vir Biotechnology, Inc and GlaxoSmithKline (GSK) 
are collaborating on the development of sotrovimab for the treatment of COVID-19, 
including the use of sotrovimab via IV infusion and IM injection. 
Sotrovimab (500 mg, IV) was assessed in participants with COVID-19 in an early 
treatment study, VIR-7831-5001 (GSK Study 214367, also known as COMET-ICE 
[NCT04545060]), with the aim of preventing disease progression in non-hospitalized 
participants. For the first planned interim analysis, the Independent Data Monitoring 
Committee (IDMC) met on 10 March 2021 and reviewed data from 583 participants. The 
IDMC recommended halting enrollment in the trial due to overwhelming efficacy, with 
an 85% reduction in the risk of hospitalization or death in the sotrovimab arm versus the 
placebo arm (primary endpoint) [Vir Biotechnology, 2021]. The results of this study 
supported the Emergency Authorization submissions. Emergency authorizations and/or 

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marketing approvals for sotrovimab (Gen2) for the treatment of mild-to-moderate 
COVID-19 have been received in the US on 26 May 2021 (EUA) [FDA, 2021e], positive 
opinion via Article 5(3) in the EU on 20 May 2021, Canada on 30 July 2021 (Interim 
Order), Singapore on 30 June 2021 (Pandemic Special Access), Italy on 29 July 2021 
(Temporary Authorization) and Australia on 20 August 2021 (Provisional Marketing 
Authorization). Similar emergency use applications have also been approved in the 
United Arab Emirates, Bahrain, Kuwait, Qatar, Oman, Switzerland, Egypt, Brazil, and a 
conditional marketing approval in Saudi Arabia.   
Sotrovimab has been formulated to allow for either IV or IM administration. 
Administration via IM dosing could allow greater access to mAb treatment without the 
requirement of facilities for IV administration. The IM administration is currently being 
evaluated in a study to evaluate safety, tolerability, pharmacokinetics (PK), and viral 
pharmacodynamics (PD) of sotrovimab administered intravenously or via IM injection in 
participants with mild to moderate COVID-19 (VIR-7831-5006/GSK Study 216912, also 
known as COMET-PEAK; NCT04779879) and in a Phase 3 study (COMET-TAIL 
[VIR-7831-5008/GSK Study 217114; NCT04913675]) to assess the efficacy, safety, and 
tolerability of sotrovimab given IM versus IV for the treatment of mild/moderate 
COVID-19 in high-risk non-hospitalized participants. The COMET-TAIL study is 
evaluating the clinical efficacy of two dose levels of IM sotrovimab compared with IV 
sotrovimab for the prevention of progression of COVID-19 in a non-inferiority setting 
and includes enrollment of adolescent participants between the age of 12 to 17 years. 
Sotrovimab is a dual action mAb derived from the parent antibody S309 identified from a 
2003 SARS-CoV survivor. It targets a highly conserved epitope in the region of the 
spike RBD that does not compete with angiotensin converting enzyme 2 (ACE2) binding 
and is outside of the receptor-binding motif (RBM) [Pinto, 2020]. Furthermore, this 
epitope does not overlap with mutations in current variants of concern and continues to 
be highly conserved; additionally, sotrovimab has a high barrier to resistance observed in 
vitro [Starr, 2021; Wang, 2021].  
Pseudotyped virus-like particle in vitro assessments indicate that sotrovimab retains 
activity against the UK (Alpha, B.1.1.7; 2.30-fold change in EC50 value); South Africa 
(Beta, B.1.351; 0.60-fold change in EC50 value); Brazil (Gamma, P.1; 0.35-fold change in 
EC50 value); California (Epsilon, B.1.427/B.1.429; 0.70-fold change in EC50 value); New 
York (Iota, B.1.526; 0.6-fold change in EC50 value), India (Kappa, B.1.617.1; 0.7-fold 
change in EC50 value, Delta, B.1.617.2; 1-fold changed in EC50 value, Delta Plus [AY.1; 
1.1-fold change in EC50 value and AY.2; 1.3-fold change in EC50 value]) and Peru 
(Lambda, C.37; 1.5-fold change in EC50 value) variant spike proteins. 
Microneutralization data from authentic SARS-CoV-2 variant virus also indicate that 
sotrovimab retains activity against the UK (3-fold change in EC50 value), South Africa 
(1.2-fold change in EC50 value) and Brazil (1.6-fold change in EC50 value) variants. 
This study will evaluate the PK, safety, and PD of sotrovimab administered IM or IV in 
children from birth to less than 18 years old with mild-to-moderate COVID-19 at high 
risk of disease progression. 

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2.2. 
Background 
In December 2019, an atypical pneumonia caused by a novel coronavirus SARS-CoV-2 
was first reported in Wuhan, China and has subsequently spread rapidly around the 
world. As of 17 June 2021, 177,156,095 cases of COVID-19 have been reported, 
including 3,835,309 associated deaths [Johns Hopkins, 2021]. The first recorded case in 
the US was reported on 20 January 2020 in the Pacific North-western area of the country 
[Holshue, 2020]; as of 15 June 2021, over 33 million cases have been reported with over 
500,000 associated deaths in the US [CDC, 2021a]. 
As of 17 June 2021, children <18 years of age accounted for 12.5% of reported 
COVID-19 cases in the US [CDC, 2021b]. The incidence of laboratory confirmed 
COVID-19 in the pediatric population is age-dependent. Average weekly incidence from 
May to September 2020 among adolescents aged 12 to 17 years of age was almost double 
that of the incidence among children aged 5 to 11 years (37.4 per 100,000 children 
compared to 19.0 per 100,000 children) [Leeb, 2020].  
Children generally have a good prognosis and recover within 1 to 2 weeks after symptom 
onset [Cavallo, 2020; Ludvigsson, 2020]. However, among children who have been 
hospitalized with COVID-19, the most common co-morbidities are obesity, chronic lung 
disease, asthma, and prematurity (<37 weeks gestational age at birth) [Kim, 2020]. Apart 
from several mAb combinations authorized only in adolescents and available only via IV 
infusion, there are no other authorized treatment option in children specifically in those at 
high risk of disease progression. Therefore, development of additional treatment 
modalities that have a more accessible administration route and preserved activity against 
emerging SARS-CoV-2 variants are warranted for the treatment of COVID-19 in 
children. 
Vir Biotechnology, Inc. has developed a human neutralizing anti-SARS-CoV-2 antibody, 
sotrovimab, which has an Fc-modification (“LS”) that is designed to improve 
bioavailability in the respiratory mucosa and increase t1/2 [Pinto, 2020]. Sotrovimab binds 
with high affinity to the RBD of the SARS-CoV-2 spike protein, retains its activity 
against SARS-CoV-2 variants of concerns, and displays a high barrier to resistance. 
2.2.1. 
Clinical Experience with Sotrovimab 
As of 31 March 2021, approximately 1350 participants have been randomized to either 
sotrovimab (500 mg dose) or placebo in two clinical studies: 1057 participants in a study 
evaluating sotrovimab for the treatment of non-hospitalized individuals with mild to 
moderate COVID-19 (COMET-ICE [NCT04545060]) and 300 participants in a study that 
evaluated sotrovimab for the treatment of individuals hospitalized with COVID-19 
(ACTIV-3-TICO [VIR-7831-5004; GSK Study 215149; NCT04501978]). 
COMET-ICE, is a seamless first-in-human (FIH) Phase II/III study assessing the safety 
and efficacy of a single 500 mg IV dose of sotrovimab for the early treatment of COVID-
19 in non-hospitalized participants at high risk for progression and subsequent 
hospitalization. Participants were randomized in a 1:1 ratio to sotrovimab or placebo. 
COMET-ICE started with a lead-in phase (N=21) in August 2020 to assess safety and 
tolerability. An IDMC met 23 September 2020 to review unblinded safety data after the 

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20th participant from the lead-in cohort completed Day 15 (1 participant was withdrawn). 
There were no deaths or SAEs reported up to this IDMC review. The IDMC 
recommended the study to proceed with the expansion-phase to enroll additional 
participants across each treatment group (~1300 participants total). 
The IDMC subsequently met on 10 March 2021 for a planned interim analysis, with 
review of data from 583 participants. There was an 85% reduction in the primary 
endpoint of hospitalization or death in the sotrovimab arm versus the placebo arm 
(p=0.002). The IDMC recommended that the study halt enrollment on the basis of 
overwhelming efficacy [Vir Biotechnology, 2021]. There have been no safety concerns 
identified at the IDMC reviews conducted to date. 
Enrolment into COMET-ICE was closed on 11 March 2021, participants continue to be 
followed-up to Week 24. Results from the COMET-ICE study at the Day 29 Analysis 
data cut-off (DCO; 27 April 2021) indicate that sotrovimab is a highly efficacious 
treatment for participants with mild-to-moderate COVID-19 who are at risk of 
progressing to severe disease, meeting an unmet medical need. A review of COMET-ICE 
efficacy data based on the intent-to-treat (Day 29) population (N=1057) who received 
either sotrovimab or placebo demonstrated that the primary efficacy endpoint was met. 
Treatment with sotrovimab resulted in a significant reduction in the proportion of 
participants with mild/moderate COVID-19 progressing to greater than 24 hours 
hospitalization or death in the sotrovimab arm when compared with placebo through 
Day 29 by 79% (adjusted relative risk reduction; p<0.001).  
In vitro neutralization data using a SARS-CoV-2 pseudotyped virus are currently 
available for 13 of the 17 unique variants detected in the sotrovimab epitope. Of the 
variants with available data, sotrovimab effectively neutralized epitope variants at most 
amino acid positions tested with fold changes in half maximal effective concentration 
(EC50) <3-fold (range: 0.70 to 1.72). The variants E340A and E340K resulted in 
significant EC50 shifts (>100-fold) indicating reduced susceptibility to sotrovimab in 
vitro. 
Limited nucleotide sequencing data from a total of 539 COMET-ICE participants 
indicated that 36 participants (16 treated with placebo and 20 treated with sotrovimab) 
carried the B.1.1.7 (Alpha, UK origin) variant. Four participants (2 treated with placebo 
and 2 treated with sotrovimab) carried the N501Y substitution. Thirty-one participants 
(19 treated with placebo and 12 treated with sotrovimab) carried the B.1.427/B.1.429 
(Epsilon, California origin) variant. Eight additional participants carried the L452R 
substitution (6 treated with placebo and 2 treated with sotrovimab). Eleven participants 
carried the P.1 (Gamma, Brazil origin) variant (3 treated with placebo and 8 treated with 
sotrovimab). Three participants carried the B.1.526 (Iota, New York origin) variant with 
the E484K substitution (2 treated with placebo and 1 treated with sotrovimab), while 
9 participants (4 treated with placebo and 5 treated with sotrovimab) carried the S477N 
substitution that has been associated with the B.1.526 (Iota, New York origin) variant. 
Additionally, 10 participants carried the E484K substitution (4 treated with placebo and 
6 treated with sotrovimab), 2 carried the S494P substitution (1 treated with placebo and 1 
treated with sotrovimab), and 3 carried the S494P substitution with the N501Y 
substitution (2 treated with placebo and 1 treated with sotrovimab). Two participants in 

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Clinical Study Protocol template V15 dated 21-Dec-2020 
the group receiving sotrovimab (1 carrying the B.1.427/B.1.429 [Epsilon, California 
origin] variant and 1 carrying the B.1.1.7 [Alpha, UK origin] variant) progressed to 
hospitalization. Four participants in the placebo group (2 carrying the E484K 
substitution, 1 carrying the P.1 [Gamma, Brazil origin] variant, and 1 carrying the B.1.1.7 
[Alpha, UK origin] variant) progressed to hospitalization. None of the participants with 
currently available baseline sequences carried the full complement of substitutions 
characteristic of the B.1.351 (Beta, South Africa origin) or B.1.617 (Delta, India origin) 
variants.  
The PK of a 500 mg IV dose of sotrovimab administered via a 1 hour IV infusion was 
evaluated in COMET-ICE. There were 10 participants in the sotrovimab arm in the 
Lead-in Phase of this study. One participant discontinued early due to withdrawal of 
consent following infusion with sotrovimab. Complete serum PK from 9 participants 
(sotrovimab) in the Lead-in phase of COMET-ICE is therefore available. The mean 
maximum observed concentration (Cmax) of 500 mg sotrovimab was 219 µg/mL 
following a 1 hour IV infusion. The mean serum level on Day 29 is 37.2 µg/mL. The 
mean clearance (CL) and volume of distribution at steady state (Vss) were 125 mL/day 
and 8.1 L, respectively. The median half-life was 48.8 days. The mean PK profile and 
parameters are presented in Figure 1 and Table 3.  
Partial sparse serum PK through study Day 29 from 363 participants in the COMET-ICE 
Expansion phase is available to date. The mean serum concentration of sotrovimab on 
study Day 29 is 25.8 μg/mL. 
Figure 1 
Mean (+ standard deviation [SD]) Sotrovimab Serum Concentration-
Time Plots (Linear and Semi-log): COMET-ICE Lead-In Phase 
 
Note: Lower limit of quantification (LLQ)=0.1 µg/mL. Excludes anomalous concentrations identified as sampling errors 
by the clinical pharmacologist. 
Data is based on 1-hour infusion time. 
 

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Table 3 
Sotrovimab PK Parameters Following a 500 mg IV Dose: COMET-ICE 
Lead-in Phase 
Parameter 
Dose 
500 mg 
(N = 9a) 
Cmax, µg/mL 
219 (45.5) 
Tmax, day 
0.04 (0.04, 0.05) 
Clast, µg/mL 
5.41 (37.2) 
Tlast, day 
161 (160, 167) 
AUCD1-29, day*µg/mL 
1529 (9.6) 
AUClast, day*µg/mL 
3714 (14.5) 
AUC % Extrapolated 
9.4 (37.9) 
AUCinf, day*µg/mL 
4116 (16.9) 
CL (mL/day) 
125 (17.9) 
Vz, L 
8.76 (15.7) 
Vss, L 
8.1 (11.1) 
t1/2, day 
48.8 (37.8, 59.4) 
Abbreviations: AUC = area under the curve; AUClast = area under the serum concentration-time curve from time zero to 
time of last measurable concentration; AUC % Extrapolated = area under the plasma concentration-time curve 
extrapolated from time to infinity as a percentage of total AUC; AUCD1-29 = area under the serum concentration-time 
curve from Day 1 to Day 29; AUCinf = area under the serum concentration-time curve from time zero to infinity; 
Clast = last measurable serum concentration; Cmax = maximum observed concentration; CL = clearance; t1/2 = 
terminal elimination half-life; tmax = time to reach Cmax; tlast = time of the last quantifiable concentration; Vss = volume 
of distribution at steady state; Vz = apparent volume of distribution during terminal phase. 
Note: Parameters are reported as mean (%CV) except for Tmax, Tlast, and t1/2, which are presented as median (min, 
max).  
Data is based on 1-hour infusion time. 
a N=8 for AUCD1-29 as participant 10016 was missing all PK samples prior to Study Day 5. 
Sotrovimab was also studied for the treatment of hospitalized participants with 
COVID-19 in GSK Study 215149, also known as ACTIV-3-TICO, sponsored by the 
National Institute of Allergy and Infectious Diseases. The ACTIV-3-TICO study was a 
randomized, blinded, placebo-controlled platform study that allows investigational drugs 
to be added and dropped during the course of the study. The sub-study evaluating 
sotrovimab administered by IV infusion started in December 2020 and aimed to enroll 
approximately 500 participants per treatment arm. 
On 01 March 2021, the Data and Safety Monitoring Board (DSMB) recommended 
recruitment in the sotrovimab sub-protocol should cease, and follow-up of already 
randomized participants is ongoing. There were no safety concerns identified by the 
DSMB [GlaxoSmithKline, 2021b]. One potentially life-threatening allergic reaction 
(anaphylaxis) was reported during infusion in ACTIV-3-TICO in a participant who 
received sotrovimab. The time to onset was 21 minutes after the start of infusion and the 
event was considered related to study treatment. The participant was treated for the 
allergic reaction and recovered. 
Sotrovimab administered by IV infusion is also being evaluated in the BLAZE-4 study 
(VIR-7831-5007/GSK Study 217079; NCT04634409), a clinical trial with multiple arms 
evaluating anti-SARS-CoV-2 mAbs from Eli Lilly and Company. One arm compared the 

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combination of bamlanivimab with sotrovimab to placebo (randomized 1:1) for the 
treatment of mild to moderate COVID-19. The study has completed enrolment and is 
currently in the follow-up period. Day 29 topline analysis showed that the study met the 
primary endpoint (percentage of participants with SARS-CoV-2 viral load greater than 
log 5.27) and combination treatment was well tolerated with regards to acute infusion-
related reactions (IRRs) and there were no safety concerns [GlaxoSmithKline, 2021a]. 
Sotrovimab 500 mg administered intravenously or via IM injection is also currently being 
evaluated for the treatment of mild-to-moderate COVID-19 (VIR-7831-5006/GSK Study 
216912], also known as COMET-PEAK [NCT04779879]).COMET-PEAK has 3 parts 
(Part A, Part B, and Part C). COMET-PEAK Parts A, B, and C are fully enrolled. Part A 
is evaluating safety, tolerability, virology, immunogenicity, and PK in participants that 
received Generation1 (Gen1) or Generation2 (Gen2) sotrovimab via a 500 mg IV 
infusion. In Part B and Part C, viral load pharmacodynamics (PD) as assessed via upper 
respiratory samples, safety, tolerability, immunogenicity, and PK are being evaluated in 
participants that receive Generation2 sotrovimab via IM injection (500 mg in Part B, 
250 mg in Part C) or IV infusion (500 mg in both Part B and Part C).  
Data from an initial analysis from COMET-PEAK Part A and B to Day 29, which 
includes 197 randomized patients, are available. In Part A (safety population N=30; Gen1 
500 mg IV: n=8, Gen2 500 mg IV: n=22), there were 3 AEs reported in the Gen2 
formulation arm (unrelated to study treatment) and no SAEs were reported. No IRRs 
were reported in Part A. In Part B (safety population N=166; Gen2 500 mg IV: n=84, 
Gen2 500 mg IM: n=82), there were 8 (10%) AEs in the 500 mg IV arm and 17 (21%) 
AEs in the 500 mg IM arm. In total, 5 SAEs, which were all unrelated to study treatment, 
were reported across both arms in Part B. No sensitivity or IRRs occurred in the Part B 
500 mg IV arm. One (1%) participant had a hypersensitivity event and 9 (11%) 
participants reported injection site pain events in the Part B 500 mg IM arm. For 
COMET-PEAK results to date, there were no new safety findings that would 
significantly impact the benefit:risk assessment. The 500 mg IM dose (given as two 4 mL 
dorsogluteal injections) was also well tolerated.   
Sotrovimab is also being evaluated in non-hospitalized participants at high risk for 
disease progression (VIR-7831-5008/GSK Study 217114 [NCT04913675], also known as 
COMET-TAIL). The COMET-TAIL study is fully enrolled. COMET-TAIL is a Phase 3 
randomized, multi-center, open label study to assess the efficacy, safety, and tolerability 
of sotrovimab given IM versus IV for the treatment of mild/moderate COVID-19 in high-
risk non-hospitalized participants. COMET-TAIL will evaluate the clinical efficacy of 
two dose levels of IM sotrovimab compared with IV sotrovimab in preventing 
progression of COVID-19 in a non-inferiority setting and will include enrollment of 
adolescent participants between the age of 12 to 17 years. Following review of available 
data, the decision was made by COMET-TAIL JSRT and IDMC to permanently 
discontinue enrollment in the sotrovimab 250 mg IM arm. This decision was made due to 
an imbalance in the limited number of hospitalizations to date, and no study-wide or 
other safety concerns were noted at this time. 
Additionally, a Phase 1 study is ongoing to evaluate the PK, safety, and tolerability of 
500 mg sotrovimab administered IV or IM in healthy Japanese and Caucasian 

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participants (VIR-7831-5009/GSK Study 217653; NCT04988152). This study started in 
July 2021 and is fully enrolled. This study has two parts: Part 1 is evaluating IV 
sotrovimab and Part 2 is evaluating IM sotrovimab. Day 29 safety data for Part 1 is 
available to date. No SAEs have been reported for Part 1. Two participants in the Part 1 
placebo arm reported AEs (1 [33%] Japanese participant and 1 [33%] Caucasian 
participant) and 3 participants in the Part 1 sotrovimab arm reported AEs (2 [22%] 
Japanese participants and 1 [11%] Caucasian participant).  
 

