A Phase I, Single-blind, Randomized, Single-dose Clinical Pharmacology Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Sotrovimab vs Placebo by Intravenous or Intramuscular Administration in Healthy Japanese and Caucasian Participants
Phase: PHASE1
Conditions: Covid19
Sponsor: Vir Biotechnology, Inc.

 
 
 
 
Protocol 
 
Study ID: 217653 
 
Official Title of Study: A Phase I, single-blind, randomized, single-dose clinical 
pharmacology study to investigate the pharmacokinetics, safety, and tolerability of 
sotrovimab vs placebo by intravenous or intramuscular administration in healthy Japanese 
and Caucasian participants. 
 
IND Identifier: 149315 
 
Date of Document: 27-MAY-2021 
 
 

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GlaxoSmithKline group of companies 
 
217653 
 
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Clinical Study Protocol template V15 dated 21-Dec-2020 
TITLE PAGE 
Protocol Title: A Phase I, single-blind, randomized, single-dose clinical pharmacology 
study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs 
placebo by intravenous or intramuscular administration in healthy Japanese and 
Caucasian participants 
Protocol Number: GSK Study 217653 (VIR-7831-5009) 
Compound Number 
or Name: 
Sotrovimab (also known as GSK4182136, VIR-7831) 
Brief Title: A Phase I single-dose study to investigate the pharmacokinetics, safety, and 
tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in 
healthy Japanese and Caucasian participants 
Study Phase: Phase I 
Sponsor Name and Legal Registered Address:  
Vir Biotechnology, Inc.  
499 Illinois Street, Suite 500  
San Francisco, CA 94158 
USA  
 
This study is sponsored by Vir Biotechnology, Inc. GlaxoSmithKline is supporting Vir 
Biotechnology, Inc. in the conduct of this study.  
 
Regulatory Agency Identifying Number(s): 
IND: 149315 
Approval Date: 27-MAY-2021 
Copyright 2021 Vir Biotechnology, Inc. and the GlaxoSmithKline group of companies.  
All rights reserved.  Unauthorised copying or use of this information is prohibited. 
 

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SPONSOR SIGNATORY: 
Protocol Title: A Phase I, single-blind, randomized, single-dose clinical pharmacology 
study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs 
placebo by intravenous or intramuscular administration in healthy Japanese and 
Caucasian participants 
Protocol Number: GSK Study 217653 (VIR-7831-5009) 
Compound Number 
or Name: 
Sotrovimab (also known as GSK4182136, VIR-7831) 
 
 
 
 
Elizabeth Alexander MD, MSc, FIDSA 
Senior Director, Clinical Research (Vir) 
 
Date 
The signed page is a separate document. 
 
Medical Monitor Name and Contact Information will be provided separately  
 

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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 2 
1. 
PROTOCOL SUMMARY .......................................................................................... 6 
1.1. 
Synopsis ....................................................................................................... 6 
1.2. 
Schema ...................................................................................................... 11 
1.3. 
Schedule of Activities (SoA) ........................................................................ 12 
2. 
INTRODUCTION .................................................................................................... 14 
2.1. 
Study Rationale .......................................................................................... 14 
2.2. 
Background ................................................................................................ 17 
2.3. 
Benefit/Risk Assessment ............................................................................ 18 
2.3.1. 
Risk Assessment ......................................................................... 19 
2.3.2. 
Benefit Assessment ..................................................................... 24 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 24 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 25 
4. 
STUDY DESIGN .................................................................................................... 27 
4.1. 
Overall Design ............................................................................................ 27 
4.2. 
Scientific Rationale for Study Design .......................................................... 28 
4.3. 
Justification for Dose .................................................................................. 29 
4.4. 
End of Study Definition ............................................................................... 30 
5. 
STUDY POPULATION ........................................................................................... 31 
5.1. 
Inclusion Criteria ......................................................................................... 31 
5.2. 
Exclusion Criteria ........................................................................................ 32 
5.3. 
Lifestyle Considerations .............................................................................. 34 
5.3.1. 
Meals and Dietary Restrictions .................................................... 34 
5.3.2. 
Caffeine, Alcohol, and Recreational Drug Use ............................. 34 
5.3.3. 
Activity ......................................................................................... 35 
5.3.4. 
Other Restrictions ........................................................................ 35 
5.4. 
Screen Failures........................................................................................... 35 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 35 
6.1. 
Study Intervention(s) Administered ............................................................. 35 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 37 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 38 
6.4. 
Study Intervention Compliance ................................................................... 39 
6.5. 
Dose Modification ....................................................................................... 39 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 39 
6.7. 
Treatment of Overdose ............................................................................... 39 
6.8. 
Concomitant Therapy.................................................................................. 39 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 40 
7.1. 
Discontinuation of Study Intervention .......................................................... 40 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 40 

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7.1.2. 
Temporary Discontinuation .......................................................... 41 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 41 
7.3. 
Lost to Follow Up ........................................................................................ 41 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 42 
8.1. 
Screening Period ........................................................................................ 43 
8.1.1. 
Medical History ............................................................................ 43 
8.1.2. 
SARS-CoV-2 Testing ................................................................... 43 
8.2. 
Efficacy Assessments ................................................................................. 43 
8.3. 
Safety Assessments ................................................................................... 43 
8.3.1. 
Physical Examinations ................................................................. 43 
8.3.2. 
Vital Signs .................................................................................... 43 
8.3.3. 
Electrocardiograms ...................................................................... 44 
8.3.4. 
Clinical Safety Laboratory Assessments ...................................... 45 
8.3.5. 
Pregnancy Testing ....................................................................... 45 
8.3.6. 
Local Injection Site Tolerability ..................................................... 46 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 46 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 46 
8.4.2. 
Assessment of Severity ............................................................... 47 
8.4.3. 
Method of Detecting AEs and SAEs ............................................. 47 
8.4.4. 
Follow-up of AEs and SAEs ......................................................... 47 
8.4.5. 
Regulatory Reporting Requirements for SAEs ............................. 47 
8.4.6. 
Pregnancy ................................................................................... 48 
8.4.7. 
Adverse Events of Special Interest .............................................. 48 
8.5. 
Pharmacokinetics ....................................................................................... 50 
8.6. 
Genetics ..................................................................................................... 50 
8.7. 
Biomarkers ................................................................................................. 50 
8.8. 
Immunogenicity Assessments ..................................................................... 50 
8.9. 
Health Economics ....................................................................................... 51 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 51 
9.1. 
Statistical Hypotheses................................................................................. 51 
9.2. 
Sample Size Determination ........................................................................ 51 
9.3. 
Analysis Sets .............................................................................................. 52 
9.4. 
Statistical Analyses ..................................................................................... 52 
9.4.1. 
General Considerations ............................................................... 52 
9.4.2. 
Primary Endpoint(s) ..................................................................... 52 
9.4.3. 
Secondary Endpoint(s) ................................................................ 54 
9.4.4. 
Tertiary/Exploratory Endpoint(s) .................................................. 56 
9.5. 
Interim Analysis .......................................................................................... 56 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 57 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 57 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 57 
10.1.2. 
Financial Disclosure ..................................................................... 57 
10.1.3. 
Informed Consent Process .......................................................... 58 
10.1.4. 
Data Protection ............................................................................ 58 
10.1.5. 
Committees Structure .................................................................. 59 

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10.1.6. 
Dissemination of Clinical Study Data ........................................... 59 
10.1.7. 
Data Quality Assurance ............................................................... 59 
10.1.8. 
Source Documents ...................................................................... 60 
10.1.9. 
Study and Site Start and Closure ................................................. 61 
10.1.10. Publication Policy ......................................................................... 61 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 62 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 64 
10.3.1. 
Definition of AE ............................................................................ 64 
10.3.2. 
Definition of SAE .......................................................................... 65 
10.3.3. 
Recording and Follow-Up of AE and SAE .................................... 66 
10.3.4. 
Reporting of SAE to GSK ............................................................. 69 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 70 
10.4.1. 
Definitions: ................................................................................... 70 
10.4.2. 
Contraception Guidance: ............................................................. 71 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 73 
10.6. 
Appendix 6: Management of Local Injection Site Reactions and 
Systemic Symptoms (Anaphylaxis) ............................................................. 75 
10.7. 
Appendix 7: Abbreviations and Definitions and Trademarks ....................... 77 
11. REFERENCES ....................................................................................................... 82 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase I, single-blind, randomized, single-dose clinical pharmacology 
study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs 
placebo by intravenous or intramuscular administration in healthy Japanese and 
Caucasian participants 
Brief Title: A Phase I single-dose study to investigate the pharmacokinetics, safety, and 
tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in 
healthy Japanese and Caucasian participants 
Rationale: 
Sotrovimab is being developed for treatment as well as for prophylaxis of Coronavirus 
disease 2019 (COVID-19). Sotrovimab is a human immunoglobulin G1 kappa (IgG1κ) 
monoclonal antibody (mAb) derived from the parental mAb S309, a mAb directed 
against the spike protein of severe acute respiratory syndrome coronavirus-1 (SARS-
CoV-1) that potently cross-neutralizes SARS-CoV-2, the causative agent of COVID-19. 
The Fc domain of sotrovimab includes the 2 amino acid “LS” modification that extends 
antibody half-life and is also expected to enhance distribution to the respiratory mucosa. 
Previous clinical experience has been gained in ongoing studies of sotrovimab as a 
treatment for participants with mild to moderate COVID-19 (COMET-ICE 
[NCT04545060], BLAZE-4 [NCT04634409], COMET-PEAK [NCT04779879], and 
COMET-TAIL [VIR-7831-5008; GSK Study 217114]) and in hospitalized participants 
with COVID-19 (ACTIV-3-TICO [NCT04501978]). 
This study is the first study in healthy Caucasian and Japanese participants. The purpose 
of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single 
fixed dose of sotrovimab administered intravenously or via intramuscular (IM) injection 
in Japanese and Caucasian healthy volunteers. These routes of administration were 
selected because of demonstrated efficacy of the intravenous (IV) route in early treatment 
of mild-to-moderate COVID-19 at high risk for progression, and to treat patients who 
lack access to IV infusion centers with IM injections; these are also the intended routes of 
administration for registration. The data from this study will be used to supplement data 
available from other clinical trials that were conducted in non-Japanese participants, will 
offer an opportunity for direct comparison of healthy Japanese to healthy Caucasian 
participants, and will support dose selection in Japan.  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Pharmacokinetics (Part 1) 
To assess the PK of sotrovimab 
administered via IV infusion in healthy 
PK parameters through Day 29: maximum 
observed serum concentration (Cmax), area under 
the serum-concentration time curve from Day 1 to 

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Objectives 
Endpoints 
Japanese and Caucasian participants 
through Day 29 
Day 29 (AUCD1-29), time to Cmax (Tmax), and 
concentration at Day 29 (CD29) of sotrovimab, as 
data permits. 
Pharmacokinetics (Part 2) 
To assess the PK of sotrovimab 
administered via IM injections in healthy 
Japanese and Caucasian participants 
through Day 29 
PK parameters through Day 29: Cmax, AUCD1-29, 
Tmax, and CD29 of sotrovimab, as data permits. 
Safety (Part 1) 
To evaluate the safety and tolerability profile 
of IV sotrovimab in healthy Japanese and 
Caucasian participants through Day 29 
• Occurrence of adverse events (AEs) through 
Day 29 
• Occurrence of serious adverse events (SAEs) 
through Day 29 
• Occurrence of adverse events of special interest 
(AESIs) through Day 29 
• Occurrence of clinically significant abnormalities 
on 12-lead electrocardiogram (ECG) readings 
through Day 29 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Day 29 
• Occurrence of clinically significant laboratory 
abnormalities through Day 29 
Safety (Part 2) 
To evaluate the safety and tolerability profile 
of IM sotrovimab in healthy Japanese and 
Caucasian participants through Day 29 
• Occurrence of AEs through Day 29 
• Occurrence of SAEs through Day 29 
• Occurrence of AESIs through Day 29 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Day 29 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Day 29 
• Occurrence of clinically significant laboratory 
abnormalities through Day 29 
Secondary 
Pharmacokinetics (Part 1) 
To assess the PK of sotrovimab 
administered via IV infusion in healthy 
Japanese and Caucasian participants 
PK parameters through Week 18: Cmax, area 
under the serum concentration-time curve 
extrapolated to infinite time (AUCinf), area under 
the curve from the time of dosing to the time of 
the last measurable (positive) concentration 

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Objectives 
Endpoints 
through Week 18 
(AUClast), Tmax, time of the last quantifiable 
concentration (Tlast), and the terminal elimination 
half-life (t1/2) of sotrovimab, as data permits. 
Pharmacokinetics (Part 2) 
To assess the PK of sotrovimab 
administered via IM injections in healthy 
Japanese and Caucasian participants 
through Week 18 
PK parameters through Week 18: Cmax, AUCinf, 
AUClast, Tmax, Tlast, and t1/2, of sotrovimab, as data 
permits. 
Safety (Part 1) 
To evaluate the safety and tolerability profile 
of IV sotrovimab in healthy Japanese and 
Caucasian participants through Week 18 
• Occurrence of AEs through Week 18 
• Occurrence of SAEs through Week 18 
• Occurrence of AESIs through Week 18 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Week 18 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Week 18 
• Occurrence of clinically significant laboratory 
abnormalities through Week 18 
Safety (Part 2) 
To evaluate the safety and tolerability profile 
of IM sotrovimab in healthy Japanese and 
Caucasian participants through Week 18 
• Occurrence of AEs through Week 18 
• Occurrence of SAEs through Week 18 
• Occurrence of AESIs through Week 18 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Week 18 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Week 18 
• Occurrence of clinically significant laboratory 
abnormalities through Week 18 
a 
Baseline is defined as assessments performed following admission to unit on Day -1 and before dosing on Day 1. 
 
Overall Design: 
This study is a randomized, multi-center, placebo-controlled, single-blind, single-dose, 
parallel group Phase I trial to assess the PK of IV and IM sotrovimab in healthy Japanese 
and Caucasian participants. This study will occur in two parts (Part 1 and Part 2).  

