A Phase 1, Open-label, Randomized, Parallel Group, Single-dose Clinical Pharmacology Study to Investigate the Relative Bioavailability, Safety, and Tolerability of Two Different Concentrations of Sotrovimab Administered at Different Injection Sites, in Male or Female Healthy Participants Aged 18 to 65 Years
Phase: PHASE1
Conditions: Covid19
Sponsor: Vir Biotechnology, Inc.

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TITLE PAGE 
Protocol Title: A Phase 1, open-label, randomized, parallel group, single-dose clinical 
pharmacology study to investigate the relative bioavailability, safety, and tolerability of 
two different concentrations of sotrovimab administered at different injection sites, in 
male or female healthy participants aged 18 to 65 years. 
Protocol Number: GSK Study 218128/VIR-7831-5012/Amendment 3 
Compound Number 
or Name: 
Sotrovimab (also known as Xevudy, GSK4182136, VIR-7831)  
 
Brief Title: Relative bioavailability, safety, and tolerability of single-dose sotrovimab 
injection in adults 
 
Study Phase: Phase 1 
Acronym: COSMIC (Clinical pharmacology study to investigate the relative 
biOavailability, safety, and tolerability of two different concentrations of SotroviMab 
administered at different InjeCtion sites) 
 
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):  
Registry 
ID 
IND 
149315 
NCT 
NCT05280717 
Approval Date: 30 Mar 2023 
©2023 Vir Biotechnology, Inc. and the GSK group of companies or its licensor. All 
rights reserved. Unauthorized copying or use of this information is prohibited. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 3 
30 Mar 2023 
TMF-15739935 
Amendment 2 
06-SEP-2022 
TMF-14575517 
Amendment 1 
01-FEB-2022 
TMF-14439761 
Original Protocol 
13-DEC-2021 
TMF-14082482 
Amendment 3: 30 Mar 2023 
This amendment is considered to be substantial based on the description of change and 
rationale mentioned in the below table.  
Overall Rationale for the Amendment: The protocol has been amended to include the 
Part C safety and PK exploratory endpoints for Japanese population and to update 
inclusion criteria related to contraception recommendation. 

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Section # and Title 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis 
Section 2.3.1 Risk Assessment 
Table 
Section 4.1: Overall Design 
Section 6.1 Study Intervention(s) 
Administered table 
Added the infusion time to 
administer single dose of IV 
sotrovimab in Part C Cohort 1  
 
Updated text in hypersensitivity 
reactions table to include Part C 
infusion time, and made minor 
editorial changes to explain 
infusion time and dose for Part C 
Cohort 2 will be added at the time 
of decision made based on safety 
review of Cohort 1 
 
Updated the study intervention 
administered table with infusion 
time of 60 minutes for Part C 
Cohort 1 
To characterize the safety 
and tolerability of IV 
sotrovimab and to potentially 
explore further IV doses of 
sotrovimab and/or 
alternative infusion time, the 
proposed range of infusion 
time was chosen to support 
clinical doses for potential 
future clinical studies 
 
Section 3: Objectives and Endpoints 
 
New information available 
Section 5.1 Inclusion Criteria 
 
Updated IC related to  
contraception recommendation to 
include the reference to 5 half-
lives of sotrovimab (and removed 
mention of 35 weeks time period) 
to align with current IB  
Updated contraception 
follow-up period to only refer 
to ~5 half-lives (the 
equivalent follow-up that this 
represents is detailed in the 
ICF) 
Section 9.2: Analysis Set 
Added the definition of Enrolled 
criteria for Part C participants 
New information available 
on Enrolled analysis set as 
Part C is not randomized 
Section 9.3.1: General 
Considerations  
Removed reference to Japanese 
population analysis only being 
conducted if data permits 
Section 9.4: Interim Analysis 
Removed reference to the wording 
regarding the pausing of Part C 
Cohort 1 recruitment at time of 
interim 
Alignment with operational 
strategy 
Appendix 9: Protocol Amendment 
History 
Minor editorial updates made to 
the statement describing 
substantial protocol changes and 
also to the summary of changes 
table  
Updates are made for better 
clarity and to maintain 
consistency 
 
 
 
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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 7 
1.2. 
Schema ...................................................................................................... 14 
1.3. 
Schedule of Activities (SoA) ........................................................................ 17 
2. 
INTRODUCTION .................................................................................................... 21 
2.1. 
Study Rationale .......................................................................................... 21 
2.2. 
Background ................................................................................................ 22 
2.2.1. 
Clinical Experience with Sotrovimab ............................................ 23 
2.3. 
Benefit/Risk Assessment ............................................................................ 24 
2.3.1. 
Risk Assessment ......................................................................... 25 
2.3.2. 
Benefit Assessment ..................................................................... 30 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 30 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 32 
4. 
STUDY DESIGN .................................................................................................... 37 
4.1. 
Overall Design ............................................................................................ 37 
4.2. 
Scientific Rationale for Study Design .......................................................... 41 
4.3. 
Justification for Dose .................................................................................. 42 
4.4. 
End of Study Definition ............................................................................... 42 
5. 
STUDY POPULATION ........................................................................................... 43 
5.1. 
Inclusion Criteria ......................................................................................... 43 
5.2. 
Exclusion Criteria ........................................................................................ 44 
5.3. 
Lifestyle Considerations .............................................................................. 46 
5.3.1. 
Meals and Dietary Restrictions .................................................... 46 
5.3.2. 
Caffeine, Alcohol, and Tobacco ................................................... 46 
5.3.3. 
Activity ......................................................................................... 46 
5.4. 
Screen Failures........................................................................................... 47 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention ................. 47 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 47 
6.1. 
Study Intervention(s) Administered ............................................................. 47 
6.2. 
Preparation, Handling, Storage and Accountability ..................................... 50 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 51 
6.4. 
Study Intervention Compliance ................................................................... 52 
6.5. 
Dose Modification ....................................................................................... 52 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 52 
6.7. 
Treatment of Overdose ............................................................................... 52 
6.8. 
Concomitant Therapy.................................................................................. 52 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 53 
7.1. 
Discontinuation of Study Intervention .......................................................... 53 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 53 
7.1.2. 
Temporary Discontinuation .......................................................... 54 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 54 

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7.3. 
Lost to Follow-up ........................................................................................ 54 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 55 
8.1. 
Screening Period ........................................................................................ 56 
8.1.1. 
Medical History ............................................................................ 56 
8.1.2. 
SARS-CoV-2 Testing ................................................................... 56 
8.2. 
Efficacy Assessments ................................................................................. 56 
8.3. 
Safety Assessments ................................................................................... 56 
8.3.1. 
Physical Examinations ................................................................. 56 
8.3.2. 
Vital Signs .................................................................................... 57 
8.3.3. 
Electrocardiograms ...................................................................... 57 
8.3.4. 
Clinical Safety Laboratory Tests .................................................. 57 
8.3.5. 
Pregnancy Testing ....................................................................... 58 
8.3.6. 
Local Injection Site Tolerability ..................................................... 58 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 58 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 59 
8.4.2. 
Method of Detecting AEs and SAEs ............................................. 59 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 59 
8.4.4. 
Regulatory Reporting Requirements for SAEs ............................. 59 
8.4.5. 
Pregnancy ................................................................................... 60 
8.4.6. 
Assessment of AE Severity .......................................................... 60 
8.4.7. 
Adverse Events of Special Interest .............................................. 60 
8.5. 
Pharmacokinetics ....................................................................................... 62 
 
 
8.7. 
Genetics ..................................................................................................... 63 
8.8. 
Biomarkers ................................................................................................. 63 
8.9. 
Immunogenicity Assessments ..................................................................... 63 
 
 
8.11. 
Health Economics ....................................................................................... 64 
8.12. 
Patient-reported Outcomes ......................................................................... 64 
8.12.1. 
Perception of Injection ................................................................. 64 
8.12.2. 
Injection Site Pain ........................................................................ 64 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 65 
9.1. 
Statistical Hypotheses................................................................................. 65 
9.2. 
Analysis Sets .............................................................................................. 65 
9.3. 
Statistical Analyses ..................................................................................... 66 
9.3.1. 
General Considerations ............................................................... 66 
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis ................................. 66 
9.3.3. 
Secondary Endpoint(s) ................................................................ 69 
9.3.4. 
Other Safety Endpoints ................................................................ 71 
9.3.5. 
Exploratory Endpoints .................................................................. 71 
9.4. 
Interim Analysis .......................................................................................... 71 
9.5. 
Sample Size Determination ........................................................................ 72 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 76 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 76 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 76 
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10.1.2. 
Financial Disclosure ..................................................................... 76 
10.1.3. 
Informed Consent Process .......................................................... 77 
10.1.4. 
Data Protection ............................................................................ 77 
10.1.5. 
Committees Structure .................................................................. 78 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 78 
10.1.7. 
Data Quality Assurance ............................................................... 78 
10.1.8. 
Source Documents ...................................................................... 79 
10.1.9. 
Study and Site Start and Closure ................................................. 80 
10.1.10. Publication Policy ......................................................................... 80 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 82 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 84 
10.3.1. 
Definition of AE ............................................................................ 84 
10.3.2. 
Definition of SAE .......................................................................... 85 
10.3.3. 
Recording and Follow-up of AE and SAE..................................... 86 
10.3.4. 
Reporting of SAE to GSK ............................................................. 89 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ....................................... 90 
10.4.1. 
Definitions: ................................................................................... 90 
10.4.2. 
Contraception Guidance: ............................................................. 91 
10.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 93 
10.6. 
Appendix 6: Management of Local Injection Site Reactions and 
Systemic Symptoms (Anaphylaxis) ............................................................. 96 
10.7. 
10.8. 
Appendix 8: Abbreviations and Definitions and Trademarks ....................... 99 
10.9. 
Appendix 9: Protocol Amendment History ................................................. 103 
11. REFERENCES ..................................................................................................... 109 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A Phase 1, open-label, randomized, parallel group, single-dose clinical pharmacology 
study to investigate the relative bioavailability, safety, and tolerability of two different 
concentrations of sotrovimab administered at different injection sites, in male or female 
healthy participants aged 18 to 65 years. 
Brief Title: Relative bioavailability, safety, and tolerability of single-dose sotrovimab 
injection in adults 
Rationale: 
There is a significant unmet need for additional therapeutics to reduce COVID‑19 
infection; reduce the progression of mild to severe disease; treat severe disease in these 
patients; and to help alleviate the burden on healthcare systems. 
As the COVID-19 pandemic continues to evolve with the rapid evolution of VOI/VOCs, 
healthcare professionals treating COVID-19 infections will need to identify the best 
treatment for their patient based on the circulating variants and underlying comorbidities. 
Sotrovimab is being developed for treatment of COVID-19. Sotrovimab is a human 
IgG1κ mAb derived from the parental mAb S309, a mAb directed against the spike 
protein of 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 t1/2 and is also expected to enhance distribution to the 
respiratory mucosa. Sotrovimab received EUA for the treatment of mild-to-moderate 
COVID-19 in the US on 26 May 2021. At the time of this amendment, due to the high 
frequency of sub-variants against which sotrovimab has reduced in vitro neutralization, 
the FDA determined that sotrovimab is not currently authorized for use in any US region.  
This is a Phase 1 healthy participant study with 3 Parts (Part A, Part B, and Part C). The 
study will evaluate both IM and IV routes of administrations at different doses and 
different IM sites of administration.  
Part A and an optional Part B of this study are open-label and will evaluate the safety, 
tolerability, and relative bioavailability of the 62.5 mg/mL concentration and the new 
100 mg/mL concentration of sotrovimab following IM injections at different sites. 
Part C of this study is open-label and will characterize the safety and tolerability of 
sotrovimab administered intravenously in Cohort 1 and an optional Cohort 2. 