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2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and potential risks of sotrovimab may be found in the Investigator’s 
Brochure (IB).  
2.3.1. 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention(s): Sotrovimab 
Hypersensitivity reactions 
(HSRs)  
While sotrovimab is a human Immunoglobulin G1 (IgG1) mAb, 
hypersensitivity is a potential general risk associated with the 
mAb class of therapeutics. 
There was no evidence of systemic infusion reactions in 
toxicology studies conducted with sotrovimab in monkeys. 
In COMET-ICE, all hypersensitivity reactions were non-serious, 
of Grade 1 (mild) or Grade 2 (moderate) severity and reported 
in 2% of participants who received sotrovimab and in <1% who 
received placebo (9 participants treated with sotrovimab; 
5 participants treated with placebo). None of the reactions in 
either arm led to pausing or discontinuation of the infusions. All 
events across both treatment groups were reported as resolved 
or resolving at the time of DCO.  
No anaphylaxis events were reported in the COMET-ICE study 
in participants with mild to moderate COVID-19 not requiring 
hospitalization at study entry. 
A potentially life-threatening allergic reaction (anaphylaxis) was 
observed in 1 adult participant who received sotrovimab in the 
study of individuals hospitalized with COVID-19 (the ACTIV-
3-TICO study). The anaphylaxis was considered by the 
• Participants will be excluded if they have a history of 
hypersensitivity to any of the constituents present in the 
investigational product. 
• Participants will be monitored for 2 hours post-administration 
of study intervention (including vital signs, see Section 8.5.1). 
After half of participants are dosed in either Cohort (Cohort A 
or Cohort B), post-dose monitoring might be reduced to 
1 hour per JSRT recommendation within the same Cohort. 
• Investigational product will be administered in the clinic with 
staff trained in emergency care and resuscitation procedures 
and emergency care kit on hand during the study intervention 
administration and post-therapy observation periods. 
• The JSRT and IDMC will review the safety data of this study 
at regular intervals.  
• General guidance on management of hypersensitivity 
reactions is provided in Section 10.5. 
• Refer to Section 8.6.4 for follow up regarding AESI.  

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
investigator to be related to study treatment. The participant 
was treated for the allergic reaction and recovered.  
Infusion Related 
Reactions (IRRs) 
Infusion related reactions are a potential general risk for 
biologic therapies with IV administration. 
 
There was no evidence of infusion reactions in toxicology 
studies conducted with sotrovimab in monkeys. 
 
In the ongoing COMET-ICE study in participants with 
mild/moderate COVID-19 with high risk of progression, IRRs 
that occurred within 24 hours post infusion (pyrexia, chills, 
dizziness, dyspnea, pruritus, rash, and infusion related reaction) 
were reported in 6 (1%) of participants in the sotrovimab arm 
and 6 (1%) of participants in the placebo arm. All IRRs were 
non-serious, and Grade 1 or 2 severity and none led to 
treatment pausing or discontinuation. In the sotrovimab arm all 
of the cases of IRRs were considered resolved and in the 
placebo arm one participant had an event considered not 
resolved at the time of DCO. 
• Participants will be monitored for 2 hours post-administration 
of study intervention (including vital signs, see Section 8.5.1). 
After half of participants are dosed in either Cohort (Cohort A 
or Cohort B), post-dose monitoring might be reduced to 
1 hour per JSRT recommendation within the same Cohort. 
• Infusion time can be extended at the discretion of the 
Investigator or Sponsor based on infusion-related symptoms 
or other safety findings. 
• Investigators are instructed to discontinue IV infusions for 
participants who develop Grade 3 or 4 infusion reactions 
using the Division of Acquired Immune-Deficiency syndrome 
(DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events, version 2.1 (July 2017) Adverse Event 
grading. See Section 7.1 for discontinuation information. For 
grading of severity see Section 8.6.3 and Section 10.3.4. 
• If a participant experiences a Grade 2 IRR, investigators are 
instructed to pause the infusion. The infusion may 
subsequently resume at a slower pace of infusion, at the 
investigator’s discretion, and/or after symptomatic treatment 
(e.g., antihistamines, IV fluids). See Section 7.1.1. 
• Investigational product will be administered in the clinic with 
staff trained in emergency care and resuscitation procedures 
and emergency care kit on hand during the infusion and 
post-therapy observation periods. 
• Refer to Section 8.6.4 for follow up regarding AESI. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
• The JSRT and IDMC will review safety data of this study at 
regular intervals. 
Injection Site Reaction (ISR) 
Sotrovimab will be administered via IM injection, which has a 
potential risk of local injection site reactions.  
In a single dose IM local tolerance study in mini pigs at a dose 
of 250 mg (4 mL, 62.5 mg/L), no injection site reactions were 
observed. 
The IM route of administration is being evaluated in the 
COMET-PEAK study. Injection site reactions (pain and/or 
tenderness) occurred in 9 out of 82 participants who were 
included in the safety population for the IM injection. All of the 
ISRs were Grade 1. One ISR occurred immediately post-dose, 
and the rest occurred within the first hour post-dose. 
•  Participants will be monitored for 2 hours after injection. 
After half of participants are dosed in either Cohort (Cohort A 
or Cohort B), post-dose monitoring might be reduced to 
1 hour per JSRT recommendation within the same Cohort. 
Refer to the SoA (Section 1.3) for more details, including 
local tolerability assessments.  
• Participants who have thrombocytopenia (platelet count 
<50,000/mm3), bleeding diathesis, or a coagulation disorder 
or are otherwise not recommended to receive an IM injection 
cannot be enrolled in Cohort B (which is IM administration 
only), but can be enrolled in Cohort A (which is IV 
administration only). 
• The JSRT and IDMC will review safety data of this study at 
regular intervals.  
• General guidance on management of ISRs is provided in 
Section 10.5.  
• Refer to Section 8.6.4 for follow up regarding AESI. 
Immunogenicity 
While sotrovimab is a human immunoglobulin G (IgG), the 
development of anti-drug antibodies (ADA) that have the 
potential to impact safety and/or efficacy are a potential general 
risk associated with the mAb class of therapeutics. 
Through Day 29 in the COMET-ICE study, the incidence of 
treatment-emergent anti-sotrovimab antibody responses has 
remained low with relatively low titers, with no detectable impact 
on safety or efficacy. 
• This study will include participant follow-up for a period of 
36 weeks (approximately 5 half-lives) and includes collection 
of samples for assessment of ADA and potential impact on 
PK/PD and safety. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Antibody-Dependent 
Enhancement (ADE) due to 
sub-neutralizing levels of 
sotrovimab enhancing fusion 
or leading to Fc gamma 
receptor (FcR) mediated 
increased viral uptake and 
replication with virus 
production  
This is a concern related to the potential for participants with 
sub-neutralizing mAb levels to experience a higher incidence of 
infection and/or more severe disease compared to participants 
with no circulating mAb and/or established protective immunity 
to SARS-CoV-2.  
ADE associated with Dengue virus serotype 1-4 infections is 
one of the most widely cited examples in which reinfection with 
a different serotype can, in a minority of patients, run a more 
severe course in the setting of limited antibodies generated by 
prior infection.  
The potential for enhanced disease in this setting is due to 
increased uptake of virus by FcR-expressing cells such as 
macrophages and increased viral replication in these cells. 
Recent data shows that SARS-CoV-2 does not replicate 
efficiently in macrophages [Hui, 2020], suggesting minimal to no 
risk of ADE via this mechanism. While there have been some 
nonclinical reports demonstrating ADE using mAb directed 
against specific epitopes in the SARS-CoV-2 spike protein [Li, 
2021; Zhou, 2021], there was no evidence of ADE either in vitro 
or in vivo in nonclinical studies with sotrovimab. These data are 
consistent with others demonstrating that SARS-CoV-2 
replication was abortive in FcR expressing cells [Hui, 2020] 
suggesting minimal to no risk of ADE via this mechanism.  
An IDMC reviewed unblinded clinical safety data from the 
COMET-ICE study. No safety concerns were identified, and the 
IDMC recommended to halt enrollment based on overwhelming 
efficacy. Further, as of the Day 29 DCO for the COMET-ICE 
study, no events consistent with ADE were observed. 
• This study will include participant follow-up for a period of 
36 weeks to assess for the potential of enhanced disease in 
participants who develop SARS-CoV-2 infection in the 
context of waning sotrovimab levels.  
• Assessment of disease severity will be performed by the 
JSRT and IDMC to assess for rates of infection or severe 
disease above what is clinically expected. 
• Safety guidelines will be provided in the IDMC Charter (see 
Section 10.1.5 for more details on the IDMC). 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
ADE due to enhanced 
disease pathology from viral 
antigen-antibody related 
immune complex deposition 
or complement activation 
and immune cell recruitment 
in target organs 
There is the possibility that a large amount of antibody that 
binds, but does not neutralize, virus in the presence of a high 
viral load could result in immune complex deposition and 
complement activation in tissue sites of high viral replication, 
such as the lungs, vascular endothelia, renal, or cardiovascular 
(CV) tissue [Hamming, 2004], leading to tissue 
damage/immune complex disease. 
This is hypothesized to have contributed to inflammation and 
airway obstruction observed in the small airways of infants who 
received a formalin-inactivated respiratory syncytial virus (RSV) 
vaccine [Polack, 2002] and in a few cases of fatal H1N1 
influenza infection [Wu, 2010]. 
The potential for enhanced disease in this setting may be due 
to low affinity or cross-reactive antibodies with poor or no 
neutralizing activity. 
Triggering of cytokine release by antibody-virus-FcγR 
interactions, although usually highly beneficial due to their direct 
antiviral effects and immune cell recruitment to control viral 
spread in tissues, also has the potential to enhance pathologic 
changes initiated by the viral infection. 
Observational data from 5000 COVID-19 patients treated with 
convalescent plasma, although not placebo controlled, is 
suggestive that even polyclonal mixtures of neutralizing and 
non-neutralizing antibodies can be safely administered [Joyner, 
2020]. 
Sotrovimab shows potent binding in vitro as well as 
neutralization of pseudovirus and live virus; thus, this risk is 
deemed to be low. 
• In this study, the JSRT and IDMC will monitor for the 
worsening of COVID-19-related end-organ complications 
and/or greater than expected incidence of end-organ 
complications in participants who develop COVID-19. 
• Safety guidelines will be provided in the IDMC Charter (see 
Section 10.1.5 for more details on the IDMC). 
•  Additional monitoring in the event a participant develops 
signs or symptoms of cardiac complications (see 
Section 8.5.4). 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
An IDMC reviewed unblinded clinical safety data from the 
COMET-ICE study. No safety concerns were identified, and the 
IDMC recommended to halt enrollment based on overwhelming 
efficacy. As of the Day 29 DCO for the COMET-ICE study, no 
events consistent with ADE were observed. 

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2.3.2. 
Benefit Assessment 
While children are more likely than adults to have asymptomatic or mild infection, 
significant morbidity and mortality can be seen during acute infection, specifically in 
those at high risk of disease progression. Although mAb combinations including 
bamlanivimab/etesevimab and casirivimab/imdevimab have an active EUA for 
adolescents aged 12 to <18 years (weighing at least 40 kg) with mild to moderate 
COVID-19 [EMA, 2021; FDA, 2020c; Roche, 2021], there are no other treatment options 
approved for these children. As a result, for outpatients, supportive care and monitoring 
remain the mainstays of current management. In addition, multiple SARS-CoV-2 variants 
are circulating globally and development of additional treatment strategies with 
conserved activity against these variants is desirable. The use of sotrovimab for the 
treatment of mild-to-moderate COVID-19 has been authorized in several countries as 
described in Section 2.1). 
The following are potential benefits to participants in this study: 
− Participants may benefit from thorough health assessments they receive during the 
course of the study. 
− Based on data in adults with mild-to-moderate COVID-19 at high risk of 
progression to severe disease or death, it is possible that treatment with 
sotrovimab may decrease the likelihood of a participant progressing from mild-to-
moderate COVID-19 to severe disease or death in children as well. 
− Participants in this study may benefit in the knowledge that they are contributing 
to the process of developing new therapies for children in an area of unmet need. 
2.3.3. 
Overall Benefit: Risk Conclusion 
There is prior clinical experience with sotrovimab in the setting of the adult early 
treatment of COVID-19 (COMET-ICE, BLAZE-4, COMET-TAIL, and COMET-PEAK) 
and hospitalized treatment in ACTIV-3-TICO. In the COMET-ICE study, there have 
been no safety concerns identified at the IDMC reviews conducted to date. One case of 
anaphylaxis was reported in an adult during sotrovimab infusion in the ACTIV-3-TICO 
study, which resolved with treatment. The COMET-ICE study was halted by the IDMC 
based on profound efficacy on the first interim analysis [Vir Biotechnology, 2021]. 
Overall, based on the available clinical data, sotrovimab provides a significant clinical 
benefit as a treatment for adults with COVID-19 who do not require oxygen 
supplementation and who are at risk of progressing to severe COVID-19. 
Considering that GSK was granted an EUA for sotrovimab for the treatment of mild-to-
moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing 
at least 40 kg [FDA, 2021e] in several countries, the limited availability of treatment 
options in children with mild-to-moderate COVID-19, the strength of the preclinical and 
clinical data for sotrovimab, and the implemented safety monitoring plan for the potential 
risks, the Sponsor believes that the potential benefit of participation in this study 
outweigh the risks.

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3. 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
The following intercurrent event applies to all endpoints specified below: use of non-permitted medication as defined in Section 6.8.1. 
A treatment policy strategy will be used for the analysis of all endpoints, including all data as collected during the study regardless of 
occurrence of the intercurrent events. 
Objectives 
Endpointsa 
Other Estimand Attributes 
Primary 
To evaluate the pharmacokinetics by IV or 
IM administration of sotrovimab in children 
from birth to <18 years 
• Body weight-adjusted serum clearance of sotrovimab 
• Serum PK of sotrovimab administered by IM injection or IV 
infusion (PK parameters may include Cmax, Tmax, AUCinf, t1/2, 
Vz, CL, F) 
Population: PK (all participants in 
Cohort A/Cohort B who are exposed to study 
intervention and who had at least 1 non-missing 
PK assessment [non-quantifiable values will be 
considered as non-missing values]) 
Summary measure: PK model parameters 
To evaluate the safety and tolerability of 
sotrovimab by IV or IM administration 
• Incidence of adverse events (AEs), serious adverse events 
(SAEs), and adverse events of special interest (AESI) through 
Day 29 and Week 36 
Population: Safety (all participants who are 
exposed to study intervention in 
Cohort A/Cohort B) 
Summary measure: Counts and percentages 
Secondary 
To evaluate disease progression following 
IV or IM administration of sotrovimab  
• Progression of COVID-19 through Day 29 as defined by need 
for attended medical visit* or escalation to higher level of 
medical care or death 
*An attended medical visit includes visit to a hospital emergency room 
for management of illness or hospitalization for acute management of 
illness  
Population: Safety 
Summary measure: Counts and percentages 

T M F -1 3 9 7 1 1 1 4  
C O N FI D E N TI A L  
 
 
 
2 1 5 2 2 6  
 
Pr ot o c ol A m d 1  
4 1  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5 d at e d 2 1 -D e c -2 0 2 0  
O bj e cti ve s  
E n d p oi nt s a 
Ot h er E sti ma n d Attri b ute s  
•  D ev el o p m e nt of s ev er e a nd/ or critic al r es pir at ory C O VI D -1 9 
as m a nif est e d by r e q uir e m e nt f or s u p pl e m ent al oxy ge n 
t hr o u g h D ay 2 9* 
*F or partici pa nts w h o re q uire o x y ge n or res pirat or y s u p p ort f or 
pre m or bi d c o n diti o ns, disease pr o gressi o n is d efi n e d as a n y s ustai n e d 
( > 2 4 h o urs) i n crease i n t he le vel or meth o d of o x y ge n s u p p ort re q uire d  
P o p ul atio n: S af ety  
S u m m ary m e as ur e: C o unts a nd p erc e nt a g es  
T o c h ar act eriz e t h e eff ect of I V or I M 
a d mi nistr ati o n of s otr ovi ma b on 
S A R S -Co V -2 vir al l o ad i n r es pir at ory tr act 
s a m ples a m o n g p artici p a nts inf ect e d with 
S A R S -Co V -2  
•  C h a n g e fr o m b aseli ne i n vir al lo a d i n nas al s ecr eti ons 
m e as ure d by q R T -P C R at D ay 5, D ay 8, an d D ay 1 1  
P o p ul atio n: Vir ol o gy (a ll particip a nts w h o ar e 
ex p ose d t o st u dy i nt erv e nti o n in 
C o h ort  A/ C o h ort B a n d h ave a q u a ntifi a ble 
S A R S -Co V -2 vir al l o ad m e as ur e m e nt at 
b as eli n e ) 
S u m m ary m e as ur e: Arith m etic m e a n  
C CI
C CI

T M F -1 3 9 7 1 1 1 4  
C O N FI D E N TI A L  
 
 
 