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Part 1:  
Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive 
a single, 500 mg IV infusion of sotrovimab or volume-matched saline placebo. Eligible 
participants will be treated with a single IV dose of sotrovimab or volume-matched saline 
placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, 
immunogenicity, and PK of IV sotrovimab will be evaluated. 
Part 2:  
Part 2 will begin after enrollment has been completed for Part 1. Healthy Japanese and 
Caucasian participants will be randomized in a 4:1 ratio to receive a single, 500 mg IM 
dose of sotrovimab or volume-matched saline placebo. Eligible participants will be 
treated with a single IM dose of sotrovimab or volume-matched saline placebo (given as 
two 4 mL injections, one in each dorsogluteal muscle) on Day 1. Participants will be 
blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IM 
sotrovimab will be evaluated. 
Brief Summary: 
The purpose of this study is to assess the safety, tolerability, immunogenicity, and PK of 
IV and IM sotrovimab in healthy Japanese and Caucasian participants. The primary 
endpoints are PK and safety through Day 29.  
• Study Duration: 18 weeks after dosing. Participants can be screened up to 28 days 
before dosing, leading to a maximum study duration of 22 weeks. 
• Treatment Duration: A single dose of sotrovimab or equal volume saline-placebo 
will be administered by IV infusion or administered IM (IM dose is administered 
as two 4 mL injections, one in each dorsogluteal muscle) on Day 1. 
• Visit Frequency: Participants will be admitted to the clinical research unit on the 
day prior to study drug administration (Day -1) and will remain in the unit until 
all Day 3 study activities are completed. Participants will need to return to the 
study site for 7 follow-up visits during the 18 week study (at Weeks 2, 3, 4, 6, 8, 
12, and 18).  
Number of Participants: 
If participants permanently discontinue the study before Day 29 additional participants 
may be enrolled as replacements and assigned to the same cohort (i.e., Part 1 or Part 2) 
and treatment at the discretion of the Sponsor or designee in consultation with the 
investigator. 
Part 1:  
A maximum of 24 participants will be randomized in Part 1 to achieve 20 evaluable 
participants in Part 1. The Part 1 cohort will enroll approximately 8 Japanese and 
8 Caucasian participants to the IV sotrovimab arm and 2 Japanese and 2 Caucasian 
participants to the placebo arm.  

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Part 2:  
A maximum of 24 participants will be randomized in Part 2 to achieve 20 evaluable 
participants in Part 2. The Part 2 cohort will enroll approximately 8 Japanese and 
8 Caucasian participants to the IM sotrovimab arm and 2 Japanese and 2 Caucasian 
participants to the placebo arm. 
Note: “Evaluable” is defined as a participant who has been randomized, has been 
exposed to study intervention and who has at least 1 non-missing PK assessment 
(including non-quantifiable samples) – i.e., PK sample collected and analyzed. 
Note: “Enrolled” means a participant'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.  
Intervention Groups and Duration: 
This study will occur in two parts (Part 1 and Part 2). For both parts, Screening 
assessments will be performed within 28 days before administration of study 
intervention. After completion of Screening and Baseline assessments, eligible 
participants in Part 1 will be randomized 4:1 to receive a single-dose of IV sotrovimab 
(500 mg) or volume-matched placebo, while participants in Part 2 will be randomized 4:1 
to receive a single-dose of IM sotrovimab (500 mg) or volume-matched placebo. 
Administration of study intervention will occur on Day 1. Participants will remain in the 
clinical research unit from admission on Day -1 through the completion of all Day 3 
study procedures. Upon completion of this in-unit observation period, participants may 
be discharged as deemed clinically appropriate by the investigator. The follow-up period 
is for 18 weeks after dosing.  
Data Monitoring/ Other Committee: No 

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1.2. 
Schema 
 

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1.3. 
Schedule of Activities (SoA) 
 
 
 
 
W1 
W2 W3 W4 W6 W8 W12 W18 
 
 
Study Visit Day  Visit Window 
Screening1 
(up to D -28) 
Day -1 
Day 1 
Day 2 
Day 3 
Day 8 
Day 15 ± 1d 
Day 29 ± 2d 
Day 43 ± 3d 
Day 57 ± 4d 
Day 85 ± 7d 
Day 127 ± 7d 
Notes 
In case of early discontinuation or withdrawal (ED or EW) all Week 18 (D127) 
activities should be performed. 
 
NOTE: Whenever vital signs, 12-lead ECGs, and blood draws are scheduled for 
the same nominal time, the assessments should occur in the following order: vital 
signs, 12-lead ECG, blood draws. The timing of the assessments should allow the 
blood draw to occur at the exact nominal time. The actual time of assessment or 
procedure must be reported in the eCRF. 
1. All screening procedures must be completed within 28 days prior to dosing. 
2. Provide details of any changes to medical history since Screening. 
3. Including height and weight. 
4. Record Day 1 vital signs within 1 hour prior to dosing (IV and IM), at 
approximately 15 minutes after the infusion is started (IV only), and at the 
end of infusion (IV only) or immediately after injections (IM only). Vital signs 
will be monitored at approximately 30 minutes, 1 hour, and 2 hours after 
infusion or injection (IV and IM). Vital signs on other days should be 
performed once at any time of the day.  
5. Local injection site tolerability assessment on Day 1 at approximately 1 hour 
post-dose and on Day 2 and Day 3. All ISRs need to be followed by the PI to 
resolution.  
6. Triplicate 12-lead ECGs will be collected at Screening. All other timepoints 
are single 12-lead ECGs (unless an abnormality is detected post-baseline, in 
which case triplicate ECGs are required). On Day 1 ECGs will be performed 
at the following timepoints: prior to administration of study intervention (IV 
and IM), end of infusion (IV only), and at 1 hour and 2 hours after the end of 
IV infusion or first IM injection. On other days, ECGs will be performed once 
and time-matched to the PK sample collection. 
7. Day 1 lab assessments should be collected pre-dose. Hematology 
assessments are performed only on Day 1.  
8. On Day 1, sample collection will occur pre-dose. 
9. Urine or serum pregnancy test, as per local guidelines. See Section 8.3.5.  
10. Day 1 sample collection will occur pre-dose (IV and IM), at end of infusion (IV 
infusion only), and at 1, 2, 6, and 8, 24 (Day 2), and 48 (Day 3) hours after 
the end of infusion or first IM injection. On other days, samples will be 
collected once at any time of the day. 
11. At screening and on Day -1, only SAEs related to study participation or a 
GSK product will be reported. 
 
Admission to unit 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Discharge from unit 
 
 
 
 
X 
 
 
 
 
 
 
 
Screening 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history (incl. medication/drug/alcohol/ 
tobacco use, allergies, illnesses, and SARS-
CoV-2 infection/therapy/vaccination) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Study intervention administration 
 
 
X 
 
 
 
 
 
 
 
 
 
Assessments 
Full physical examination 
X3 
 
X 
 
X 
 
 
 
 
 
 
 
Vital Signs (BP, PR, RR, temperature, SpO2)4 
X 
 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Local injection site tolerability assessment 
(intramuscular injections only) 
 
 
X5 X5 X5 
 
 
 
 
 
 
 
12-lead ECG6 
X6 
 
X6 
 
 
X 
X 
X 
 
X 
 
X 
Sample collection 
Lab assessments (hematology, clinical 
chemistry, coagulation) 
X 
 
X7 
X 
 
X 
 
X 
X 
X 
X 
X 
Urinalysis and urine albumin to creatinine 
ratio 
X 
 
X8 
 
 
X 
X 
X 
 
X 
 
X 
Urine drug/alcohol screening 
X 
X 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B and C screening 
X 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 molecular test 
X 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy test9 
X 
X 
 
 
 
 
 
 
 
 
 
X 
Blood sample for PK analysis10 
 
 
X10 X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for immunogenicity testing 
(anti-drug antibody and drug-neutralizing 
antibody)  
 
 
X8 
 
 
 
 
X 
 
 
X 
X 
 
AE review 
 
 
<================ X =================> 
 
SAE review 
X11 
X11 <================ X =================> 
 
AESI and concomitant medication review 
 
 
<================ X =================> 
 
 
 
 
 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; BP = blood pressure; GSK = GlaxoSmithKline; ECG = electrocardiogram; eCRF = electronic case 
report form; ED = early discontinuation; EW = early withdrawal; HIV = human immunodeficiency virus; IM = intramuscular; ISRs = injection site reactions; IV = intravenous; PI = 
Principal investigator; PK = pharmacokinetic; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2; SpO2 = oxygen saturation; PK = 
pharmacokinetics; PR = pulse rate; RR = respiratory rate 

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• The timing of planned study assessments may change during the course of the study based on emerging data/in-stream data 
review (e.g., to obtain data closer to the time of peak serum concentrations) to ensure appropriate monitoring.  
• Any changes in the timing of time points for any planned study assessments as the result of emerging 
pharmacokinetic/pharmacodynamic data from this study must be documented and approved by the relevant study team 
member and then archived in the sponsor/designee and site study files but will not constitute a protocol amendment. 
• The Competent Authority (CA) and ethics committee (EC) will be informed of any safety issues that constitute a substantial 
amendment and require alteration of the safety monitoring scheme or amendment of the informed consent form (ICF). The 
changes will be approved by the CA and the EC before implementation. 
 

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2. 
INTRODUCTION 
2.1. 
Study Rationale  
Sotrovimab is being developed for treatment as well as for prophylaxis of Coronavirus 
disease 2019 (COVID-19). Sotrovimab is a human immunoglobulin G1 kappa (IgG1κ) 
monoclonal antibody (mAb) derived from the parental mAb S309, a mAb directed 
against the spike protein of severe acute respiratory syndrome coronavirus-1 (SARS-
CoV-1) that potently cross-neutralizes SARS-CoV-2, the causative agent of COVID-19 
[Pinto, 2020]. The Fc domain of sotrovimab includes the 2 amino acid “LS” modification 
that extends antibody half-life and is also expected to enhance distribution to the 
respiratory mucosa [Ko 2014; Zalevsky, 2010; Gaudinski, 2018]. Previous clinical 
experience has been gained in ongoing studies of sotrovimab as a treatment for 
participants with mild to moderate COVID-19 (COMET-ICE [NCT04545060], BLAZE-
4 [NCT04634409], COMET-PEAK [NCT04779879], and COMET-TAIL [VIR-7831-
5008; GSK Study 217114]) and in hospitalized participants with COVID-19 (ACTIV-3-
TICO [NCT04501978]). 
This study is the first study in healthy Caucasian and Japanese participants. The purpose 
of this study is to evaluate the safety, tolerability, and PK of a single fixed dose of 
sotrovimab administered intravenously or via IM injection in Japanese and Caucasian 
healthy volunteers. These routes of administration were selected because of demonstrated 
efficacy of the IV route in early treatment of mild-to-moderate COVID-19 at high risk for 
progression, and to treat patients who lack access to IV infusion centers with IM 
injections; these are also the intended routes of administration for registration. The data 
from this study will be used to supplement data available from other clinical trials that 
were conducted in non-Japanese participants, will offer an opportunity for direct 
comparison of healthy Japanese to healthy Caucasian participants, and will support dose 
selection in Japan. 
As of 31 MAR 2021, approximately 1350 participants have been randomized to either 
sotrovimab (500 mg IV 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) and 300 participants in a study that evaluated 
sotrovimab for the treatment of individuals hospitalized with COVID-19 (ACTIV-3-
TICO). 
COMET-ICE was followed by an Independent Data Monitoring Committee (IDMC), 
whose most recent meeting was on 10 MAR 2021 for review of a planned interim 
analysis, which included 583 participants. There was an 85% reduction in the rate of 
hospitalization or death in the sotrovimab arm versus the placebo arm (p=0.002), which 
was the primary endpoint. The IDMC recommended that the study should halt enrollment 
on the basis of overwhelming efficacy [Vir Biotechnology, Inc., 2021]. 
ACTIV-3-TICO was followed by a Data and Safety Monitoring Board (DSMB) who met 
on 25 JAN 2021 to evaluate data from 148 participants who had been randomized to 
sotrovimab or shared placebo. One potentially life-threatening allergic reaction 
(anaphylaxis) was reported during infusion in ACTIV-3-TICO in a participant that 

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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. The DSMB recommended the sotrovimab sub-study 
should continue as planned.  
Most recently, the DSMB met on 01 MAR 2021 for a pre-planned safety and efficacy 
data review. While sotrovimab met initial pre-specified criteria to continue to the next 
phase of the ACTIV-3-TICO trial and there were no reported safety signals, sensitivity 
analyses of the available data raised concerns about the magnitude of potential benefit. 
The DSMB therefore recommended that the trial be closed to future enrollment 
[GlaxoSmithKline plc, 2021]. 
Sotrovimab administered by IV infusion is also being evaluated in the BLAZE-4 study, a 
clinical trial with multiple arms evaluating anti-SARS-CoV-2 mAbs from Eli Lilly and 
Company. One arm compared the combination of bamlanivimab with sotrovimab to 
placebo (randomized 1:1) for the treatment of mild to moderate COVID-19. Enrollment 
for this arm concluded at approximately 200 participants on 05 FEB 2021, with no new 
safety concerns for sotrovimab identified as of 17 MAR 2021. The BLAZE-4 study met 
the primary endpoint, with a 70% (p<0.001) relative reduction in persistently high viral 
load (>5.27; cycle threshold value <27.5) at Day 7 compared with placebo for 
bamlanivimab 700 mg co-administered with sotrovimab 500 mg. Co-administration of 
bamlanivimab and sotrovimab also demonstrated a statistically significant reduction in 
the key virologic secondary endpoints of mean change from baseline for SARS-CoV-2 
viral load to Days 3, 5, and 7 compared with placebo [Eli Lilly and Company, 2021]. 
Sotrovimab administered intravenously (500 mg) or via IM injection (250 mg and 
500 mg) is also currently being evaluated for the treatment of mild-to-moderate COVID-
19 (COMET-PEAK) and in a study evaluating sotrovimab for the treatment of mild-to-
moderate COVID-19 in non-hospitalized participants at high risk for disease progression 
(COMET-TAIL). As of 13 MAY 2021, safety data from approximately 30 participants 
who received 500 mg IV sotrovimab in Study Part A and from 66 participants who 
received 500 mg IV or IM sotrovimab in Study Part B of COMET-PEAK has been 
reviewed and no new safety concerns have been identified. Studies to evaluate IM 
injection (500 mg) of sotrovimab as a prophylaxis in immunocompromised participants 
and in persons living with HIV are also planned. 
Partial blinded serum PK through Day 57 from the Lead-in phase of COMET-ICE is 
available to date. PK sampling will continue for 6 months for all participants in COMET-
ICE. The preliminary pharmacokinetic (PK) profile and PK parameters for sotrovimab, 
based on nominal times are presented in Figure 1 and Table 1, respectively. The mean 
maximum 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. Based on the partial data 
available to date, >20% of the area under curve (AUC) is being extrapolated and the 
observation range for the apparent terminal elimination rate constant (λz) spans <2 half-
lives in all except one subject, so summary statistics for clearance (CL), apparent volume 
of distribution (V), terminal elimination half-life (t1/2), and area under the serum 
concentration-time curve extrapolated to infinite time (AUCinf) will be reported once 
sufficient data are available.   