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Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
Pharmacokinetics  
Part A: 
To estimate the relative bioavailability of 100 mg/mL 
IM sotrovimab at the dorsogluteal injection site 
relative to the 62.5 mg/mL formulation administered 
dorsogluteally through Day 29 
Sotrovimab PK parameters: AUCD1-29 and Cmax  
Safety  
Part A:  
• 
To evaluate the safety and tolerability profile 
of 100 mg/mL IM sotrovimab and the 
62.5 mg/mL formulation at the dorsogluteal 
injection site through Day 29 
Part C: 
• 
To evaluate the safety and tolerability profile 
of IV sotrovimab in Cohort 1 and/or Cohort 
2 through Day 29 
Incidence of AEs, SAEs, and AESI through Day 29 
Secondary 
Pharmacokinetics  
Part A: 
• 
To estimate the relative bioavailability of 
100 mg/mL IM sotrovimab at 2 alternative 
injection sites (anterolateral thigh and deltoid) 
relative to the 62.5 mg/mL formulation 
administered dorsogluteally through Day 29 
Part B:  
• 
To estimate the relative bioavailability of 
100 mg/mL and/or 62.5 mg/mL IM sotrovimab at 
up to 2 injection sites relative to the 62.5 mg/mL 
formulation administered dorsogluteally through 
Day 29 
Part C: 
• 
To characterize the PK of IV sotrovimab in 
Cohort 1 and/or Cohort 2 through Day 29 
Sotrovimab PK parameters: AUCD1-29 and Cmax  
Pharmacokinetics  
Part A: 
Sotrovimab PK parameter: AUCinf  

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Objectives 
Endpoints 
• 
To estimate the relative bioavailability of 
100 mg/mL IM sotrovimab at 3 injection sites 
(dorsogluteal, anterolateral thigh, and deltoid) 
relative to the 62.5 mg/mL formulation 
administered dorsogluteally through Week 24 
Part B:  
• 
To estimate the relative bioavailability of 
100 mg/mL and/or 62.5 mg/mL IM sotrovimab at 
up to 2 injection sites relative to the 62.5 mg/mL 
formulation administered dorsogluteally through 
Week 24 
Pharmacokinetics  
Part A and Part B: 
• 
To characterize the PK of 100 mg/mL and 
62.5 mg/mL IM sotrovimab through Day 29 and 
Week 24 
Part C: 
• 
To characterize the PK of IV sotrovimab in 
Cohort 1 and/or Cohort 2 through Day 29 and 
Week 24 
• 
Serum PK of sotrovimab  
 
Safety  
Part A: 
• 
To evaluate the safety and tolerability profile of 
100 mg/mL IM sotrovimab administered at 
anterolateral thigh and deltoid injection sites and 
the 62.5 mg/mL formulation administered 
dorsogluteally through Day 29 
• 
To evaluate the safety and tolerability profile of 
100 mg/mL IM sotrovimab administered at the 
dorsogluteal, anterolateral thigh, and deltoid 
injection sites and the 62.5 mg/mL formulation 
administered dorsogluteally through Week 35 
Part B: 
• 
To evaluate the safety and tolerability profile of 
100 mg/mL and/or 62.5 mg/mL IM sotrovimab 
administered at up to 2 injection sites through 
Day 29 and Week 35 
Part C:  
• 
To evaluate the safety and tolerability profile of IV 
sotrovimab in Cohort 1 and/or Cohort 2 through 
Week 35 
 
Part A and Part B: 
• Incidence of AEs, SAEs, and AESI through 
Day 29/Week 35 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part C: 
• 
Incidence of AEs, SAEs, and AESI through 
Week 35 
 

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Overall Design: 
This is a Phase 1, parallel group, randomized, single-dose study to evaluate the PK, 
safety, and tolerability of IM and IV sotrovimab, at different concentrations, doses, 
routes, and/or sites of administration, in male or female healthy participants aged 
18 to 65 years.  
The study consists of 3 parts (Part A, an optional Part B, and Part C).  
Part A and Part B will be open-label and the enrollment will be sequential, starting with 
Part A. Part A and Part B participants will receive a single 500 mg dose of sotrovimab for 
IM injection.  
Part C will be open-label, wherein participants in Cohort 1 will receive a single 3000 mg 
dose of IV sotrovimab infused over 60 minutes and participants in optional Cohort 2 will 
receive up to 3000 mg dose of IV sotrovimab infused over the time period to be specified 
in the pharmacy manual.  
Brief Summary: 
The purpose of this study is to evaluate PK, safety, and tolerability of sotrovimab 
administered by IM injection or IV infusion in healthy participants aged 18 to 65 years. 
Study details include: 
• Study Duration:  
The study duration is 35 weeks after dosing. Participants can be screened up to 28 
days before dosing; therefore, the maximum duration a participant will be in the 
study is 39 weeks.  
• Treatment Duration:  
o Part A and Part B: A single dose of 500 mg IM sotrovimab injection will 
be administered on Day 1. 
o Part C: A single infusion of 3000 mg IV sotrovimab in Cohort 1 and up to 
3000 mg IV sotrovimab in optional Cohort 2 will be administered on Day 
1. 
• Visit Frequency:  
o 
In Part A, Part B, and Part C, on Day 1, participants will have a study site 
visit for study intervention administration. Additionally, participants in Part 
A and Part B will need to complete a PRO assessment at home on Day 1, 
and will also need to complete a PRO assessment at the site on Days 2, 3, 
5, and 8. 
o 
In all Parts, participants will need to return to the study site on Days 2, 3, 
and 5 and at Weeks 2, 3, and 4 (Day 29). At Weeks 8, 12, 20, and 24, the 
participants will also need to return to the site or have a home visit. 
o 
In Part A, Part B, and Part C, at Week 35, the participants will have a 
phone call visit.  

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Number of Participants: 
Part A: 
Part A will consist of 4 treatment arms. Participants will be randomized in a 2:2:1:1 ratio 
to 4 treatment arms, as described under “Intervention Groups and Duration”. 
Approximately 190 participants will be enrolled assuming a 20% rate of non-evaluable 
participants to achieve approximately 150 evaluable participants across the 4 treatment 
arms.  
Part B: 
Part B is optional and will consist of either 1 or 2 treatment arms (N=32/arm), described 
under “Intervention Groups and Duration”. 
Approximately 32 participants will be enrolled per treatment arm assuming a 20% rate of 
non-evaluable participants to achieve approximately 25 evaluable participants within 
each treatment arm. 
If 2 treatment arms are opened in parallel in Part B, then participants will be equally 
randomized to both treatment arms. However, if only 1 treatment arm is opened for Part 
B or 2 treatment arms are opened sequentially, then participants will not be randomized.  
Part C:  
Part C will consist of one cohort (Cohort 1: 3000 mg) with an additional optional cohort 
(Cohort 2: up to 3000 mg) to potentially explore further IV doses of sotrovimab and/or 
alternative infusion rates. This is further described under “Intervention Groups and 
Duration.” Cohort 1 and optional Cohort 2 enrollment are sequential. 
Approximately 200 evaluable participants (intend to target up to approximately 20 
Japanese participants) will be enrolled to Cohort 1, and approximately 50 evaluable 
participants will be enrolled to Cohort 2 to supplement the Cohort 1 data. 
Evaluable participants:  
Part A and Part B:  
Evaluable participants are defined as those who have PK concentration data to allow 
estimation of the primary endpoints (i.e., AUCD1-29 and Cmax). 
Part C:  
Evaluable participants are defined as those who have received study intervention. 
Intervention Groups and Duration: 
For all three parts of the study, screening assessment will be performed within 28 days 
prior to dosing, leading to a maximum study duration of 39 weeks. 

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Part A: 
Participants will be randomized in a 2:2:1:1 ratio to the following 4 treatment arms: 
• 500 mg IM of 62.5 mg/mL sotrovimab administered into the dorsogluteal muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the dorsogluteal muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the anterolateral thigh 
muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the deltoid muscles 
Approximately 63 participants will be randomized to each of the 62.5 mg/mL and 
100 mg/mL dorsogluteal arms, respectively, and approximately 32 participants will be 
randomized to each of the 100 mg/mL anterolateral thigh and deltoid arms, respectively. 
Participants will be stratified by sex and 2 BMI strata (18 to 25 and >25 to 30 kg/m2) to 
aim for a balance of treatment arms within each stratum in the study.  
Part B: 
Part B is optional and will consist of 1 or 2 treatment arms with 32 participants per 
treatment arm, to allow for assessment of 500 mg IM dose of 100 mg/mL and/or 
62.5 mg/mL sotrovimab administered at the same and/or different injection 
volume/number of injections/sites of injections than those evaluated in Part A. Potential 
injection sites to be evaluated in Part B include deltoid, thigh, dorsogluteal, and/or 
ventrogluteal. Part B will start enrolling participants once Part A has completed 
enrollment.  
Participants will be enrolled to target a similar representation of sex and BMI groups with 
those from Part A.   
Part A and Part B:  
For both Part A and Part B, injection volumes in the deltoid muscle will not exceed 
2.5 mL/injection and injection volumes in thigh and gluteal muscles will not exceed 
5 mL/injection. Follow-up will occur via site and home visits for 24 weeks, a phone call 
visit at Week 35, and PRO assessments through Day 8.  
Part C: 
Part C will assess a single 3000 mg dose of IV sotrovimab in Cohort 1 and up to 3000 mg 
dose of IV sotrovimab in an optional Cohort 2 in healthy participants.  
The sotrovimab formulation used in this part will be the 100 mg/mL concentration, which 
will be diluted as described in the pharmacy manual prior to administration.  
The enrollment of Part C participants will not be linked to Part A and Part B enrollment. 
Data Monitoring/Other Committee:  
A JSRT will perform the following reviews during the study: 

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• Review of safety data at regular intervals as described in the JSRT charter. 
• Review of data from a sentinel cohort for Part A and Part B will occur after all of 
the treatment arms within a study Part have approximately 5 participants who 
have completed at least Day 8. The JSRT will decide for each treatment arm 
whether to: 
o continue enrollment 
o stop enrollment 
o have the dose administered using a lower volume of injection by 
increasing the number of injections (e.g., 2 injections consisting of 2.5 mL 
instead of 1 injection consisting of 5 mL)  
o enroll an additional 5 participants per treatment arm before making a 
decision. 
• Review of data from Part A to inform the decisions on whether to proceed with 
Part B and which treatment arms would be included in Part B.  
• Review of data for Part C: 
o An in-stream safety lead-in data review will occur after approximately 30 
participants in Cohort 1 have completed at least Day 8. JSRT will decide 
whether to continue with Cohort 1 and may request additional data before 
making a decision. 
o No dosing of further participants will take place until after the review is 
completed. 

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1.2. 
Schema 
 
 
 

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1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities: Part A and Part B 
 
 
 
 
W1 
W2 W3 W4 W8 W12 W20 W24 W35 
 
 Study Visit Day  Visit Window 
Screening1 
(up to Day -
28)
Day -1 
Day 1 
Day 2 
Day 3 
Day 5±1d 
Day 8±1d 
Day 15±1d 
Day 29±2d 
Day 57±4d 
Day 85±7d 
Day 140±7d 
Day 168±7d 
Day 
245±7d 
Notes16 
 
 
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, and 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, and immediately 
after injections. Vital signs will be monitored at approximately 15 minutes, 
30 minutes, and 1 hour after dosing. 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 15 
minutes, 30 minutes, and 1 hour post-dose and on Day 2, Day 3, Day 5, 
and Day 8. All ISRs need to be followed by the PI to resolution.  
6. Triplicate 12-lead ECGs will be collected at Screening.  
7. On Day 1, PIN_TS3.0 assessment will be performed before bedtime (at 
home). Assessments on Days 2, 3, 5, and 8 will be performed when 
participants arrive at the site.  
8. On Day 1, Pain-NRS will be assessed at 15 minutes, 30 minutes, and 1 
hour after dosing (at site) and before bedtime (at home). Assessments on 
Days 2, 3, 5, and 8 will be performed when participants arrive at the site.   
9. Baseline laboratory assessments should be collected on Day -1.  
10. Hematology assessments will be performed only on Days -1, 2, 5, 8, and 
29. 
11. Screening and Day -1 tests must be >24 hours apart. 
12. Urine or serum pregnancy test, as per local guidelines. See Section 
8.3.5.  
13.  Day 1 sample collection will occur pre-dose, and at 1, 2, 6, 8, 24 (Day 2), 
and 48 (Day 3) hours after the first injection. On other days, samples will 
be collected once at any time during the day. 
 
Site visit (S), home visit (H), or call (C) 
S 
S S S S S S S S S/H S/H S/H S/H C 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history (including 
medication/drug/alcohol/tobacco use, allergies, 
illnesses, and SARS-CoV-2 
infection/therapy/vaccination) 
X 
X2  
 
 
 
 
 
 
 
 
 
 
 
 
Randomization  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study intervention administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Assessments 
Complete (C) or brief (B) physical examination 
C3 
 
B 
 
B B 
 
 
 
 
 
 
 
 
Vital signs (BP, PR, RR, temperature, SpO2)4 
X 
 X4 X X X X X X X 
X 
X 
X 
 
Local injection site tolerability assessment 
 
 X5 X5 X5 X5 X5  
 
 
 
 
 
 
12-lead ECG 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
PIN_TS3.07 
 
 
X X X X X 
 
 
 
 
 
 
 
Pain-NRS8 
 
 
X X X X X 
 
 
 
 
 
 
 
Sample collection 
Safety laboratory assessments (hematology10, clinical 
chemistry, coagulation) 
X 
X9  
X 
 
X X 
 
X X 
X 
 
X 
 
Urinalysis and urine albumin to creatinine ratio 
X 
X 
 
 
 
 
X X X X 
 
 
X 
 
Urine drug/alcohol screening 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B and C screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 molecular test11 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test12 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Blood sample for PK analysis13 
 
 X13 X X X X X X X 
X 
X 
X 
 
Blood sample for immunogenicity testing (ADA and 
drug-neutralizing antibody) 
 
 X14  
 
 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE review 
 
 <================ X =================> 
 
SAE review 
X15 
X15 <================ X =================> 
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AESI and concomitant medication review 
 
 <================ X =================> 
14. On Day 1, sample collection will occur pre-dose. 
15. At Screening and on Day -1, only SAEs related to study participation or a 
GSK product will be reported. 
16. If participant withdraws early from the study prior to Week 24, then the 
W24 visit assessments will be performed as the ED/EW visit. If the 
participant withdraws early from the study after Week 24, the W35 visit 
assessments will be performed as the EW visit. 