2 1 5 2 2 6  
 
4 2  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5 d at e d 2 1 -D e c -2 0 2 0  
A b br evi ati o ns: A D A = a nti -dr u g a nti b o di es; A Es = a dv ers e ev e nts; A E SI = a dv ers e ev e nts of s p eci al i nt er est; a nti -N = a nti -n ucl e oc a psi d; A U C i nf = ar e a u n d er t h e s er u m c o nc e ntr ati o n -
ti m e c urv e fr o m ti m e z er o t o i nfi nity; Cm ax  = m axi m u m o bs erv e d c o nc e ntr ati o n; C L = cl e ar a nc e; E C Gs = el ectr oc ar di o gr a ms; F = bi o av ail a bility; I M = i ntr a m usc ul ar; I V = 
i ntr av e n o us; P K =  p h ar m ac oki n etics; S A Es = s eri o us a dv ers e ev e nts; S A R S -C o V -2 = s ev er e ac ut e r es pir at ory sy n dr o m e c or o n avir us -2; t 1/2 = t er mi n al eli mi n ati o n h alf -lif e; Tm ax  = 
ti m e t o r e ac h Cm ax ; q R T -P C R = q u a ntit ativ e r ev ers e tr a nscri pt as e p oly m er as e c h ai n r e acti o n; V z = a p p ar e nt v ol u m e of distri b uti o n d uri n g t er mi n al p h as e.  
a E n d p oi nts will b e ass ess e d s e p ar at ely f or I V a n d I M i nt erv e nti o n.  
C CI

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study is a Phase 2b open-label, non-comparator, multi-center study to evaluate PK, 
safety, and PD of IM or IV administration of sotrovimab in pediatric participants aged 
from birth to <18 years with mild/moderate COVID-19 at high risk of disease 
progression.  
This study includes 2 cohorts (Cohort A and Cohort B). Participants in Cohort A will 
receive IV sotrovimab and participants in Cohort B will receive sotrovimab via IM 
injections.  
Cohort A and Cohort B will each enroll approximately 36 participants; therefore, a total 
of approximately 72 participants will be enrolled in this study. Four age bands are 
planned to be enrolled2 in this this study. The following number of participants will be 
enrolled in each age band for each Cohort:  
• Adolescents aged 12 to less than 18 years: approximately 6 participants  
• Children aged 6 to less than 12 years: approximately 12 participants 
• Children aged 2 to less than 6 years: approximately 12 participants 
• Birth to less than 2 years: approximately 6 participants 
Recruitment will start with Cohort A as follows: 
• The Cohort A 2 to <18 years age bands will be recruited simultaneously. 
• The Cohort A birth to <2 years age band will be recruited if deemed appropriate 
by the JSRT and IDMC after review of safety data once half of Cohort A 
participants 2 to <18 years (i.e., 15 participants) complete Day 29. 
Recruitment in Cohort B will occur as follows: 
• Cohort B will start recruitment if deemed appropriate after review of PK data 
through Day 29 from all adolescents in the Cohort A 12 to <18 years age band 
(i.e., 6 participants) and after the efficacy of IM dosing is confirmed in adults. 
Safety data through Day 29 from all Cohort A 12 to <18 years age band 
participants will also be reviewed by the JSRT and the IDMC prior to initiating 
Cohort B recruitment. Following favorable review, the Cohort B 2 to <18 years 
age bands will be recruited simultaneously.  
                                                 
2 For this study, "enrolled" means a participant's, or their legally acceptable representative’s, agreement to 
participate in a clinical study following completion of the informed consent process and Screening. 
Potential participants who are screened for the purpose of determining eligibility for the study, but do 
not participate in the study, are not considered enrolled, unless otherwise specified by the protocol. A 
participant will be considered enrolled if the informed consent is not withdrawn prior to participating in 
any study activity after Screening. 

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• The Cohort B birth to <2 years age band will be recruited if deemed appropriate 
by the JSRT and IDMC after review of safety data once half of Cohort B 
participants 2 to <18 years (i.e., 15 participants) complete Day 29. 
The decision to enroll participants in Cohort A or Cohort B will be per investigator 
discretion when both Cohorts enroll a given age group simultaneously. Refer to 
Section 6.3 for additional details regarding dispensation monitoring. 
All participants in Cohort A and Cohort B will be actively monitored on an outpatient 
basis through 36 weeks after dosing (Week 36) with frequent collection of nasal 
mid-turbinate swabs for virology and resistance analyses. Participants will have blood 
draws for PK sampling, anti-drug antibodies (ADA) testing, and for safety assessments; 
participants will have other in-clinic or home evaluations as detailed in the Schedule of 
Activities (SoA; Section 1.3). Additionally, all participants 2 years of age will have 
blood draws for assessment of anti-nucleocapsid (anti-N) and anti-spike (anti-S) SARS-
CoV-2 antibodies. 
Dosing will be based on weight in each age band (Table 4). Intravenous sotrovimab will 
be administered undiluted using a syringe pump for participants under <15 kg, and 
diluted in 40 mL saline for participants 15 kg (Section 4.3). Because endotoxin 
specification limits for sotrovimab exceeds allowable levels for infants weighing 
<1.88 kg, infants <2 kg will be excluded from the study. Intramuscular sotrovimab may 
be administered in dorsogluteal, anterolateral thigh, or deltoid muscles. The injection site 
location will be per participant/legally authorized representative (LAR) preference and 
the clinical discretion of the investigator. Dosing will be performed within 2 days of 
Screening assessment. Dosing must occur 7 days from onset of COVID-19 symptoms. 
Screening can occur on the same day as dosing. Eligible participants will be treated with 
a single IM or IV dose of sotrovimab on Day 1.  
After IV infusion or IM injection, participants will be monitored for 2 hours. Local 
injection site tolerability will also be monitored during the 2 hours post-dose. Throughout 
the study, a JSRT and IDMC will review safety data from all participants enrolled in 
either Cohort. After half of participants are dosed in either Cohort (Cohort A or Cohort 
B), the JSRT will review safety data and, if there are no safety concerns, a 
recommendation may be made by the JSRT to reduce the post-dose Day 1 monitoring 
and observation time to 1 hour within the same Cohort. Further information about the 
IDMC and the JSRT are provided in Section 10.1.5.  
COVID-19 disease progression will be monitored daily from Day 1 through Day 14 by a 
phone call on days when a home visit or clinic visit is not scheduled. COVID-19 disease 
progression will also be monitored on Day 22 and Day 29. Additionally, a weekly phone 
call will be conducted starting at Week 5 on weeks when there is not a scheduled 
clinic/home visit. Participants will be followed for a period of 36 weeks from dosing. 
4.2. 
Scientific Rationale for Study Design 
This study is a non-comparator, multicenter, open-label study to evaluate PK, safety, and 
PD of IM or IV administration of sotrovimab in pediatric participants aged from birth to 

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<18 years with mild to moderate COVID-19 at high risk of disease progression. 
Currently SARS-CoV-2 infection remains an extremely important public health issue, 
with the current pandemic causing significant morbidity and mortality. Despite the 
relatively mild presentation and positive prognosis of COVID-19 in children, there are a 
significant number of children that are infected and progress to severe disease or develop 
complications requiring hospitalization. Pediatric patients with COVID-19 are more 
likely to be hospitalized with severe disease or die if they are young (≤1 year) or have a 
history of obesity, gastrointestinal conditions, congenital heart disease, genetic or 
metabolic conditions, neurologic disease, diabetes mellitus, asthma or chronic lung 
disease, immunosuppression, sickle cell disease, or baseline medical complexity 
[CDC, 2021c; Graff, 2021; Kim, 2020]. Given the potential for severe disease in 
high-risk children, there is a significant unmet need for a medication that could prevent 
COVID-19 progression. Therefore, this study will enroll pediatric participants from birth 
to less than 18 years with mild to moderate COVID-19 at high risk of disease 
progression.  
While there are few data in children on the absolute risk of progression, the existing data 
in pediatric literature support each of these CDC-designated at-risk categories 
[CDC, 2021c]. Therefore, CDC criteria were considered to be an appropriate reference 
source [Dong, 2020; Graff, 2021; Kim, 2020; Shekerdemian, 2020] and the study will use 
these categories to define the pre-morbid conditions for participants at high risk of 
disease progression (Section 10.6). As in adults, immunocompromised status is a risk 
factor in children and they will be eligible for inclusion in this trial [CDC, 2021c]. This 
study will also recruit participants who have pre-morbid (non-COVID-19 related) 
oxygen/respiratory support requirements, or pre-morbid medical technology-dependence 
in addition to some conditions unique or over-represented in children [CDC, 2020; 
Mulder, 2012; Clark, 2017]. COMET-ICE and the ongoing adolescent/adult sotrovimab 
studies have greatly increased the safety characterization of the drug, and no 
unanticipated safety issues have emerged from the clinical program to date.  
With no approved or authorized vaccines for age 12 and under, treatment of 
immunocompromised children and children dependent on medical technologies in this 
age group presently represent an urgent unmet medical need. Extrapolation of efficacious 
exposure levels and overall efficacy from the COMET-ICE population to these 
populations is, on balance, reasonable. 
The co-primary objectives of this study are to characterize PK of sotrovimab to support 
dosing in pediatric participants with mild to moderate COVID-19 and to evaluate safety 
of sotrovimab in this population. Cohort A and Cohort B will provide data to evaluate 
safety and to characterize PK across age and weight bands, to support IV and IM dosing 
in pediatric participants as well as safety.  
Cohort B initiation will be contingent upon 1) acceptable PK and safety from adolescents 
aged 12 to <18 years in cohort A and 2) data from COMET-TAIL supporting the efficacy 
of IM dosing in adults. The exposure-response relationship has not yet been established 
for sotrovimab in adults following IM administration. This will be determined after the 
read-out from the COMET-TAIL study and will be used to support initiation of IM 
administration and enrollment in Cohort B. 

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The secondary endpoints include evaluation of disease progression through Day 29 and 
viral load change from baseline in nasal secretions measured by quantitative reverse 
transcriptase polymerase chain reaction (qRT-PCR) at Day 5, Day 8, and Day 11. Disease 
progression is defined by need for attended medical visit or escalation to higher level of 
medical care or death and development of severe/and or critical COVID-19 as manifested 
through requirement for supplemental oxygen. This study enrolls participants with mild 
to moderate COVID-19 at high risk of disease progression; therefore, for participants 
who require oxygen or respiratory support due to pre-morbid conditions, disease 
progression is defined as any sustained (>24 hours) increase in the level or method of 
oxygen support required. 
4.3. 
Justification for Dose 
Conventional allometric scaling, assuming fixed powers of 0.75 and 1.00 for clearance 
and volume, respectively, were used to scale preclinical pharmacokinetics from 
cynomolgus monkey to human, and subsequently adult pharmacokinetic data down to 
pediatrics. Using data from the COMET-ICE study, the target adult dose of 500 mg IV 
provides a serum AUCinf of 4116 day*g/mL (from Lead-in phase, median body weight 
of 76 kg). This study in adults with mild to moderate COVID-19 at risk of progression 
demonstrated a clinically and statistically significant reduction in the primary endpoint of 
hospitalization or death by Day 29 in the sotrovimab arm vs placebo without any major 
safety concerns, and hence represents an appropriate serum exposure target. Although 
body weight was confirmed as a covariate of sotrovimab exposure, dose adjustment in 
adults for this or other covariates is not necessary. 
Using National Health and Nutrition examination Survey (NHANES)- and World Health 
Organization (WHO)- validated weight-for-age simulations of various age bands 
(including conventional WHO bands), doses and dose ratios to adult were selected based 
on balancing; i) target AUC exposure across each age band, ii) pragmatism in delivery of 
formulation (multiples of 1 mL for IM injection) and iii) intended dose of excipients 
(including endotoxin). No dose adjustment for absolute IM bioavailability is required due 
to the age of the study participants, lower BMI and conservatively chosen adult 
efficacious dose (i.e., 10x tissue-adjusted IC90 upper bound of the 95% CI at 28 days 
post-dose). 
The dosing scheme is shown in Table 4.  
Table 4 
Sotrovimab Dosage per Weight  
Age  
Weight Band 
Dose (mg) 
Volume (mL) 
0 to <2 years 
2 to <5 kg 
5 to <15 kg 
15 to <40 kg 
62.5 
125 
250 
1 
2 
4 

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Age  
Weight Band 
Dose (mg) 
Volume (mL) 
2 to <6 years 
5 to <15 kg 
15 to <40 kg 
125 
250 
2 
4 
6 to <12 years 
15 to <40 kg 
≥40 kg 
250 
500 
4 
8 
12 to <18 years 
15 to <40 kg 
≥40 kg 
250 
500 
4 
8 
Intravenous sotrovimab will be administered undiluted using a syringe pump for 
participants <15 kg, and diluted in 40 mL saline for participants 15 kg. Because 
endotoxin specification limits for sotrovimab exceeds allowable levels for infants 
weighing <1.88 kg, infants <2 kg will be excluded from the study. Intramuscular 
injections will be administered without any saline dilution. 
All doses can be accommodated by the current drug product presentation. The 
presentation is a 10R vial containing 500 mg of sotrovimab at a concentration of 
62.5 mg/mL active ingredient.  
For participants receiving undiluted IV sotrovimab (Section 6.1), the appropriate quantity 
will be removed from the drug product vial and administered IV via an infusion syringe 
pump within 30 minutes from the start of administration. For participants receiving 
diluted intravenous sotrovimab, the appropriate quantity will be removed from the drug 
product vial and injected into an IV bag and administered by IV infusion within 
30 minutes from the start of administration. The need for appropriate pediatric dosing 
volumes, especially for neonates, will be taken into account once pediatric doses are 
confirmed. 
4.4. 
End of Study Definition 
The end of the study is defined as the date of last scheduled procedure shown in the SoA 
(Section 1.3) for the last participant in the study globally. 
A participant is considered to have completed the study if he/she completes the Week 36 
visit. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 

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Age 
1. Participant must be 32 weeks estimated gestational age (EGA), day of life 
(DOL) 0 to <18 years of age inclusive, at either the time of participant’s signed 
assent (if age-appropriate) or parent(s)/legally authorized representative signing the 
informed consent. 
Type of Participant and Disease Characteristics 
2. Participants with mild-moderate COVID-19, as defined by: 
• A positive SARS-CoV-2 test result by any validated qRT-PCR or other nucleic 
acid amplification test (NAAT) [FDA, 2021a] 
AND 
• SpO2 ≥94% on room air*  
AND 
• Have one or more of the following symptoms: fever, chills, cough, sore throat, 
malaise, headache, joint or muscle pain, change in smell or taste, vomiting, 
diarrhea, shortness of breath, poor appetite or poor feeding, nasal 
congestion/runny nose, lethargy 
AND 
• Less than or equal to 7 days from onset of symptoms to dosing day (Day 1). 
*Note: Some participants may be on baseline oxygen supplementation or respiratory support (CPAP, BiPAP, or 
ventilator-dependence) prior to contracting COVID-19. Others, such as participants with some unrepaired 
congenital heart disease, may have baseline SPO2 that is <94% on room air prior to contracting COVID-19. If a 
participant can maintain his/her baseline SpO2 while on his/her baseline oxygen supplementation (including room 
air) and baseline respiratory support (modality, pressures, and frequency of use), he/she may be included in the 
study. 
3. Participants at risk of disease progression with at least one of the following criteria 
(suggested diagnoses for categories are included in Section 10.6):  
• Age <1 year 
• Diabetes mellitus 
• Genetic or metabolic diseases 
• Obesity (as defined as body mass index (kg/m2) ≥95th percentile for age and sex 
based on local growth charts for children ≥2 years of age [or if not available based 
on the CDC or WHO growth charts in Section 10.7 and Section 10.8, 
respectively]) 
• Cardiovascular disease  
• Sickle cell disease 
• Pulmonary disease 
• Neurologic disease  
• Immunosuppressed (due to certain medical conditions or being on medications 
that weaken the immune system 

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o Use of systemic corticosteroids is included as defined by dose 
≥0.5 mg/kg/day or 20 mg/day prednisone equivalents (whichever dose is 
the lower of the two) taken for ≥2 weeks 
• Baseline medical complexity (gastrostomy- or jejunostomy-dependence, 
parenteral nutrition dependence, tracheostomy-dependence, baseline oxygen 
requirement, use of CPAP/BiPAP/ventilator support). 
Weight 
4. Body weight with the range stated below: 
• Preterm newborn infants and term newborn infants: ≥2 kg 
• Children 2 years to <18 years:  
o Body mass index (BMI) ≥5th percentile for age based on local 
growth charts (or if not available based on the CDC or WHO growth 
charts in Section 10.7 and Section 10.8, respectively). 
 
Sex and Contraceptive/Barrier Requirements 
5. Male and/or female (according to their reproductive organs and functions assigned 
by chromosomal complement) [FDA, 2016]. 
• Contraception and barriers as well as pregnancy testing is required for females 
only, as appropriate for the age and sexual activity of pediatric participants and as 
required by local regulations regarding the methods of contraception for those 
participating in clinical studies.  
• A female participant is eligible to participate if she is not breastfeeding and is 
either: 
• 
Premenarcheal or  
• 
Not pregnant as confirmed by a negative pregnancy test (serum or highly 
sensitive urine as required by local regulations) at Screening, before the 
first dose of study intervention, if of reproductive potential. 
o If a urine test cannot be confirmed as negative (e.g., an ambiguous result), 
a serum pregnancy test is required. In such cases, the participant must be 
excluded from participation if the serum pregnancy result is positive. 
o See Section 8.5.6 for additional requirements for pregnancy testing during 
the study participation. 
Women of childbearing potential (WOCBP; as defined in Section 10.4.1) must 
commit to using a contraceptive method that is highly effective, with a failure rate of 
<1%, as described in Section 10.4 during the study intervention period and for at 
least 36 weeks after the last dose of study intervention. The investigator should 
evaluate potential for contraceptive method failure (e.g., noncompliance, recently 
initiated) in relationship to the first dose of study intervention. 

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The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a female with an early 
undetected pregnancy. 
Note: If the childbearing potential changes after start of the study (e.g., a 
premenarcheal female participant experiences menarche) or the risk of pregnancy 
changes (e.g., a female participant who is not heterosexually active becomes active), 
the participant must discuss this with the investigator, who should determine if a 
female participant must begin a highly effective method of contraception. If 
reproductive status is questionable, additional evaluation should be considered. 
Informed Consent and Assent 
6. The investigator, or a person designated by the investigator, will obtain written 
informed consent from each study participant’s legal guardian (as defined in 
Section 10.1.3) and the participant’s assent, when applicable, before any 
study-specific activity is performed (unless a waiver of informed consent has been 
granted by an Institutional Review Board [IRB]/Ethics Committee [EC]). All legal 
guardians should be fully informed, and participants should be informed to the fullest 
extent possible, about the study in language and terms they are able to understand. 
7. The participant capable of providing signed and dated written assent signs and dates 
a written assent form (age appropriate) and the parent/guardian signs and dates a 
written informed consent form (ICF) for study participation prior to the initiation of 
any study-related activities. Informed consent is described in Section 10.1.3. 
Other 
8. A legal guardian or primary caregiver must be available to help the study-site 
personnel ensure follow-up; support the participant to attended assessment days 
according to the SoA (e.g., able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures); consistently and consecutively be 
available to provide information on the participant using the rating scales during the 
scheduled study visits; accurately and reliably dispense study intervention as 
directed. 
9. A legal guardian or primary caregiver must be able to accurately maintain the child’s 
take-home record, including items of general health. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Pregnant or breastfeeding. 
2. Currently hospitalized, or judged by the investigator as likely to require 
hospitalization in the next 24 hours, due to severe or critical COVID-19. 