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Figure 1 
Preliminary Mean Concentration vs Time Profile of Sotrovimab in 
Serum: COMET-ICE Intensive Lead-in Pharmacokinetics 
 
Note: Concentrations are displayed as mean ± standard deviation. 
Table 1 
Preliminary Sotrovimab Pharmacokinetic Parameters Following a 
Single 500 mg Intravenous Dose 
Parameter 
Dose 500 mg 
(N=9a) 
Cmax, µg/mL 
219 (45.5) 
Tmax, hour 
1.0 (1.0, 1.0) 
Clast, µg/mL 
24.1 (19.7) 
Tlast, day 
56.0 (56.0, 56.0) 
CD29, µg/mL 
37.2 (7.6) 
AUCD1-29, day*µg/mL 
1550 (10.1) 
AUClast, day*µg/mL 
2350 (9.64) 
%AUCexp, % 
39.1 (29.5) 
AUCinf, day*µg/mL 
TBDb 
CL (mL/day) 
TBDb 
Vz, L 
TBDb 
t1/2, day 
TBDb 
Abbreviations: AUCD1-29 = Area under the serum concentration-time curve, from Day 1 to Day 29; AUClast = area under 
the curve from the time of dosing to the time of the last measurable (positive) concentration; AUCinf = area under the 
serum concentration-time curve extrapolated to infinite time; %AUCexp = The extrapolated portion of AUCinf; CD29 = 
observed concentration on Day 29; Clast = observed concentration corresponding to Tlast; Cmax = maximum observed 
concentration; CL = clearance; t1/2 = terminal elimination half-life; Tmax = time to reach Cmax; TBD = to be determined; Vz 
= apparent volume of distribution during the elimination. 
Parameters are reported as mean (percent coefficient of variation [%CV]) except for Tmax, Tlast and t1/2, which are 
presented as median (Q1,Q3).   
a. 
N=9 for Cmax, Tmax, Clast, Tlast; CD29, N=8 for AUCD1-29, AUClast, %AUCexp.  
b. 
Final summary statistics for AUCinf, as well as CL, V, and t1/2 will be reported when sufficient data are 
available so that ≤20% of the AUCinf is extrapolated observation range for λz spans >2 half-lives. 

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2.2. 
Background 
A novel beta-coronavirus causing severe pneumonia was first reported in December 2019 
in Wuhan, China. Since that time, SARS-CoV-2 has spread throughout the world. As of 
04 MAY 2021, there have been approximately 153 million confirmed cases and 
>3.2 million deaths globally with approximately 32 million cases and 577,584 deaths in 
the United States (US). In Japan, 613,819 cases and 10,441 deaths have been reported as 
of 04 MAY 2021 [Johns Hopkins COVID Dashboard, 2021].  
Monoclonal antibodies directed against SARS-CoV-2 have the potential to be used for 
both the prevention and treatment of COVID-19 [Marovich, 2020]. Indeed, given 
developmental consideration [Kelley, 2020], mAbs could serve as an important bridge 
until vaccines are widely available. Specifically, neutralizing mAbs, given as early 
treatment in outpatients with mild to moderate COVID-19 disease could prevent need for 
hospitalization due to disease progression in patients at risk for complications such as 
respiratory compromise, respiratory failure, or other organ failure. Additionally, an 
efficacious neutralizing mAb given early in the disease course could ameliorate the 
severity and duration of COVID-19 and potentially reduce transmission. Given data 
demonstrating that viral loads are highest early in the course of disease [Wölfel, 2020; 
Zheng, 2020], the non-hospitalized patient population at high risk for disease progression 
may particularly benefit from early intervention with a mAb. 
There are limited specific treatment options for patients with COVID-19, particularly for 
the outpatient population where the mainstay of treatment is monitoring and supportive 
care. In the US, an Emergency Use Authorization (EUA) was granted on 21 NOV 2020 
for casirivimab and imdevimab (to be administered together), and on 09 FEB 2021 for 
bamlanivimab and etesevimab (to be administered together) for the treatment of mild to 
moderate COVID-19 in adults and pediatric patients (12 years of age and older and 
weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing who are 
at high risk for progressing to severe COVID-19 and/or hospitalization. Early reports 
from studies of mAbs in non-hospitalized patients with COVID-19 at high risk of 
progression to severe disease, as well as the recent EUAs for bamlanivimab/etesevimab 
and casirivimab/imdevimab, support the utility of mAbs in the treatment of COVID-19 in 
outpatients [Chen, 2021; Eli Lilly and Company, 2021; FDA, 2020; FDA, 2021].  
Given that these mAbs are currently indicated for IV administration, a mAb that can be 
administered via IM injection would be of particular benefit in the outpatient setting 
where there are significant logistical challenges to IV administration. For example, most 
clinics require a dedicated infusion center with appropriate infection prevention and 
control measures to administer these mAbs to patients with early SARS-CoV-2 infection, 
as well as targeted allocation of resources and personnel for the close monitoring that is 
required during and post-infusion. A mAb that can be administered via IM injection 
could be provided in a substantially greater number of outpatient clinics that are currently 
not equipped for administration and monitoring of IV infusions, as well as possibly in the 
home care setting. Administration by an IM route also enables the potential to treat 
patients at high risk for poor outcomes in geographic areas where medical infrastructure 
is weak and the capacity to administer IV infusion is inadequate, including rural and 
underdeveloped regions. 

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2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of sotrovimab may be found in the Investigator’s Brochure 
(IB). 
 

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2.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention: sotrovimab 
Infusion-related reactions (IRRs) including 
serious hypersensitivity reactions (HSR) 
While sotrovimab is a human Immunoglobulin G1 (IgG1) 
mAb, IRRs are a potential general risk associated with the 
mAb class of therapeutics. 
Participant selection: Participants will be excluded if 
they have a history of hypersensitivity to other mAbs 
or any of the excipients present in the investigational 
product. 
Monitoring:  
• 
Guidelines for monitoring relevant AEs 
encompassing hypersensitivity, angioedema 
and anaphylaxis as well as for the 
management of acute anaphylactic shock 
and minor allergic episodes will be in place at 
investigational sites. 
• 
Infusion time can be extended at the 
discretion of the Investigator or Sponsor 
based on local infusion-related symptoms or 
other safety findings. 
• 
Vital signs will be monitored approximately 
15 minutes into the infusion and at the end of 
infusion. Vital signs will also be monitored at 
30 minutes, 1 hour, and 2 hours in the post-
infusion period.  
• 
Infusion-related reactions are categorized as 
AESI. 
 
Mitigation:  
• 
General guidance on management of HSRs 
is provided in Section 8.4.7.1 and such 
reactions will be managed appropriately per 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
local guidelines/medical judgment. Pre-
medications will be permitted at the 
investigator’s discretion and will be 
appropriately documented. 
• 
Investigators will be instructed to discontinue 
IV infusions for participants who develop 
Grade 3 or higher 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 (Section 10.3.3).  
• 
If a participant experiences a Grade 2 IRR, 
investigators will be 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).  
• 
IV infusion 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. 
Injection Site Reaction (ISR) 
Sotrovimab will be administered via IM injection.  
A similar human IgG1 mAb specific to influenza A (VIR-
2482) has been studied in a recent Phase I trial. 
Intramuscular injection of this IgG1 mAb, including at 
similar volumes as planned for the current study, was 
well-tolerated with minimal injection site reactions [Sager, 
2020]. Specifically, dosing was well tolerated, with 6/100 
Injection site reactions will be monitored very closely 
for 1 hour after injection and on Day 2 and Day 3 for 
all participants. Monitoring will also be performed for 
systemic symptoms post-dosing (e.g., fever, chills, 
malaise).  

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
participants experiencing mild injection site reactions that 
generally resolved within 48 hours. Through 12 weeks 
post-dosing, the majority (124/126) of AEs were mild to 
moderate in nature, no SAEs were reported, and no 
participants discontinued due to an AE. 
Immunogenicity 
While sotrovimab is a human IgG1 mAb, the development 
of anti-drug antibodies (ADAs) that have the potential to 
impact safety and/or efficacy are a potential general risk 
associated with the mAb class of therapeutics. Drug-
neutralizing antibodies, a subset of ADAs, have the 
potential to bind the drug and render it ineffective. 
Monitoring: This study will include participant follow-
up for a period of 18 weeks to assess for the potential 
of immunogenicity (measurement of ADA and drug-
neutralization antibodies) as well as whether ADA and 
drug neutralizing antibodies are potentially causally 
associated with specific safety concerns. 
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 re-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 1-4 serotype 
infections is one of the most widely cited examples in 
which re-infection 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. 
Monitoring: This study will include participant follow-
up for a period of 18 weeks to assess for the potential 
of enhanced disease in the context of waning 
sotrovimab levels.  

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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 
endothelial, 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 (FI) 
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-FcR 
interactions, although usually highly beneficial due to 
their direct anti-viral 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]. 
Monitoring: 
• 
Additional monitoring in the event a participant 
develops signs or symptoms of cardiac 
complications (See Section 8.3.3.1). 
 

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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Sotrovimab shows potent binding as well as 
neutralization of pseudovirus and live virus in vitro, thus 
this risk is deemed to be low. 
Sotrovimab Clinical Experience: As of 31 MAR 2021, 
approximately 1350 participants have been randomized 
to either sotrovimab (500 mg IV 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) and 300 participants in a study that evaluated 
sotrovimab for the treatment of individuals hospitalized 
with COVID-19 (ACTIV-3-TICO). Sotrovimab 
administered by IV infusion is also being evaluated in the 
BLAZE-4 study, with enrollment concluding at 
approximately 200 participants in the arm comparing the 
combination of bamlanivimab with sotrovimab to 
placebo. As of 13 May 2021 approximately 
96 participants have been enrolled in COMET-PEAK. 
Further details regarding review of safety data from 
these trials are provided in Section 2.1.  
 
 

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2.3.2. 
Benefit Assessment 
Participation in this study will provide valuable scientific knowledge about sotrovimab in 
the Japanese population. Sotrovimab is being developed for the treatment of COVID-19.  
Interim analysis of data from 583 participants in COMET-ICE, a study evaluating 
sotrovimab for the treatment of non-hospitalized individuals with mild to moderate 
COVID-19, was reviewed on 10 MAR 2021. There was an 85% reduction in the rate of 
hospitalization or death in the sotrovimab arm versus the placebo arm (p=0.002), which 
was the primary endpoint. The IDMC recommended that the study halt enrollment on the 
basis of overwhelming efficacy [Vir Biotechnology, Inc., 2021]. 
Although studies are planned or underway to evaluate sotrovimab for COVID-19 
prophylaxis in immunocompromised individuals, no studies to assess direct benefit to 
healthy volunteers for prophylaxis have been completed; therefore, no direct benefit for 
healthy participants in this study is currently known. However, participants may benefit 
in the knowledge that they are contributing to the process of developing new therapies in 
an area of unmet need. Participants may also benefit from the thorough medical 
assessments they receive during the course of the study. 
Mitigation strategies, including physical examinations, laboratory evaluations, and 
electrocardiograms, as outlined in the SoA (Section 1.3), are included to limit the risk to 
participants. 
2.3.3. 
Overall Benefit: Risk Conclusion 
The overall benefit-risk assessment takes into account the potential benefit of sotrovimab 
treatment for COVID-19 in the Caucasian and Japanese populations.  
No clinical studies of sotrovimab have been completed to date. There is prior clinical 
experience with sotrovimab in the setting of the early treatment of COVID-19 (COMET-
ICE, COMET_PEAK, and BLAZE-4) and hospitalized treatment in ACTIV-3-TICO. In 
the COMET-ICE study, there have been no significant safety concerns identified at the 
IDMC reviews conducted to date. As of 17 MAR 2021, there have been no safety 
concerns identified in the BLAZE-4 study. In the ACTIV-3-TICO study, one case among 
360 participants who received sotrovimab experienced anaphylaxis during infusion of the 
drug, which resolved with treatment. As of 13 MAY 2021, safety data from 
approximately 96 participants who received 500 mg IV or IM sotrovimab in COMET-
PEAK has been reviewed and no new safety concerns have been identified. 
Sotrovimab has the potential to be an effective therapeutic in mild to moderately ill 
patients with COVID-19. This benefit has been demonstrated in the interim analysis of 
the COMET-ICE study, a study of participants with mild to moderate COVID-19 at high 
risk of disease progression [Vir Biotechnology, Inc., 2021]. Human-derived mAbs with 
similar Fc modifications as sotrovimab have a well-established safety profile [Gaudinski, 
2018]. Considering the measures taken to minimize risk to participants in this study, data 
supporting the safety of sotrovimab, the limited disease-directed therapeutic options for 
COVID-19, and the existing knowledge gap in healthy participants in general and 