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Table 2 
Schedule of Activities: Part C 
 
 
 
 
W1 
W2 W3 W4 W8 W12 W20 W24 W35 COVID-
19 Test 
 
 
Study Visit Day  Visit Window 
Screening1 
(up to Day -28) 
Day -1 
Day 1 
Day 2 
Day 3 
Day 5±1d 
Day 8±1d 
Day 15±1d 
Day 29±2d 
Day 57±4d 
Day 85±7d 
Day 140±7d 
Day 168±7d 
Day 245±7d 
Notes13 
 
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, and 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 IV Infusion, and 
immediately after IV infusions. Vital signs will be monitored at 
approximately 15 minutes, 30 minutes, 45 minutes, 1 hour, and 
2 hours post dose. Participants will remain on site for 8 hours 
post-administration of study intervention for PK assessments. 
They will also have vitals measured prior to discharge. Vital 
signs on other days should be performed once at any time of 
the day.  
5. 
Triplicate 12-lead ECGs will be collected at Screening. Single 
ECG will be performed on Day 1 (post dose) and Days 2 and 8 
unless an abnormality is noted, in which case a triplicate ECG 
should be obtained.  
6. 
Baseline laboratory assessments should be collected on Day -1. 
7. 
Hematology assessments will be performed only on Days -1, 2, 
5, 8, 15 and 29. 
8. 
Screening and Day -1 tests must be >24 hours apart. 
 
 
9. 
Urine or serum pregnancy test, as per local guidelines. See 
Section 8.3.5.  
10. On Day 1, PK sample collection will occur pre-dose, end of 
infusion, and at approximately 1, 2, 6, and 8 hours following end 
of infusion. On other days, PK samples will be collected once 
per visit. 
11. On Day 1, sample collection will occur pre-dose. 
12. At Screening and on Day -1, only SAEs related to study 
participation or a GSK product will be reported. 
13. If participant withdraws early from the study prior to Week 24, 
then the W24 visit assessments will be performed as the 
ED/EW visit. If the participant withdraws early from the study 
after Week 24, the W35 visit assessments will be performed as 
the EW visit. 
 
Site visit (S), home visit (H), or call (C) 
S 
S 
S 
S 
S 
S 
S 
S 
S S/H S/H S/H S/H 
C 
S/C 
 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history (including medication/drug/alcohol/tobacco use, 
allergies, illnesses and SARS-CoV-2 infection/therapy/vaccination) 
X 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study intervention administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assessments 
Complete (C) or brief (B) physical examination 
C3 
 
B 
 
B 
B 
 
 
 
 
 
 
 
 
 
COVID-19 signs/symptoms review 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, RR, temperature, SpO2)4 
X 
 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG 
X5 
 
X5 
X5 
 
 
X5 
 
 
 
 
 
 
 
 
Sample collection 
Safety laboratory assessments (hematology7, clinical chemistry, 
coagulation) 
X 
X6 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Urinalysis and urine albumin to creatinine ratio 
X 
X 
 
 
 
 
X 
X 
X 
X 
 
 
X 
 
 
Urine drug/alcohol screening 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B and C screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 molecular test8 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Pregnancy test9 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Blood sample for PK analysis10 
 
 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Blood sample for immunogenicity testing (ADA and drug-neutralizing 
antibody) 
 
 
X11 
 
 
 
 
 
X 
 
X 
X 
X 
 
 
 
AE review 
 
 
<================ X =================> 
 
 
SAE review 
X12 
X12 
<================ X =================> 
 
 
AESI and concomitant medication review 
 
 
<================ X =================> 
 
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Abbreviations: Ab = antibody; ADA = anti-drug antibodies; AE = adverse event; AESI = adverse events of special interest; anti-N = anti-nucleocapsid; anti-S = anti-spike; BP = blood 
pressure; COVID-19 = Coronavirus disease 2019; d = day; GSK = GlaxoSmithKline; ECG = electrocardiogram; eCRF = electronic case report form; ED = early discontinuation; EW = 
early withdrawal; HIV = human immunodeficiency virus; PI = principal investigator; PK = pharmacokinetic; PR = pulse rate; RR = respiratory rate; SAE = serious adverse event; SARS-
CoV-2 = severe acute respiratory syndrome coronavirus-2; SpO2 = oxygen saturation; W = week. 
• 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 plasma 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 CA and 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 ICF. The changes will be approved by the CA and the EC before implementation. 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
This is a Phase 1, parallel group, randomized, single-dose study to evaluate the PK, 
safety, and tolerability of IM and IV sotrovimab, at different concentrations, doses, 
routes, and/or sites of administration, in male or female healthy participants aged 18 to 65 
years. 
Preventing infection and reducing the risk of progression of COVID-19 remains an 
urgent public health priority. While currently available vaccines have been shown to be 
highly efficacious, the elderly population and those with comorbidities remain at higher 
risk of hospitalization following COVID‑19 infection than the general population. Many 
patients who are at high risk of hospitalization with COVID-19 require extensive 
in‑hospital care, including ICU and mechanical ventilation, which heightens the resource 
burden on hospitals, particularly during infection peak periods. There remains an unmet 
need for effective treatments to prevent infection and prevent the progression from mild 
to severe disease and treat severe disease. 
As the COVID-19 pandemic continues to evolve with the rapid evolution of VOI/VOCs, 
healthcare professionals treating COVID-19 infections will need to identify the best 
treatment for their patient based on the circulating variants and underlying comorbidities. 
In addition to the current 62.5 mg/mL concentration, a 100 mg/mL ready-to-fill bulk drug 
substance, leveraging the same formulation, is being pursued in an effort to lower the 
injection volume when injected intramuscularly. This will allow additional injection sites 
to be used. The 100 mg/mL concentration is also being studied as an IV infusion. Both 
release testing and extended characterization results for the Gen2, 100 mg/mL samples 
showed a high degree of comparability to results from the Gen2 62.5 mg/mL batches, 
with the exception of attributes expected to be impacted by the change in product 
concentration and change in vial configuration.  
Considering the infrastructural and infection control-related concerns associated with IV 
mAbs for SARS-CoV-2, there remains a critical unmet medical need for treatments with 
a convenient route of administration [Sitlani, 2021; Snowbeck, 2021]. A mAb 
administered via IM injection could increase access in the outpatient setting and among 
certain groups who may be at high risk for severe disease. Administration via IM dosing 
could also reduce the drug delivery-related burden on the healthcare system [Lin, 2021; 
Ordal, 2021; Sakata T, 2021; Traynor, 2021], substantially increasing the availability of 
efficacious early treatment for patients with COVID-19 at high risk for disease 
progression. 
Sotrovimab has been studied in a Phase 3 placebo-controlled study evaluating the 
efficacy of sotrovimab in preventing progression of COVID-19 in high-risk participants 
with mild/moderate COVID-19 (VIR-7831-5001; COMET-ICE). On 10 March 2021, the 
Independent Data Monitoring Committee for COMET-ICE recommended that the study 
be stopped for enrollment due to evidence of clinical efficacy. This was based on an 
interim analysis of data from 583 participants which demonstrated an 85% (p=0.002) 

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reduction in hospitalization or death in participants receiving sotrovimab compared to 
placebo. Sotrovimab was well-tolerated with no safety signals detected [Vir, 2021]. 
The COMET-TAIL study was then designed to assess the efficacy, safety, and 
tolerability of IM sotrovimab versus IV sotrovimab when given to high-risk participants 
for the treatment of mild/moderate COVID-19. This study evaluated the clinical efficacy 
of two dose levels of IM sotrovimab compared with IV sotrovimab in preventing 
progression of COVID-19 by utilizing a NI design. Enrollment was completed on 19 
August 2021 and the Day 29 analysis indicated the following: in the IM administration 
(500 mg) arm of the study, there was a 2.7% rate of progression to hospitalization for 
more than 24 hours or death through Day 29 of the study, compared to 1.3% in the IV 
administration arm (also 500 mg). The adjusted difference between the IM and IV arms 
of the study was 1.11% with a 95% CI of -1.24% to 3.45%. The upper bound of the 95% 
CI was within the predetermined 3.5% NI margin set for the study’s primary endpoint in 
consultation with the US FDA. Sotrovimab 500 mg IM injection was found to be well-
tolerated and non-inferior to IV administration [Shapiro, 2022]. 
Since then, several factors have contributed to the need for evaluation of different doses 
of sotrovimab. First, the emergence of the Omicron variant and its sub-lineages have 
caused the landscape to evolve substantially as described in the COVID-19 treatment 
guidelines from the NIH [NIH, 2022]. 
This COSMIC study consists of 3 parts (Part A, an optional Part B, and Part C). The aim 
of Part A of this study is to provide the safety, tolerability, and relative bioavailability 
data to support the transition from the current concentration of 62.5 mg/mL to the higher 
concentration of 100 mg/mL of 500 mg IM sotrovimab following dorsogluteal injection 
and to explore 2 additional IM injection sites: anterolateral thigh and deltoid.  
Part B of this study is optional and will allow an assessment of 500 mg IM dose of 
100 mg/mL and/or 62.5 mg/mL sotrovimab administered at the same and/or different 
injection sites or volumes than those evaluated in Part A. Potential injection sites to be 
evaluated in Part B include deltoid, thigh, dorsogluteal, and/or ventrogluteal. 
Part C of this study is an open-label, single IV infusion part to characterize the safety and 
tolerability of 3000 mg sotrovimab in Cohort 1 and up to 3000 mg sotrovimab in an 
optional Cohort 2. Cohort 2 will be opened to potentially assess a different infusion rate 
and/or dose than Cohort 1. A decision on whether to proceed with Cohort 2 including the 
selection of dose and infusion rate will be made by the JSRT and the clinical team based 
on the review of safety lead-in data from Cohort 1. This will provide safety and 
tolerability data to support the intended clinical doses to be evaluated in COVID-19 
treatment and prophylactic indications.  
2.2. 
Background 
In December 2019, SARS-CoV-2, a novel betacoronavirus, was first reported to cause 
severe pneumonia in Wuhan, China and subsequently had a rapid spread around the 
world. As of 11 August 2022, 587,497,872cases of COVID-19 have been reported 
globally, including 6,427,420 associated deaths [Johns Hopkins University and Medicine, 

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2022]. As of 11 August 2022, around 92,296,142 cases have been reported with over 
1,030, 010 associated deaths in the US [CDC, 2022]. 
Sotrovimab is being developed for treatment of COVID-19. Sotrovimab is a human 
IgG1κ mAb derived from the parental mAb S309, a mAb directed against the spike 
protein of SARS-CoV-1 that potently cross-neutralizes SARS-CoV-2, the causative agent 
of COVID-19 [Pinto, 2020]. Sotrovimab received EUA and temporary market 
authorization based on the results from VIR-7831-5001 (214367, also known as 
COMET-ICE [NCT04545060]). COMET-ICE is a seamless FIH/Phase II/III study 
assessing the safety and efficacy of a single 500 mg IV dose of sotrovimab for the early 
treatment of COVID-19 in non-hospitalized participants at high risk for progression and 
subsequent hospitalization. 
Sotrovimab retains neutralization activity in vitro against almost all of the current 
VOCs/VOIs of the SARS-CoV-2 virus as defined by the World Health Organization, 
including, but not limited to, B.1.1.7 (Alpha, UK origin), B.1.351 (Beta, South Africa 
origin), P.1 (Gamma, Brazil origin), B.1.427/B.1.429 (Epsilon, California origin) B.1.526 
(Iota, New York origin), B.1.617.1 (Kappa, India origin), B.1.617.2 (Delta, India origin), 
AY.1 (Delta Plus, India origin), AY.2 (Delta Plus, India origin), C.37 (Lambda, Peru 
origin), B.1.621 (Mu, Colombia origin), and B.1.1.529 (Omicron, South Africa origin) 
[Cathcart, 2022] variant spike proteins with fold-changes in EC50 values of less than 5-
fold as compared to wild-type spike. In vitro neutralization experiments indicate that 
sotrovimab neutralizes authentic Omicron BA.2 virus with a 15.7-fold change in EC50 
value relative to wild-type [Cathcart, 2022]. Sotrovimab neutralized authentic Omicron 
BA.2 virus with a geometric mean EC90 value of 9476.3 ng/mL (range: 6796.8 to 
14760.0 ng/mL; 35.1-fold change in EC90 value relative to wild-type) (PC-7831-0155). 
Sotrovimab neutralized authentic Omicron BA.4 and Omicron BA.5 virus with an EC50 
value of 2650.7 ng/mL (48.4-fold change) and 1001.2 (21.6-fold change), respectively 
(PC-22-0117). 
2.2.1. 
Clinical Experience with Sotrovimab 
As of 18 August 2021, a total of 1843 participants have received sotrovimab (500 mg 
dose) administered IV or IM in the Vir sponsored clinical studies.  
Sotrovimab received an EUA and temporary market authorization based on the results 
from the VIR-7831-5001 study (GSK Study 214367, also known as COMET-ICE). 
COMET-ICE is a seamless FIH/Phase II/III study assessing the safety and efficacy of a 
single 500 mg IV dose of sotrovimab for the early treatment of COVID-19 in non-
hospitalized participants at high risk for progression and subsequent hospitalization.  
Other ongoing Vir-sponsored study includes COMET-TAIL (NCT04913675), and 
completed studies include COMET-PEAK (VIR-7831-5006/GSK Study 216912; 
NCT04779879) and a pharmacokinetic (PK) study with Japanese participants (VIR-7831-
5009/GSK Study 217653; NCT04988152). A summary of SAE and other safety data are 
included for these studies in the IB update, version 3. GSK has been supporting Vir in the 
conduct of the Vir-sponsored clinical studies. 