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Note: If the infant has been hospitalized due to other reasons (e.g., prematurity) or 
will be hospitalized for reason of administering the study treatment then they can be 
included in the study. 
3. Respiratory rate: 
• 0-6 months: >60 breaths/minute (min) 
• 6 months to 5 years: >30 breaths/min 
• 6 years to <18 years: >20 breaths/min 
4. Shortness of breath at rest or respiratory distress. 
5. Shock (septic, neurogenic, anaphylactic, cardiogenic, or hypovolemic shock; systemic 
inflammatory response syndrome).  
6. Multiorgan dysfunction. 
7. Participants who, in the judgement of the investigator are likely to die in the next 
7 days. 
8. Multisystem inflammatory syndrome in children (MIS-C) [CDC HAN, 2020], 
defined as a participant: 
a. Participants presenting with fever ≥38°C, laboratory evidence of inflammation 
(such as elevated C-reactive protein [CRP], erythrocyte sedimentation rate 
[ESR], fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid, lactate 
dehydrogenase [LDH], interleukin 6 [IL-6], neutrophilia, lymphopenia or 
hypoalbuminemia) and evidence of clinically severe illness requiring 
hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, 
respiratory, hematologic, gastrointestinal, dermatologic or neurological);  
AND 
b. No alternative plausible diagnoses;  
AND 
c. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or 
antigen test; or exposure to a suspected or confirmed COVID-19 case within the 
4 weeks prior to the onset of symptoms. 
9. Post-conceptional age less than 32 completed weeks at time of Screening. 
10. History of sudden infant death or unexplained death in a sibling. 
11. For Cohort B only: Participant has any condition that would prohibit receipt of IM 
injections in the investigator’s opinion such as coagulation disorder, bleeding 
diathesis, or thrombocytopenia (platelet count <50,000/mm3).  
Prior/Concomitant Therapy 
12. Prior, current, or planned future use of any of the following treatments during the 
study period: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (e.g., 
casirivimab/imdevimab), intravenous immunoglobulin (IVIG) for any indication, or 
dexamethasone specifically for treatment of COVID-19. 
13. Current use of COVID-19 treatment (authorized, approved, or investigational).  

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14. The following exclusions related to use of an authorized or approved vaccine for 
SARS-CoV-2 are applicable:  
a) Receipt of any authorized or approved vaccine for SARS-CoV-2 within 
48 hours prior to dosing. 
b) Planned use of any authorized or approved vaccine for SARS-CoV-2 
within 90 days of study drug administration per current CDC 
recommendations [CDC, 2021d]. 
15. Receipt of any non-SARS-CoV-2 vaccines within 14 days (for non-live vaccines) or 
28 days (for live vaccine) of Screening. 
Prior/Concurrent Clinical Study Experience 
16. Has participated, or is participating, in a clinical research study evaluating COVID-19 
convalescent plasma, mAbs against SARS-CoV-2 (e.g. casirivimab/imdevimab) or 
IVIG within 3 months or within 5 half-lives of the investigational product (whichever 
is longer) prior to the Screening visit. 
17. Has participated, is participating, or plans to participate during the study period in a 
clinical research study evaluation of any authorized, approved or investigational 
vaccine for SARS-CoV-2. 
18. Currently enrolled in another clinical study. 
Other Exclusions 
19. Infants <24 weeks of age: maternal receipt of IVIG, SARS-CoV-2-directed 
convalescent plasma or SARS-CoV-2-directed mAb(s) within 3 months prior to birth 
or within 5 half-lives of the investigational product (whichever is longer). 
20. Participants who, in the judgment of the investigator, will be unlikely or unable to 
comply with the requirements of the protocol through the end of the study. 
21. Known hypersensitivity to any constituent present in the investigational product. 
5.3. 
Lifestyle Considerations 
Lifestyle considerations are not applicable to this study. Participants should be 
encouraged to comply with the institutional or government-recommended protocols for 
reducing risk of SARS-CoV-2 infection (e.g., social distancing, wearing masks). 
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical 
study is not subsequently enrolled. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, any protocol deviations and any SAEs. Re-screening is 
not permitted in this study. 

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5.5. 
Criteria for Temporarily Delaying Enrollment 
There is no reason for enrollment to be delayed in this study when inclusion/exclusion 
criteria are met. 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
An overview of the study interventions is provided in Table 5. Detailed instructions for 
the administration of study drug will be provided in a separate pharmacy manual.  
Table 5 
Overview of Study Interventions 
Arm Name 
Sotrovimab IV 
Sotrovimab IM 
Intervention Label 
Sotrovimab 
Sotrovimab 
Type  
Biologic 
Biologic 
Dose Formulation  
Solution in single use vial 
(62.5 mg/mL) 
Solution in single use vial 
(62.5 mg/mL) 
Unit Dose Strength(s)  
500 mg/vial (500 mg/8 mL) 
500 mg/vial (500 mg/8 mL) 
Dosage Level(s) by 
Weight:  
0 to <2 years: 
• 2 to <5 kg: 62.5 mg = 1 mL 
• 5 to <15 kg: 125 mg = 2 mL 
• 15 to <40 kg: 250 mg = 4 mL 
 
2 to <6 years: 
• 5 to <15 kg: 125 mg = 2 mL 
• 15 to <40 kg: 250 mg = 4 mL 
 
6 to <12 years: 
• 15 to <40 kg: 250 mg = 4 mL 
• 40 kg: 500 mg = 8 mL 
 
12 to <18 years: 
• 15 to <40 kg: 250 mg = 4 mL 
• 40 kg: 500 mg = 8 mL 
0 to <2 years: 
• 2 to <5 kg: 62.5 mg = 1 mL 
• 5 to <15 kg: 125 mg = 2 mL 
• 15 to <40 kg: 250 mg = 4 mL 
 
2 to <6 years: 
• 5 to <15 kg: 125 mg = 2 mL 
• 15 to <40 kg: 250 mg = 4 mL 
 
6 to <12 years: 
• 15 to <40 kg: 250 mg = 4 mL 
• 40 kg: 500 mg = 8 mL 
 
12 to <18 years: 
• 15 to <40 kg: 250 mg = 4 mL 
• 40 kg: 500 mg = 8 mL 
Route of Administration 
IV infusion 
IM injection 

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Arm Name 
Sotrovimab IV 
Sotrovimab IM 
Dilution with Saline 
• Participants <15 kg: none 
• Participants 15 kg: 40 mL saline 
None 
Duration of Infusion 
30 minutes 
Not applicable 
Use 
Experimental 
Experimental 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Sotrovimab will be provided centrally 
by the sponsor/designee 
Saline will be provided by the study 
site. 
Sotrovimab will be provided 
centrally by the sponsor/designee 
 
Packaging and Labeling 
Sotrovimab will be provided in a 
single-use vial and labeled as 
required per country requirement 
Sotrovimab will be provided in a 
single-use vial and labeled as 
required per country requirement 
Current/Former Name(s) 
or Alias(es) 
VIR-7831, GSK4182136 
VIR-7831, GSK4182136 
Intramuscular injection for groups receiving 1 mL, 2 mL, 4 mL or 8 mL of sotrovimab 
will be performed as two 0.5 mL, two 1 mL, two 2 mL, or two 4 mL injections, 
respectively—one in each dorsogluteal, anterolateral thigh, or deltoid muscle. Location of 
IM injections will be per participant/LAR preference and the clinical discretion of the 
investigator. All IM injections should be given at approximately the same time. 
Intravenous infusion will be administered over a 30 minute period. In the adult program 
the length of infusions were 15 minutes, 30 minutes, and 1 hour in the COMET-PEAK, 
BLAZE-4, and COMET-ICE studies, respectively (COMET-PEAK included both 
15 minute and 30 minute infusions). To date, 101 participants have been dosed with IV 
sotrovimab infused over 30 minutes in BLAZE-4 and no IRRs related to study treatment 
have been reported. In 159 participants that were given sotrovimab via IV infusion over 
15 minutes or 30 minutes in COMET-PEAK, there were no reports of IRRs as of 
23 July 2021. 
Infusion time can be extended at the discretion of the Investigator or Sponsor based on 
infusion-related symptoms or other safety findings. Refer to Section 7.1 for procedures to 
follow if a participant experiences a Grade 3 or 4 IRR and Section 7.1.1 for procedures to 
follow if a participant experiences a Grade 2 IRR. Study intervention should be infused 
via a participant’s central venous catheter (e.g., port, percutaneously inserted central 
catheter [PICC]) if he/she has one in place.  
Investigational product will be administered in the clinic with staff trained in emergency 
care and resuscitation procedures and emergency care kit on hand during the 
infusion/injection and post-therapy observation periods.  

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Additional information about administration methods and saline dilution is provided in 
Section 4.3. 
6.2. 
Preparation, Handling, Storage, and Accountability 
Instructions for the preparation of study drug will be provided in a separate pharmacy 
manual. 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study 
intervention are provided in the Pharmacy Manual.  
5. Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists. In the case of 
unintentional occupational exposure notify the monitor, Medical Monitor, and/or 
GSK study contact. 
6. A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from 
GSK. 
7. The excipients used in the sotrovimab formulation are safe for administration in the 
pediatric population participating in the study. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label treatment study and participants are not randomized. All screened 
participants will be identified by a unique participant number that will remain consistent 
for the duration of the study. Upon completion of all the required Screening assessments, 
eligible participants will be registered into the study by the investigator or authorized site 
staff.  
By using the Interactive Response Technology (IRT) system, the dispensation will be 
monitored to ensure that the target number of participants in each Cohort and in each age 
band will receive IV infusion or IM injection. 

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6.4. 
Study Intervention Compliance 
Participants will receive sotrovimab directly from the investigator or designee, under 
medical supervision. The date and time of each dose administered in the clinic will be 
recorded in the source documents. When multiple IM injections are performed, the time 
recorded should be the first injection. The infusion start and stop times will be recorded 
for IV administration. 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. 
Dose Modification 
This is a single dose study and dose modifications are not applicable. 
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
There will not be continued access to study intervention after the end of the study. Re-
dosing with sotrovimab has not been studied; therefore, there is no evidence to support 
benefit of continued access to study intervention. 
6.7. 
Treatment of Overdose 
For this study, any dose of sotrovimab greater than the protocol-defined dose and 
frequency (one-time dose) will be considered an overdose. No specific treatment is 
recommended for an overdose. The treating physician may provide supportive measures 
depending on the symptoms. In the event of an overdose, the treating physician should: 
1. Contact the medical monitor immediately. 
2. Closely monitor the participant for AEs/SAEs and laboratory abnormalities. 
3. Document the quantity and/or frequency of the excess dose in the electronic case 
report form (eCRF). 
6.8. 
Concomitant Therapy 
Any vaccine or medication (including over-the-counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) that the participant is receiving 
at the time of enrollment or receives during the study must be recorded in the eCRF, 
along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
While prioritizing standard clinical care, efforts should be made not to administer 
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The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1. 
Medication Not Permitted During the Study 
Receipt of convalescent plasma from a recovered COVID-19 patient, anti-SARS-CoV-2 
mAb, IVIG for any indication, or dexamethasone specifically for treatment of COVID-19 
are not permitted during the study.  
Receipt of any authorized or approved SARS-CoV-2 vaccine is not permitted within 
90 days after dosing per CDC guidelines [CDC, 2021d].  
6.8.2. 
Permitted Concomitant Medication 
All medication that the participant is receiving as local, established standard of care for 
acute COVID-19 is permitted with the exception of those mentioned under exclusion 
criteria (Section 5.2). 
Any concerns regarding the acceptability of potential treatments should be discussed with 
the medical monitor(s). 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are described in 
Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention 
For IV administration, a participant will be permanently discontinued from completion of 
drug infusion if they experience a Grade 3 or 4 IRR (for example, life-threatening, IRRs 
including severe allergic or hypersensitivity reactions or severe cytokine release 
syndrome). Refer to Section 10.5 for management guidelines for events of anaphylaxis. 
Discontinuation of study intervention does not apply to IM injection. 
If study intervention is permanently discontinued the participant will remain in the study 
to be evaluated for follow-up safety assessments as indicated in the SoA (Section 1.3).  
7.1.1. 
Temporary Discontinuation 
For IV administration, if a participant experiences a Grade 2 (moderate) IRR, 
investigators will be instructed to pause the infusion. The infusion may subsequently 
resume at a slower pace at the investigator’s discretion, and/or after symptomatic 
treatment (e.g., antihistamines, IV fluids).  
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• The legal guardian and the pediatric participant have the right to withdraw 
permission (consent or assent, respectively) at any time during the study. If the 

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study staff identify any reluctance in the legal guardian or pediatric participant 
(e.g., signs of verbal or physical dissent) about continued participation in the 
study, the pediatric participant’s continuation in the study should be re-evaluated. 
The same principles that govern permission/assent/consent also govern its 
withdrawal.  
• A participant may withdraw from the study at any time at his/her own request, at 
the request of their 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 withdrawal from the study, if possible, an early withdrawal (EW) 
visit should be conducted, as shown in the SoA (Section 1.3). Participants may be 
contacted by phone. See the SoA (Section 1.3) for data to be collected at the time 
of study discontinuation and follow-up and for any further evaluations that need 
to be completed. 
• The participant will be permanently discontinued from the study intervention and 
the study at that time. 
• If the participant withdraws consent or the LAR requests that the participant is 
withdrawn for disclosure of future information, the sponsor/designee may retain 
and continue to use any data collected before such a withdrawal of consent. 
• If the participant withdraws from the study, he/she or the LAR may request 
destruction of any samples taken and not tested, and the investigator must 
document this in the site study records. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to adhere to 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to complete a scheduled visit or 
phone call: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• If participants cannot be reached after 3 telephone calls at least 24 hours apart, 
their listed secondary contact person(s) or health care provider will be contacted. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  

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7.4. 
Liver Chemistry Increased Monitoring Criteria 
Participants meeting the following liver chemistry criteria will have more frequent liver 
chemistry assessments performed. Refer to Section 10.9 for details. 
Level 1 Monitoring 
• Alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN) and ≥1.5x 
baseline value and not meeting any of the Level 2 Monitoring criteria 
Level 2 Monitoring 
• Both ALT ≥5xULN and ≥2x baseline value 
• Both ALT ≥3xULN and ≥1.5x baseline value that persists for 4 weeks 
• ALT ≥3xULN and total bilirubin 2xULN (for participants with known Gilbert’s 
syndrome these criteria only apply if total bilirubin 2xULN, and direct bilirubin 
>2xULN and at least doubled from baseline value) 
• ALT ≥3xULN and International normalized ratio (INR) >1.5 
• Both ALT ≥3xULN and ≥1.5x baseline value associated with symptoms (new or 
worsening) believed to be related to liver injury or hypersensitivity. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA see (Section 1.3).  
• Protocol waivers or exemptions are not allowed.  
• Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
• Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
• All Screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.  
• Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of the ICF may be utilized for 
Screening or baseline purposes provided the procedure met the protocol-specified 
criteria and was performed within the time frame defined in the SoA 
(Section 1.3). 
• Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 
• Blood samples may be stored for a maximum of 15 years (or according to local 
regulations) following the last participant’s last visit for the study at a facility 
selected by the sponsor/designee to enable future analysis of exploratory 
endpoints as described in the Study Reference Manual (SRM). 

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• Validated and secure electronic access will be granted to Clinical Research 
Associates to review the participants’ electronic records to verify that the 
information in the records matches the information entered in the Electronic Data 
Capture (EDC) system. If required, in the event of a Quality Assurance audit, 
auditor(s) may be granted access to electronic records. 
• In cases where validated and secure electronic access to the participant’s 
electronic records is not available, unredacted Source Documents (including ICF, 
Regulatory Documents and Source data) will be uploaded into a regulatory and 
data privacy-compliant cloud environment, generating certified copies of source 
documents (as per ICH/GCP guidelines) to be verified by the Clinical Research 
Associate against the information entered in the EDC. As per ICH/GCP 
guidelines, the PI and site staff users remain in control of the Source Documents, 
only site personnel can upload or invalidate source data, while only Clinical 
Research Associates (or auditors, as required) assigned to a given site can view 
the Source Documents remotely.  
• The volume of blood collected should be minimized whenever possible.  
• For participants ≥2 years of age 
o The total blood loss from sampling in any 24 hour period is not expected 
to exceed 1% of total blood volume (e.g., for a 10 kg 2 year old, 19 mL). 
The total blood loss from sampling during any 4-week period of time is 
not expected to exceed 3% of total blood volume (e.g., for a 10 kg 2 year 
old, 54 mL) [EMEA, 2009]. 
• For participants <2 years of age 
o The total blood loss from sampling on a single day is not expected to 
exceed 5 mL/kg of body weight (e.g., for a 2 kg neonate, 10 mL). The 
total blood loss from sampling during any 8-week period of time is not 
expected to exceed 9.5 mL/kg of body weight (e.g., for a 2 kg neonate, 
19 mL) [NIH Clinical Center, 2009].  
8.1. 
Efficacy 
Not Applicable  
8.2. 
Screening Period 
Informed consent must be obtained before conducting any study procedures. Dosing will 
be performed within 2 days of Screening. Screening will include the assessments outlined 
in the SoA (Section 1.3).  
The Screening visit and the Day 1 visit may occur on the same day. 
8.2.1. 
Medical History 
Relevant medical history within the last three years, as determined by the Investigator, 
should be reported. Details regarding illnesses and allergies, date(s) of onset, and whether 
condition(s) is currently ongoing will be collected for all participants and should be 

T M F -1 3 9 7 1 1 1 4  
C O N FI D E N TI A L  
 
 
 