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ethnically Japanese participants in particular, the overall benefit-risk assessment of this 
study is considered favorable based on the available data. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
Pharmacokinetics (Part 1) 
To assess the PK of sotrovimab 
administered via IV infusion in healthy 
Japanese and Caucasian participants 
through Day 29 
PK parameters through Day 29: maximum 
observed serum concentration (Cmax), area under 
the serum-concentration time curve from Day 1 to 
Day 29 (AUCD1-29), time to Cmax (Tmax), and 
concentration at Day 29 (CD29) of sotrovimab, as 
data permits. 
Pharmacokinetics (Part 2) 
To assess the PK of sotrovimab 
administered via IM injections in healthy 
Japanese and Caucasian participants 
through Day 29 
PK parameters through Day 29: Cmax, AUCD1-29, 
Tmax, and CD29 of sotrovimab, as data permits. 
Safety (Part 1) 
To evaluate the safety and tolerability profile 
of IV sotrovimab in healthy Japanese and 
Caucasian participants through Day 29 
• Occurrence of adverse events (AEs) through 
Day 29 
• Occurrence of serious adverse events (SAEs) 
through Day 29 
• Occurrence of adverse events of special interest 
(AESIs) through Day 29 
• Occurrence of clinically significant abnormalities 
on 12-lead electrocardiogram (ECG) readings 
through Day 29 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Day 29 
• Occurrence of clinically significant laboratory 
abnormalities through Day 29 
Safety (Part 2) 
To evaluate the safety and tolerability profile 
of IM sotrovimab in healthy Japanese and 
Caucasian participants through Day 29 
• Occurrence of AEs through Day 29 
• Occurrence of SAEs through Day 29 
• Occurrence of AESIs through Day 29 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Day 29 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 

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Objectives 
Endpoints 
Day 29 
• Occurrence of clinically significant laboratory 
abnormalities through Day 29 
Secondary 
Pharmacokinetics (Part 1) 
To assess the PK of sotrovimab 
administered via IV infusion in healthy 
Japanese and Caucasian participants 
through Week 18 
PK parameters through Week 18: Cmax, area 
under the serum concentration-time curve 
extrapolated to infinite time (AUCinf), area under 
the curve from the time of dosing to the time of 
the last measurable (positive) concentration 
(AUClast), Tmax, time of the last quantifiable 
concentration (Tlast), and the terminal elimination 
half-life (t1/2) of sotrovimab, as data permits. 
Pharmacokinetics (Part 2) 
To assess the PK of sotrovimab 
administered via IM injections in healthy 
Japanese and Caucasian participants 
through Week 18 
PK parameters through Week 18: Cmax, AUCinf, 
AUClast, Tmax, Tlast, and t1/2, of sotrovimab, as data 
permits. 
Safety (Part 1) 
To evaluate the safety and tolerability profile 
of IV sotrovimab in healthy Japanese and 
Caucasian participants through Week 18 
• Occurrence of AEs through Week 18 
• Occurrence of SAEs through Week 18 
• Occurrence of AESIs through Week 18 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Week 18 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Week 18 
• Occurrence of clinically significant laboratory 
abnormalities through Week 18 
Safety (Part 2) 
To evaluate the safety and tolerability profile 
of IM sotrovimab in healthy Japanese and 
Caucasian participants through Week 18 
• Occurrence of AEs through Week 18 
• Occurrence of SAEs through Week 18 
• Occurrence of AESIs through Week 18 
• Occurrence of clinically significant abnormalities 
on 12-lead ECG readings through Week 18 
• Occurrence of clinically significant changes in 
vital signs compared to Baselinea through 
Week 18 
• Occurrence of clinically significant laboratory 
abnormalities through Week 18 

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Objectives 
Endpoints 
Exploratory 
Immunogenicity (Part 1) 
To assess the immunogenicity of IV 
sotrovimab in healthy Japanese and 
Caucasian participants 
Incidence and titers (if applicable) of serum ADAs 
and drug-neutralizing antibodies to sotrovimab 
through Week 18. 
Immunogenicity (Part 2) 
To assess the immunogenicity of IM 
sotrovimab in healthy Japanese and 
Caucasian participants 
Incidence and titers (if applicable) of serum ADAs 
and drug-neutralizing antibodies to sotrovimab 
through Week 18. 
a 
Baseline is defined as assessments performed following admission to unit on Day -1 and before dosing on Day 1. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study is a randomized, multi-center, placebo-controlled, single-blind, single-dose, 
parallel group Phase I trial to assess the PK of IV and IM sotrovimab in healthy Japanese 
and Caucasian participants.  
This study will occur in two parts (Part 1 and Part 2). For both parts, screening 
assessments will be performed within 28 days before administration of study 
intervention. Administration of study intervention will occur on Day 1. Participants will 
remain in the clinical research unit from admission on Day -1 through the completion of 
all Day 3 study procedures. Upon completion of this in-unit observation period, 
participants may be discharged as deemed clinically appropriate by the investigator. 
Participants will return for outpatient visits throughout the 18 weeks following 
administration of study intervention, as shown in the SoA (Section 1.3). Participants can 
be screened up to 28 days before dosing, leading to a maximum study duration of 
22 weeks. 
Part 1:  
Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive 
a single, 500 mg IV infusion of sotrovimab or volume-matched saline placebo. A 
maximum of 24 participants will be randomized to Part 1 to achieve 20 evaluable 
participants in Part 1. The Part 1 cohort will enroll approximately 8 Japanese and 
8 Caucasian participants to the IV sotrovimab arm and 2 Japanese and 2 Caucasian 
participants to the placebo arm. Eligible participants will be treated with a single IV dose 
of sotrovimab or placebo on Day 1. Participants will be blinded to study intervention. 
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Part 2:  
Part 2 will begin after enrollment for Part 1 is completed. Healthy Japanese and 
Caucasian participants will be randomized in a 4:1 ratio to receive a single 500 mg IM 
dose of sotrovimab (administered as two 4 mL injections, one in each dorsogluteal 
muscle) or volume-matched saline placebo. A maximum of 24 participants will be 
randomized to Part 2 to achieve 20 evaluable participants in Part 2. The Part 2 cohort will 
enroll approximately 8 Japanese and 8 Caucasian participants to the IM sotrovimab arm 
and 2 Japanese and 2 Caucasian participants to the placebo arm. Eligible participants will 
be treated with a single IM dose of sotrovimab or placebo on Day 1. Participants will be 
blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IM 
sotrovimab will be evaluated.  
Note: “Evaluable” is defined as a participant who has been randomized, has been 
exposed to study intervention and who has at least 1 non-missing PK assessment 
(including non-quantifiable samples) – i.e., PK sample collected and analyzed. 
Note: “Enrolled” means a participant'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.  
4.2. 
Scientific Rationale for Study Design 
This study includes a placebo arm to allow for a valid evaluation of AEs attributable to 
sotrovimab versus those independent of sotrovimab (such as regression towards the 
mean). A single-blind design is a common methodology for randomized, controlled PK 
bridging studies to minimize bias arising from study participants based on their 
knowledge of receipt of study drug. To date, SARS-CoV-2-directed mAbs as a class have 
had favorable safety profiles [Regeneron Pharmaceuticals, Inc., 2020; Eli Lilly and 
Company, 2020]. Therefore, the marginal benefit when comparing single-blind to 
double-blind design is minimal; however, single-blinding will minimize bias originating 
from participants that may occur during study assessments, including during evaluation 
of AEs and disease-related safety outcomes.  
Body weight is the principal determinant of mAb exposure. Body weight is expected to 
be the primary determinant of differences in the drug PK; therefore, all analyses will be 
adjusted for body weight. A difference in the average body weight of Japanese and 
Caucasian participants necessitates a direct comparison of the PK and safety profiles in 
these two populations. Ethnically Japanese patients with mild-to-moderate COVID-19 
were not represented in the safety and efficacy studies included in COMET-ICE. 
Therefore, this study represents the first evaluation of sotrovimab in the Japanese 
population. Additionally, this study is the first use of sotrovimab in healthy volunteers; 
therefore, data previously obtained for Caucasian patients with COVID-19 in COMET-
ICE cannot be used for direct comparison to healthy Japanese participants.  
The number of participants randomized to each arm will provide acceptable precision for 
PK estimation. Due to the extended half-life of sotrovimab, 18 weeks is the minimum 

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duration predicted to have the extrapolated portion of the AUC being less than 20% 
(Figure 2). 
Figure 2 
Concentration and Percent Area Under the Curve (AUC) 
Extrapolated vs Time 
 
4.3. 
Justification for Dose 
The 500 mg IV dose of sotrovimab to be evaluated in this study was selected based on 
extensive nonclinical data and expected human PK extrapolated from cynomolgus 
monkeys. This 500 mg IV dose is currently being evaluated in ongoing clinical trials 
COMET-ICE, ACTIV-3-TICO, and BLAZE-4, with approximately 1550 participants 
randomized to either sotrovimab (500 mg dose) or placebo to date.  
A 500 mg IM dose was selected for Part 2 of this study based on in vitro neutralization 
data, in vitro resistance data, and simulated IM PK based on preliminary IV PK from the 
500 mg dose that is being evaluated in ongoing clinical studies (COMET-ICE, ACTIV-3-
TICO, BLAZE-4, COMET-PEAK, and COMET-TAIL). The 500 mg IV and 500 mg IM 
doses are currently being evaluated in ongoing clinical trial COMET-PEAK, with 
approximately 96 participants receiving 500 mg IV or 500 mg IM sotrovimab as of 
13 MAY 2021, and these doses will also be evaluated in COMET-TAIL.  
Sotrovimab neutralizes SARS-CoV-2 live virus with an average 90% effective 
concentration (EC90) value of 186.3 ng/mL (range: 125.8–329.5 ng/mL) (PC-7831-0105). 

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In resistance analyses, no viral breakthrough was observed through 10 passages at fixed 
concentrations of antibody, indicating the potential for sotrovimab to have a high barrier 
to resistance (PC-7831-0109). Using an increasing concentration selection method to 
force resistance emergence, E340A was identified as a monoclonal antibody-resistant 
mutant (MARM) conferring a >100-fold reduction in susceptibility to sotrovimab. 
Notably, E340 is 99.9% conserved among available SARS-CoV-2 sequences. Due to the 
binary nature of the resistance selection results, a specific inhibitory quotient was not 
informed by the resistance profiling. 
Based on preliminary IV PK data from the Lead-in phase of an ongoing clinical study 
evaluating sotrovimab in the early treatment of COVID-19 (COMET-
ICE; NCT04545060), the mean Day 29 serum concentration of sotrovimab following a 
single 500 mg IV dose is 37.2 µg/mL (N=9). Based on the PK data available to date, 
>20% of the AUC is being extrapolated so final CL, V, AUC and t1/2 have not been 
determined; however, a preliminary estimate of the median half-life of sotrovimab is 
approximately 47 days. 
A 500 mg IM dose was selected to ensure that sotrovimab concentrations in lung are 
maintained at or above levels anticipated to be neutralizing for the duration of the 
treatment window. Based on the EC90 (0.33 g/mL) from the highest end of the EC90 
range (PC-7831-0105), and accounting for the lung:serum ratio for immunoglobin G 
(IgG; assumed conservative value of 0.25; reported range 0.25 to 0.68 for whole lung and 
interstitial fluid, respectively [Baxter, 1994; Covell, 1986; Datta-Mannan, 2019; Lobo, 
2004]); and assuming 70% bioavailability following IM administration, an IM dose of 
500 mg is expected to maintain serum levels at or above 10x lung tissue adjusted EC90 
through the Day 29 primary endpoint. 
Prior clinical experience with a 500 mg IV dose of sotrovimab has been gained in the 
setting of the early treatment of COVID-19 (COMET-ICE, BLAZE-4, and COMET 
PEAK) and hospitalized treatment in ACTIV-3-TICO. In the COMET-ICE study, there 
have been no significant safety concerns identified at the IDMC reviews conducted to 
date. Furthermore, an interim analysis of data from 583 high-risk patients demonstrated 
an 85% (p=0.002) reduction in hospitalization or death in patients receiving sotrovimab 
compared to placebo [Vir Biotechnology, Inc., 2021]. In ACTIV-3-TICO, one case of 
anaphylaxis was reported during infusion of sotrovimab which resolved with treatment. 
In the BLAZE-4 study, there have been no safety concerns identified as of 
17 MAR 2021. A Joint Safety Review Team (JSRT) met on 13 MAY 2021 to review data 
from participants enrolled in COMET-PEAK to date and no emerging safety issues were 
detected; the JSRT recommended a reduction in monitoring time for this study. 
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit for the last participant in the 
study. 
A participant is considered to have completed the study if he/she has completed all 
phases of the respective part of the study to which he/she was enrolled (Part 1 or Part 2) 
through Week 18.  

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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. Participants who do not meet 
screening criteria may be rescreened, as described in Section 5.4.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Participant must be 18 (or the legal age of consent in the jurisdiction in which the 
study is taking place) to 65 years of age inclusive, at the time of signing the informed 
consent. Additionally, participants 55 years or older, at the time of signing informed 
consent will be permitted only if they have received all doses in a SARS-CoV-2 
vaccine series. 
Type of Participant and Disease Characteristics 
2. Participants who are healthy as determined by medical evaluation including medical 
history, physical examination, laboratory tests, and cardiac monitoring.  
3. Participants must be negative for COVID-19, determined by two consecutive 
negative results by any validated SARS-CoV-2 molecular test (e.g. reverse 
transcriptase polymerase chain reaction [RT-PCR] on any respiratory type) separated 
by >24 hours prior to unit admission. The first test may be carried out at any time 
during Screening, the second test will be at Day -1. 
4. For Japanese participants, participant must meet all of the following: Japanese 
ancestry, defined as having been born in Japan, being descendants of four ethnic 
Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport 
or identity papers, and being able to speak Japanese. Participants should have lived 
outside Japan for fewer than 10 years at the time of Screening.  
5. For Caucasian participants, participant must meet all of the following: Caucasian 
ancestry, defined as Caucasian descent as evidenced by appearance and verbal 
confirmation of familial heritage (a participant has 2 Caucasian parents and 
4 Caucasian grandparents). 
Weight 
6. Body weight considering body mass index (BMI) within the range of 
18 to 29.9 kg/m2 (inclusive). 
Sex and Contraceptive/Barrier Requirements 
7. No gender restrictions. 
8. Female participants must meet and agree to abide by the following contraceptive 
criteria. Contraception use by women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 

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A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
a. Is a woman of non-childbearing potential (WONCBP) as defined in 
Section 10.4. 
OR 
b. Is a woman of child-bearing potential (WOCBP) and 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 24 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. 
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum 
as required by local regulations) at Screening and on Day -1, before the first dose 
of study intervention. See Section 8.3.5 Pregnancy Testing. 
− 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. 
• Additional requirements for pregnancy testing during and after study intervention 
are located in Section 8.3.5. 
• The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an 
early undetected pregnancy. 
Informed Consent 
9. Capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol. 
 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly altering 
the absorption, metabolism, or elimination of drugs; constituting a risk when taking 
the study intervention or interfering with the interpretation of data. 
2. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal 
cell or squamous epithelial carcinomas of the skin that have been resected with no 
evidence of metastatic disease for 3 years. 