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GSK is sponsoring an ongoing pediatric clinical study (COMET-PACE [GSK Study 
215226/VIR-7831-5005]) of sotrovimab in participants aged birth to <18 years. 
In addition, Vir/GSK supported clinical studies (ACTIV-3-TICO [VIR-7831-5004, GSK 
Study 215149], BLAZE-4 [VIR-7831-5007, 217079], and Study 217940 [OPTIMISE-
C19]) are evaluating sotrovimab as a single agent or in combination. Details of these 
studies are included in the IB update, version 3.   
Sotrovimab at 1000 mg IV is also being evaluated in the UK-based RECOVERY 
platform study (NCT04381936). In this study, hospitalized participants with confirmed 
COVID-19 are randomized to receive different candidate therapies. The RECOVERY 
Trial Independent Data Monitoring Committee’s 10 June 2022 review of safety and 
efficacy data, inclusive of 1070 participants that received 1000 mg IV sotrovimab, 
suggested no reason to modify the protocol [DMC Report, 2022].  
Sotrovimab at 2000 mg IV is also being evaluated in the ongoing COMET-TAIL safety 
sub-study (VIR-7831-5008/GSK Study 217114; expected n=81) for early treatment and 
PROTECT-V study (Investigator Sponsored Study; GSK Study 218216; expected 
n=1760) for prophylaxis.  
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 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(s): Sotrovimab 
Hypersensitivity reactions 
(HSRs) reported any time 
post dose  
While sotrovimab is a human immunoglobulin G1 (IgG1) mAb, 
hypersensitivity is a potential general risk associated with the mAb class of 
therapeutics. 
Patients who are treated with monoclonal antibodies are at potential risk for 
developing HSR. This risk may be higher for higher doses or faster infusion 
rates.  
In Part C Cohort 1, 3000 mg of the study intervention will be administered 
over 60 minutes. It is the first time that this particular dose and infusion rate 
of sotrovimab have been used (refer to IB for further details of sotrovimab 
dose and infusion time previously used). 
There was no evidence of systemic infusion reactions in toxicology studies 
conducted with sotrovimab in monkeys. 
In COMET-ICE, all HSRs were non-serious, of Grade 1 (mild) or Grade 2 
(moderate) severity and reported in 2% of participants who received 
sotrovimab and in <1% who received placebo (9 participants treated with 
sotrovimab; 5 participants treated with placebo). None of the reactions in 
either treatment arm led to pausing or discontinuation of the infusions. All 
events across both treatment groups were reported as resolved or resolving 
at the time of DCO.  
No anaphylaxis events were reported in the COMET-ICE study in 
participants with mild to moderate COVID-19 not requiring hospitalization at 
study entry. 
A potentially life-threatening allergic reaction (anaphylaxis) was observed in 1 
adult participant who received sotrovimab in the study of individuals 
• Participants will be excluded if they have a history 
of hypersensitivity to any of the constituents 
present in the investigational product. 
• Participants will be monitored for 1 hour in Part A 
and Part B. 
• Participants will remain on site for 8 hours post-
administration of study intervention for PK 
assessments. They will also have vitals measured 
prior to discharge (see SoA in Section 1.3).  
• Investigational product will be administered in the 
clinic with staff trained in emergency care and 
resuscitation procedures and emergency care kit 
on hand during the study intervention 
administration and post-therapy observation 
periods. 
• In Part C, initial dosing in Cohort 1 and Cohort 2 
will be staggered so that the first 2 participants 
will be considered sentinels and will be dosed at 
the same clinical trial site. After at least 24 hours 
(post dose), and provided the investigator 
considers the safety and tolerability of the 
sentinels to be acceptable, the remainder of the 
participants will be dosed as non-sentinel 
participants. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
hospitalized with COVID-19 (the ACTIV-3-TICO study). Spontaneous post 
marketing cases of anaphylaxis have been reported. 
As of 16 March 2022, no anaphylaxis or serious HSRs were reported in any 
of the 500 mg IV, 500 mg IM, or 250 mg IM sotrovimab arms in COMET-TAIL 
study. 
The RECOVERY trial DMC letter dated 10 June 2022 noted that recruitment 
is ongoing and as of 07 June 2022, 1070 participants had been randomized 
1:1 (sotrovimab: standard of care). This trial DMC letter (dated 10 June 2022) 
also confirmed that review of safety data on 1070 patients (1:1 sotrovimab: 
standard of care) was completed and that the trial may continue with no 
changes in conduct [DMC Report, 2022]. The RECOVERY team has 
confirmed that there have been only 2 related SAEs reported. The first was a 
case of suspected anaphylaxis treated with adrenaline. The participant 
apparently improved within 2 hours without further complication and was 
discharged 5 days later. The second was a rash shortly after finishing the 
infusion considered to be an HSR. The participant was discharged 2 days 
later. 
• Approximately 30 participants will be enrolled in a 
safety lead-in in Part C Cohort 1, and relevant 
safety data through Day 8 will be reviewed by the 
JSRT. 
• The JSRT will review the safety data of this study 
at regular intervals.  
• In Part C Cohort 2, the dose and infusion rate of 
the study intervention will be decided based on a 
safety review of Cohort 1.  
• For details on discontinuation of study 
intervention and temporary discontinuation, refer 
to Section 7.1 and Section 7.1.2. 
• General guidance on management of HSRs is 
provided in Section 10.6. 
• Refer to Section 8.4.7 for follow up regarding 
AESI.  
Infusion-Related Reactions 
(IRRs) within 24 hours post 
dose (Part C) 
IRRs are a potential general risk for biologic therapies with IV administration. 
This risk may be higher for higher doses or shorter infusion times. However, 
sotrovimab and other COVID-19 mAbs have been generally well-tolerated.  
There was no evidence of infusion reactions in toxicology studies conducted 
with sotrovimab in monkeys. 
In the COMET-ICE study, in participants with mild/moderate COVID-19 with 
high risk of progression, IRRs that occurred within 24 hours post infusion 
(pyrexia, chills, dizziness, dyspnea, pruritus, rash, and IRR) were reported in 
7 (1%) of participants in the sotrovimab arm and 6 (1%) of participants in the 
placebo arm. All IRRs were non-serious, and Grade 1 or 2 severity and none 
led to treatment interruption or discontinuation. In the sotrovimab arm, all of 
• 
Participants will remain on site for 8 hours post-
administration of study intervention for PK 
assessments. They will also have vitals 
measured prior to discharge (see SoA in Section 
1.3).  
• In Part C, initial dosing in Cohort 1 and Cohort 2 
will be staggered so that the first 2 participants 
will be considered sentinels and will be dosed at 
the same clinical trial site. After at least 24 hours 
(post dose), and provided the investigator 
considers the safety and tolerability of the 
sentinels to be acceptable, the remainder of the 

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Potential Risk of Clinical 
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Summary of Data/Rationale for Risk 
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the cases of IRRs were considered resolved and in the placebo arm 1 
participant had an event considered not resolved at the time of EoS analysis 
(Week 24). 
participants will be dosed as non-sentinel 
participants. 
• Approximately 30 participants will be enrolled in a 
safety lead-in in Part C Cohort 1, and relevant 
safety data through Day 8 will be reviewed by the 
JSRT. 
• 
Infusion time can be extended at the discretion 
of the Investigator or Sponsor based on infusion-
related symptoms or other safety findings.  
• 
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). See Section 
7.1.2. 
• 
Investigators are instructed to discontinue IV 
infusions for participants who develop Grade 3 or 
4 infusion reactions using the DAIDS Table for 
Grading the Severity of Adult and Pediatric 
Adverse Events, version 2.1 (July 2017) Adverse 
Event grading. See Section 10.3.3. 
• 
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.  
• 
Refer to Section 8.4.3 for follow up regarding 
AESI. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Injection Site Reaction (ISR) 
(Part A and Part B) 
Sotrovimab will be administered via IM injection, which has a potential risk of 
local ISRs.  
In a single dose IM local tolerance study in mini pigs at a dose of 250 mg 
(4 mL, 62.5 mg/L), no ISRs were observed. 
The IM route of administration is being evaluated in the COMET-PEAK study. 
Injection site reactions (dorsogluteal) were reported in 10 out of 82 
participants, who were included in the safety population for the IM 
dorsogluteal injection in COMET-PEAK Part B and showed an acceptable 
tolerability profile for IM [GlaxoSmithKline, 2021]. One ISR occurred 
immediately post-dose, and the rest occurred within the first hour post-dose. 
All of the ISRs were Grade 1.  
• ISRs will be monitored very closely for 1 hour 
after injection and on Day 2, Day 3, Day 5, and 
Day 8 for all participants. Monitoring will also be 
performed for systemic symptoms post-dosing 
(e.g., fever, chills, malaise). 
• The JSRT will review safety data of this study at 
regular intervals as described in Section 10.1.5.1. 
Immunogenicity 
While sotrovimab is a human IgG, the development of ADA that have the 
potential to impact safety and/or efficacy are a potential general risk 
associated with the mAb class of therapeutics. 
Through Day 29 in the COMET-ICE study, the incidence of treatment-
emergent anti-sotrovimab antibody responses has remained low with 
relatively low titers, with no detectable impact on safety or efficacy. 
• This study includes collection of samples for 
assessment of ADA and potential impact on 
PK/PD and safety. ADA samples will be collected 
for a period of 24 weeks.  
ADE due to sub-neutralizing 
/levels of sotrovimab 
enhancing fusion or leading 
to FcγR mediated increased 
viral uptake and replication 
with virus production; ADE 
due to enhanced disease 
pathology from viral antigen-
antibody related immune 
complex deposition or 
complement activation and 
This is a concern related to the potential for participants who are infected 
with COVID-19 after administration of study intervention with sub-neutralizing 
mAb levels to experience a higher incidence of infection and/or more severe 
disease compared to participants with no circulating mAb and/or established 
protective immunity to SARS-CoV-2.  
ADE associated with Dengue virus 1-4 serotype infections is one of the most 
widely cited examples in which reinfection with a different serotype can, in a 
minority of patients, run a more severe course in the setting of limited 
antibodies generated by prior infection. 
The potential for enhanced disease in this setting is due to increased uptake 
of virus by FcγR-expressing cells, such as macrophages, and increased viral 
This study will include participant follow-up for a 
period of 35 weeks in all Parts to assess for the 
potential of enhanced disease in the context of 
waning sotrovimab levels. 
Periodic review of clinical signs and symptoms of 
COVID-19, clinical chemistry, AEs, end-organ 
disease and histopathological diagnoses will be 
performed by the JSRT to identify potential cases of 
immune complex disease. 
Assessments for unusually severe disease in mAb-
treated participants will be performed by the JSRT. 

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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
immune cell recruitment in 
target organs 
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. 
There is the possibility that a large amount of antibody that binds, but does 
not neutralize virus in the presence of a high viral load could result in immune 
complex deposition and complement activation in tissue sites of high viral 
replication, such as the lungs, vascular endothelia, renal or cardiovascular 
tissue [Hamming, 2004], leading to tissue damage/immune complex disease. 
This is hypothesized to have contributed to inflammation and airway 
obstruction observed in the small airways of infants who received a formalin-
inactivated respiratory syncytial virus vaccine [Polack, 2002] and in a few 
cases of fatal H1N1 influenza infection [Wu , 2010]. 
The potential for enhanced disease in this setting may be due to low affinity 
or cross-reactive antibodies with poor or no neutralizing activity.  
Triggering of cytokine release by antibody-virus-FcγR interactions although 
usually highly beneficial due to their direct antiviral effects and immune cell 
recruitment to control viral spread in tissues, also has the potential to 
enhance pathologic changes initiated by the viral infection. 
Observational data from 20,000 COVID-19 patients treated with 
convalescent plasma, although not placebo controlled, is suggestive that 
even polyclonal mixtures of neutralizing and non-neutralizing antibodies can 
be safely administered [Joyner, 2020]. 
Sotrovimab shows potent binding in vitro as well as neutralization of 
pseudovirus and live virus thus this risk is deemed to be low. In clinical 
studies to date there is no evidence ADE associated with sotrovimab. 
Infection will be assessed as new AEs/SAEs related 
to COVID-19 infection during follow-up period. 

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2.3.2. 
Benefit Assessment 
There is an unmet need for treatments for COVID-19 both in an outpatient and inpatient 
setting. Participation in this study will provide valuable scientific knowledge about 
sotrovimab administered with different doses, routes, and concentrations. Sotrovimab is 
being developed for the treatment of COVD-19. 
Part A and Part B of this study will evaluate the relative bioavailability, safety, and 
tolerability of the higher concentration IM sotrovimab at different sites of injection.  
Data from Part C of the study may support dosing options for therapeutics and effective 
preventive measures for COVID-19 against emerging variants. This may include higher 
doses in hospitalized and non-hospitalized patients or repeat dosing in prophylaxis 
especially for vulnerable patients who do not respond optimally to vaccines or 
appropriate people who cannot tolerate COVID-19 vaccinations. In addition, given the 
pressure on healthcare resources during the pandemic and the need to find treatments that 
ease the burden on healthcare facilities, data from the study may support a range of 
infusion times to ensure continued access in an inpatient and outpatient setting.  
No studies to assess direct benefit to healthy volunteers (e.g., as a prophylaxis) have been 
completed, although a pre-exposure prophylaxis study is underway and participants may 
benefit from an unknown duration of protection from COVID-19 disease (PROTECT-V 
GSK Study 218216). Therefore, no direct benefit for healthy participants in this study is 
currently known.  
Sotrovimab has been demonstrated to be a highly potent human IgG1 neutralizing 
SARSCoV-2 antibody with additional antibody effector functions that has been well-
tolerated to date. The nonclinical pharmacology, PK, toxicology, and clinical results to 
date support the evaluation of sotrovimab in healthy volunteers. 
Mitigation strategies, including physical examinations and laboratory evaluations 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 considers the potential benefit of treatment for 
COVID-19 with IM and IV administration of sotrovimab.  
Sotrovimab has the potential to be an effective therapeutic in mild to moderately ill 
participants with COVID-19. This benefit has been demonstrated among participants 
with mild to moderate COVID-19 at high risk of disease progression [Vir, 2021]. The 
data from this Phase 1 study may support future development of optionality in terms of 
IV doses and IM route of administration.  
Human-derived mAbs with similar Fc modifications as sotrovimab have a well-
established safety profile [Gaudinski, 2018].  
To date, sotrovimab is well-tolerated in clinical trials with no safety concerns that would 
preclude single-dose evaluation in healthy volunteers. 