2 1 5 2 2 6  
 
Pr ot o c ol A m d 1  
6 1  
Cli ni c al St u d y Pr ot o c ol t e m pl at e V 1 5 d at e d 2 1 -D e c -2 0 2 0  
u p date d pri or t o d osi n g. Me dical hist or y will i ncl u de baseli ne C O VI D -1 9 s y m pt o ms, 
c o m or bi dities, a n d t o bacc o use  (t o bacc o use will n ot be c ollecte d f or parti ci pa nts 
< 2  years of a ge ).  
8. 2. 2.  
S A R S -C o V -2 Di a g n o sti c T e sti n g  
D oc u me ntati o n of la b orat or y -co nfir me d S A R S -C o V -2 i nfecti o n via a n y vali date d 
q R T -P C R or ot her N A A T fr o m a n y res pirat or y s p eci me n c ollect e d ≤7 da ys pri or t o st u d y 
e ntr y m ust be c o nfir me d f or eli gi bilit y (refer t o t he S o A i n Secti o n 1. 3 ) [F D A , 2 0 2 1a].  
Partici pa nts wit h a ne gati ve test pri or t o Scree ni n g, w h o are test e d a gai n at Scree ni n g a n d 
are p ositi ve f or S A R S -C o V -2 ca n b e i ncl u de d as l o n g as t h e partici pa nt h as ha d 
s y m pt o ms ≤7 d a ys fr o m d osi n g.  
8. 2. 3.  
S e c o n d ar y C o nt a ct I nf or m ati o n  
I n or der t o mi ni miz e t he p ote ntial f or missi n g data relate d t o t he safet y assess me nts of 
m ortalit y or nee d f or h os pitalizati o n, sites s h o ul d c ollect partici pa nt c o ntact i nf or mati o n 
f or t w o sec o n d ar y c o nt acts (e. g., care gi ver, fa mil y me m ber, frie n d). T he sit e ma y als o 
re q uest he alt h care pr o vi der c o nta ct i nf or mati o n a n d me dical care facilities t he partici pa nt 
is li kel y t o g o t o if t he y get sic k.  
− C o ntact i nf or mati o n f or s ec o n dar y c o ntacts or h ealt h care pr o vi de r will n ot be 
rec or de d i n a n y e C R F. C o ntact i nf or mati o n s h o ul d be re vie we d a n d u p d ate d at 
eac h h o me visit or o ut patie nt cli nic visit.  
8. 3.  
Vir ol o gi c A s s e s s m e nt s  
Sa m ples f or vir ol o gi cal a nal ysis will be c ollecte d fr o m partici pa nts i n C o h ort A a n d 
C o h ort B i n acc or da n ce wit h t he la b orat or y ma n ual a n d S o A ( Secti o n  1. 3 ).  
•  Nasal mi d -t ur bi nate s wa bs will be c ollecte d f or S A R S-C o V -2 R T -P C R 
( vali date d q R T-P C R)  
•  Sa m ples ma y als o b e use d f or resista nce s ur veilla nce a n al ysis  
•  O n Da y 1, sa m ple c ollecti o n will occ ur pre -d os e  
•  
•  Da y 1 sa m ples will be e v al uate d f or S A R S -C o V -2 c haracterizati o n (e. g., 
i de ntificati o n of varia nts) 
Viral l oa d data will be s u m marize d a n d c o m pare d wit h baseli ne. Details of t he P D 
a nal ys es will be pr o vi de d i n t he statistical a nal ysis pla n.  
C CI
C CI

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SARS-CoV-2 tests, only antibodies directed against the nucleocapsid protein will be 
measured on Day 29. 
Participants <2 years of age will not have blood testing of anti-N or anti-S SARS-CoV-2 
antibodies. 
8.4. 
COVID-19 Monitoring 
8.4.1. 
Monitoring of COVID-19 Signs and Symptoms 
COVID-19 signs and symptoms will be reviewed at timepoints shown in the SoA 
(Section 1.3) to monitor COVID-19 symptom change over time. 
8.4.2. 
 Monitoring of COVID-19 Progression 
Participants will be monitored daily from Day 1 through Day 14 and on Day 22 and 
Day 29 for progression of disease as shown in the SoA (Section 1.3). On days without a 
clinic or home visit, this monitoring will occur via a phone call. This will include 
questions regarding serious or life-threatening conditions such as dyspnea at rest or 
severe dyspnea on exertion, hemoptysis, cyanosis, or mental status changes. If a 
participant exhibits any of these symptoms, the site will direct the participant to seek 
medical attention. In addition, any healthcare encounters or new concomitant medications 
will be recorded. 
8.4.3. 
Phone Call for Subsequent COVID-19 Illness 
To monitor participants for subsequent COVID-19 illness after Day 29, participants will 
be called weekly from Week 5 to Week 11 and Week 13 to Week 35 (Section 1.3). This 
phone call will assess whether the participant was diagnosed again with COVID-19 and 
whether this illness resulted in any healthcare encounters. Any medications given as a 
result of this illness will also be recorded.  
8.5. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.5.1. 
Vital Signs 
• Vital signs will be recorded at visits as provided in the SoA (Section 1.3).  
• Temperature (in infants, rectal preferred; otherwise, oral preferred), pulse rate, 
respiratory rate, blood pressure, and oxygen saturation (SpO2) will be assessed. 
• Day 1 vital signs will initially be monitored for 2 hours after dose administration as 
described in the SoA (Section 1.3). After half of participants are dosed in either 
Cohort (Cohort A or Cohort B), the JSRT will review safety data and, if there are no 
safety concerns, a recommendation may be made by the JSRT to reduce the post-dose 
Day 1 monitoring and observation time to 1 hour within the same Cohort.  

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• Blood pressure and pulse measurements will be assessed in a supine or semi-supine 
position used consistently for that participant. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones). 
• Vital signs (to be taken before blood collection for laboratory tests) will consist of 
1 pulse and 3 blood pressure measurements (3 consecutive blood pressure readings 
will be recorded at intervals of at least 1 minute). The average of the 3 blood pressure 
readings will be recorded. 
• An appropriately sized cuff should be used for accurate blood pressure measurement. 
For children in whom the appropriate cuff size is difficult to determine, the midarm 
circumference (measured as the midpoint between the acromion of the scapula and 
olecranon of the elbow, with the shoulder in a neutral position and the elbow flexed) 
should be obtained for an accurate determination of cuff size. The bladder length 
should be 80% to 100% of the circumference of the arm, and the width should be at 
least 40% [Flynn, 2017]. 
8.5.2. 
Physical Examinations 
A complete (full) physical examination will be performed at Screening and on Day 1 as 
shown in the SoA (Section 1.3). The complete physical exam only needs to be performed 
once if Screening and dosing occur on the same day. A brief physical exam is required at 
the timepoints specified in the SoA (Section 1.3). 
• A complete physical examination will include, at a minimum, assessments of the 
skin, cardiovascular (CV), respiratory, gastrointestinal and neurological systems.  
• Height (or length) and weight will also be measured and recorded at Screening. 
Body mass index (BMI) will be calculated from these measurements.  
• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, CV system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses.  
Height (or length) and weight will be measured using the appropriate method for the 
participant’s age and plotted on age- and gender-appropriate charts so that a visual 
assessment can be performed relative to normative standards for height and weight and 
change in height and weight over time. Website links to CDC and WHO height (or 
length) and weight charts are provided in Section 10.7 and Section 10.8, respectively. 
8.5.3. 
Electrocardiograms 
A 12-lead ECG will be obtained at the timepoints described in the SoA (see Section 1.3) 
using an ECG machine that automatically calculates the heart rate and measures PR, 
QRS, QT, and QTc intervals. Triplicate ECGs will be obtained at Screening to serve as a 
baseline ECG for the participant; triplicate ECGs are defined as 3 individual ECGs 
obtained as closely as possible in succession but no more than 2 minutes apart. The full 
set of triplicates should be completed over a brief (e.g., 5 to 10 minutes) recording period. 

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If Screening occurs on the day of dosing, only one set of triplicate ECGs will be obtained 
prior to dose (the additional pre-dosing ECG is not required). 
Subsequent scheduled or unscheduled evaluations will be obtained as a single 12-lead 
ECG unless an abnormality is noted, in which case a triplicate ECG should be obtained.  
Lead placement should be appropriate for the participant’s age. Normal ECG values for 
pediatric age groups may differ from normal values in adults; therefore, normal values 
based on the participant’s age should be used when interpreting ECGs. ECGs should be 
interpreted by a pediatric cardiologist. 
The review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding on ECGs should be reported as an AE. 
Before each ECG test, the participant should be at rest for approximately 10 minutes. The 
participant should be in the semi-recumbent or supine position; the same position must be 
used for all ECG tests. 
8.5.4. 
Cardiac Monitoring  
Given the potential for direct myocardial involvement by SARS-CoV-2, it is possible that 
ADE of disease could manifest as cardiac toxicity [Huang, 2020]. To monitor this, 
participants who develop new or worsening cardiac symptoms, signs or ECG findings 
suggestive of myocarditis, acute myocardial infarction, or cardiac failure, cardiology 
consultation (outpatient or inpatient, depending on if the participant is hospitalized) will 
be recommended to guide further cardiac work up and assessment of potential cardiac 
events. Event details should be captured in the appropriate EDC forms. 
8.5.5. 
Clinical Safety Laboratory Tests 
• See Section 10.2 for the list of clinical laboratory tests to be performed and the 
SoA (Section 1.3) for the timing and frequency.  
• Laboratory assessments for safety purposes will be performed as noted in the SoA 
(Section 1.3). 
• Baseline for safety laboratory tests is defined as the last value obtained prior to 
dosing.  
• Urine will be collected on Day 1 (pre-dose), Day 8, and Day 29 for analysis of 
albumin to creatinine ratio.  
• All protocol-required laboratory tests performed, as defined in Section 10.2, must 
be conducted in accordance with the laboratory manual and SoA (Section 1.3). 
• 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.  

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• All laboratory tests with values considered clinically significantly abnormal 
during participation in the study (either at any timepoint as per SoA or any 
unscheduled assessment) 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 do not return to normal/baseline 
within a period judged reasonable by the investigator, the etiology should be 
identified, and the Sponsor notified. 
• If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE), then the 
results must be recorded. 
8.5.6. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• If the participant is a WOCBP (refer to Section 10.4.1 for definition), pregnancy 
testing (serum or high sensitivity urine as required by local regulations) should be 
conducted at Screening to confirm eligibility and at Week 36 or the Early 
Withdrawal visit.  
• Additional serum or high sensitivity urine pregnancy tests may be performed, as 
determined necessary by the investigator or required by local regulation, to 
establish the absence of pregnancy at any time during the participant’s 
participation in the study. 
8.5.7. 
Monitoring of Multisystem Inflammatory Syndrome in Children 
(MIS-C) 
During the course of the study, participants will be monitored for occurrence of 
multisystem inflammatory syndrome in children (MIS-C). MIS-C cases will be defined as 
per the CDC definition [CDC, 2021e]. 
8.6. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
• The definitions of adverse events (AEs) or serious adverse events (SAEs) can be 
found in Section 10.3. 
• The definitions of unsolicited and solicited AEs can be found in Section 10.3. 
• AEs will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's LAR). 
• The investigator and any qualified designees are responsible for detecting, 
documenting, and recording events that meet the definition of an AE or SAE and 
remain responsible for following up AEs that are serious, considered related to the 
study intervention or the study, or that caused the participant to discontinue the 
study (see Section 7).  

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• The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Section 10.3. 
8.6.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs will be collected from dose administration until Week 36 at the 
timepoints specified in the SoA (Section 1.3). 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. 
• All AEs will be collected from dose administration until Week 36 at the 
timepoints specified in the SoA (Section 1.3). 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical 
conditions not as AEs. 
• All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Section 10.3. 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. 
8.6.2. 
Method of Detecting AEs and SAEs 
• Study-site staff should instruct the legal guardians and caregivers, on how to 
report signs and symptoms (e.g., crying and pain) in the individual pediatric 
participant. They will be instructed to report both specific and non-specific 
symptoms (including vomiting, diarrhea, sleepiness, variation in the intensity and 
pattern of crying, etc.). These non-specific symptoms may be the only 
manifestations of some adverse reaction observed in neonates, infants, or toddlers. 
Care should be taken that the clinical presentation of adverse reactions is not 
misinterpreted as the manifestation of a pre-existing or unrelated condition. 
• Moreover, symptoms that are dependent on participant communication ability 
(e.g., nausea, pain, mood alterations) in younger or mentally-disabled children 
could potentially be at risk for under- or mis-reporting. 
• Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence.  

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8.6.3. 
Assessment of Severity  
Standard toxicity grading according to the DAIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events, version 2.1 (July 2017) will be used to grade all AEs (see 
Section 10.3.4 and the Study Reference Manual).  
8.6.4. 
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 AEs of special interest (as 
defined in Section 8.6.9), will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is given in Section 10.3. 
8.6.5. 
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 (IRBs)/Independent Ethics Committees (IECs), 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 IB and will notify the IRB/IEC, 
if appropriate according to local requirements. 
• Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSARs) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary. 
8.6.6. 
Pregnancy 
• Any pregnancies in female participants after the dose of study intervention and 
until 36 weeks after study drug administration will be documented. 
• If a pregnancy is reported, the investigator will record pregnancy information on 
the appropriate form and submit it to GSK within 24 hours of learning of the 
female participant’s pregnancy. While pregnancy itself is not considered to be an 
AE or SAE, any pregnancy complication or elective termination of a pregnancy 
for medical reasons will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be 
reported as such. 
• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the 

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neonate/child for 6 to 8 weeks after the birth, and the information will be 
forwarded to the sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.6.5. While the investigator is not obligated to actively seek this 
information in former study participants he or she may learn of an SAE through 
spontaneous reporting. 
• Any female participant who becomes pregnant after administration of study 
intervention should not be withdrawn from the study, unless the participant 
chooses to be withdrawn. 
• For a female participant who becomes pregnant, this information will be shared 
with the study participant’s legal guardian as required by local regulations. 
8.6.7. 
Cardiovascular and Death Events 
For any CV events detailed in Section 10.3 and all deaths, whether or not they are 
considered SAEs, specific CV and Death sections of the eCRF will be required to be 
completed. These sections include questions regarding CV (including sudden cardiac 
death) and non-CV death.  
The CV eCRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms. The CV information should be 
recorded in the specific CV section of the eCRF within 1 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 1 week 
of when the death is reported. 
8.6.8. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Adverse events related to expected progression, signs, or symptoms of COVID-19, unless 
more severe than expected for the participant’s current clinical status and medical history, 
should not be reported as an AE or SAE. 
However, if the underlying disease (i.e., progression) is greater than that which would 
normally be expected for the clinical course of the disease and/or the participant’s clinical 
status, or if the investigator considers that there was a causal relationship between 
treatment with study treatment(s) or protocol design/procedures and the disease 
progression, then this must be reported as an AE or SAE. 
For example, the following constitute events NOT meeting the AE definition: 
• Hypoxemia due to COVID-19 requiring more than pre-morbid supplemental 
oxygen 
• Hypoxemia due to COVID-19 requiring new non-invasive ventilation, positive 
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• Respiratory failure due to COVID-19 requiring invasive mechanical ventilation or 
extracorporeal membrane oxygenation (ECMO). 
 
NOTE: If either of the following conditions apply, then the event must be recorded and 
reported as an AE or SAE (instead of a disease-related event): 
• The event is, in the investigator’s opinion, of greater intensity, frequency, or 
duration than expected for the natural history of the disease, or 
• The investigator considers that there is a reasonable possibility that the event was 
related to treatment with study treatment(s).  
8.6.9. 
Adverse Events of Special Interest  
Adverse events of special interest are defined in the study protocol as relevant known 
toxicities of other therapeutic mAbs that will be monitored by the Sponsor either during 
or at the end of the study. Participants will be monitored for AEs and SAEs during the 
2 hours post-dose (Section 1.3). After half of participants are dosed in either Cohort 
(Cohort A or Cohort B), the JSRT will review safety data and, if there are no safety 
concerns, a recommendation may be made by the JSRT to reduce the post-dose Day 1 
monitoring and observation time to 1 hour within the same Cohort. 
Adverse events of special interests include: 
• Hypersensitivity reactions (HSRs) including serious: refer to Section 2.3.1 for 
details and Section 10.5 for management guidance.  
• Injection site reactions (ISRs): refer to Section 2.3.1 for details. Local injection 
site tolerability will be assessed as described in the SoA (Section 1.3). Refer to 
Section 8.6.3 for assessment of AE severity. and Section 10.5 for management 
guidance.  
• Infusion related reactions (IRRs): refer to Section 2.3.1 for details and Section 7.1 
and Section 7.1.1 for management guidance. 
• Immunogenicity-related adverse events: refer to Section 2.3.1 for details. 
• Adverse events potentially related to ADE of disease 
ADE of disease theoretically can occur via one of three previously described 
mechanisms: 
• By facilitating viral entry into host cells and enhancing viral replication in 
these cells; 
• By increasing viral fusion with target host cells, enhancing viral 
replication in these cells; 
• By enhancing disease pathology from viral antigen-antibody related 
immune complex deposition or complement activation and immune cell 
recruitment in target organs.  
The first two mechanisms are hypothesized to occur at sub-neutralizing antibody 
concentrations [Arvin, 2020]. This study will include participant follow-up for a 
period of 36 weeks to assess for the potential of enhanced disease in the context 

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of waning sotrovimab levels, which may manifest as an increased incidence of re-
infection or increased severity of re-infections after recovery from initial illness. 
The third mechanism is hypothesized to occur at high levels of antigen (i.e., viral 
load) and antibody potentially leading to immune complex deposition and 
complement activation in tissue sites of high viral replication. This may manifest 
as acute deterioration in clinical status temporally associated with sotrovimab 
infusion or as increased severity or duration of illness in sotrovimab-treated, 
COVID-19 positive participants compared to what would be clinically expected. 
As described in Section 2.3.1, AEs potentially related to ADE of the disease will 
be reviewed by the JSRT and IDMC to assess if there is a greater than expected 
incidence of re-infection or disease severity (see Section 8.5.4 for cardiac 
monitoring). 
Refer to Section 8.6.4 for requirements for follow-up assessments for all AESI.  
8.7. 
Pharmacokinetics 
Blood samples for serum PK will be collected as detailed in the SoA (Section 1.3). 
Instructions for the collection and handling of biological samples will be provided by the 
sponsor or designee in the laboratory manual. 
• The actual date and time (24-hour clock time) of each sample will be 
recorded. 
• Pharmacokinetic samples will be analyzed using an appropriately validated 
assay method. 
• Samples collected for analyses of sotrovimab serum concentration may also 
be used to evaluate safety or efficacy aspects related to concerns arising 
during or after the study. 
• At visits during which whole blood samples are collected to obtain serum 
endpoints other than PK of sotrovimab, one sample of sufficient volume can 
be used. 
• Genetic analyses will not be performed on these whole blood or serum 
samples unless consent for this was included in the informed consent. 
Participant confidentiality will be maintained.  
A population pharmacokinetic model will be used to estimate body weight-adjusted 
serum clearance, volume of distribution, and (where possible) absolute IM 
bioavailability. Additional posterior Bayes PK parameters Cmax, Tmax, AUC0-D5, AUC0-D8, 
AUC0-D29 and AUCinf will be calculated and summarized. A non-compartmental 
evaluation of t1/2 will also be conducted. 
Serum concentrations may also be combined with data from other studies evaluating 
sotrovimab for the purpose of population PK model performance evaluation. These 
analyses may include graphical plots, tabular summaries, and various linear and/or 

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nonlinear analyses. Details of the PK analyses will be provided in the statistical analysis 
plan. 
8.8. 
Resistance Analysis 
In order to monitor for potential resistance to sotrovimab, resistance surveillance will be 
conducted for all participants at baseline and at the last timepoint with virus above the 
limit for the sequencing assay for all participants up to Day 8 and an additional timepoint 
will be sequenced at Day 11 and Day 29 if still above the limit for the sequencing assay 
(see the SoA [Section 1.3]). Other timepoints may also be subjected to sequence analysis 
as needed. Deep sequence analysis of the SARS-CoV-2 spike gene may be attempted on 
nasal mid-turbinate samples to determine amino acid variants. For identified substitutions 
that qualify for phenotypic analysis, the antiviral activity of sotrovimab will be evaluated 
in vitro using a SARS-CoV-2 spike pseudovirus system. 
8.9. 
Genetics 
Genetics are not evaluated in this study. 
8.10. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.11. 
Immunogenicity Assessments 
Antibodies to sotrovimab will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). Additionally, serum samples should also 
be collected at the final visit from participants who discontinued study intervention or 
were withdrawn from the study. These samples will be tested by the sponsor or sponsor's 
designee. 
Serum samples will be screened for antibodies binding to sotrovimab and the titer of 
confirmed positive samples will be reported. Samples that have positive titers will 
undergo assessment for neutralizing activity. Other analyses may be performed to verify 
the stability of antibodies to sotrovimab and/or further characterize the immunogenicity 
of sotrovimab. 
• The detection and characterization of antibodies to sotrovimab will be performed 
using a validated assay method by or under the supervision of the sponsor or 
designee. Samples collected for detection of antibodies to study intervention may 
also be evaluated for sotrovimab serum concentration as described in Section 8.7 
to enable interpretation of the antibody data. Antibodies may be further 
characterized and/or evaluated for their ability to neutralize the activity of the 
study intervention(s). Genetic analyses will not be performed on these serum 
samples unless consent for this was included in the informed consent. Participant 
confidentiality will be maintained. At visits during which whole blood samples 
are collected to obtain other serum endpoints, one sample of sufficient volume 
can be used. 