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3. Breast cancer within the past 10 years. 
4. Abnormal blood pressure as defined as greater than 140 mm/Hg systolic, greater than 
90 mm/Hg diastolic, or less than 90 mm/Hg systolic at Screening. Blood pressure at 
Screening is the average of 3 blood pressure readings taken using the methods 
described in Section 8.3.2. 
5. Significant allergies to humanized monoclonal antibodies.  
6. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions (including, but 
not limited to, erythema multiforme major, linear immunoglobulin A (IgA) 
dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis). 
7. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).  
8. Total bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if total 
bilirubin is fractionated and direct bilirubin <35%).  
9. Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones). 
Prior/Concomitant Therapy 
10. Use of any prescription medications within the 28 days prior to dosing or 
concomitantly, unless permitted in Section 6.8 or approved by the Investigator in 
conjunction with the GSK medical monitor.  
11. Treatment with biologic agents (such as monoclonal antibodies including marketed 
drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing. 
12. Receipt of convalescent plasma from a recovered COVID-19 patient or anti-SARS-
CoV-2 mAb within the last 3 months. 
13. Receipt of any vaccine within 48 hours prior to enrollment. Vaccination will not be 
allowed for 90 days after dosing. 
14. Has received a SARS-CoV-2 vaccine but has not completed all doses in the series 
more than 28 days prior to Screening. SARS-CoV-2 vaccinations will not be allowed 
for 90 days after dosing. 
Prior/Concurrent Clinical Study Experience 
15. Participation in the study would result in loss of blood or blood products in excess of 
500 mL within a 56 day period. 
16. Exposure to more than 4 new chemical entities (e.g., investigational 
pharmaceuticals) within 12 months prior to the first dosing day. 
17. Current enrollment or past participation in this clinical study. 
18. Enrollment in any investigational vaccine study within the last 180 days or any other 
investigational drug study within 30 days prior to Day 1 or within 5 half-lives of the 
investigational compound, whichever is longer. 

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Diagnostic assessments 
19. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months 
prior to first dose of study intervention. 
20. Positive hepatitis C antibody test result at Screening or within 3 months prior to first 
dose of study intervention. NOTE: Participants with positive hepatitis C antibody 
due to prior resolved disease can be enrolled, only if a confirmatory negative 
hepatitis C ribonucleic acid (RNA) test is obtained. 
21. Positive hepatitis C RNA test result at Screening or within 3 months prior to first 
dose of study intervention. NOTE: Test is optional and participants with negative 
hepatitis C antibody test are not required to also undergo hepatitis C RNA testing. 
22. Positive pre-study drug/alcohol screen. 
23. Positive HIV antibody test. 
Other Exclusions 
24. History of regular alcohol consumption within 6 months prior to the study defined 
as:  
• An average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a 
half pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of 
spirits.  
25. Regular use of known drugs of abuse.  
26. Sensitivity to any of the study interventions, or components thereof, or other allergy 
that, in the opinion of the investigator or medical monitor, contraindicates 
participation in the study. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants should arrive fasted for the Screening Visit only and will be allowed to eat 
during the Screening Visit after blood draw for clinical chemistry has been completed. 
5.3.2. 
Caffeine, Alcohol, and Recreational Drug Use 
• Participants will abstain from ingesting caffeine- or xanthine-containing products 
(e.g., coffee, tea, cola drinks and chocolate) for 6 hours prior to the visits that 
include ECG assessments, and during those visits. 
• Participants will abstain from alcohol for 24 hours prior to each visit to the clinic 
and during the in-patient period. 
• Participants must have a negative drug test at screening and admission to the 
clinical unit and must abstain from recreational drug use from screening until after 
the final follow-up visit. 

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5.3.3. 
Activity 
Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests.  
5.3.4. 
Other Restrictions 
Participants cannot donate blood or blood products for 24 weeks after administration of 
study intervention. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. 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. 
If a participant fails any of the laboratory exclusion criteria, the test may be repeated once 
within the Screening period. If the participant fails the laboratory criteria for a second 
time, they will be considered a screen failure. Retesting within screening window of any 
blood sample withdrawn due to sample handling problems, breakage or sample integrity 
is not considered a rescreening. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened a maximum of 2 times. Rescreened participants should be assigned a 
new participant number for every screening/rescreening event. 
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 
Details of study interventions for Part 1 are provided Table 2 in and details for Part 2 are 
provided in Table 3. An ingredient in the sotrovimab formulation that may cause 
hypersensitivity is the surfactant polysorbate-80. The sotrovimab formulation also 
contains sucrose, histidine and methionine.  
For IM injections, the study intervention will be given as two 4 mL injections, one in 
each dorsogluteal muscle. 

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Table 2 
Part 1 Study Interventions 
Arm Name 
IV Sotrovimab 
IV Placebo 
Intervention Name 
VIR-7831 
Placebo 
Type  
Biologic 
Placebo to Biologic 
Dose Formulation 
Solution in single use vial 
(62.5 mg/mL) 
Sterile 0.9% (w/v) sodium chloride 
solution 
Unit Dose Strength(s)  500 mg/vial (500 mg/8 mL) 
Not applicable 
Dosage Level(s) 
500 mg once diluted in saline 
to 5 mg/mL to 10 mg/mL.  
Volume range: 50 mL 
to 100 mL  
Given in equal volume to VIR-7831 IV 
Route of 
Administration 
IV infusion 
IV infusion 
Duration of infusion 
30 minutes 
30 minutes 
Use 
Experimental 
Placebo-comparator 
IMP and NIMP 
IMP 
IMP 
Sourcing 
 
Sotrovimab will be provided 
centrally by the 
sponsor/designee 
Saline for placebo will be provided by 
the site. 
Packaging and 
Labeling 
 
Sotrovimab study intervention 
will be provided in a single-
use vial and labeled as 
required per country 
requirement. 
Site to provide commercially available 
saline. 
Current/Former 
Name(s) or Alias(es) 
VIR-7831, GSK4182136, 
sotrovimab 
Not applicable 
Table 3 
Part 2 Study Interventions 
Arm Name 
IM Sotrovimab 
IM Placebo 
Intervention Name 
VIR-7831 
Placebo 
Type  
Biologic 
Placebo to Biologic 

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Arm Name 
IM Sotrovimab 
IM Placebo 
Dose Formulation 
Solution in single use vial 
(62.5 mg/mL) 
Sterile 0.9% (w/v) sodium 
chloride solution 
Unit Dose Strength(s)  
500 mg/vial (500 mg/8 mL) 
Not applicable 
Dosage Level(s) 
8 mL=500 mg once 
8 mL=500 mg once 
Route of Administration 
IM injection 
IM injection 
Duration of infusion 
Not applicable 
Not applicable 
Use 
Experimental 
Placebo-comparator 
IMP and NIMP 
IMP 
IMP 
Sourcing 
 
Sotrovimab will be provided 
centrally by the 
sponsor/designee 
Saline for placebo will be 
provided by the site. 
Packaging and Labelling 
 
Sotrovimab study 
intervention will be provided 
in a single-use vial and 
labeled as required per 
country requirement. 
Site to provide commercially 
available saline. 
Current/Former Name(s) or 
Alias(es) 
VIR-7831, GSK4182136, 
sotrovimab 
Not applicable 
 
6.2. 
Preparation/Handling/Storage/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). 

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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 
Sponsor 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. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a single-blind study. Only the participant will be blinded to the treatment. The 
investigator or treating physician, site staff, GSK, and the Sponsor will be unblinded. 
The investigator should assure and maintain the blindness of information relating to the 
assigned investigational product to participants. The investigator or treating physician, 
site staff, GSK, and the Sponsor must not share any potentially unblinding investigational 
product information with the participants during the study conduct period, until formal 
unblinding has taken place. 
All participants will be centrally randomized using an Interactive Web Response System 
(IWRS). Before the study is initiated, the log in information and directions for the IWRS 
will be provided to each site. 
In Part 1, participants will be randomized in a 4:1 ratio to receive an IV infusion of 
sotrovimab or volume-matched saline placebo. In Part 2, participants will be randomized 
in a 4:1 ratio to receive sotrovimab or volume-matched saline placebo via IM injection. 
Participants will be blinded to study intervention; however, site staff will not be blinded. 
Monitors and in the event of a Quality Assurance audit, the auditor(s) will be allowed 
access to study intervention records at the site(s) to verify that randomization/dispensing 
has been done accurately. 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded. 
GlaxoSmithKline’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may 
unblind the intervention assignment for any participant with an SAE. If the SAE requires 
that an expedited regulatory report be sent to one or more regulatory agencies, a copy of 
the report, identifying the participant’s intervention assignment, may be sent to 
investigators in accordance with local regulations and/or GSK policy. 

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6.4. 
Study Intervention Compliance 
Participants will be dosed at the site and they will receive study intervention (sotrovimab 
or volume-matched saline placebo) directly from the investigator or designee, under 
medical supervision. The date and start and stop times of the IV dose (Part 1) and the date 
and administration time of each IM injection (Part 2) will be recorded in the source 
documents. The dose of study intervention and study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention.   
6.5. 
Dose Modification 
Dose modifications are not applicable for this study. See Section 7.1 for instructions to 
discontinue study treatment for safety reasons. 
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.  
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 AE/SAE and laboratory abnormalities. 
3. Document the quantity of the excess dose as well as the duration of the overdosing in 
the case report form (CRF). 
6.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) or other specific categories of 
interest that the participant is receiving at the time of enrollment or receives during the 
study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 

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Receipt of any vaccine is not permitted within 90 days after dosing. Receipt of any 
investigational (not authorized or approved) SARS-CoV-2 vaccine is not permitted 
during the study. Receipt of any authorized or approved SARS-CoV-2 vaccine is 
permitted following 90 days post-dosing. Participants should consult with the primary 
investigator and their primary care physician on local guidelines for vaccine 
administration and guidance on the risks associated with administration of a SARS-CoV-
2 vaccine while on study. 
Participants must abstain from taking prescription or non-prescription drugs for 28 days 
before the start of study intervention until completion of the Week 18 visit, unless, in the 
opinion of the investigator in consultation with the Medical Monitor, the medication will 
not interfere with the study. Medications that could potentially affect the renal system 
should be avoided, e.g., NSAIDs (non-steroidal anti-inflammatory drugs).  
Over the counter medications for nutritional support such as vitamins, minerals, amino 
acids, and herbal or botanical supplements are permitted for use at any time during the 
study. Paracetamol/acetaminophen, at doses of 2 grams/day, is permitted for use any 
time during the study. Other concomitant medication may be considered on a case-by-
case basis by the investigator in consultation with the Medical Monitor if required.   
All prior and concomitant medication should be captured in the eCRF. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue 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, infusion-related reactions including severe allergic or HSRs or severe 
cytokine release syndrome). 
If study intervention is permanently discontinued, the participant will remain in the study 
to be evaluated for follow-up assessments. Post-dose monitoring, assessments and 
procedures, per the SoA (Section 1.3), should be completed as planned. 
7.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping, and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. As this is a single-dose study, 
liver chemistry stopping criteria for a single participant are not applicable; however, 
further enrollment in this study may be stopped if liver chemistry tests during follow-up 
visits indicate abnormal liver function without an identifiable underlying etiology. 
Refer to Section 10.5 for required Liver Safety Actions and Follow up Assessments. 
ALT 3 times the ULN needs to reported within 24 hours. If it is a possible Hy’s Law 
case, report as an SAE. A possible Hy’s Law case is defined as ALT 3xULN and total 

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bilirubin 2xULN (>35% direct) or INR>1.5 (INR value not applicable to participants on 
anticoagulants). 
7.1.2. 
Temporary Discontinuation 
For IV administration, if a participant experiences a Grade 2 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). If a participant experiences a Grade 1 IRR the infusion can continue with close 
follow-up at the Investigator’s discretion. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, or compliance reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, if possible, an early discontinuation 
visit (ED) should be conducted, as shown in the SoA (Section 1.3). See SoA 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 both the study intervention and from the study at that time. 
• If the participant withdraws consent for disclosure of future information, the 
sponsor/designee may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• If participants permanently discontinue the study before Day 29, additional 
participants may be enrolled as replacements and assigned to the same cohort and 
treatment at the discretion of the Sponsor or designee in consultation with the 
investigator. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 

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3 telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are described in 
Section 10.1.9. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). 
Whenever vital signs, 12-lead ECGs, and blood draws are scheduled for the same 
nominal time, the assessments should occur in the following order: vital signs, 12-
lead ECG, blood draws. The timing of the assessments should allow the blood 
draw to occur at the exact nominal time. The actual time of assessment or 
procedure must be reported in the eCRF.  
• Participants will remain in the clinical research unit from admission on Day -1 
through the completion of all Day 3 study procedures. Upon completion of this in-
unit observation period, participants may be discharged as deemed clinically 
appropriate by the investigator. Participants will return for outpatient visits 
throughout the 18 weeks following administration of study intervention, as shown 
in the SoA (Section 1.3). 
• Protocol waivers or exemptions are not allowed.  
• Immediate safety concerns should be discussed with the medical monitor 
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 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). 
• The maximum amount of blood collected from each participant over the duration 
of the study, including any extra assessments that may be required, will not 
exceed 500 mL. Typical blood volumes expected during the usual course of study 
participation will be approximately 150 mL. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 

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8.1. 
Screening Period 
Informed consent must be obtained before conducting any study procedures. Screening 
will be performed no more than 28 days prior to randomization and include the 
assessments outlined in the SoA (Section 1.3). 
8.1.1. 
Medical History 
Relevant medical history within the last three years, as determined by the Investigator, 
should be reported. Details regarding history of medication, drug, alcohol, and tobacco 
use will be reported. Details regarding illnesses (including COVID-19) and allergies, 
date(s) of onset, and whether condition(s) is currently ongoing will be collected for all 
participants and should be updated prior to dosing as indicated in the SoA (Section 1.3). 
8.1.2. 
SARS-CoV-2 Testing 
Participants will be tested for SARS-CoV-2 as outlined in the SoA (Section 1.3). The 
following criteria must be met for a participant to be included in this study: 
• Two consecutive negative results by any validated SARS-CoV-2 molecular tests 
(e.g., RT-PCR on any respiratory type) separated by >24 hours. The first test may 
be carried out at any time during Screening, the second test will be at Day -1.   
8.2. 
Efficacy Assessments 
Not applicable. 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 
Physical examinations will be conducted as described in the SoA (Section 1.3). 
• A full physical examination will include, at a minimum, assessments of the Skin, 
CV, Respiratory, Gastrointestinal and Neurological systems. Height and weight 
will also be measured and recorded. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
8.3.2. 
Vital Signs 
• Temperature (oral preferred), pulse rate, respiratory rate, SpO2 and blood pressure 
will be assessed. 
• Blood pressure and pulse measurements will be assessed semi-supine or sitting with a 
completely automated device. Manual techniques will be used only if an automated 
device is not available. 