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There may be little or no direct benefit to healthy volunteers participating in the study 
beyond the knowledge that they may have contributed to the development of a medicine 
that may be used in the COVID-19 pandemic. A potential for benefit from prophylaxis 
from infection or progression to disease in those who acquire COVID-19 during the study 
may also exist, though this is as yet unproven and unquantified and may be negligible in 
a healthy volunteer population. The potential risks associated with sotrovimab can be 
appropriately mitigated by the proposed inclusion and exclusion criteria and safety 
monitoring procedures. As such, the risk to potential participants is considered low. The 
overall benefit-risk assessment of this study is considered favorable.  
 
 

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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
Pharmacokinetics  
Part A: 
To estimate the relative bioavailability of 
100 mg/mL IM sotrovimab at the dorsogluteal 
injection site relative to the 62.5 mg/mL 
formulation administered dorsogluteally 
through Day 29 
Sotrovimab PK parameters: AUCD1-29 and 
Cmax  
Safety  
Part A: 
To evaluate the safety and tolerability 
profile of 100 mg/mL IM sotrovimab and 
the 62.5 mg/mL formulation at the 
dorsogluteal injection site through Day 29 
Part C:  
• To evaluate the safety and tolerability 
profile of IV sotrovimab in Cohort 1 
and/or Cohort 2 through Day 29 
Incidence of all AEs, SAEs, and AESI through 
Day 29  
Secondary 
Pharmacokinetics  
Part A: 
• To estimate the relative bioavailability 
of 100 mg/mL IM sotrovimab at 2 
alternative injection sites 
(anterolateral thigh and deltoid) 
relative to the 62.5 mg/mL formulation 
administered dorsogluteally through 
Day 29 
Part B: 
• To estimate the relative bioavailability 
of 100 mg/mL and/or 62.5 mg/mL IM 
sotrovimab at up to 2 injection sites 
Sotrovimab PK parameters: AUCD1-29 and 
Cmax  

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Objectives 
Endpoints 
relative to the 62.5 mg/mL formulation 
administered dorsogluteally through 
Day 29 
Part C: 
• 
To characterize the PK of IV sotrovimab 
in Cohort 1 and/or Cohort 2 through Day 
29 
Pharmacokinetics  
Part A: 
• To estimate the relative bioavailability of 
100 mg/mL IM sotrovimab at 3 injection 
sites (dorsogluteal, anterolateral thigh, and 
deltoid) relative to the 62.5 mg/mL 
formulation administered dorsogluteally 
through Week 24 
 
Part B:  
• To estimate the relative bioavailability of 
100 mg/mL and/or 62.5 mg/mL IM 
sotrovimab at up to 2 injection sites relative 
to the 62.5 mg/mL formulation 
administered dorsogluteally through Week 
24 
Sotrovimab PK parameter: AUCinf  
Pharmacokinetics  
Part A and Part B: 
• To characterize the PK of 100 mg/mL and 
62.5 mg/mL IM sotrovimab through 
Day 29 and Week 24 
Part C: 
• To characterize the PK of IV sotrovimab in 
Cohort 1 and/or Cohort 2 through Day 29 
and Week 24 
• Serum PK of sotrovimab  
 
Safety  
Part A: 
• To evaluate the safety and tolerability 
profile of 100 mg/mL IM sotrovimab 
administered at anterolateral thigh and 
 
Part A and Part B: 
• Incidence of AEs, SAEs, and AESI through 
Day 29/Week 35 

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Objectives 
Endpoints 
deltoid injection sites and the 62.5 mg/mL 
formulation administered dorsogluteally 
through Day 29 
• To evaluate the safety and tolerability 
profile of 100 mg/mL IM sotrovimab 
administered at the dorsogluteal, 
anterolateral thigh, and deltoid injection 
sites and the 62.5 mg/mL formulation 
administered dorsogluteally through 
Week 35 
Part B: 
• To evaluate the safety and tolerability 
profile of 100 mg/mL and/or 62.5 mg/mL 
IM sotrovimab administered at up to 2 
injection sites through Day 29 and Week 
35 
Part C:  
• To evaluate the safety and tolerability 
profile of IV sotrovimab in Cohort 1 and/or 
Cohort 2 through Week 35 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Part C: 
• Incidence of AEs, SAEs, and AESI through 
Week 35 
Other Safety 
Part A and Part B: 
• To evaluate the safety and tolerability of 
sotrovimab following IM administration 
through Day 29 and Week 35 
Part C: 
• To evaluate the safety and tolerability of 
IV sotrovimab in Cohort 1 and/or Cohort 2 
through Day 29 and Week 35 
• Incidence of clinically significant changes 
in vital signs and laboratory abnormalities 
change from baseline through Day 29 and 
Week 35 
 
Exploratory 
PRO (Part A and Part B) 
• Evaluate the pain, ISR, and acceptability 
of both the 62.5 mg/mL and 100 mg/mL 
formulations of sotrovimab administered 
intramuscularly 
• Totally acceptable or very acceptable pain 
and totally acceptable or very acceptable 
local reaction acceptability score on 
PIN_TS3.0 at Days 1, 2, 3, 5, and 8 
• Pain intensity on pain-NRS at 15 minutes, 
30 minutes and 1 hour after dosing and 
before bedtime on Day 1, and Days 2, 3, 5, 
and 8 

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Objectives 
Endpoints 
• Scores of PIN_TS3.0 domains 
(bothersomeness of ISRs, impact on sleep, 
impact on movement), and scores of four 
individual items (anxiety before injection, 
bothersomeness during injection, 
satisfaction with the injection system, and 
willingness to receive as a treatment) on 
Days 1, 2, 3, 5, and 8 
Co-primary Estimands (Part A) 
The primary clinical question of interest is: what is the relative bioavailability and safety 
profile of 100 mg/mL IM sotrovimab administered at the dorsogluteal injection site 
relative to the 62.5 mg/mL IM formulation administered dorsogluteally in participants 
through Day 29? 
CCI

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The PK primary estimand is described by the following attributes: 
• Population: Male or female healthy participants aged 18 to 65 years who would 
be able to complete the IM dose.  
• Endpoints: Sotrovimab serum PK parameters: AUCD1-29 and Cmax.  
• Treatments: 100 mg/mL IM sotrovimab vs 62.5 mg/mL IM sotrovimab 
(dorsogluteal injections). 
• Strategy for intercurrent event: The intercurrent event of interest is participants 
receiving an incomplete IM dose. The strategy for handling this intercurrent event 
will be a Principal Stratum Strategy, where we are only interested in the strata of 
participants who would be able to receive a complete IM dose. Exclusion of 
participants who did not receive a complete IM dose will not introduce bias as the 
reasons for dose interruption are not related to their PK. 
• Population-level summary: The point estimate for the ratio of the geometric 
means of 100 mg/mL treatment group compared to the 62.5 mg/mL treatment 
group and the related 90% CI will be calculated. 
The Safety primary estimand is described by the following attributes: 
• Population: Male or female healthy participants aged 18 to 65 years. 
• Endpoints: Incidence of all AEs, SAEs, and AESI through Day 29 (i.e., all events 
on the database at the time of DCO).  
• Treatments: 100 mg/mL IM sotrovimab and 62.5 mg/mL IM sotrovimab 
(dorsogluteal injections). 
• Strategy for intercurrent event: The intercurrent event of interest is participants 
receiving an incomplete IM dose. The strategy for handling this intercurrent event 
will be a Treatment Policy Strategy, where all safety data after the intercurrent 
event will be included.  
• Population-level summary: Frequency and percentage of participants. 
Primary Estimand (Part C) 
The primary clinical question of interest is: what is the safety and tolerability of IV 
infusion of sotrovimab at 3000 mg dose in Cohort 1 and also not exceeding 3000 mg dose 
in an optional Cohort 2? 
The Safety primary estimand is described by the following attributes: 
• Population: Male or female healthy participants aged 18 to 65 years. 
• Endpoints: Incidence of all AEs, SAEs, and AESI through Day 29 (i.e., all events 
on the database at the time of DCO).  
• Treatments: Single IV infusion of sotrovimab at 3000 mg dose in Cohort 1 and 
single IV infusion of sotrovimab at up to 3000 mg dose in an optional Cohort 2. 
• Strategy for intercurrent event: The intercurrent event of interest is participants 
receiving an incomplete IV dose. The strategy for handling this intercurrent event 

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will be a Treatment Policy Strategy, where all safety data after the intercurrent 
event will be included.  
• Population-level summary: Frequency and percentage of participants. 
Rationale for Estimands: 
Two different strategies are proposed for the same intercurrent event of participants 
receiving an incomplete IM/IV dose, as interest lies in:  
• the PK of treatment effect in participants who received complete dose, and  
• safety of treatment effect for any level of exposure to study intervention.   
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 1, parallel group, randomized, open-label, single-dose study to evaluate 
the PK, safety, and tolerability of IM and IV at different concentrations, doses, routes, 
and/or sites of administration, in male or female healthy participants aged 18 to 65 years.  
The study consists of 3 parts (Part A, an optional Part B, and Part C).  
The aim of Part A of this study is to evaluate the safety, tolerability, and relative 
bioavailability of the 62.5 mg/mL concentration and the new 100 mg/mL concentration 
of sotrovimab following dorsogluteal injection, as well as the relative bioavailability of 
the 100 mg/mL concentration at 2 additional IM injection sites, anterolateral thigh, and 
deltoid.  
The aim of Part B of this study, if conducted, is to evaluate the relative bioavailability of 
100 mg/mL and/or 62.5 mg/mL IM sotrovimab at up to two injection sites (deltoid, thigh, 
dorsogluteal, and/or ventrogluteal) relative to the 62.5 mg/mL dorsogluteal arm that is 
enrolled in Part A, as well as characterize the PK and evaluate the safety of 100 mg/mL 
sotrovimab at up to two injection sites. 
Enrollment will be sequential for Parts A and B, starting with Part A. An IA will be 
performed once half of the participants in Part A complete at least Day 8. A decision on 
whether to proceed with Part B will be made by the JSRT and the clinical team after the 
IA. If the decision is made to proceed with Part B, then Part B of this study will include 1 
or 2 treatment arms that would allow for the evaluation of additional injection 
volumes/number of injections/sites of injections than those evaluated in Part A. The 
decision about which treatment arms to include in Part B will be informed by tolerability 
data during part A and clinical considerations. Part B will start enrolling participants once 
Part A has completed enrollment.  
The aim of Part C of this study is to characterize the safety and tolerability of single IV 
infusion of 3000 mg sotrovimab in Cohort 1 and up to 3000 mg sotrovimab in an optional 
Cohort 2. Cohort 2 will be opened to potentially assess a different infusion rate and/or 
dose than Cohort 1. The sotrovimab formulation used in this part will be the 100 mg/mL 
concentration, which will be diluted as described in the pharmacy manual prior to 

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administration. Part C is a single IV infusion study, and the enrollment of participants 
will not be linked to Part A and Part B enrollment. 
In Parts A, B and C of the study, all participants will receive a single dose of sotrovimab 
on Day 1. Additionally, participants in Part A and Part B will need to complete a PRO 
assessment at home on Day 1, and will also need to complete a PRO assessment at the 
site on Days 2, 3, 5, and 8.  
In all Parts, participants will need to return to the study site on Days 2, 3 and 5 and at 
Weeks 2, 3, and 4 (Day 29). At Weeks 8, 12, 20, and 24, the participants will need to 
return to the site or have a home visit. At Week 35, the participants in all Parts will have 
a phone call visit.  
The study duration is 35 weeks after dosing. Participants can be screened up to 28 days 
before dosing; therefore, the maximum duration a participant will be in the study is 39 
weeks.  
Part A: 
Part A is open-label and participants will be randomized in a 2:2:1:1 ratio to the 
following 4 treatment arms: 
• 500 mg IM of 62.5 mg/mL sotrovimab administered into the dorsogluteal muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the dorsogluteal muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the anterolateral thigh 
muscles  
• 500 mg IM of 100 mg/mL sotrovimab administered into the deltoid muscles 
Approximately 190 participants will be enrolled assuming a 20% rate of non-evaluable 
participants to achieve approximately 150 evaluable participants across the 4 treatment 
arms. Therefore, the randomization ratio of 2:2:1:1 will result in approximately 
63 participants randomized to each of the 62.5 mg/mL and 100 mg/mL dorsogluteal 
arms, respectively, and approximately 32 participants randomized to each of the 
100 mg/mL anterolateral thigh and deltoid arms, respectively. Participants will be 
stratified by sex and 2 BMI strata (18 to ≤25 and >25 to 30 kg/m2).  
Part B: 
Part B is optional and will consist of either 1 or 2 treatment arms (N=32/arm), as 
described under “Intervention Groups and Duration”. 
Approximately 32 participants will be enrolled per treatment arm assuming a 20% rate of 
non-evaluable participants to achieve approximately 25 evaluable participants within 
each treatment arm. 
If 2 treatment arms are opened in parallel in Part B, then participants will be equally 
randomized to both treatment arms. However, if only 1 treatment arm is opened for Part 
B or 2 treatment arms are opened sequentially, then participants will not be randomized. 
Participants will be enrolled to target a similar representation of sex and BMI groups with 
those from Part A.   