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Samples may be stored for a maximum of 15 years (or according to local regulations) 
following the last participant’s last visit for the study at a facility selected by the 
sponsor/designee to enable analysis of immune responses to sotrovimab as described. 
Samples will be collected in accordance with the laboratory manual and SoA 
(Section 1.3). 
8.12. 
Health Economics 
Health economics parameters are not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
There are no formal hypothesis tests associated with these objectives and no formal 
significance tests will be performed.  
9.2. 
Analysis Sets 
Separate Analysis Sets are defined for Cohorts A and B. Results will be presented by 
Cohort. 
Participant Analysis Set 
Description 
Safety (Cohort A/Cohort B) 
All participants who are exposed to study intervention in 
Cohort A/Cohort B.  
Pharmacokinetic (PK) 
(Cohort A/Cohort B) 
All participants in Cohort A/Cohort B who are exposed to study 
intervention and who had at least 1 non-missing PK assessment 
(Non-quantifiable [NQ] values will be considered as non-missing 
values). 
Virology 
(Cohort A/Cohort B) 
All participants who are exposed to study intervention in 
Cohort A/Cohort B and have a quantifiable SARS-CoV-2 viral 
load measurement at baseline. 
9.3. 
Statistical Analyses 
The statistical analysis plan will include a more technical and detailed description of the 
statistical analyses described in this section. The analysis plan will only include planned 
analysis of data from this study. This section is a summary of the planned statistical 
analyses of the most important endpoints including primary and key secondary endpoints. 

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9.3.1. 
Primary Endpoint(s) 
Primary Estimand 
Objective 
To evaluate the pharmacokinetics by IV or IM administration 
of sotrovimab in children from birth to <18 years 
Variable/Endpoints 
Body weight-adjusted serum clearance of sotrovimab 
Serum PK of sotrovimab administered by IM injection or IV 
infusion (PK parameters may include Cmax, Tmax, AUCinf, t1/2, 
Vz, CL, F) 
Participant Analysis Set 
Pharmacokinetic (Cohort A/Cohort B) 
Intercurrent Event Strategy 
Data analyzed as collected (treatment policy strategy) 
Population Level Summary 
PK model parameters 
 
Primary Estimand 
Objective 
To evaluate the safety and tolerability of sotrovimab by IV or 
IM administration 
Variable/Endpoints 
Incidence of adverse events (AEs), serious adverse events 
(SAEs), and adverse events of special interest (AESI) 
through Day 29 and Week 36 
Participant Analysis Set 
Safety (Cohort A/Cohort B) 
Intercurrent Event Strategy 
Data analyzed as collected (treatment policy strategy) 
Population Level Summary 
Descriptive summary: Number and percentage of 
participants with ≥1 event 
 
9.3.2. 
Secondary Endpoints 
Full details of all analysis methods for the secondary endpoints will be provided in the 
statistical analysis plan.  
9.3.3. 
Other Safety Endpoints 
Full details of all analysis methods for the other safety endpoints will be provided in the 
statistical analysis plan. 

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9.3.4. 
Exploratory Endpoints 
Full details of all analysis methods for the exploratory endpoints will be provided in the 
statistical analysis plan.  
9.4. 
Interim Analysis 
Interim analysis of safety and PK data will be conducted at the following points: 
• Safety data will be reviewed by the JSRT and IDMC once half of Cohort A 
participants ages 2 to <18 years complete Day 29. Data will be used to decide 
whether to open recruitment to participants aged from birth to <2 years in 
Cohort A. 
• PK data will be reviewed and safety data will be reviewed by the JSRT and 
IDMC once all participants in Cohort A aged 12 to <18 years complete Day 29. 
Data will be reviewed to decide whether to open recruitment to participants aged 
2 to <18 years in Cohort B. 
• Safety data will be reviewed by the JSRT and IDMC once half of Cohort B 
participants ages 2 to <18 years complete Day 29. Data will be used to decide 
whether to open recruitment to participants aged from birth to <2 years in 
Cohort B. 
• Safety data will be reviewed by the JSRT after half of participants are dosed in 
either Cohort (Cohort A or Cohort B). Data will be used to decide whether the 
post-dose Day 1 monitoring should be reduced to 1 hour within the same Cohort. 
Further details will be added to the statistical analysis plan. The primary objectives for 
each cohort will be assessed once the last participant recruited in the cohort completes the 
Day 29 assessment. Participants will continue to complete the remaining scheduled 
assessments up to Week 36. 
9.5. 
Sample Size Determination 
Sample size evaluation for PK evaluation (IV and IM separately) was conducted using 
trial simulation methods. NHANES- and WHO-validated weight-for-age distributions for 
four standard age bands were simulated for large, medium and small trials with dense, 
medium and sparse sampling (5 samples). A minimum of 1,000 trials were simulated per 
scenario using allometric scaling from preliminary adult PK data and fitted with a 
non-linear mixed effects PK model. Precision of estimation, together with degree of 
exposure matching to adult reference AUCinf exposure was determined for all scenarios. 
The final trial design (medium trial, sparse sampling) was simulated 10,000 times and 
final precision estimated for the four reference age bands; 36 participants and no more 
than 5 samples per participant. Precision of estimation (relative standard error [RSE]) for 
the primary endpoint (body weight-adjusted clearance) was less than 20%, which is well 
below the suggested 40% guidance for trials of this type. 
 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences (CIOMS) international ethical guidelines 
• Applicable ICH Good Clinical Practice (GCP) guidelines 
• Applicable laws and regulations 
• The protocol, protocol amendments, ICF, 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: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device 
Regulation 2017/745 for clinical device research (if applicable), and all 
other applicable local regulations 
• The investigator will be responsible for reporting cases of suspected child 
abuse and/or neglect according to local medical association (e.g., American 
Academy of Pediatrics [AAP], EU Academy of Pediatrics [EAP]) or Health 
Department guidelines. 

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10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed Consent and Assent Process 
Legal Guardian Consent and Pediatric Participant Assent Processes: 
• The investigator, or a person designated by the investigator, will provide the legal 
guardian (refer to Section 10.10: Abbreviations and Definitions) with the written 
ICF and the participant with the assent if applicable. They must be informed that 
participation is voluntary. The legal guardian will be required to sign written 
consent, and the participant if applicable will be required to sign written assent, 
that meets the requirements of 21 CFR 50, local regulations, International 
Conference on Harmonisation (ICH) guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center after the nature 
of the study has been fully explained, including answering all questions regarding 
the study and explaining the risks and benefits, and before performance of any 
study-related activity. 
• Assent requirements for pediatric participants may vary across regions and 
countries; local regulations should be followed as appropriate. 
• The medical record must include a statement that written informed consent from 
the legal guardian and assent from the pediatric participant (if deemed appropriate 
by local ethics review or local regulations) were obtained before the participant 
was enrolled in the study and the date the written consent and assent were 
obtained. The medical record should describe how the clinical investigator 
determined that the person signing the ICF was the participant’s legal guardian. 
The authorized person obtaining the informed consent must also sign the ICF and 
assent form attesting that the pediatric participant did not show signs of dissent 
particularly in those studies including toddlers and small children; it should be 
written in language appropriate to the child’s developmental and functional status. 
• Participants and their legal guardian must be re-consented and re-assented to the 
most current version of the ICF(s) during their participation in the study.  
• Minor participants who assent to a study and later withdraw that assent should not 
be maintained in the study against their will, even if their legal guardian still 
wants them to participate. 
• Minor participants must be re-consented if they reach the age of majority during 
the course of the study, in order to continue participating. 

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• A copy of the informed consent and assent forms must be provided to the 
participant and the participant’s legal guardian. 
• As appropriate, participants may be given the opportunity to meet privately with a 
member of the site staff to ask confidential questions and to decline assent for 
confidential reasons, which, at their request, would not be shared with their legal 
guardian, unless required by local law. 
• Stored samples will be coded throughout the sample storage and analysis process 
and will not be labelled with personal identifiers. Participants may withdraw their 
consent/assent for their samples to be stored for research. 
10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information that would make the participant 
identifiable will not be transferred.  
• The participant and legal guardian 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 his/her data to be used as described in the informed 
consent.  
• The participant and legal guardian 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. 
• The participant must be informed that information on pregnancy or contraception 
use may be shared with the legal guardian, subject to local regulations. 
10.1.5. 
Committees Structure 
An IDMC will review safety data throughout the conduct of the study at regular intervals 
as outlined by the IDMC charter. The roles and responsibilities of the IDMC, including 
membership, scope, frequency of meetings and communication plan are defined in the 
IDMC charter. Throughout the study, the IDMC will review safety data from all 
participants enrolled in either Cohort. The IDMC and JSRT will review safety data as 
described in Section 4.1 prior to starting subsequent stages of recruitment.  
10.1.5.1. 
Joint Safety Review Team 
A JSRT comprised of team members from clinical research, global safety, and statistics 
from GSK and Vir, will review safety data throughout the study and will determine if a 
safety concern identified during instream data review needs to be escalated to the IDMC. 
The responsibilities of the JSRT and frequency of assessments will be outlined in the 

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JSRT charter. Throughout the study, the JSRT will review safety data from all 
participants enrolled in either Cohort. 
The IDMC and JSRT will review safety data as described in Section 4.1 prior to starting 
subsequent stages of recruitment.  
Additionally, after half of participants are dosed in either Cohort (Cohort A or Cohort B), 
the JSRT will review safety data and, if there are no safety concerns, a recommendation 
may be made by the JSRT to reduce the post-dose Day 1 monitoring and observation 
time to 1 hour within the same Cohort.  
10.1.6. 
Dissemination of Clinical Study Data 
• Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
sponsor site or other mutually agreeable location. 
• Sponsor or designee 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 study 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, the sponsor intends to make 
anonymized participant-level data from this study available to external 
researchers for scientific analyses or to conduct research that can help advance 
medical science or improve patient care. This helps ensure the data provided by 
study participants are used to maximum effect in the creation of knowledge and 
understanding. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• GSK intends to make anonymized patient-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF.  
• Guidance on completion of CRFs will be provided in data entry guidelines. 

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• Quality tolerance limits (QTLs) will be pre-defined in the Integrated Quality Risk 
Management Plan to identify systematic issues that can impact participant safety 
and/or reliability of study results. These pre-defined parameters will be monitored 
during and at the end of the study and all deviations from the QTLs and remedial 
actions taken will be summarized in the clinical study report. 
• The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• Monitoring details describing strategy including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as 
risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of noncompliance 
issues and monitoring techniques (central, remote, or on-site monitoring) are 
provided in the monitoring plan. 
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process including systems used can be found in the 
study Data Management Plan or equivalent CRO document. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
• Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the sponsor. 
No records may be transferred to another location or party without written 
notification to the sponsor. 
10.1.8. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained. The investigator may need to request previous medical records 
or transfer records, depending on the study. Also, current medical records must be 
available. 
• Definition of what constitutes source data and its origin can be found in Source 
Data Acknowledgment. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 

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verifiable from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
Study/Site Termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• Discontinuation of further study intervention development 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate or no recruitment of participants (evaluated after a reasonable amount 
of time) by the investigator 
• If the study is prematurely terminated or suspended, the sponsor shall promptly 
inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up 
10.1.10. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as 

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individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 

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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 6 will be performed by a local laboratory at Screening for 
participants of all ages and at all timepoints for children <2 years. A central laboratory 
will be used for all timepoints besides Screening for participants 2 years of age.   
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Table 6 
Protocol-required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Hematocrit 
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Platelet count  
RBC count 
Hemoglobin 
Clinical Chemistry 
BUN 
Potassium 
Aspartate 
aminotransferase 
(AST)/ Serum 
glutamic-oxaloacetic 
transaminase (SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
Alanine 
aminotransferase 
(ALT)/ Serum glutamic-
pyruvic transaminase 
(SGPT)1 
Total protein 
Glucose (non-
fasting) 
Calcium 
Alkaline phosphatase2 
Gamma-glutamyl 
transferase (GGT) 
Carbon 
dioxide/bicarbonate 
Chloride 
Lactate 
dehydrogenase (LDH) 
Albumin 
Amylase 
Lipase 
Coagulation 
parameters 
International 
Normalized Ratio 
(INR) time 
Prothrombin 
time (PT) 
Partial thromboplastin time (PTT) / Activated 
PTT (aPTT) 
Routine Urinalysis 
• 
Urine albumin and urine creatinine (urine albumin-to-creatinine ratio)3 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
• 
Microscopic examination (if blood, protein, or leukocyte esterase is 
abnormal) 
Pregnancy testing 
Serum/plasma or highly sensitive urine human chorionic gonadotropin (hCG) 
pregnancy test (as needed for women of childbearing potential)4 
Other Screening 
Tests 
All study-required Screening laboratory tests will be performed by a local laboratory 
Notes: 
1. 
Details of liver chemistry increased monitoring criteria and required actions and follow-up assessments after a 
liver increased monitoring event are given in Section 7.4 and Section 10.9. All events of ALT ≥3×ULN and total 
bilirubin ≥2×ULN (>35% direct bilirubin) or ALT ≥3×ULN and INR >1.5, if INR measured, which may indicate 

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severe liver injury (possible Hy’s Law), must be reported to GSK in an expedited manner (excluding studies of 
hepatic impairment or cirrhosis). 
2. 
If alkaline phosphatase (total) is elevated, consider fractionating (e.g.: liver, bone, kidney, and intestinal 
isoenzymes, if available). 
3. 
Bagged urine collection is permitted in infants and pre-continent participants for urine chemistries. Instrumentation 
of pediatric participants (e.g.: bladder catheterization) should be avoided wherever possible. 
4. 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or IRB/IEC. 
Investigators must document their review of each laboratory safety report. 
 
 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
• Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a Participant Diary or by 
asking questions about specific symptoms, events or conditions and that is 
communicated by a participant/participant’s caregiver(s)/LAR(s) who has signed 
the informed consent. Unsolicited AEs include serious and non-serious AEs. 
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or emergency room visit, or visit to/by a healthcare 
provider). The participants/participant’s caregiver(s)/LAR(s) will be instructed to 
contact the site as soon as possible to report medically attended event(s), as well as 
any events that, though not medically attended, are of participant/caregiver/LAR’s 
concern. Detailed information about reported unsolicited AEs will be collected by 
qualified site personnel and documented in the participant’s records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant/participant’s caregiver(s)/LAR(s) will be collected during an interview 
with the participants/participant’s caregiver(s)/LAR(s) and by review of available 
medical records at the next visit. 
• Solicited AEs are predefined local injection site events for which the 
participant/participant’s caregiver(s) or LAR(s) is specifically questioned.  
 
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. 

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• 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 fulfill the definition of an AE 
or SAE.  
 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 

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a. 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
b. 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: 
• Possible Hy’s Law case: ALT ≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE. 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
 

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10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 
10.3.4. 
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 
Standard toxicity grading according to the DAIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events, version 2.1 (July 2017) will be used to grade all 
AEs. DAIDS Grading Table for Severity of Adult and Pediatric Adverse Events is 
provided in the Study Reference Manual. 

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• All AEs with fatal outcome should be classified as Grade 5. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an SAE as per Section 10.3.2, 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. The investigator will use clinical judgment 
to determine the relationship. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure (IB), in his/her 
assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide GSK with a copy of any post-mortem 
findings including histopathology.  

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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. 
10.3.5. 
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. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor/SAE coordinator by telephone. 
• Contacts for SAE reporting can be found in Study Reference Manual (SRM). 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the medical monitor or 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 the Study Reference Manual (SRM). 
 
 

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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
• 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. 
For individuals with permanent infertility due to a medical cause, investigator discretion 
should be applied. 
10.4.2. 
Contraception Guidance: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
Intrauterine device (IUD) 
Intrauterine hormone-releasing system (IUS)c 
Bilateral tubal occlusion 
Azoospermic partner (vasectomized or due to a medical cause) 
• 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 
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• oral 
• intravaginal 
• transdermal 
• injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• oral 
• 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. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the participant. 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from 
those when used consistently and correctly. 
c. 
If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational 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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10.5. 
Appendix 5: Management of Local Injection Site Reactions 
and Systemic Symptoms (Anaphylaxis) 
The following information for the management of local injection site reactions and 
systemic symptoms is based on guidelines from the Advisory Committee on 
Immunization Practices (ACIP), Immunization Action Coalition (IAC), and the National 
Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network 
[ACIP, 2021; IAC, 2019; Sampson, 2006]. 
A. 
Local Injection Site Reactions 
Signs and Symptoms 
Management 
Redness, soreness or 
swelling at the injection 
site 
Apply a cold compress to the injection site(s) 
Consider giving an analgesic (e.g., ibuprofen, acetaminophen, paracetamol) 
Itching and redness 
Consider giving an anti-pruritic (e.g., diphenhydramine) 
Observe patient closely for the development of generalized symptoms 
Slight bleeding 
Apply pressure and an adhesive compress 
Continuous bleeding 
Place gauze pads over the site and maintain direct and firm pressure 
If a participant has evidence of necrosis/ulceration, the participant should be referred to a 
higher level of acute care (e.g., hospital Emergency Department) for appropriate 
management.  
B. 
Systemic Reactions/Anaphylaxis 
As with any antibody, allergic reactions to study drug are possible. Therefore, appropriate 
drugs and medical equipment to treat acute anaphylactic reactions must be immediately 
available, and study personnel must be trained to recognize and treat anaphylaxis.  
Diagnosis of Anaphylaxis 
The most common signs and symptoms of anaphylaxis are cutaneous (e.g., sudden onset 
of generalized urticaria, angioedema, flushing, pruritis). However, 10-20% of patients 
have no skin findings. 
Danger Signs include: 
• Rapid progression of symptoms 
• Evidence of respiratory distress (stridor, wheezing, dyspnea, increased work 
of breathing, persistent cough, cyanosis) 
• Vomiting 
• Abdominal pain 
• Hypotension 
• Dysrhythmia 

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• Chest pain 
• Collapse 
Management of Anaphylaxis  
The following procedures should be followed in the event of a suspected anaphylactic 
reaction:  
1. Call for additional medical assistance; activate emergency medical services. 
2. Ensure appropriate monitoring is in place, such as continuous ECG and pulse 
oximetry. 
3. First-line treatment [Sicherer, 2017;Hegenbarth, 2008; IAC, 2019]: 
• Administer epinephrine (1.0 mg/mL) aqueous solution 
(1:1000 dilution) – 0.01 mg/kg (maximum 0.3 mg [0.3 mL] in a 
prepubertal child, maximum 0.5 mg [0.5 mL] in a teenager) IM in the 
anterolateral thigh. May be repeated every 5 to 15 minutes up to 
3 times. 
• If using an epinephrine auto-injector (round weight to nearest kg):  
o infant 7.5 to 14 kg (approximately 16.5 to 30 lbs): 0.1 mg 
autoinjector IM in the anterolateral thigh. (If 0.1 mg 
autoinjector is unavailable, use a 0.15 mg autoinjector) 
o child 15 to 29 kg (approximately 33 to 64 lbs): 0.15 mg 
autoinjector IM in the anterolateral thigh  
o child or teenager ≥30 kg (approximately greater than 66 lbs): 
0.3 mg autoinjector IM in the anterolateral thigh 
o May be repeated every 5 to 15 minutes up to 3 times. 
4. Optional treatment (antihistamine) [IAC, 2019]: 
Diphenhydramine 1-2 mg/kg/dose oral/IV/IM (40 mg maximum single dose 
for patients <12 years; 100 mg maximum single dose for patients ≥12 years) 
OR 
Hydroxyzine 0.5-1 mg/kg/dose oral/IM (maximum 100 mg single dose). 
5. Give oxygen (8-10 L/minute) via facemask, as needed. 
6. Normal saline rapid bolus – treat hypotension with rapid infusion of 20 mL/kg IV. 
Re-evaluate and repeat fluid boluses (20 mL/kg), as needed. 
7. Monitor patient until emergency medical services arrive. 
 