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• 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 (the first heart rate reading) 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. 
Part 1:  
Day 1: Vital signs will be monitored within 1 hour prior to the infusion. Vital signs will 
be monitored at approximately 15 minutes into the infusion and at the end of infusion. 
Vital signs will also be monitored at approximately 30 minutes, 1 hour, and 2 hours after 
the end of infusion.  
Vital signs on study visit days other than Day 1 will be collected once at any time of the 
day, as indicated in the SoA (Section 1.3). 
Part 2: 
Day 1: Vital signs will be monitored within 1 hour prior to IM injections. Vital signs will 
be monitored immediately after injections and at approximately 30 minutes, 1 hour, and 
2 hours after injection.  
Vital signs on study visit days other than Day 1 will be collected once at any time of the 
day, as indicated in the SoA (Section 1.3). 
8.3.3. 
Electrocardiograms 
ECGs will be obtained as described in the SoA (see Section 1.3) using an ECG machine 
that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT 
(QTc) intervals.  
Electrocardiograms will be performed locally. Digital ECG waveforms will be archived 
centrally. Fridericia’s correction formula will be used to determine the QTc. 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 subsequent ECG tests. 
For triplicate 12-lead ECGs, each of the 3 individual ECG tracings should be obtained as 
closely as possible in succession, but no more than 2 minutes apart. The full set of 
triplicates should be completed over a brief (e.g., 5 to 10 minutes) recording period. 
If an ECG abnormality is detected post-Baseline, ECGs should be performed in triplicate.  

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8.3.3.1. 
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, for 
participants who develop new or worsening cardiac symptoms, signs, or ECG findings 
suggestive of an acute myocardial infarction or cardiac failure, cardiology consultation 
will be recommended to guide further cardiac work up and assessment of potential 
cardiac events. Event details should be captured in the appropriate electronic data capture 
(EDC) forms. 
8.3.4. 
Clinical Safety Laboratory Assessments 
• See Section 10.2 for the list of clinical laboratory tests to be performed and refer 
to the SoA (Section 1.3) for the timing and frequency. Clinical laboratory tests 
will be performed by local laboratories. 
• 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.  
• All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 24 weeks after the last dose of study 
intervention should be repeated until the values return to normal or Baseline or 
are no longer considered significantly abnormal by the investigator or medical 
monitor.  
o If any values do not return to normal/Baseline within a period of time 
judged reasonable by the investigator, the etiology should be identified 
and the sponsor/designee notified. 
• All protocol-required laboratory tests, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA (Section 1.3). 
• 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 or dose 
modification), then the results must be recorded. 
8.3.5. 
Pregnancy Testing 
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at Screening, on Day -1, and at Week 18 or the Early Withdrawal Visit. 
• Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the 
absence of pregnancy at any time during the participant’s participation in the 
study. 

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8.3.6. 
Local Injection Site Tolerability 
For IM injections in Part 2 of the study, a local injection site tolerability assessment will 
be performed per the Schedule of Activities (Section 1.3). Injection sites should be 
monitored for any adverse events. Refer to Section 8.4.2 for assessment of AE severity. 
A local injection site tolerability assessment will be performed approximately 1 hour after 
injection and on Day 2 and Day 3 for all participants. Any ISRs will need to be followed 
by the principal investigator (PI) for resolution.  
At the discretion of the investigator, unscheduled visits are permitted as needed for 
follow up of any unresolved local injection site tolerability symptoms. Management 
guidelines for these symptoms are provided in Section 10.6. 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
NOTE:GSK is acting on behalf of the Sponsor, Vir, for the purposes of global safety 
reporting for this study. 
The definitions of AEs or 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 legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up all AEs considered related to the study intervention or the study, or that 
caused the participant to discontinue the study (see Section 7).  
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. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All SAEs and AEs will be collected from the administration of study intervention 
until Week 18 (EOS) at the time points specified in the SoA (Section 1.3). However, 
any SAEs assessed as related to study participation (e.g., study intervention, protocol-
mandated procedures, invasive tests, or change in existing therapy) or related to a 
GSK product will be recorded from the time a participant consents to participate in 
the study. 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as Medical History/Current Medical 
Conditions not as AEs. 

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• All SAEs will be recorded and reported to GSK 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 GSK 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 GSK. 
8.4.2. 
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 (refer 
to Section 10.3.3). 
8.4.3. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.4.4. 
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 non-serious AEs of special 
interest (as defined in Section 8.4.7), will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up (as defined in 
Section 7.3). Further information on follow-up procedures is given in Section 10.3. 
8.4.5. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to GSK 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.  
• GSK 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. GSK will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
• An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from GSK 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 (SUSAR) according to local regulatory requirements and GSK policy and 
forwarded to investigators as necessary. 

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8.4.6. 
Pregnancy 
• Details of all pregnancies in female participants will be collected after the start of 
study intervention and until Week 18 or the EW Visit. 
• 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 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 
neonate/child for 8 weeks after the birth and the information will be forwarded to the 
GSK. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the GSK as described in 
Section 8.4.5. 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. 
8.4.7. 
Adverse Events of Special Interest  
Adverse events of special interest are defined in the study protocol as relevant known 
toxicities of other therapeutic mAbs or as a result of signals observed from previous 
studies in the nonclinical programs of sotrovimab that will be monitored by the sponsor 
or designee either during or at the end of the study (through Week 18). These will be 
updated during the course of the study based on accumulating safety data. 
AESI include: 
• Infusion-related reactions including HSRs; reactions on same day as infusion 
• Injection site reactions 
• Immunogenicity related adverse drug reactions 
• Adverse events potentially related to antibody-dependent enhancement of disease 
8.4.7.1. 
Infusion-Related Reactions and Serious Hypersensitivity 
Guidelines for monitoring relevant AEs encompassing hypersensitivity, angioedema and 
anaphylaxis as well as for the management of acute anaphylactic shock and minor 
allergic episodes will be in place at investigational sites. Investigators will be provided 
with general guidance on management of serious HSRs and such reactions will be 

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managed appropriately per local guidelines/medical judgment. Pre-medications will be 
permitted at the investigator’s discretion and will be appropriately documented. 
8.4.7.2. 
Injection Site Reactions  
Study participants should be monitored after administration of study intervention for 
signs or symptoms of any injection site reactions as described in the SoA (Section 1.3). 
Any events observed or reported should be noted utilizing the DAIDS criteria as 
described in Section 10.3.3. 
8.4.7.3. 
Immunogenicity 
Therapeutic proteins, including mAbs, have the potential to induce an unwanted immune 
response (immunogenicity) in humans. This reaction leads to production of ADAs which 
may inactivate the therapeutic effects of the treatment and, in rare cases, induce AEs. 
This study will include participant follow-up for a period of 18 weeks to assess for the 
development of ADA and drug-neutralizing antibodies and potential impacts on safety, 
PK, and/or efficacy. 
8.4.7.4. 
Antibody-Dependent Enhancement 
Antibody-Dependent Enhancement 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 recruit healthy volunteers without evidence 
of SARS-CoV-2 infection at the time of dosing with sotrovimab. Due to the long half-life 
of this antibody, it is possible for participants to become infected with SARS-CoV-2 as 
serum concentrations of sotrovimab wane during the course of the 18 week follow-up 
period. This study will assess for the potential of enhanced disease in the context of 
waning sotrovimab levels followed by infection or re-infection in participants who 
recovered from prior COVID-19. ADE may manifest as an increased incidence of severe 
disease in participants infected with SARS-CoV-2 for the first time or increased 
incidence or severity of re-infection in participants who recovered from prior 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. The third mechanism is highly unlikely to occur in 
this study in healthy participants who are not infected with SAR-CoV-2 at the time of 
dosing. In the very unlikely event that it could occur, this may manifest as increased 
severity or duration of illness in sotrovimab-treated participants compared to what would 
be clinically expected. 

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8.5. 
Pharmacokinetics 
Blood samples for sotrovimab serum PK will be collected as detailed in the Schedule of 
Activities (Section 1.3). 
• Serum concentration time data for sotrovimab will be analyzed by non-
compartmental methods 
• The actual collection date and time (24-hour clock time) of each sample will be 
recorded. 
• Samples collected for analyses of sotrovimab serum concentration may also be 
used to evaluate safety 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 sotrovimab, one sample of sufficient volume can be used. 
• Instructions for the collection and handling of biological samples will be provided 
by the sponsor or designee. 
• The timing of sampling may be altered during the course of the study based on 
newly available data (e.g., to obtain data closer to the time of peak serum 
concentrations) to ensure appropriate monitoring. 
PK parameters will be computed using standard noncompartmental methods. Parameters 
may include, but are not be limited to, those shown in Table 4. 
Table 4 
PK Parameters 
Objective  
Parameters 
Primary PK (through D29) 
Cmax, AUCD1-29, Tmax, CD29  
Secondary PK (through Week 18) 
Cmax, AUCinf, AUClast, Tmax, Tlast, t1/2 
As data permits other PK parameters in addition to the listed above may be calculated 
and will be listed and summarized using descriptive statistics. Definitions of PK 
parameters, methods for estimation and details of PK analyses for each study Part will be 
included in the analysis plan. 
8.6. 
Genetics  
Genetics are not evaluated in this study. 
8.7. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.8. 
Immunogenicity Assessments 
Antibodies to sotrovimab will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). If a participant was discontinued early 
from study intervention or was withdrawn from the study, serum samples should also be 

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collected at the final visit. 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. 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. All 
samples collected for detection of antibodies to study intervention will also be evaluated 
for sotrovimab serum concentration 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. 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 or designee to enable further analysis of immune 
responses to sotrovimab. 
8.9. 
Health Economics 
Health Economics parameters are not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The primary objectives are to assess the pharmacokinetics, safety, and tolerability of 
single-dose sotrovimab administered via IV infusion (Part 1) or IM injection (Part 2) in 
healthy Japanese and Caucasian participants. There are no formal statistical hypotheses 
planned. 
 
9.2. 
Sample Size Determination 
No formal statistical techniques were used to calculate the sample size for this study.  
In each Part, a maximum of 24 participants will be randomized to achieve 20 evaluable 
participants in Part 1 and 20 evaluable participants in Part 2. In Part 1, 8 Japanese and 
8 Caucasian participants will be randomized to the IV sotrovimab arm and 2 Japanese 
and 2 Caucasian participants to the placebo arm. In Part 2, 8 Japanese and 8 Caucasian 
participants will be randomized to the IM sotrovimab arm and 2 Japanese and 
2 Caucasian participants to the placebo arm. The number of participants randomized to 
each arm will provide acceptable precision for PK estimation. 
Note: “Evaluable” is defined as a participant who has been randomized, has been 
exposed to study intervention and who has at least 1 non-missing PK assessment 
(including non-quantifiable samples) – i.e., PK sample collected and analyzed. 

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If participants permanently discontinue the study before Day 29, additional participants 
may be enrolled as replacements and assigned to the same cohort and treatment, at the 
discretion of the Sponsor or designee, in consultation with the investigator 
9.3. 
Analysis Sets 
The following analysis sets are defined for the purpose of analysis. 
Participant Analysis Set 
Description 
Screened  
All participants who were screened for eligibility. 
Enrolled 
All participants who entered the study. Note: screen failures are 
excluded from the Enrolled analysis set as they did not enter the 
study. 
Randomized 
All participants who were randomly assigned to study intervention. 
Data will be reported according to the randomized intervention. 
Safety 
All randomized participants who were exposed to study 
intervention. Participants will be reported according to the 
intervention they actually received. 
Pharmacokinetic 
All participants in the Safety analysis set who had at least 1 non-
missing PK assessment – i.e., PK sample collected and analysed. 
Note: Non-quantifiable [NQ] values will be considered as non-
missing values. Participants will be reported according to the 
intervention they actually received. 
 
9.4. 
Statistical Analyses 
9.4.1. 
General Considerations 
The statistical analysis plan (SAP) will include a more technical and detailed description 
of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints, including the primary and 
key secondary endpoints. 
9.4.2. 
Primary Endpoint(s) 
For the analyses planned in the following sections, potential intercurrent events or events 
leading to missing data that will be considered are discontinuation or interruption of 
administration of study intervention and participant withdrawal from study or lost to 
follow-up. 
9.4.2.1. 
Pharmacokinetics  
For Part 1 (IV) the primary estimand for the analyses of the primary PK endpoint will be 
as defined in Table 5. The same estimand is considered for Part 2 (IM). Part 1 and Part 2 
results will be reported separately, and further details will be included in the SAP. 