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Part B will allow assessment of 500 mg IM dose of 100 mg/mL and/or 62.5 mg/mL 
sotrovimab administered at the same and/or different injection volume/number of 
injections/sites of injections than those evaluated in Part A. Potential injection sites to be 
evaluated in Part B include deltoid, thigh, dorsogluteal, and/or ventrogluteal. An IA will 
be performed once half of the participants in Part A complete at least Day 8. The 
selection of treatment arms will be informed by the JSRT and the clinical study team 
after the IA. Part B will start enrolling participants once Part A has completed enrollment. 
Part A and Part B: 
The injection volume in the deltoid will not exceed 2.5 mL/injection. The injection 
volume in the gluteal muscles and thigh will not exceed 5 mL/injection. Follow-up will 
occur via site and home visits, and a phone call visit (as per the SoA, Section 1.3) for 35 
weeks. Part A and Part B participants will receive a single 500 mg dose of sotrovimab for 
IM injection. 
As an exploratory endpoint, this study will assess participant perception of the ISR, 
including pain (pain-NRS), bothersomeness of ISR, impact on sleep, impact on 
movement, and acceptability of the ISR (PIN_TS3.0 assessment).  
For both Parts A and B, the JSRT will assess ISRs by reviewing data from a sentinel 
cohort. The sentinel cohort review will occur after all of the treatment arms within a 
study Part have approximately 5 participants who have completed at least Day 8. During 
review of the sentinel cohort, the JSRT will make one of the following decisions for each 
treatment arm: 
• to continue enrollment in that treatment arm 
• to stop enrollment in that treatment arm 
• to have the dose administered using a lower volume of injection for that treatment 
arm by increasing the number of injections (e.g., 2 injections consisting of 2.5 mL 
instead of 1 injection consisting of 5 mL) 
• to enroll an additional 5 participants in the treatment arm before making a 
decision. 
The JSRT will also review safety data at regular intervals as described in the JSRT 
charter for both Parts A and B. Refer to Section 10.1.5 for details regarding the JSRT.  
Evaluable participants are defined as those who have PK concentration data to allow 
estimation of the primary endpoints (i.e., AUCD1-29 and Cmax) and inclusion in the 
analysis. 
Part C: 
Part C is open-label, and participants will receive single IV infusion. Enough healthy 
participants will be screened to ensure approximately 200 participants (intend to target up 
to approximately 20 Japanese participants) are enrolled in Cohort 1 to receive a 3000 mg 
dose of sotrovimab infused over 60 minutes. Cohort 2 is optional and participants will 
receive a dose of up to 3000 mg infused over the time period to be specified in the 
pharmacy manual. 

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Part C participants will receive study intervention as sotrovimab (100 mg/mL) diluted for 
IV infusion. Refer to Section 6.1 and pharmacy manual for details. Cohort 1 and optional 
Cohort 2 enrollment are sequential.  
Cohort 1:  
• Initial dosing in this cohort will be staggered so that the first 2 participants will be 
considered sentinels and will be dosed 3000 mg sotrovimab administered 
intravenously at the same clinical trial site. After at least 24 hours (post dose), and 
provided the investigator considers the safety and tolerability of the sentinels to be 
acceptable, the remainder of the participants will be dosed as non-sentinel 
participants.  
• An in-stream safety lead-in data review will occur after approximately 30 
participants have completed at least Day 8. JSRT will decide whether to continue 
with Cohort 1 and whether to proceed with Cohort 2 including the selection of 
dose and infusion rate. No dosing of further participants will take place until after 
the review is completed. 
• Approximately 170 additional participants will then be enrolled into this cohort.  
• An IA, including all data collected, will be conducted after approximately half of 
the participants in Cohort 1 complete at least Day 15 to support periodic data 
reviews across the program. 
Cohort 2:  
• A decision on whether to proceed with Cohort 2 including the selection of dose 
and infusion rate will be made by the JSRT and the clinical team based on the 
review of safety lead-in data from Cohort 1.  
• Initial dosing in this cohort for the 2 sentinel participants will follow the same 
procedure as mentioned above in Cohort 1.  
The JSRT will also review safety data at regular intervals as described in the JSRT 
charter for Part C. Refer to Section 10.1.5 for details regarding the JSRT.  
Participants in Part C will be enrolled in the study for up to 28 days screening; will 
receive a single dose of sotrovimab on Day 1 at the study site; will return to the study site 
on Days 2, 3, and 5 and at Weeks 2, 3, and 4 (Day 29); will also return to the study site or 
have a home visit at Weeks 8, 12, 20 and 24; and will have an end-of-treatment follow-up 
period through 35 weeks. 
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. A 
participant will be considered enrolled if the informed consent is not withdrawn prior to 
participating in any study activity after screening. 

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4.2. 
Scientific Rationale for Study Design 
This is a Phase 1 healthy participant study with 3 parts (Part A, an optional Part B, and 
Part C).  
In addition to the current 62.5 mg/mL concentration, a 100 mg/mL ready-to-fill bulk drug 
substance, leveraging the same formulation, is being pursued in an effort to lower the 
injection volume when injected intramuscularly. This will allow additional injection sites 
to be used. The 100 mg/mL concentration is also being studied as an IV infusion. 
Part A and an optional Part B of this study are open-label, parallel group, randomized 
parts, which will evaluate the safety, tolerability, and relative bioavailability of the 
62.5 mg/mL concentration and the new 100 mg/mL concentration of sotrovimab 
following IM injections at different sites. Part A and Part B participants will receive a 
single 500 mg dose of sotrovimab for IM injection. 
Part C is an open-label, single IV infusion study, which will characterize the safety and 
tolerability of 3000 mg sotrovimab in Cohort 1 and up to 3000 mg sotrovimab in an 
optional Cohort 2. Cohort 2 will be opened to potentially assess a different infusion rate 
and/or dose than Cohort 1. 
Part A and Part B  
An open-label design is chosen as the injections are given at different sites and different 
number of injections may be used. Given the open-label design, investigators, site study 
staff, and participants will not be blinded.  
BMI and sex are principal determinants of parenterally administered mAb exposure. 
Therefore, in Part A, randomization to treatment arms will be stratified by sex and BMI 
to aim for a balance of strata between treatment arms. In Part B, participants will be 
enrolled to target similar representation of BMI and sex groups as in Part A. 
The number of participants randomized to each treatment arm will provide acceptable 
precision for estimation of relative bioavailability. Due to the extended t1/2 of 
sotrovimab, 24 weeks is expected to provide sufficient duration to ensure the extrapolated 
portion of the AUC will be less than 20%. 
Part C 
The safety profile of sotrovimab has been evaluated at doses up to 2000 mg across the 
sotrovimab program, and there are no data to suggest that a 3000 mg dose may not 
demonstrate equivalent safety and tolerability. Based on preclinical toxicology studies, 
the margins for Cmax and AUC of the 3000 mg at the monkey NOAEL are 14.8× and 
6.7×, respectively, providing a significant safety margin for the proposed dose. Taking 
these factors into account, it is considered that an open-label design is appropriate. 
CCI

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4.3. 
Justification for Dose 
The dose justification for the 500 mg dose (Part A and Part B) and the up to 3000 mg 
dose (Part C) are described below. 
Parts A and B 
A 500 mg IM dose of sotrovimab was selected for evaluation in Parts A and B of this 
study. A 250 mg and a 500 mg IM dose (dorsogluteal injection) are currently being 
evaluated in studies COMET-TAIL and COMET-PEAK. To date, in COMET-TAIL, 387 
participants have been dosed with 500 mg IM sotrovimab (dorsogluteal injection). In 
COMET-TAIL, treatment with 500 mg IM sotrovimab was demonstrated to be non-
inferior to 500 mg IV sotrovimab as measured by the proportion of study participants 
with mild or moderate COVID-19 progressing to >24 hours of hospitalization for acute 
management of any illness due to any cause or death through Day 29. The safety profile 
was also acceptable with a low rate of AEs in the 500 mg IM arm.   
Part C 
The proposed IV dose (up to 3000 mg) selected for Part C of this study was chosen to 
establish safety and tolerability across a range expected to encompass the intended 
clinical doses to be evaluated in treatment and prophylactic indications and be potential 
to cover future variants. 
The NOAEL for VIR-7831 was 500 mg/kg, the highest dose tested, when VIR-7831 was 
administered via IV infusion once a week for 2 weeks in cynomolgus monkeys (TX-
7831-0102). No IRRs were observed in the monkey toxicology study. Based on simulated 
Gen2 IV PK, the predicted AUCinf following a 3000 mg dose is 32,100 µg*day/mL and 
predicted Cmax is 912 µg/mL. Based on the proposed 3000 mg IV dose, the margins 
based on nonclinical Cmax and AUC at the monkey NOAEL are 14.8× and 6.7×, 
respectively. 
In addition, sotrovimab (500 mg IV/IM) has been well-tolerated within the clinical 
program. While anaphylaxis and HSR have been observed in patients treated with 
sotrovimab, 1 patient in a study evaluating sotrovimab in patients hospitalized with 
COVID-19 had anaphylaxis reported, was treated, and recovered. Review of other mAbs 
clinical programs showed that proportion of HSRs was similar across treatment arms and 
did not occur more frequently in higher dose groups. Therefore, both the toxicity and 
clinical studies support the use of sotrovimab for the treatment of COVID-19 in 
accordance with the proposed dose regimen and intended indications.  
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
A participant is considered to have completed the study if he/she completes the Week 35 
visit. 

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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. 
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. 
2. Participants must have received completed dose(s) in a SARS-CoV-2 vaccine series 
at the time of signing informed consent. Booster vaccines are permitted but not 
required. 
Type of Participant and Disease Characteristics 
3. Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, laboratory tests, and cardiac monitoring.  
4. Participants must be negative for COVID-19, determined by two consecutive 
negative results by any validated SARS-CoV-2 molecular test (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. 
5. For Part C, inclusion in the Japanese subgroup analysis, a participant must meet all 
of the following criteria: Japanese ancestry, defined as being a descendant of 4 ethnic 
Japanese grandparents and 2 ethnic Japanese parents. 
Weight 
Body weight must be 40 kg considering BMI within the range of 18 to 30 kg/m2.  
Sex and Contraceptive/Barrier Requirements 
6. Male and/or female. 
7. 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.   
• 
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: 
Contraceptive and Barrier Guidance. 
OR 

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b. Is a woman of childbearing potential (WOCBP) and using a contraceptive method 
that is highly effective, with a failure rate of <1%, as described in Section 10.4 
during the study intervention period and for at least ~5 half-lives 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. 
c. 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 for 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 
8. 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. Abnormal BP as defined as greater than 140 mm/Hg systolic, greater than 90 mm/Hg 
diastolic, or less than 90 mm/Hg systolic at Screening. BP at Screening is the 
average of 3 BP readings taken using the methods described in Section 8.3.2. 
3. Known hypersensitivity to any constituent present in the investigational product or 
history of severe hypersensitivity or anaphylaxis after receiving a COVID-19 
vaccine.  
4. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment HSRs (including, but not limited to, 
erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic 
epidermal necrolysis, and exfoliative dermatitis). 

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5. 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. 
6. For Part A and Part B, any condition that would prohibit receipt of IM injections in 
the investigator’s opinion, such as coagulation disorder, bleeding diathesis, or 
thrombocytopenia. 
7. Breast cancer within the past 10 years. 
8. Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN).  
9. Total bilirubin >1.5 × ULN (isolated total bilirubin >1.5 × ULN is acceptable if total 
bilirubin is fractionated and direct bilirubin <35%).  
10. Current or chronic history of liver disease or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones). 
11. Participants exposed to an individual known to be infected with COVID-19 by PCR 
testing within the 14 days prior to Screening.  
12. QT interval corrected using Fridericia’s formula (QTcF) >450 msec. 
Prior/Concomitant Therapy 
13. Use of any over-the-counter or prescription medications within 7 days (or 14 days if 
the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to 
dosing until completion of the follow-up visit, unless permitted in Section 6.8.  
14. Treatment with biologic agents (such as mAbs including marketed drugs) within 3 
months or 5 half-lives (whichever is longer) prior to dosing. 
15. Receipt of convalescent plasma from a recovered COVID-19 patient or anti-
SARS-CoV-2 mAb within the last 3 months. 
16. Receipt of any vaccine within 48 hours prior to enrollment.  
17. 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 
18. Participation in the study would result in loss of blood or blood products in excess of 
500 mL within a 56-day period. 
19. Exposure to more than 4 new chemical entities (e.g., investigational pharmaceuticals) 
within 12 months prior to the first dosing day. 
20. Enrollment in any investigational vaccine study within the last 180 days or enrollment 
in any other investigational drug study within 30 days prior to Day 1 or within 5 half-
lives of the investigational compound, whichever is longer.  
21. Current enrollment or past participation in this clinical study. 