 

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10.6. 
Appendix 6: Medical Diagnoses with Regards to Participants 
at High Risk of Disease Progression 
Cardiovascular Disease: congenital heart disease, hypertension, cardiomyopathy, heart 
failure 
Genetic or Metabolic Diseases: Pompe Disease, Mucopolysaccharidoses, glycogen 
storage diseases, fatty acid oxidation disorders, maple syrup urine disease, organic 
acidemias 
Pulmonary Disease: moderate to severe asthma, chronic lung disease, obstructive sleep 
apnea, Cystic Fibrosis 
Neurologic Disease: seizure disorder, global developmental delay, cerebral palsy, or 
structural brain defect/malformation 
Immunosuppressed: primary immunodeficiency (e.g., Severe Combined 
Immunodeficiency), HIV infection with CD4+ count <200 cells/mm3, solid organ or bone 
marrow transplant, long-term use of systemic corticosteroids (defined by either 
≥0.5 mg/kg/day by body weight or 20 mg/day prednisone equivalents [whichever is the 
lower dose of the two] taken for 2 weeks, immunosuppressive biologic agents (e.g., 
rituximab), and disease-modifying anti-rheumatic drugs (e.g., azathioprine, methotrexate, 
leflunomide). 
 
 

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10.7. 
Appendix 7: CDC Weight and BMI Growth Charts 
Refer to the following CDC length-for-age; weight-for-age percentiles or BMI charts: 
• Boys birth to 36 months: Birth to 36 months: Boys length-for-age and weight-
for-age percentiles. Developed by the National Center for Health Statistics in 
collaboration with the National Center for Chronic Disease Prevention and Health 
Promotion (2000). Published May 30, 2000 and modified April 20, 2001. 
https://www.cdc.gov/growthcharts/data/set1clinical/cj41l017.pdf. Accessed 
July 26, 2021. 
• Girls birth to 36 months: Birth to 36 months: Girls length-for-age and weight-
for-age percentiles. Developed by the National Center for Health Statistics in 
collaboration with the National Center for Chronic Disease Prevention and Health 
Promotion (2000). Published May 30, 2000 and modified April 20, 2001. 
https://www.cdc.gov/growthcharts/data/set1clinical/cj41l018.pdf. Accessed 
July 26, 2021 
• Boys 2 to >18 years: 2 to 20 years: Boys body mass index-for-age percentiles. 
Developed by the National Center for Health Statistics in collaboration with the 
National Center for Chronic Disease Prevention and Health Promotion (2000). 
Published May 30, 2000 and modified October 16, 2000. 
https://www.cdc.gov/growthcharts/data/set1clinical/cj41l023.pdf. Accessed 
July 26, 2020. 
• Girls 2 to >18 years: 2 to 20 years: Girls body mass index-for-age percentiles. 
Developed by the National Center for Health Statistics in collaboration with the 
National Center for Chronic Disease Prevention and Health Promotion (2000). 
Published May 30, 2000 and modified October 16, 2000. 
https://www.cdc.gov/growthcharts/data/set1clinical/cj41l024.pdf. Accessed 
July 26, 2021. 
 
 
 

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10.8. 
Appendix 8: World Health Organization (WHO) Weight-For-
Age Curves 
Refer to the following WHO weight-for-age percentiles: 
• Boys birth to 6 months: World Health Organization (WHO). WHO Child 
Growth Standards. Weight-for-age: Boys. https://cdn.who.int/media/docs/default-
source/child-growth/child-growth-standards/indicators/weight-for-age/boys-
charts---weight-for-age-birth-to-6-months-(percentiles).pdf?sfvrsn=2a49ab55_6. 
Accessed July 26, 2021. 
• Girls birth to 6 months: World Health Organization (WHO). WHO Child 
Growth Standards. Weight-for-age: Girls. https://cdn.who.int/media/docs/default-
source/child-growth/child-growth-standards/indicators/weight-for-age/girls-
charts---weight-for-age-birth-to-6-months-(percentiles).pdf?sfvrsn=52e7206c_6. 
Accessed July 26, 2021.  
• Boys: 2 to 5 years: World Health Organization (WHO). WHO Child Growth 
Standards. BMI-for-age Boys. https://cdn.who.int/media/docs/default-
source/child-growth/child-growth-standards/indicators/body-mass-index-for-
age/boys-chart--length-for-age-2-to-5-years-(percentiles).pdf?sfvrsn=e2a33b7a_0. 
Accessed July 26, 2021.  
• Girls 2 to 5 years: World Health Organization (WHO). WHO Child Growth 
Standards. BMI-for-age Girls. https://cdn.who.int/media/docs/default-
source/child-growth/child-growth-standards/indicators/body-mass-index-for-
age/girls-table--length-for-age-2-to-5-years-(percentiles).pdf?sfvrsn=b7ccd64e_2. 
Accessed July 26, 2021. 
 
 

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10.9. 
Appendix 9: Liver Event Increased Monitoring Criteria 
10.9.1. 
Level 1 Monitoring 
In the event that the participant develops elevations in liver enzyme parameters as 
defined below, an increase to liver chemistry monitoring (i.e., at weekly intervals), will 
apply.  
Liver Chemistry Increased Monitoring Criteria - Level 1 Liver Monitoring  
Criteria 
Actions 
 
ALT ≥3x ULN and ≥1.5x baseline value and 
not meeting any Level 2 monitoring criteria, 
without symptoms believed to be related to 
liver injury, or hypersensitivity and who can be 
monitored weekly for 4 weeks 
• Notify the GSK medical monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety.  
• Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, total 
bilirubin and INR) until they stabilize or return to 
within baseline or normal limits 
• If, during monitoring, ALT increases to ≥5xULN and 
≥2x baseline value or remains ≥3x ULN and ≥1.5x 
baseline value for ≥4 weeks, or if total bilirubin 
increases to ≥2xULN, refer to Level 2 monitoring 
guidance below. 
• If, after 4 weeks of monitoring, ALT <3xULN and 
<1.5x baseline value, and bilirubin <2xULN and INR 
≤1.5, monitor participants twice monthly until they 
stabilize or return to within baseline or normal limits. 
Alternatively, the monitoring can return to standard 
as per protocol (if applicable) or stopped when the 
investigator and medical monitor agree that values 
are stable or no longer significantly abnormal (this 
may require local investigation of potential causes 
for liver chemistry abnormality) 
 
10.9.2. 
Level 2 Monitoring 
In the event that the participant develops elevations in liver enzyme parameters as 
defined below, an increase to liver chemistry monitoring at more frequent intervals (i.e., 
twice weekly), will apply.  
Liver Chemistry Monitoring Criteria - Level 2 Liver Monitoring 
ALT absolute 
Both ALT ≥5xULN and ≥2x baseline value 
ALT Increase 
Both ALT ≥3xULN and ≥1.5x baseline value that persists for 4 weeks 

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Liver Chemistry Monitoring Criteria - Level 2 Liver Monitoring 
Bilirubin1, 2 
ALT ≥3xULN and total bilirubin ≥2xULN (for participants with known Gilbert’s 
syndrome these criteria only apply if total bilirubin ≥2xULN, and direct bilirubin 
>2xULN and at least doubled from baseline value)  
INR2  
ALT ≥3xULN and INR>1.5 
Symptomatic3 
Both ALT ≥3xULN and ≥1.5x baseline value associated with symptoms (new or 
worsening) believed to be related to liver injury or hypersensitivity 
Required Actions, Monitoring and Follow up Assessments 
Actions 
Follow Up Assessments 
• Report the event to GSK within 24 hours 
• Complete the liver event form and 
complete SAE data collection tool if the 
event also meets the criteria for an SAE2 
• Perform liver event follow up 
assessments as described in the Follow 
up Assessment column 
• Monitor the participant until liver 
chemistries stabilize or return to within 
baseline or normal limits (see 
MONITORING) 
MONITORING: 
If ALT ≥3xULN AND total bilirubin 
≥2xULN or INR >1.5:  
• Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total bilirubin 
and INR) and perform liver event follow 
up assessments within 24 hours 
• Monitor participants twice weekly until liver 
chemistries stabilize or return to within 
baseline or normal limits 
• A specialist or hepatology consultation is 
recommended 
For All other criteria (total bilirubin 
<2xULN and INR ≤1.5):  
• Viral hepatitis serology4 
• Obtain INR and recheck with each liver chemistry 
assessment until the aminotransferases values show 
downward trend 
• Serum creatine phosphokinase (CPK) and lactate 
dehydrogenase (LDH), gamma glutamyl transferase 
[GGT], glutamate dehydrogenase [GLDH], and serum 
albumin. 
• Fractionate bilirubin, if total bilirubin1 ≥2xULN 
• Obtain complete blood count with differential to 
assess eosinophilia 
• Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on the 
liver event form 
• Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, recreational drugs 
and other over the counter medications 
• Record alcohol use on the liver event alcohol intake 
form 
If ALT ≥3xULN AND total bilirubin ≥2xULN or INR 
>1.5 obtain the following in addition to the assessments 
listed above: 
• Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 

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Liver Chemistry Monitoring Criteria - Level 2 Liver Monitoring 
• Repeat liver chemistries (include ALT, 
AST, alkaline phosphatase, total bilirubin 
and INR) and perform liver event follow up 
assessments within 24-72 hours  
• Monitor participants weekly until liver 
chemistries stabilize or return to within 
baseline or normal limits 
 
quantitative total immunoglobulin G (IgG or gamma 
globulins) 
• Serum acetaminophen adduct assay should be 
conducted (where available) to assess potential 
acetaminophen contribution to liver injury  
• Liver imaging (ultrasound, magnetic resonance, or 
computed tomography) to evaluate liver disease; 
complete Liver Imaging forms 
• Liver biopsy may be considered and discussed with 
local specialist if available, for instance: 
o In patients when serology raises the possibility 
of autoimmune hepatitis (AIH) 
o In patients when suspected drug induced liver 
injury (DILI) progresses or fails to resolve on 
withdrawal of study intervention 
o In patients with acute or chronic atypical 
presentation:  
• If liver biopsy conducted complete liver biopsy form. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT ≥3xULN and total bilirubin 
≥2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. 
All events of ALT ≥3xULN and total bilirubin ≥2xULN (for participants with known Gilbert’s syndrome these 
criteria only apply if total bilirubin ≥2xULN, and direct bilirubin >2xULN and at least doubled from baseline 
value) or ALT ≥3xULN and INR>1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must be 
reported as an SAE (excluding studies of hepatic impairment or cirrhosis); the INR threshold value stated will 
not apply to participants receiving anticoagulants 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, 
rash or eosinophilia) 
4. 
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); 
Hepatitis C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing); Hepatitis E IgM antibody or RNA PCR test.  
 
 

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10.10. 
Appendix 10: Abbreviations and Trademarks 
Term 
Definition 
µg 
Micrograms 
λz 
Apparent terminal elimination rate constant 
%AUCexp 
Area under the plasma concentration-time curve extrapolated 
from time to infinity as a percentage of total AUC 
%CV 
Percent coefficient of variation 
AAP 
American Academy of Pediatrics 
ACE 
angiotensin converting enzyme 
ACIP 
Advisory Committee on Immunization Practices 
ADA 
Anti-drug antibodies 
ADE 
Antibody dependent enhancement 
AE(s) 
Adverse event(s) 
AESI 
Adverse events of special interest 
AIH 
autoimmune hepatitis 
ALT 
Alanine aminotransferase 
Anti-N 
Anti-nucleocapsid 
Anti-S 
Anti-spike 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUC0-DX 
Area under the serum concentration-time curve from time zero to 
study Day X 
AUCDX-Y 
Area under the serum concentration-time curve, from Day X to 
Day Y 
AUCinf 
Area under the serum concentration-time curve from time zero to 
infinity 
AUClast 
Area under the serum concentration-time curve from time zero to 
time of last measurable concentration 
BiPAP 
Bilevel positive airway pressure 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
Clast 
Last measurable serum concentration 
Cmax 
Maximum observed concentration 
CA 
Competent Authority 

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Term 
Definition 
Caregiver 
Delegated primary caregiver(s) who will be responsible for 
ensuring the study activities are conducted per protocol, e.g., 
accompany the participant to the study site on each assessment 
day according to the Schedule of Activities (SoA); consistently and 
consecutively be available to provide information on the 
participant using the rating scales during the scheduled study 
visits; accurately and reliably dispense study intervention as 
directed; help the study-site personnel ensure follow-up. This 
person may be the legal guardian, or another appropriate person, 
delegated by the legal guardian. 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
Clearance 
CLIA 
Clinical Laboratory Improvement Amendments 
CONSORT 
Consolidated Standards of Reporting Trials 
CoV 
Coronavirus 
COVID-19 
Coronavirus disease 2019 
CPAP 
Continuous positive airway pressure 
CPK 
Creatine phosphokinase 
CRF 
Case report form 
CRP 
C-reactive protein 
CSR 
Clinical study report 
CTFG 
Clinical Trial Facilitation Group 
CV 
Cardiovascular 
d 
Day(s) 
DAIDS 
Division of acquired immune-deficiency syndrome 
DCO 
Data cut off 
DILI 
Drug induced liver injury 
DOL 
Day of life 
DSMB 
Data and Safety Monitoring Board 
EAP 
EU Academy of Pediatrics 
EC 
Ethics committee 
EC50 
Half maximal effective concentration 
EC90 
90% effective concentration 

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Term 
Definition 
ECG(s) 
Electrocardiogram(s) 
ECMO 
Extracorporeal membrane oxygenation 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EEA 
European economic area 
EGA 
Estimated gestational age 
EOS 
End of study 
ESR 
Erythrocyte sedimentation rate 
EU 
European Union 
EUA 
Emergency use authorization 
EW 
Early withdrawal 
F 
Bioavailability 
FcR 
Fc Gamma Receptor 
FDA 
Food and Drug Administration 
FI 
Formalin-inactivated 
FIH 
First-in-human 
GCP 
Good clinical practice 
Gen1 
Generation1 
Gen2 
Generation2 
GGT 
Gamma-glutamyl transferase 
GLDH 
Glutamate dehydrogenase 
GSK 
GlaxoSmithKline 
HCG 
Human chorionic gonadotropin 
HHS 
Health and Human Services 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HSRs 
Hypersensitivity reactions 
IB 
Investigator’s brochure 
IAC 
Immunization Action Coalition 
IC90 
90% inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation of technical 
requirements for registration of pharmaceuticals for human use 
ICU 
Intensive care unit 

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Term 
Definition 
IDMC 
Independent data monitoring committee 
IEC(s) 
Independent ethics committee(s) 
IgG 
Immunoglobulin G 
IgG1 
Immunoglobulin G1 
IL-6 
Interleukin 6 
IM 
Intramuscular 
INR 
International normalized ratio 
IQ 
Inhibitory quotient 
IRB(s) 
Institutional review board(s) 
IRR 
Infusion related reaction 
IRRs 
Infusion related reactions 
IRT 
Interactive Response Technology 
ISR 
Injection site reaction 
iSRC 
Internal Safety Review Committee 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IVIG 
Intravenous immunoglobulin 
JSRT 
Joint safety review team 
kg 
kilograms 
kg/m2 
Kilograms per meter square 
L 
Liter 
LAM 
Lactational amenorrhea method 
lbs 
Pounds 
LDH 
Lactate dehydrogenase 
LLQ 
Lower limit of quantification 
LS 
Fc modification 
LAR 
Legally authorized representative 
Legal guardian 
Parent(s) (preferably both if available or as per local 
requirements), legally appointed guardian(s), or legally acceptable 
representative(s), as defined by national and local laws and 
regulations, who consent(s) on behalf of the minor. For the 
purposes of this study, all references to informed consent and 
assent refer to the pediatric participant (child) and his or her legal 
guardian who have provided consent (and assent as applicable) 
according to the Informed Consent Process and Assent Form 

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Term 
Definition 
described in Section 10.1.3 Informed Consent and Assent 
Process. 
mAb 
Monoclonal antibody 
MARM 
Monoclonal antibody-resistant mutant 
MCH 
Mean corpuscular volume 
MCV 
Mean corpuscular hemoglobin 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
MIS-A 
Multisystem inflammatory syndrome in adults 
MIS-C 
Multisystem inflammatory syndrome in children 
min 
Minute 
mL 
Milliliter 
mm3 
Cubic milliliter 
Mm Hg 
Millimeters of mercury 
MSDS 
Material safety data sheet 
NAAT 
nucleic acid amplification test 
NHANES 
National Health and Nutrition Examination Survey 
NIH 
National Institute of Health 
NQ 
Non-quantifiable 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
Pediatric participant 
Minor child participating in research study 
PI 
Principal investigator 
PICC 
Percutaneously inserted central catheter 
PK 
Pharmacokinetic(s) 
PT 
Prothrombin time 
qRT-PCR 
Quantitative reverse transcriptase polymerase chain reaction 
QTLs 
Quality tolerance limits 
RBC 
Red blood cell 
RBD 
Receptor binding domain 
RBM 
receptor-binding motif 
RNA 
Ribonucleic acid 
RSE 
Relative standard error 
RSV 
Respiratory syncytial virus 