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Table 5 
Primary Estimand for Primary Pharmacokinetics Endpoint  
Primary Estimand  
Variable/Endpoints 
PK parameters will be computed using standard non-compartmental 
methods. Calculations will be based on the actual sampling times 
recorded during the study. From the serum concentration-time data, 
PK parameters through Day 29 may include, but are not limited to: 
• Cmax 
• CD29 
• AUCD1-29 
• Tmax, as data permits 
Analysis Set 
Analysis will be performed using the Pharmacokinetic analysis set, 
as defined in Section 9.3. 
Strategy for 
Intercurrent Events or 
Events Leading to 
Missing Data  
Available data will be analyzed as collected regardless of events that 
may occur (treatment policy). 
Summary Measure 
Log transformed parameters will be presented with:  Geometric 
mean, 95% confidence interval for the geometric mean, Standard 
deviation of the log-transformed data (SD logs), Between subject 
coefficient of variation (%CVb). 
 
Untransformed parameters will be presented with: Arithmetic mean, 
95% confidence interval for the arithmetic mean, Standard deviation 
of the untransformed data (SD), Median, Min, Max. 
 
Supplementary analysis will be performed (if sufficient data is available) to determine the 
point estimate for the comparison of Japanese to Caucasian participants for each of the 
PK parameters: Cmax and AUCD1-29, after adjusting for body weight. The 90% CI based on 
the geometric least square mean of Japanese:Caucasian participants will also be provided. 
Analysis will be performed on the Pharmacokinetic analysis set (as defined in 
Section 9.3) using all available data as collected regardless of any intercurrent events or 
events resulting to missing data. Further details will be included in the SAP. 
In addition, bioavailability analysis will be performed (if sufficient data is available) to 
determine the point estimate for absolute bioavailability (Fabs) after adjusting for body 
weight and ethnicity. The 90% CI based on the geometric least square mean of 
test/reference ratio will be provided. Analysis will be performed on the Pharmacokinetic 
analysis set (as defined in Section 9.3) using all available data as collected regardless of 
any intercurrent events or events resulting to missing data. The definition of Fabs and 
further details on the planned analyses will be included in the SAP. 
Pharmacokinetics data through Day 29 will be displayed in the form of summaries, 
listings and graphs, where appropriate. Definitions of PK parameters, methods for 
estimation and details of PK analyses for each study part will be included in the SAP. 

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9.4.2.2. 
Safety 
For Part 1 (IV), the primary estimand for the analyses of the primary safety endpoints 
will be as defined in Table 6. The same estimand is considered for Part 2 (IM). Part 1 and 
Part 2 results will be reported separately. 
Table 6 
Primary Estimand of the Primary Safety Endpoint 
Primary Estimand 
Variable/Endpoints 
• Occurrence of AEs through Day 29 
• Occurrence of SAEs through Day 29 
• Occurrence of AESIs through Day 29 
• Occurrence of clinically significant abnormalities on 12-lead ECG 
readings through Day 29 
• Occurrence of clinically significant changes in vital signs compared 
to Baseline through Day 29 
• Occurrence of clinically significant laboratory abnormalities through 
Day 29 
Analysis Set 
Analysis will be performed using the Safety analysis set, as defined 
in Section 9.3. 
Strategy for 
Intercurrent Events or 
Events Leading to 
Missing Data  
Available data will be analyzed as collected regardless of events that 
may occur (treatment policy). 
Summary Measure 
Frequency and Percentages 
 
Occurrence of AEs, SAEs, and AESIs as well as ECG abnormalities, laboratory 
abnormalities and changes in vital signs through Day 29 will be displayed in the form of 
summaries, listings and graphically presented, where appropriate. Further details will be 
provided in the SAP. 
 
9.4.3. 
Secondary Endpoint(s) 
9.4.3.1. 
Pharmacokinetics 
For Part 1 (IV), the primary estimand for the analyses of the secondary PK endpoint will 
be as defined in Table 7. The same estimand is considered for Part 2 (IM). Part 1 and 
Part 2 results will be reported separately, and further details will be included in the SAP. 

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Table 7 
Primary Estimand for Secondary Pharmacokinetics Endpoint  
Primary Estimand 
Variable/Endpoints 
PK parameters will be computed using standard non-compartmental 
methods. Calculations will be based on the actual sampling times 
recorded during the study. From the serum concentration-time data, 
PK parameters through Week 18 may include but are not limited to: 
• Cmax 
• AUCinf 
• AUClast 
• Tmax 
• Tlast 
• t1/2, as data permits 
Analysis Set 
Analysis will be performed using the Pharmacokinetic analysis set, as 
defined in Section 9.3. 
Strategy for 
Intercurrent Events 
or Events Leading to 
Missing Data  
Available data will be analyzed as collected regardless of events that 
may occur (treatment policy). 
Summary Measure 
Log transformed parameters will be presented with: Geometric mean, 
95% CI for the geometric mean. SD logs, Between subject coefficient 
of variation (%CVb). 
 
Untransformed parameters will be presented with: Arithmetic mean, 
95% CI for the arithmetic mean, SD, Median, Min, Max. 
 
Ethnicity comparison for Cmax and AUCinf, as well as bioavailability analyses, will also be 
performed as described in Section 9.4.2.1. Further details will be included in the SAP. 
Pharmacokinetics data through Week 18 will be displayed in the form of summaries, 
listings and graphs, where appropriate. Definitions of PK parameters, methods for 
estimation and details of PK analyses for each study part will be included in the SAP. 
9.4.3.2. 
Safety 
For Part 1 (IV), the primary estimand for the analyses of the secondary safety endpoints 
will be as defined in Table 8. The same estimand is considered for Part 2 (IM). Part 1 and 
Part 2 results will be reported separately. 

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Table 8 
Primary Estimand of the Secondary Safety Endpoint 
Primary Estimand 
Variable/Endpoints 
• Occurrence of AEs through Week 18 
• Occurrence of SAEs through Week 18 
• Occurrence of AESIs through Week 18 
• Occurrence of clinically significant abnormalities on 12-lead 
ECG readings through Week 18 
• Occurrence of clinically significant changes in vital signs 
compared to Baseline through Week 18 
• Occurrence of clinically significant laboratory abnormalities 
through Week 18 
Analysis Set 
Analysis will be performed using the Safety analysis set, as defined 
in Section 9.3. 
Strategy for 
Intercurrent Events or 
Events Leading to 
Missing Data  
Available data will be analyzed as collected regardless of events that 
may occur (treatment policy). 
Summary Measure 
Frequency and Percentages 
 
Occurrence of AEs, SAEs, and AESIs as well as ECG abnormalities, laboratory 
abnormalities and changes in vital signs through Week 18 will be displayed in the form 
of summaries, listings and graphs, where appropriate. Further details will be provided in 
the SAP. 
9.4.4. 
Tertiary/Exploratory Endpoint(s) 
Incidence and titers (if applicable) of serum ADA and drug-neutralizing antibodies to 
sotrovimab will be assessed for Part 1 and Part 2. Further details of the analysis methods 
for the immunogenicity endpoint will be provided in the SAP. 
9.5. 
Interim Analysis 
No interim analyses are planned for either Part 1 or Part 2 in the study. 
However, once the last participant recruited in Part 1 completes the primary assessment 
(Day 29) the data will be formally unblinded in the systems to allow a readout of the 
primary endpoints for Part 1. Participants will continue to complete the remaining 
scheduled assessments up to Week 18. A similar approach may be followed for Part 2 at 
Day 29. This will be determined at a later stage and details will be included in the 
planned SAP. 

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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 International Council on Harmonisation of technical 
requirements for registration of pharmaceuticals for human use (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/IEC 
▪ 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 Code of Federal Regulations (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 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor or designee with sufficient, 
accurate financial information as requested to allow the sponsor or designee to submit 

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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 Process 
• The investigator or his/her representative will explain the nature of the study to 
the participant and answer all questions regarding the study.  
• Participants must be informed that their participation is voluntary. Participants 
will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and 
the IRB/IEC or study center.  
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• A copy of the ICF(s) must be provided to the participant. 
• Participants who are rescreened are required to sign a new ICF. 
GlaxoSmithKline (alone or working with others) may use participant’s coded study data 
and samples and other information to carry out this study; understand the results of this 
study; learn more about sotrovimab or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have the sotrovimab 
approved for medical use or approved for payment coverage.  
10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by the sponsor or designee. Any 
participant records or datasets that are transferred to the sponsor/designee will 
contain the identifier only; participant names or any information which would 
make the participant identifiable will not be transferred.  
• The participant must be informed that his/her personal study-related data will be 
used by the sponsor/designee in accordance with local data protection law. The 
level of disclosure must also be explained to the participant who will be required 
to give consent for their data to be used as described in the informed consent.  
• The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed by 
the sponsor/designee, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 

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10.1.5. 
Committees Structure 
Not applicable.  
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. 
• The 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 patients received. The investigator(s) is/are encouraged to share 
the summary results with the study participants, as appropriate. 
• Under the framework of the SHARE initiative, GSK intends to make anonymized 
participant-level data from this trial available to external researchers for scientific 
analyses or to conduct further research that can help advance medical science or 
improve patient care. This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding. 
Requests for access may be made through www.clinicalstudydatarequest.com. 
• The Sponsor or designee will provide the investigator with the randomization 
codes for their site only after completion of the full statistical analysis. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with Sponsor/GSK Policy. 
• The Sponsor/GSK intends to make anonymized patient-level data from this trial 
available to external researchers for scientific analyses or to conduct further 
research that can help advance medical science or improve patient care. This 
helps ensure the data provided by trial participants are used to maximum effect in 
the creation of knowledge and understanding 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF.  
• Guidance on completion of CRFs will be provided in eCRF completion 
guidelines. 
• 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. 

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• 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 Contract Research Organizations 
(CRO) document. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., CRO). 
• 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 
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.  

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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 
GlaxoSmithKline 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 
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 9 will be performed by the local laboratory.  
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Table 9 
Protocol-Required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
Mean 
corpuscular 
volume (MCV) 
Mean 
corpuscular 
hemoglobin 
(MCH) 
%Reticulocytes 
White blood cell (WBC) count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red blood cell 
(RBC) Count 
 
Hemoglobin 
 
 
Coagulation 
International 
Normalized 
Ratio (INR) 
Prothrombin 
Time (PT) 
 
Activated Partial Thromboplastin Time 
(aPTT) 
Clinical 
Chemistry1 
Blood urea 
nitrogen (BUN) 
Potassium 
Aspartate 
Aminotransferase 
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
ALT/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
Total Protein 
 
Glucose  
(fasting at 
Screening and 
non-fasting at all 
other timepoints) 
Calcium 
Alkaline 
phosphatase2 
 
Urine Testing 
• Routine Urinalysis 
o Specific gravity 

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o pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
o Microscopic examination (if blood, protein, or leukocyte esterase is 
abnormal) 
• Urine creatinine and urine albumin 
Pregnancy 
testing 
• Highly sensitive serum/plasma or urine human chorionic gonadotropin 
(hCG) pregnancy test (as needed for women of childbearing potential)3 
Other 
Screening 
Tests 
• Follicle-stimulating hormone (as needed in women of non-childbearing 
potential only) 
• Serum or urine alcohol and drug screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, marijuana, and 
benzodiazepines) 
• Serology (HIV antibody, HBsAg, and hepatitis C virus antibody)  
NOTES : 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1 and Section 10.5 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 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 is elevated, consider fractionating. 
3. 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
 

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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 adverse event is an adverse event that was not solicited using a  
diary or form with pre-specified criteria. Unsolicited adverse events are obtained 
either by asking a general question or unprompted by a participant 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 hospitalisation, or emergency room visit, or visit to/by a health care 
provider). The participants 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 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 
participant will be collected during interview with the participants and by review of 
available medical records at the next visit. 
• Solicited AEs are predefined local at the injection site and systemic events for 
which the participant 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 
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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. 
 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 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 serious adverse event that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 

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“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from Baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT ≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or 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. 
10.3.3. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (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. 

T M F -1 3 7 8 8 1 4 9  
C O N FI D E N TI A L  
 
 
 
2 1 7 6 5 3  
 
6 7  
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  
•  T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s y m pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis ( n ot 
t he i n di vi d ual si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
A s s e ss m e nt of Se v erit y  
Sta n dar d t o xicit y gra di n g acc or di n g t o t he D AI D S T a ble f or Gr a di n g t he Severity of 
A d ult a n d Pe di atric A dverse Eve nts , versi o n 2. 1 (J ul y 2 0 1 7) will be use d t o gra de all 
A Es.  
Ta ble 1 0  s h o ul d be use d t o gra d e t he se v erit y of a n A E t hat is n ot s pecificall y 
i de ntifie d i n t he gra di n g ta ble s wit hi n D AI D S T a ble f or Gr a di n g t he Severit y of A d ult 
a n d Pe di atric A dverse Eve nts , versi o n 2. 1 (J ul y 2 0 1 7). I n a d diti o n,
are t o be cl assifie d as Gra d e 5.  
A n e ve nt is defi ne d as ‘s eri o us’ w he n it meets at least 1 of t he pre defi n e d o utc o mes as 
descri be d i n t he d efi niti o n of a n S A E  as per Secti o n  1 0. 3. 2 , N O T w he n it is rate d as 
se vere. 
T a bl e 1 0  
D AI D S T a bl e f or Gr a di n g t h e S e v erit y of A d ult a n d P e di atri c A d v er s e 
E v e nt s  N ot Ot h er wi s e S p e cifi e d i n D AI D S v er si o n 2. 1  
P A R A M E T E R  Gr a de 1  
Mil d  
Gr a de 2  
M o der ate  
Gr a de 3  
Se vere  
Gr a de 4  
P ote nti all y 
life-
t hre ate ni n g 
 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e 
pr ot e ct e d b y t hir d p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.
C CI
C CI

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

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10.3.4. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• The investigator or medically-qualified sub-investigator must show evidence within 
the eCRF (e.g., check review box, signature, etc.) of review and verification of the 
relationship of each SAE to IP/study participation (causality) within 72 hours of 
SAE entry into the eCRF. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the medical monitor by telephone. 
• 
Contacts for SAE reporting can be found in the 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. 
• 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 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 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the 
absence of 12 months of amenorrhea, confirmation with more than one FSH 
measurement (at least 1 week apart) is required.  
o Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Woman of Nonchildbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 

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1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
2. Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the 
absence of 12 months of amenorrhea, confirmation with more than one FSH 
measurement (at least 1 week apart) is required. 
o Females on HRT and whose menopausal status is in doubt must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
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. 