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Diagnostic Assessments 
22. Presence of hepatitis B surface antigen (HBsAg) at Screening or within 3 months 
prior to first dose of study intervention. 
23. 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. 
24. 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. 
25. Positive pre-study drug/alcohol screen. 
26. Positive HIV antibody test. 
Other Exclusions 
27. 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.  
28. Regular use of known drugs of abuse. 
29. Sensitivity to any of the study interventions, or components thereof, or drug 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 be fasting while arriving at the Screening Visit. Participants will be 
allowed to eat during the Screening Visit after the blood sample is drawn for clinical 
chemistry analysis. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
• Participants will abstain from ingesting caffeine- or xanthine-containing products 
(e.g., coffee, tea, cola drinks and chocolate) for 6 hours prior to Screening. 
• Participants will abstain from alcohol for 24 hours prior to each visit to the clinic. 
• Participants must have a negative drug test at screening and must abstain from 
recreational drug use from screening until after the final follow-up visit. 
5.3.3. 
Activity 
Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests.  

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5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical 
study is 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 the 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.  
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study 
Intervention 
Not applicable.  
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 
Table 3 
Study Intervention(s) Administered 
Intervention 
Label 
Sotrovimab 
Injection, 
62.5 mg/mL 
Sotrovimab 
Injection, 
100 mg/mL  
Sotrovimab 
Infusion, 
100 mg/mL  
Sotrovimab 
Infusion, 
100 mg/mL  
Intervention on 
Label 
VIR-7831 
VIR-7831 
VIR-7831 
VIR-7831 
Type  
Biologic 
Biologic 
Biologic 
Biologic 
Dose 
Formulation  
Solution in single 
use vial 
(62.5 mg/mL) 
Solution in single 
use vial 
(100 mg/mL) 
Solution in single 
use vial 
(100 mg/mL) 
Solution in single 
use vial 
(100 mg/mL) 

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Unit Dose 
Strength(s)  
62.5 mg/mL 
(500 mg/8 mL) 
100 mg/mL 
(250 mg/2.5 mL) 
100 mg/mL 
(250 mg/2.5 mL) 
100 mg/mL 
(500 mg/5 mL) 
Dosage Level(s) 
500 mg (1 vial) 
500 mg (2 vials) 
Part C IV: Cohort 
1 – 3000 mg (12 
vials) 
 
Part C IV Optional 
Cohort 2 – up to 
3000 mg (up to 6 
vials) 
Route of 
Administration 
IM injection 
IM injection  
IV infusion 
IV infusion 
Infusion Time 
NA 
NA 
60 minutes 
Sotrovimab dose 
and infusion time 
will be decided 
based on a safety 
review of Cohort 1 
participants and 
will be specified 
in the pharmacy 
manual.  
Use 
Experimental 
Experimental 
Experimental 
Experimental 
IMP and NIMP 
IMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally 
by the 
sponsor/designee 
Provided centrally 
by the 
sponsor/designee 
Provided centrally 
by the 
sponsor/designee 
Provided centrally 
by the 
sponsor/designee 
Packaging and 
Labeling 
Study intervention 
will be provided in 
a single-use vial. 
Each single-use 
vial will be labeled 
as required per 
country 
requirement. 
Study intervention 
will be provided in 
a single-use vial. 
Each single-use 
vial will be labeled 
as required per 
country 
requirement. 
Study intervention 
will be provided in 
a single-use vial. 
Each single-use 
vial will be labeled 
as required per 
country 
requirement. 
Study intervention 
will be provided in 
a single-use vial. 
Each single-use 
vial will be labeled 
as required per 
country 
requirement. 
Current/Former 
Name(s) or 
Alias(es) 
Sotrovimab, 
Xevudy, VIR-7831, 
GSK4182136 
Sotrovimab, 
Xevudy, VIR-
7831, 
GSK4182136 
Sotrovimab, 
Xevudy, VIR-
7831, 
GSK4182136 
Sotrovimab, 
Xevudy, VIR-
7831, 
GSK4182136 
 

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Table 4 
Study Arms: Part A 
Arm Title 
IM 62.5 mg/mL 
sotrovimab into 
dorsogluteal  
IM 100 mg/mL 
sotrovimab into 
dorsogluteal 
IM 100 mg/mL 
sotrovimab into 
anterolateral 
thigh 
IM 100 mg/mL 
sotrovimab into 
deltoid 
Arm Type 
Experimental  
Experimental 
Experimental 
Experimental 
Arm Description 
Participants will 
receive 500 mg 
sotrovimab via two 
4 mL injections, 
one in each 
dorsogluteal 
muscle on Day 1. 
Participants will 
receive 500 mg 
sotrovimab on Day 
1. Injection volume 
in the dorsogluteal 
muscles will not 
exceed 
5 mL/injection. 
Participants will 
receive 500 mg 
sotrovimab on Day 
1. Injection volume 
in the anterolateral 
thigh will not 
exceed 
5 mL/injection. 
Participants will 
receive 500 mg 
sotrovimab on Day 
1. Injection volume 
in the deltoid will 
not exceed 
2.5 mL/injection. 
Associated 
Intervention 
Labels 
Sotrovimab 
Injection, 
62.5 mg/mL 
Sotrovimab 
Injection, 
100 mg/mL  
Sotrovimab 
Injection, 
100 mg/mL  
Sotrovimab 
Injection, 
100 mg/mL  
 
Table 5 
Study Arms: Part B 
Arm Title 
Optional Arm 1  
Optional Arm 2  
Arm Type 
Experimental  
Experimental 
Arm Description 
Participants will receive 500 mg of 
100 mg/mL and/or 62.5 mg/mL 
sotrovimab on Day 1.  
Participants will receive 500 mg of 
100 mg/mL and/or 62.5 mg/mL 
sotrovimab on Day 1.  
Associated 
Intervention 
Labels 
Sotrovimab Injection, 100 mg/mL 
and/or 62.5 mg/mL 
Sotrovimab Injection, 100 mg/mL and/or 
62.5 mg/mL 
 
The decision on the Part B treatment arms will be made as described in Section 4.1. 
Potential injection sites to be evaluated in Part B include deltoid, thigh, dorsogluteal, 
and/or ventrogluteal. Injection volume in the gluteal or thigh muscles will not exceed 
5 mL/injection. Injection volume in the deltoid will not exceed 2.5 mL/injection. 

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Table 6 
Study Cohorts: Part C 
Cohort Title 
Cohort 1  
Optional Cohort 2 
Cohort Type 
Experimental  
Experimental 
Cohort Description 
Participants will receive 3000 mg on 
Day 1  
Participants will receive up to 
3000 mg on Day 1  
Associated Intervention 
Labels 
Sotrovimab Infusion, 100 mg/mL 
diluted as per pharmacy manual 
Sotrovimab Infusion, 
100 mg/mL diluted as per 
pharmacy manual 
 
Part A, Part B, and Part C:  
Injections/infusions will be administered in the clinic with staff trained in emergency care 
and resuscitation procedures and an emergency care kit on hand during study intervention 
administration and post-therapy observation periods. 
 
6.2. 
Preparation, Handling, Storage and Accountability 
Instructions for the preparation of study intervention will be provided in a separate 
Pharmacy Manual. 
• 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. 
• 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. 
• The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study intervention accountability, 
reconciliation, and record maintenance (i.e., receipt, reconciliation, and final 
disposition records). 
• Further guidance and information for the final disposition of unused study 
intervention are provided in the Pharmacy Manual.  
• 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 

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or mists. In the case of unintentional occupational exposure notify the 
monitor, Medical Monitor and/or sponsor/designee study contact. 
• A MSDS/equivalent document describing occupational hazards and 
recommended handling precautions either will be provided to the investigator, 
where this is required by local laws, or is available upon request from GSK. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally randomized using an IVRS/IWRS. Before the study is 
initiated, the telephone number and call-in directions for the IVRS and/or the log in 
information and directions for the IWRS will be provided to each site.  
Study intervention will be dispensed on Day 1, as shown in the SoA (Section 1.3).  
Part A:  
In Part A, participants will be randomized 2:2:1:1 to receive  
• 500 mg of 62.5 mg/mL sotrovimab administered into the dorsogluteal muscles,  
• 500 mg of 100 mg/mL sotrovimab administered into the dorsogluteal muscles,  
• 500 mg of 100 mg/mL sotrovimab administered into the anterolateral thigh 
muscles, or  
• 500 mg of 100 mg/mL sotrovimab administered into the deltoid muscles, 
respectively.  
Participants will be stratified by sex and 2 BMI strata (18 to 25 and >25 to 30 kg/m2).  
Part B:  
In Part B, participants will receive a 500 mg IM dose of 100 mg/mL and/or 62.5 mg/mL 
sotrovimab. If two arms are opened in parallel in Part B, then participants will be equally 
randomized to both arms (N=32/arm). However, if Part B consists of just 1 treatment arm 
(N=32), or two arms opened sequentially (N=32/arm), then participants will not be 
randomized (N=32). Participants will be enrolled to target a similar representation of 
BMI and sex as in Part A. Enrollment into a specific sex and/or BMI group may be 
capped to achieve this target.  
Part C 
Part C will assess a single 3000 mg dose of IV sotrovimab in Cohort 1 and up to 3000 mg 
dose of IV sotrovimab in an optional Cohort 2 to investigate alternative dose and infusion 
rates in healthy participants. As Cohort 1 and Cohort 2 consist of just 1 treatment arm, 
participants will not be randomized.  
Part A, Part B and Part C:  
This is an open-label study; however, the specific intervention to be administered to a 
participant will be assigned using an IVRS/IWRS. The site will contact the IVRS/IWRS 
prior to the start of study intervention administration for each participant. The site will 

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record the intervention assignment on the applicable CRF, if required. Potential bias will 
be reduced by central randomization for Part A and Part B if 2 additional treatment arms 
are simultaneously recruited. 
6.4. 
Study Intervention Compliance 
Participants will receive study intervention directly from the investigator or designee, 
under medical supervision. The date and administrations time of each injection 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 intervention 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 CRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
6.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) that the participant is receiving 
at the time of enrollment or receives during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 

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• dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
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 not permitted following 90 days post-dosing per CDC guidelines 
(https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html). 
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 all vaccines while on study. 
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days 
if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the 
start of study intervention until completion of the follow-up visit, unless, in the opinion of 
the investigator and Medical Monitor, the medication will not interfere with the study.  
Paracetamol/acetaminophen, at doses of 2 g/day, is permitted for use any time during 
the study. Other concomitant medications may be considered on a case-by-case basis by 
the investigator in consultation with the medical monitor if required. 
Pharmaceutical methods of contraception as described in Section 10.4.2 are permitted for 
use at any time during the study. 
All prior and concomitant medication should be captured in the eCRF. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are detailed in Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention 
A participant will be permanently discontinued from completion of drug 
infusion/injection if they experience a Grade 3 or higher systemic reaction (see Section 
10.3 for AE grading). 
If treatment intervention is permanently discontinued after a partial dose is received, the 
participant will remain in the study to be evaluated for follow-up safety assessments as 
indicated in the SoA (Section 1.3).  
7.1.1. 
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. Liver 
chemistry increased monitoring criteria will apply if participant’s ALT is ≥ 3xULN and 

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are described in Section 10.5. Potential Hy’s Law case (ALT≥3xULN AND total 
bilirubin ≥ 2xULN (>35% direct bilirubin) or INR >1.5) must be reported as SAE. 
7.1.2. 
Temporary Discontinuation 
For Part A and Part B: If a participant experiences a Grade 2 systemic reaction after the 
first injection, investigators will be instructed to pause prior to the second injection. A 
subsequent injection may be administered at the investigator’s discretion, and/or after 
symptomatic treatment (e.g., antihistamines, IV fluids).  
For Part C: A participant will be temporarily discontinued from completion of drug 
infusion if they experience a Grade 2 (moderate) IRR, investigators will be instructed to 
pause the infusion. The infusion may subsequently resume at a slower pace at the 
investigator’s discretion, and/or after symptomatic treatment (e.g., antihistamines, IV 
fluids). 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• 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 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 the study intervention and 
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. 
7.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/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, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 

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• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.  
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. 
• 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 timeframe 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 3 years, as determined by the Investigator, 
should be reported. Details regarding history of medication, COVID-19 vaccination, 
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 [FDA, 2021]. The 
first test may be carried out at any time during Screening, the second test will be 
at Day -1 
 
 
. 
8.2. 
Efficacy Assessments 
Efficacy is not evaluated as a primary or secondary endpoint in this study; 
 
. 
8.3. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Height 
and weight will also be measured and recorded. 
• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
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8.3.2. 
Vital Signs 
• Temperature (oral preferred), pulse rate (PR), oxygen saturation, respiratory rate 
(RR), and BP will be assessed. 
• BP 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. 
• BP and pulse measurements should be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (e.g., television, cell phones). 
• Vital signs (to be taken before blood collection for laboratory tests) will consist of 
1 pulse and 3 BP measurements (3 consecutive BP readings will be recorded at 
intervals of at least 1 minute). The average of the 3 BP readings will be recorded. 
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 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.  
Before the ECG test, the participant should be at rest for approximately 10 minutes. The 
participant should be in the semi-recumbent or supine position. 
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. 
8.3.4. 
Clinical Safety Laboratory Tests 
• See Section 10.2 for the list of clinical laboratory tests to be performed and the 
SoA (Section 1.3) for the timing and frequency.  
• 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 (either at any timepoint as per SoA or any 
unscheduled assessment) should be repeated until the values return to normal or 
baseline or are no longer considered significantly abnormal by the investigator or 
medical monitor.  
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 Medical Monitor notified. 