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Term 
Definition 
RT-PCR 
Reverse transcriptase polymerase chain reaction 
SA 
South Africa 
SAE(s) 
Serious adverse event(s) 
SARS 
Severe acute respiratory syndrome 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus-2  
SD 
Standard deviation 
SGOT 
Serum glutamic-oxaloacetic transaminase 
SGPT 
Serum glutamic-pyruvic transaminase 
SoA 
Schedule of activities 
SoC 
Standard of care 
SRM 
Study reference manual 
SRT 
Safety review team 
SUSARs 
Suspected unexpected serious adverse reactions 
t1/2 
Terminal elimination half-life 
Tlast 
Time of the last quantifiable concentration 
Tmax 
Time to reach Cmax 
ULN 
Upper limit of normal 
UK 
United Kingdom 
US 
United States of America 
V 
Variance 
Vss 
Volume of distribution at steady state 
Vz 
Apparent volume of distribution during terminal phase 
Vir 
Vir Biotechnology, Inc. 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Woman of childbearing potential 
WT 
Wild type 
Yr 
Years 
 

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Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
None 
 
MedDRA 
 

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11. 
REFERENCES 
Advisory Committee on Immunization Practices (ACIP): Best practices guidance - 
preventing and managing adverse reactions, general best Practice Guidelines for 
Immunization. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/adverse-
reactions.html. Last reviewed February 4, 2021. Accessed on June 14, 2021. 
American Academy of Pediatrics (AAP). Children and COVID-19: State-level data 
report. American Academy of Pediatrics website. https://services.aap.org/en/pages/2019-
novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/. 
Updated June 14, 2021. Accessed June 15, 2021. 
Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, et al. A 
perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature. 
2020;584(7821):353–363. doi: 10.1038/s41586-020-2538-8. 
Booth A, Reed AB, Ponzo S, Yassaee A, Aral M, Plans D, et al. Population risk factors 
for severe disease and mortality in COVID-19: A global systematic review and meta-
analysis. PLoS One. 2021 Mar 4;16(3):e0247461. doi: 10.1371/journal.pone.0247461.  
Cavallo F, Rossi N, Chiarelli F. Novel coronavirus infection and children. Acta Biomed. 
2020 May 11;91:172-76. doi: 10.23750/abm.v91i2.9586.  
CDC COVID-19 Response Team. Severe Outcomes Among Patients with Coronavirus 
Disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR Morb 
Mortal Wkly Rep. 2020 Mar 27;69(12):343-346. doi: 10.15585/mmwr.mm6912e2. 
Centers for Disease Control and Prevention (CDC). Congenital Heart Defects (CHDs). 
Centers for Disease Control and Prevention website. 
https://www.cdc.gov/ncbddd/heartdefects/data.html. Updated December 09, 2020. 
Accessed July 26, 2021. 
Centers for Disease Control and Prevention (CDC). COVID data tracker. Centers for 
Disease Control and Prevention website. https://covid.cdc.gov/covid-data-
tracker/#trends_dailytrends. Accessed June 15, 2021(a). 
Centers for Disease Control and Prevention (CDC). COVID data tracker: Demographic 
Trends for COVID-19 cases and deaths in the US reported to CDC. Centers for Disease 
Control and Prevention website. https://covid.cdc.gov/covid-data-tracker/#demographics. 
Accessed June 17, 2021(b). 
Centers for Disease Control and Prevention (CDC). People with Certain Medical 
Conditions. Centers for Disease Control and Prevention website. 
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-
medical-conditions.html. Updated March 17, 2021. Accessed August 04, 2021(c). 
Centers for Disease Control and Prevention (CDC). Interim clinical considerations for 
use of COVID-19 vaccines currently authorized in the United States, 2021. 

TMF-13971114 
CONFIDENTIAL 
 
 
 
215226 
 
Protocol Amd 1 
108 
Clinical Study Protocol template V15 dated 21-Dec-2020 
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-
us.html. Updated June 1, 2021. Accessed June 15, 2021(d).  
Centers for Disease Control and Prevention (CDC). Information for Healthcare Providers 
about Multisystem Inflammatory Syndrome in Children (MIS-C). 
https://www.cdc.gov/mis/hcp/index.html. Page last reviewed May 20, 2021. Accessed 
September 15, 2021(e). 
Centers for Disease Control and Prevention Health Alert Network (CDC HAN). 
Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus 
Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp 
Distributed on May 14, 2020. Accessed on June 15, 2021. 
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 
deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 
Mar;368:m1091. doi: 10.1136/bmj.m1091. 
Clark PA and Myers AT. To Treat or Not To Treat: The Case of Methylmalonic 
Acidemia. J Neonatol Clin Pediatr. 2017;4:019. doi: 10.24966/NCP-878X/100019. 
Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The 
immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 
2020 Nov 12;183(4):968-981.e7. doi: 10.1016/j.cell.2020.09.016. 
Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 Among 
Children in China. Pediatrics. 2020 Jun;145(6):e20200702. doi: 10.1542/peds.2020-
0702.  
Eli Lilly and Company. Important Prescribing Information. Subject: United States 
National Pause for the Distribution and Utilization of Bamlanivimab and Etesevimab for 
the Treatment of Mild to Moderate COVID-19. 25 June 2021. 
https://www.covid19.lilly.com/assets/pdf/bam-ete/bam-ete-pause.pdf. Accessed July 14, 
2021. 
EMA issues advice on casirivimab and imdevimab antibody cocktail for the treatment of 
mild-to-moderate COVID-19 [news release]. Basel, Switzerland. 26 February 2021. 
Roche. https://www.roche.com/media/releases/med-cor-2021-02-26b.htm. Accessed July 
20, 2021. 
EMA issues advice on use of antibody combination (bamlanivimab / etesevimab) [news 
release]. 03 May 2021. European Medicines Agency (EMA). 
https://www.ema.europa.eu/en/news/ema-issues-advice-use-antibody-combination-
bamlanivimab-etesevimab. Accessed August 06, 2021. 
European Centre for Disease Prevention and Control (ECDC). COVID-19 in children and 
the role of school settings in transmission - second update. 8 July 2021. 
https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-in-children-and-
the-role-of-school-settings-in-transmission-second-update.pdf. Accessed July 20, 2021. 

TMF-13971114 
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Protocol Amd 1 
109 
Clinical Study Protocol template V15 dated 21-Dec-2020 
European Medicines Agency Evaluation of Medicines for Human Use (EMEA). 
Committee for Medicinal Products for Human Use (CHMP) and Paediatric Committee 
(PDCO).Guideline on the investigation of medicinal products in the term and preterm 
neonate. 25 June 2009. https://www.ema.europa.eu/en/documents/scientific-
guideline/guideline-investigation-medicinal-products-term-preterm-neonate-first-
version_en.pdf. 
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. 
Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 
2020 Jul 23;383(4):334-346. doi: 10.1056/NEJMoa2021680. 
Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. 
Clinical Practice Guideline for Screening and Management of High Blood Pressure in 
Children and Adolescents. Pediatrics. 2017 Sep;140(3):e20171904. doi: 
10.1542/peds.2017-1904. 
Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients 
hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 
states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(15):458-464. 
https://www.cdc.gov/mmwr/volumes/69/wr/mm6915e3.htm. 
Gottlieb M, Bridwell R, Ravera J, Long B. Multisystem inflammatory syndrome in 
children with COVID-19. Am J Emerg Med. 2021 Jun 8;49:148-152. doi: 
10.1016/j.ajem.2021.05.076. Epub ahead of print. 
Graff K, Smith C, Silveira L, Jung S, Curran-Hays S, Jarjour J, et al. Risk factors for 
severe COVID-19 in children. Pediatr Infect Dis J. 2021 Apr 1;40(4):e137-e145. doi: 
10.1097/INF.0000000000003043. 
Gruber CN, Patel RS, Trachtman R, Lepow L, Amanat F, Krammer F, et al. Mapping 
systemic inflammation and antibody responses in multisystem inflammatory syndrome in 
children (MIS-C). Cell. 2020 Nov 12;183(4):982-995.e14. doi: 
10.1016/j.cell.2020.09.034. 
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution 
of ACE2 protein, the functional receptor for SARS coronavirus. A first step in 
understanding SARS pathogenesis. J. Pathol. 2004;203(2):631–637. doi: 
10.1002/path.1570. 
Hegenbarth MA; American Academy of Pediatrics Committee on Drugs. Preparing for 
pediatric emergencies: drugs to consider. Pediatrics. 2008 Feb;121(2):433-43. doi: 
10.1542/peds.2007-3284.  
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 
2019 novel coronavirus in the United States. N Engl J Med. 2020 Mar 5;382:929-936. 
doi: 10.1056/NEJMoa2001191. 

TMF-13971114 
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215226 
 
Protocol Amd 1 
110 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected 
with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-
506. doi: 10.1016/S0140-6736(20)30183-5.  
Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-
nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel 
coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264-266. doi: 
10.1016/j.ijid.2020.01.009. 
Immunization Action Coalition (IAC) - Medical management of vaccine reactions in 
children and teens in a community setting. https://www.immunize.org/catg.d/p3082a.pdf. 
Distributed July 2019. Last accessed July 14, 2021. 
Johns Hopkins University and Medicine - Coronavirus Resource Center. Johns Hopkins 
University website. https://coronavirus.jhu.edu. Last accessed on June 17, 2021. 
Joyner MJ, Wright RS, Fairweather D, Senefeld JW, Bruno KA, Klassen SA, et al. Early 
safety indicators of COVID-19 convalescent plasma in 5,000 patients. Clin Invest. 2020 
Sep 1;130(9):4791-4797. doi: 10.1172/JCI140200. 
Kim L, Whitaker M, O’Halloran A, Kambhampati A, Chai SJ, Reingold A, et al. 
Hospitalization rates and characteristics of children aged <18 years hospitalized with 
laboratory-confirmed COVID-19—COVID-NET, 14 states, March 1–July 25, 2020. 
MMWR Morb Mortal Wkly Rep. 2020 Aug 14; 69(32): 1081–1088. doi: 
10.15585/mmwr.mm6932e3 
Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, 
et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. 
Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013.  
Li D, Edwards RJ, Manne K, Martinez DR, Schafer A, Alam SM, et al. In vitro and in 
vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. Cell. 
2021 Aug 5;184(16):4203-4219.e32. doi: 10.1016/j.cell.2021.06.021. Epub 2021 Jun 18. 
Leeb RT, Price S, Sliwa S, Kimball A, Szucs L, Caruso E, et al. COVID-19 trends among 
school-aged children — United States, March 1–September 19, 2020. MMWR Morb 
Mortal Wkly Rep. 2020;69:1410–1415. doi: 10.15585/mmwr.mm6939e2. 
Levin Z, Choyke K, Georgiou A, Sen S, Karaca-Mandic P. Trends in pediatric 
hospitalizations for coronavirus disease 2019. JAMA Pediatr. 2021 Apr 1;175(4):415-
417. doi: 10.1001/jamapediatrics.2020.5535. 
Lilly, Vir Biotechnology and GSK announce positive topline data from the phase 2 
BLAZE-4 trial evaluating bamlanivimab with VIR-7831 in low-risk adults with COVID-
19 [news release]. London UK; San Francisco, CA; and Indianapolis, IN. Eli Lilly and 
Company, Vir Biotechnology Inc., GlaxoSmithKline plc. March 29, 2021. 
https://us.gsk.com/en-us/media/press-releases/lilly-vir-biotechnology-and-gsk-announce-
positive-topline-data-from-the-phase-2-blaze-4-trial-evaluating-bamlanivimab-with-vir-
7831-in-low-risk-adults-with-covid-19/. Accessed June 14, 2021(a).  

TMF-13971114 
CONFIDENTIAL 
 
 
 
215226 
 
Protocol Amd 1 
111 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Ludvigsson JF. Children are unlikely to be the main drivers of the COVID‐19 pandemic–
a systematic review. Acta Paediatr. 2020 Aug;109(8):1525-1530. doi: 
10.1111/apa.15371. 
Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of 
multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection - 
United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly 
Rep. 2020 Oct 9;69(40):1450-1456. doi: 10.15585/mmwr.mm6940e1. 
Mulder BJ. Epidemiology of adult congenital heart disease: demographic variations 
worldwide. Neth Heart J. 2012 Dec;20(12):505-8. doi: 10.1007/s12471-012-0335-1. 
National Academies of Sciences, Engineering, and Medicine. Rapid Expert Consultation 
on Allocating COVID-19 Monoclonal Antibody Therapies and Other Novel Therapeutics 
(January 29, 2021). Washington, DC: The National Academies Press; 2021:1-34. doi: 
10.17226/26063. 
National Institute of Health (NIH) COVID-19 treatment guidelines: Special 
considerations in children. National Institute of Health website. 
https://www.covid19treatmentguidelines.nih.gov/special-populations/children/. Updated 
April 21, 2021. Accessed June 16, 2021. 
NIH Clinical Center. Policy and Communications Bulletin. POLICY: Guidelines for 
Limits of Blood Drawn for Research Purposes in the Clinical Center M95-9(rev) 5 June 
2009. https://irb.research.chop.edu/sites/default/files/documents/g_nih_blooddraws.pdf 
Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y, et al. Factors 
associated with hospital admission and critical illness among 5279 people with 
coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020 May 
22;369:m1966. doi: 10.1136/bmj.m1966. 
Pinto D, Park YJ, Beltramello M, Walls AC, Tortorici MA, Bianchi S, et al. Cross-
neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 
2020 Jul;583(7815):290-295. doi: 10.1038/s41586-020-2349-y.  
Polack FP, Teng MN, Collins PL, Prince GA, Exner M, Regele H, et al. A role for 
immune complexes in enhanced respiratory syncytial virus disease. J Exp Med. 
2002;196(6):859‐865. doi:10.1084/jem.20020781. 
Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. 
Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients 
Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 
26;323(20):2052-2059. doi: 10.1001/jama.2020.6775.  
Rosenthal N, Cao Z, Gundrum J, Sianis J, Safo S. Risk Factors Associated With In-
Hospital Mortality in a US National Sample of Patients With COVID-19. JAMA Netw 
Open. 2020 Dec 1;3(12):e2029058. doi: 10.1001/jamanetworkopen.2020.29058. 

TMF-13971114 
CONFIDENTIAL 
 
 
 
215226 
 
Protocol Amd 1 
112 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, 
et al. Second symposium on the definition and management of anaphylaxis: summary 
report-Second National Institute of Allergy and Infectious Disease/Food Allergy and 
Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 
10.1016/j.jaci.2005.12.1303  
Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ, Ross CE, McKiernan CA, et al. 
Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) 
Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 
2020 Sep 1;174(9):868-873. doi: 10.1001/jamapediatrics.2020.1948. 
Sicherer SH and Simons ER, Section on Allergy and Immunology. Epinephrine for First-
aid Management of Anaphylaxis. Pediatrics. 2017 Mar;139(3):e20164006. doi: 
10.1542/peds.2016-4006. 
Starr TN, Greaney AJ, Addetia A, Hannon WW, Choudhary MC, Dingens AS, et al. 
Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. 
Science. 2021 Feb 19;371(6531):850-854. doi: 10.1126/science.abf9302. 
The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with 
COVID-19. N Engl J Med. 2021 Feb 25; 384:693-704. doi: 10.1056/NEJMoa2021436. 
United States Food and Drug Administration (FDA). Collection of race and ethnicity data 
in clinical trials: Guidance for industry and food and drug administration staff. United 
States Food and Drug Administration website. 
https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126396.pdf. Issued 
October 26, 2016. Last Accessed June 14, 2021. 
United States Food and Drug Administration (FDA). In vitro diagnostics EUAs. United 
States Food and Drug Administration website. https://www.fda.gov/medical-
devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-
devices/vitro-diagnostics-euas. Updated 10 February 2021. Accessed June 16, 2021(a). 
United States Food and Drug Administration (FDA). Letter of Authorization: Emergency 
Use Authorization (EUA) for baricitinib (Olumiant), in combination with remdesivir 
(Veklury), for the treatment of suspected or laboratory confirmed coronavirus disease 
2019 (COVID-19). July 28, 2021. United States Food and Drug Administration website. 
https://www.fda.gov/media/143822/download. Accessed on August 4, 2021(b). 
United States Food and Drug Administration (FDA). Letter of Authorization: Emergency 
Use Authorization (EUA) for emergency use of casirivimab and imdevimab, 
administered together, for the treatment of mild to moderate coronavirus disease 2019 
(COVID-19). November 21, 2020. United States Food and Drug Administration website. 
https://www.fda.gov/media/143891/download. Accessed on July 26, 2021(c).  
United States Food and Drug Administration (FDA). Letter of Authorization: Emergency 
Use Authorization (EUA) for emergency use of bamlanivimab and etesevimab 
administered together for the treatment of mild to moderate COVID-19 in adults and 

TMF-13971114 
CONFIDENTIAL 
 
 
 
215226 
 
Protocol Amd 1 
113 
Clinical Study Protocol template V15 dated 21-Dec-2020 
pediatric patients (12 years of age and older weighing at least 40 kg) with positive results 
of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe 
COVID-19 and/or hospitalization. February 25, 2021. United States Food and Drug 
Administration website. https://www.fda.gov/media/145801/download. Accessed on July 
26, 2021(d). 
United States Food and Drug Administration (FDA). Letter of Authorization: Emergency 
Use Authorization (EUA) for the emergency use of sotrovimab for the treatment of mild-
to-moderate coronavirus disease 2019 (COVID-19). May 26, 2021. United States Food 
and Drug Administration website. https://www.fda.gov/media/149532/download. 
Accessed on July 26, 2021(e). 
Vir Biotechnology and GSK Announce VIR-7831 Reduces Hospitalization and Risk of 
Death in Early Treatment of Adults with COVID-19 [news release]. San Francisco, CA; 
London UK. March 10, 2021. Vir Biotechnology, Inc. https://investors.vir.bio/news-
releases/news-release-details/vir-biotechnology-and-gsk-announce-vir-7831-reduces. 
Accessed June 16, 2021. 
Vir Biotechnology and GSK Provide Update on NIH-Sponsored ACTIV-3 Trial 
Evaluating VIR-7831 in Hospitalized Adults with COVID-19 [news release]. London, 
UK. March 03, 2021. GlaxoSmithKline plc. https://us.gsk.com/en-us/media/press-
releases/vir-biotechnology-and-gsk-provide-update-on-nih-sponsored-activ-3-trial-
evaluating-vir-7831-in-hospitalised-adults-with-covid-19/. Accessed June 16, 2021(b). 
Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, et al. Antibody resistance of SARS-
CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021 May;593(7857):130-135. doi: 
10.1038/s41586-021-03398-2. 
WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, 
Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between 
administration of systemic corticosteroids and mortality among critically ill patients with 
COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341. doi: 
10.1001/jama.2020.17023. 
Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors 
associated with COVID-19-related death using OpenSAFELY. Nature. 2020 
Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. 
Wu JT, Ma ES, Lee CK, Chu DK, Ho PL, Shen AL, et al. The infection attack rate and 
severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis. 2010 Nov 
15;51(10):1184-91. doi: 10.1086/656740.  
Zhou Y, Zezhong L, Li S, Xu W, Zhang Q, Silva IT, et al. Enhancement versus 
neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with 
distinct epitopes on the RBD. Cell Rep. 2021 Feb 2;34(5):108699. doi: 
10.1016/j.celrep.2021.108699.