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• 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• oral 
• intravaginal 
• transdermal 
• injectable 
• Progestogen-only hormone contraception associated with inhibition of ovulationc 
• oral 
• injectable 
• Sexual abstinence 
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: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase 1 Liver Chemistry Monitoring Criteria and Required Follow Up Assessments 
Liver Chemistry Monitoring Criteria  
 
ALT-absolute 
 
ALT≥3xULN 
If ALT≥3xULN AND total bilirubin 2xULN (>35% direct bilirubin) or INR  
>1.5, report to GSK as an SAE1,2. 
 
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 
an 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 resolve, stabilise, or return to 
within Baseline (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 participant twice weekly until liver 
chemistries resolve, stabilise or return to 
within Baseline 
• A specialist or hepatology consultation is 
recommended 
 
If ALT≥3xULN AND total bilirubin < 2xULN 
and INR ≤1.5: 
• Perform liver chemistries (include ALT, 
• Viral hepatitis serology3 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show 
downward trend 
• Obtain blood sample for pharmacokinetic 
(PK) analysis, obtained within 127 days of 
the most recent dose4  
• Obtain serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), 
gamma-glutamyl transferase (GGT), 
glutamate dehydrogenase (GLDH) and 
serum albumin. 
• Fractionate bilirubin, if total 
bilirubin2xULN 
• Obtain complete blood count with 
differential to assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the 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 

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Liver Chemistry Monitoring Criteria  
AST, alkaline phosphatase, total bilirubin 
and INR) and perform liver event follow up 
assessments within 24-72 hours 
• Monitor participant weekly until liver 
chemistries resolve, stabilize or return to 
within Baseline 
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 quantitative 
total immunoglobulin G (IgG) or gamma 
globulins. 
• Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging form. 
• Liver biopsy may be considered and 
discussed with local specialists if 
available, for instance: 
o In patients when serology raises 
the possibility of autoimmune 
hepatitis (AIH) 
o In patients when suspected DILI 
progresses or fails to resolve on 
withdrawal of study intervention 
o In patients with acute or chronic 
atypical presentation. 
• If liver biopsy is conducted, then complete 
liver biopsy form 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation testing is 
unavailable, record the absence/presence of detectable urinary bilirubin on dipstick, which is indicative of 
direct bilirubin elevations suggesting liver injury.  
2. All events of ALT  3xULN and total bilirubin  2xULN (>35% direct bilirubin) or ALT  3xULN and INR>1.5, 
which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported to GSK as an SAE (excluding 
studies of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving 
anticoagulants. 
3. Includes: hepatitis A immunoglobulin (IgM) antibody; HBsAg and hepatitis B core antibody (HBcAb); hepatitis C 
RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile 
antibody or monospot testing) and hepatitis E IgM antibody  
4. Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
PK blood sample draw. If the date or time of the last dose is unclear, provide the participant’s best approximation. 
If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in the time period 
indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in the SRM.  
 
 

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10.6. 
Appendix 6: Management of Local Injection Site Reactions 
and Systemic Symptoms (Anaphylaxis) 
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 
• Chest pain 
• Collapse 

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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: 
Administer epinephrine (1.0 mg/mL) aqueous solution (1:1000 dilution) – 0.5 
mg (0.5 mL) IM in the anterolateral thigh 
If using an epinephrine auto-injector – use 0.3 mg IM into the anterolateral 
thigh 
May be repeated every 5-15 minutes up to 3 times 
4. Optional treatment (antihistamine): 
Diphenhydramine 50 mg oral/IV/IM 
OR 
Hydroxyzine 25 mg oral/IM 
5. Give oxygen (8-10 L/minute) via facemask, as needed 
6. Normal saline rapid bolus – treat hypotension with rapid infusion of 1-2 liters IV 
7. Monitor patient until emergency medical services arrive. 
References 
1. Medical Management of Vaccine Reactions in Adults in a Community Setting, 
Immunization Action Coalition, https://www.immunize.org/catg.d/p3082.pdf. 
Accessed May 27, 2021. 
2. Preventing and Managing Adverse Reactions, General Best Practice Guidelines 
for Immunization: Best Practices Guidance of the Advisory Committee on 
Immunization Practices (ACIP). Centers for Diseases Control and Prevention 
website. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/adverse-
reactions.html. Accessed May 27, 2021. 
3. 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; 117:391-7. 
 
 
 

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10.7. 
Appendix 7: Abbreviations and Definitions and Trademarks 
Term 
Definition 
µg 
Micrograms 
%AUCexp 
The extrapolated portion of AUCinf  
%CV 
Percent coefficient of variation 
%CVb 
Between subject coefficient of variation 
ADA 
Anti-drug antibody 
ADE 
Antibody dependent enhancement 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AIH 
Autoimmune hepatitis 
ALT 
Alanine Aminotransferase 
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
AUC 
Area under the curve 
AUCD1-29 
Area under the serum-concentration time curve from Day 1 to Day 29 
AUCinf 
Area under the serum concentration-time curve extrapolated to infinite time 
AUClast 
Area under the curve from the time of dosing to the time of the last measurable 
(positive) concentration 
BMI 
body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CA 
Competent Authority 
CD29 
Concentration at Day 29 
Clast 
Observed concentration corresponding to Tlast. 
Cmax 
Maximum observed serum concentration 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
Clearance 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus disease 2019 
CPK 
Creatine phosphokinase 
CRF 
Case report form 

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Term 
Definition 
CRO 
Contract research organization 
CSR 
Clinical study report 
CTFG 
Clinical Trial Facilitation Group 
CV 
Cardiovascular 
DAIDS 
Division of acquired immune-deficiency syndrome 
DILI 
Drug induced liver injury 
DSMB 
Data and Safety Monitoring Board 
EC 
Ethics committee 
EC90 
90% effective concentration 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ED 
Early discontinuation 
EDC 
Electronic data capture 
EOS 
End of study 
EUA 
Emergency use authorization 
EW 
Early withdrawal 
FcR 
Fc Gamma Receptor 
Fabs 
Absolute bioavailability 
FI 
Formalin-inactivated 
FSH 
Follicle stimulating hormone 
GCSP 
Global Clinical Safety and Pharmacovigilance 
GCP 
Good clinical practice 
GGT 
Gamma-glutamyl transferase 
GLDH 
Glutamate dehydrogenase 
GSK 
GlaxoSmithKline 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
hCG 
Human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HRT 
Hormone replacement therapy 
HSR 
Hypersensitivity reactions 
IB 
Investigator’s brochure 

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Term 
Definition 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation of technical requirements for registration of 
pharmaceuticals for human use 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent ethics committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgG1 
Immunoglobulin G1 
IgG1κ 
Immunoglobulin G1 kappa 
IgM 
Immunoglobulin M 
IM 
Intramuscular 
INR 
International normalized ratio 
IRB 
Institutional review board 
IRR 
Infusion related reaction 
ISR 
Injection site reaction 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
JSRT 
Joint safety review team 
kg/m2 
Kilograms per meter square 
L 
Liter 
LAM 
Lactational amenorrhea method 
LDH 
Lactate dehydrogenase 
mAb 
Monoclonal antibody 
MARM 
Monoclonal antibody-resistant mutant 
MCH 
Mean corpuscular volume 
MCV 
Mean corpuscular hemoglobin 
Max 
Maximum 
Min 
Minimum 
mg 
Milligram 
mL 
Milliliter 
mm/Hg 
Millimeter of mercury 
MSDS 
Material safety data sheet 

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Term 
Definition 
NQ 
Non-quantifiable 
PI 
Principal investigator 
PK 
Pharmacokinetic(s) 
PR 
Pulse rate 
PT 
Prothrombin time 
QTc 
Corrected QT interval 
QTLs 
Quality tolerance limits 
RBC 
Red blood cell count 
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
RSV 
Respiratory syncytial virus 
RT-PCR 
Reverse transcriptase polymerase chain reaction 
SAE 
Serious adverse event 
SARS-CoV-1 
Severe acute respiratory syndrome coronavirus-1 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus-2 
SAP 
Statistical analysis plan 
SD 
Standard deviation of the untransformed data 
SD logs 
Standard deviation of the log-transformed data 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvic Transaminase 
SoA 
Schedule of activities 
SpO2 
Oxygen saturation 
SRM 
Study reference manual 
SUSAR 
Suspected unexpected serious adverse reactions 
t1/2 
Terminal elimination half-life 
Tlast 
Time of the last quantifiable concentration 
Tmax 
Time to reach Cmax 
TBD 
To be determined 
ULN 
Upper limit of normal 
US 
United States 
V 
Apparent volume of distribution 
Vir 
Vir Biotechnology, Inc. 
WBC 
White blood cell 

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Term 
Definition 
WOCBP 
Woman of Childbearing Potential 
WONCBP 
Woman of non-childbearing potential 
Vz 
Volume of distribution during the elimination 
λz 
Apparent terminal elimination rate constant, calculated by linear regression of the 
terminal linear portion of the log concentration vs. time curve. 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
None 
 
None 
 
 

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11. 
REFERENCES 
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. https://doi.org/10.1038/s41586-020-2538-8 
Baxter LT, Zhu H, Mackensen DG, Jain RK. Physiologically based pharmacokinetic 
model for specific and nonspecific monoclonal antibodies and fragments in normal 
tissues and human tumor xenografts in nude mice. Cancer Res. 1994;54(6):1517–1528. 
Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, et al. SARS-CoV-2 
Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. The New England 
Journal of Medicine. 2021;384:229-237. https://doi.org/10.1056/NEJMoa2029849 
Covell DG, Barbet J, Holton OD, Black CD, Parker R.J, Weinstein, JN. 
Pharmacokinetics of monoclonal immunoglobulin G1, F(ab')2, and Fab' in mice. Cancer 
Res. 1986;46(8):3969–3978. 
Datta-Mannan A. Mechanisms Influencing the Pharmacokinetics and Disposition of 
Monoclonal Antibodies and Peptides. Drug Metab Dispos. 2019;47(10): 1100–1110. 
https://doi.org/10.1124/dmd.119.086488. 
Eli Lilly and Company. Emergency Use Authorization (EUA) for bamlanivimab 700 mg 
and etesevimab 1400 mg IV administered together Center for Drug Evaluation and 
Research (CDER) Review. Submitted on November 16, 2020. 
https://www.fda.gov/media/146255/download. Accessed on May 12, 2021.  
FDA News Release. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal 
Antibodies for Treatment of COVID-19. Released on November 21, 2020. 
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-
fda-authorizes-monoclonal-antibodies-treatment-covid-19. Accessed on May 04, 2021. 
FDA News Release. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal 
Antibodies for Treatment of COVID-19. Released on February 09, 2021. 
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-
fda-authorizes-monoclonal-antibodies-treatment-covid-19-0. Accessed on May 04, 2021. 
Gaudinski, MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, et al. 
Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody 
VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS Medicine. 
2018;15(1):e1002493. https://doi.org/10.1371/journal.pmed.1002493 
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. 
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 (London, England). 
2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5. 

TMF-13788149 
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217653 
 
83 
Clinical Study Protocol template V15 dated 21-Dec-2020 
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;91:264-266. doi: 
10.1016/j.ijid.2020.01.009. 
Johns Hopkins University and Medicine - Coronavirus Resource Center. 
https://coronavirus.jhu.edu. Last accessed April 27, 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. medRxiv preprint 
doi: https://doi.org/10.1101/2020.05.12.20099879.this version posted May 14, 2020. 
Kelley B. Developing therapeutic monoclonal antibodies at pandemic pace. Nature 
biotechnology. 2020;38(5), 540–545. https://doi.org/10.1038/s41587-020-0512-5 
Ko S-Y, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, et al. Enhanced neonatal Fc 
receptor function improves protection against primate SHIV infection. Nature. 2014 Oct 
30; 514(7524):642-5. doi: 10.1038/nature13612 
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 April 30, 2021.  
Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. 
Journal of Pharmaceutical Sciences. 2004;93(11):2645-2668. 
https://doi.org/10.1002/jps.20178. 
Marovich M, Mascola JR, Cohen MS. Monoclonal Antibodies for Prevention and 
Treatment of COVID-19. JAMA. 2020;324(2):131–132. 
doi:10.1001/jama.2020.10245. 
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;583(7815):290-295.  
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 
Regeneron Pharmaceuticals, Inc. Emergency Use Authorization (EUA) for casirivimab 
and imdevimab Center for Drug Evaluation and Research (CDER) Review. Submitted on 
October 08, 2020. https://www.fda.gov/media/144468/download. Accessed on May 12, 
2021. 

TMF-13788149 
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84 
Clinical Study Protocol template V15 dated 21-Dec-2020 
Sager J, Hong DK, Bonavia A, Connolly L, Cebrik D, Fanget MC, et al. 631. Preliminary 
safety and pharmacokinetic profile of VIR-2482: a monoclonal antibody for the 
prevention of influenza A illness. Open Forum Infectious Diseases. 2020; 
7(Suppl 1):S376. https://doi.org/10.1093/ofid/ofaa439.825 
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 May 16, 2021. 
Vir Biotechnology and GSK Announce VIR-7831 Reduces Hospitalization and Risk of 
Death in Early Treatment of Adults with COVID-19 [news release]. San Franscisco, 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 April 29, 2021. 
Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. 
Virological assessment of hospitalized patients with COVID-2019. Nature. 2020. 
https://doi.org/10.1038/s41586-020-2196-x 
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;51(10):1184-91. doi: 10.1086/656740. PMID: 20964521; PMCID: PMC3034199 
Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, et al. 
Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 2010 ;28(2):157-
9. doi: 10.1038/nbt.1601. 
Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease 
severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-
March 2020: retrospective cohort study. BMJ. 2020;369:m1443. doi: 10.1136/bmj.m1443