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• 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 24 or at the Early Withdrawal 
Visit if a participant is withdrawn from the study prior to Week 24 during study 
intervention period. 
• 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. 
8.3.6. 
Local Injection Site Tolerability 
A local injection site tolerability assessment will be performed per the SoA (Section 1.3). 
Injection sites should be monitored for any AEs. Refer to Section 8.4.6 for assessment of 
AE severity. 
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 recording events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7).  

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The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• All AEs and SAEs will be collected from dose administration until Week 35 at the 
timepoints specified in the SoA (Section 1.3). However, any SAEs assessed as related 
to study participation (e.g., study intervention, protocol-mandated procedures, 
invasive tests, or change in existing therapy) or related to a GSK product will be 
recorded from the time a participant consents to participate in the study. 
• Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded as medical history/current medical 
conditions not as AEs. 
• All SAEs will be recorded and reported to 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 
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. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and nonleading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest (as defined in Section 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. 
8.4.4. 
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 
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• 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 SUSARs according to local 
regulatory requirements and GSK policy and forwarded to investigators as necessary. 
8.4.5. 
Pregnancy 
• Details of all pregnancies in female participants will be collected after the start of 
study intervention and until Week 35.  
• If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the female 
participant’s pregnancy. While pregnancy itself is not considered to be an AE or 
SAE, any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate for 
6 to 8 weeks after the date of delivery and the information will be forwarded to GSK. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to GSK as described in Section 8.4.4. 
While the investigator is not obligated to actively seek this information in former 
study participants, he or she may learn of an SAE through spontaneous reporting. 
8.4.6. 
Assessment of AE 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). 
8.4.7. 
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 GSK either 
during or at the end of the study (through Week 35). These will be updated during the 
course of the study based on accumulating safety data. 
Adverse event of special interest includes: 
• 
HSRs occurring any time post dose 
• 
IRRs within 24 hours post dose 
• 
Injection site reactions 

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• 
Immunogenicity  
• 
AEs potentially related to ADE of disease. 
8.4.7.1. 
Injection-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 
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 
Injections may be associated with local reactions (e.g., swelling, redness, pain). Study 
participants should be monitored after IM administration of study intervention for signs 
or symptoms of any ISRs as described in the SoA (Section 1.3). Local tolerability 
assessment is discussed in Section 8.3.6. 
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 24 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 
This AESI is relevant to participants who are infected with COVID-19 after 
administration of study intervention. ADE of disease theoretically can occur via 1 of 3 
previously described mechanisms: 
• By facilitating viral entry into host cells and enhancing viral replication in these 
cells 
• By increasing viral fusion with target host cells, enhancing viral replication in 
these cells 
• By enhancing disease pathology from viral antigen-antibody related immune 
complex deposition or complement activation and immune cell recruitment in 
target organs. 
The first two mechanisms are hypothesized to occur at sub-neutralizing antibody 
concentrations [Arvin, 2020]. This study will include participant follow-up for a period of 
5 half-lives to assess for the potential of enhanced disease in the context of waning 
sotrovimab levels, which may manifest as an increased incidence of re-infection or 
increased severity of re-infections after recovery from initial illness. The third mechanism 
is hypothesized to occur at high levels of antigen (i.e., viral load) and antibody potentially 
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viral replication. This may manifest as acute deterioration temporally associated with 
sotrovimab dosing or as increased severity or duration of illness in sotrovimab-treated 
participants vs. placebo-treated participants. 
As of 10 March 2021, enrollment into the COMET-ICE study, evaluating sotrovimab for 
the treatment of non-hospitalized individuals with mild to moderate COVID-19, has been 
stopped based on the recommendation of IDMC. The total of 1057 participants have been 
randomized to either the IV infusion of sotrovimab Gen1 (500 mg dose) or placebo. 
Based on the Joint SRT review of blinded data, there has been no confirmed events of 
ADE. The ACTIV-3 TICO study of sotrovimab treatment in hospitalized participants 
with COVID-19 symptoms, which was terminated due to futility, did not reveal any 
safety concerns overall and no ADE. The COMET-TAIL study did not reveal any safety 
concerns overall and no ADE. 
As described in Section 2.3.1, AEs potentially related to ADE of the disease will be 
reviewed by the JSRT to see if there are unusually severe manifestations of COVID-19 in 
treated individuals. 
8.5. 
Pharmacokinetics 
Blood samples for sotrovimab serum PK will be collected as detailed in the SoA 
(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, 1 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. 
Serum PK concentrations will be listed and summarized by treatment arm and visit in the 
PK analysis set. Pharmacokinetic parameters will be computed using standard 
noncompartmental methods. Parameters may include, but are not limited to AUCD1-29, 
Cmax, Clast, Tmax, Tlast, AUCinf, AUClast, %AUCexp, t1/2, z, Vz (IV), Vss (IV), CL 
(IV), V/F (IM), CL/F (IM). 
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 additional PK analyses will be included 
in the analysis plan. 

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8.7. 
Genetics 
Genetics are not evaluated in this study. 
8.8. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9. 
Immunogenicity Assessments 
Antibodies to sotrovimab will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). Additionally, serum samples should also 
be collected at the final visit from participants who discontinued study intervention or 
were withdrawn from the study. These samples will be tested by the sponsor or sponsor’s 
designee. 
Serum samples will be screened for antibodies binding to sotrovimab and the titer of 
confirmed positive samples will be reported. 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/designee. Samples collected for detection of antibodies to study 
intervention may also be evaluated for sotrovimab serum concentration as 
described in Section 8.5 to enable interpretation of the antibody data. Antibodies 
may be further characterized and/or evaluated for their ability to neutralize the 
activity of the study intervention(s). Genetic analyses will not be performed on 
these serum samples unless consent for this was included in the informed consent. 
Participant confidentiality will be maintained. At visits during which serum 
samples for the determination of PK and immunogenicity of sotrovimab will be 
taken, 1 sample of sufficient volume can be used. 
Samples may be stored for a maximum of 15 years (or according to local regulations) 
following the last participant’s last visit for the study at a facility selected by the 
sponsor/designee to enable further analysis of immune responses to sotrovimab. 
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8.11. 
Health Economics 
Health economics parameters are not evaluated in this study. 
8.12. 
Patient-reported Outcomes 
8.12.1. 
Perception of Injection 
Perception of Injection version 3 (PIN_TS3.0) will be used to assess the participant’s 
perception of the injection across four dimensions (how bothersome ISRs are, impact on 
sleep, impact on movement, and the acceptability of ISRs) and 4 individual items 
(anxiety before injection, bothersomeness during injection, satisfaction with the injection 
system, and willingness to receive as a treatment).  
PIN_TS3.0 is a 20-item questionnaire slightly modified from PIN version 1 for use in this 
study. PIN version 1 has been used previously in clinical trials studying ISR related to 
HIV treatment. PIN version 1 itself was adapted from VAPI questionnaire developed by 
Sanofi Pasteur, initially used for evaluating influenza vaccinations. Participants will 
provide a response for each PIN_TS3.0 item on a 5-point scale (1=most positive, 5=least 
positive). The timepoints for this assessment are provided in the SoA (Section 1.3). Paper 
PRO measures will be used in case ePRO is unavailable. Paper PRO will be brought to 
the site for data entry at the next visit. 
8.12.2. 
Injection Site Pain 
Pain-NRS will be used to assess the intensity of the pain at the injection site. Participants 
are asked to rate their pain at the injection site at this moment on an 11-point scale (0=No 
Pain, 10=Worst Pain Imaginable). Paper PRO measures will be used in case ePRO is 
unavailable. Paper PRO will be brought to the site for data entry at the next visit. 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
Part A: 
The primary objectives are to estimate the relative bioavailability, safety, and tolerability 
of single-dose high-concentration sotrovimab administered intramuscularly in healthy 
participants. There are no formal statistical hypotheses planned. 
Part B: 
The secondary objectives are to estimate the relative bioavailability, safety, and 
tolerability of single-dose high-concentration sotrovimab administered intramuscularly in 
healthy participants. There are no formal statistical hypotheses planned. 
Part C: 
The primary objectives are to characterize the safety and tolerability of IV sotrovimab 
administered in healthy participants. There are no formal statistical hypotheses planned. 
9.2. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis Set 
Description 
Screened  
All participants who were screened for eligibility. 
Enrolled 
All participants who entered the study. 
Note: screening failures (who never passed screening even if 
rescreened) 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 (PK) 
All participants in the Safety analysis set who had at least 1 non-missing 
PK assessment – i.e., PK sample collected and analyzed. Note: Non-
quantifiable [NQ] values will be considered as non-missing values. 
Participants will be reported according to the intervention they actually 
received. 
PK Principal Stratum  
All participants in the PK analysis set who would be able to complete the 
IM dose. Participants will be reported according to the treatment arm 
they actually received. 

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9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
The SAP will include a 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. 
Modelling and analysis for Part A will be separate from the analysis for Part B, with only 
the 62.5 mg/mL IM formulation from Part A being included as the comparative arm for 
the analysis of Part B treatment arms. 
For Part C, safety and PK data will be analyzed separately from Part A and Part B. 
A JSRT will review safety data at regular intervals as described in the JSRT charter for 
Parts A, B, and C.  
For both Parts A and B, the JSRT will assess ISRs by reviewing data from a sentinel 
cohort as described in Section 4.1. One of the decisions that can be made by the JSRT 
following review of safety data for the sentinel cohort would be to decrease the volume 
of each injection by increasing the number of injections. If the situation arises where the 
JSRT recommends the number of injections for the 100 mg/mL IM formulation at the 
dorsogluteal site is increased from 1 × 5 mL to 2 × 2.5 mL, PK data from all participants 
in the treatment arm will be combined and included in PK analyses. The same approach 
will be followed for secondary and exploratory endpoints. 
For Part C, a subgroup analysis of Japanese participants will be further explored. 
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis 
Part A 
The co-primary objectives of this study are to assess relative bioavailability and safety 
profile of 100 mg/mL IM sotrovimab at the dorsogluteal injection site relative to the 
62.5 mg/mL IM formulation administered dorsogluteally in participants through Day 29 
regardless of initiation of prohibited medications. For the analyses planned in the 
following sections, a potential intercurrent event that will be considered is participants 
receiving an incomplete IM dose. 
Events leading to missing data are participant withdrawal from study, lost to follow-up, 
or insufficient PK samples (determined per NCA analysis). 
Only participants who have sufficient PK samples (determined per NCA analysis) to 
estimate AUCD1-29 and Cmax will be included in the PK parameter summaries. The 
concentration data of such participants will also be included in the PK concentration 
summaries. For participants who had incomplete dose, their available PK data will be 
only listed. 
Part C 

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The primary objective of Part C of this study is to assess the safety profile of sotrovimab 
following administration of a single IV dose in participants through Day 29 regardless of 
initiation of prohibited medications. For the analyses planned in the following sections, a 
potential intercurrent event that will be considered is participants receiving an incomplete 
IV dose.  
9.3.2.1. 
Pharmacokinetics  
Table 7 
Primary Estimand for Primary Pharmacokinetics Endpoint (Part A) 
Primary Estimand  
Population 
Male or female healthy participants aged 18 to 65 years who would be able 
to complete the IM dose  
Variable/Endpoints 
Sotrovimab serum PK parameters: AUCD1-29 and Cmax 
Treatment 
100 mg/mL IM sotrovimab vs 62.5 mg/mL IM sotrovimab (dorsogluteal 
injections) 
Strategy for Intercurrent 
Events or Events 
Leading to Missing Data  
The intercurrent event of interest is participants receiving an incomplete IM 
dose. The strategy for handling this intercurrent event will be a Principal 
Stratum Strategy, where we are only interested in the strata of participants 
who would be able to receive a complete IM dose. Exclusion of participants 
who did not receive a complete IM dose will not introduce bias as the 
reasons for dose interruption are not related to their PK. 
Population-Level 
Summary 
The point estimate for the ratio of the geometric means of 100 mg/mL 
treatment group compared to the 62.5 mg/mL treatment group and the 
related 90% CI will be calculated.  
 
Log-transformed parameters (AUCD1-29 and Cmax) will be compared between treatment 
groups using ANCOVA models that include all four treatment groups, sex, and BMI (in 
kg/m2) as variables. Least square estimates of treatment differences (contrasts for each 
comparison of interest) will be back-transformed to estimate relative bioavailability with 
two-sided 90% CIs. This analysis will be based on the PK Principal Stratum Analysis Set. 
Further details will be included in the SAP. 

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9.3.2.2. 
Safety 
Table 8 
Primary Estimand of the Primary Safety Endpoint 
Part A: 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years 
Variable/Endpoints 
Incidence of all AEs, SAEs, and AESI through Day 29 (i.e., all events on 
the database at the time of DCO)  
Treatment 
100 mg/mL IM sotrovimab and 62.5 mg/mL IM sotrovimab (dorsogluteal 
injections) 
Strategy for Intercurrent 
Events or Events 
Leading to Missing Data  
The intercurrent event of interest is participants receiving incomplete IM 
dose. The strategy for handling this intercurrent event will be a Treatment 
Policy Strategy, where all safety data after the intercurrent event will be 
included. 
Missing data will not be imputed. 
Population-Level 
Summary 
Frequency and percentages of participants 
 
Part C Cohort 1: 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years 
Variable/Endpoints 
Incidence of all AEs, SAEs, and AESI through Day 29 (i.e., all events on 
the database at the time of DCO)  
Treatment 
Single IV infusion of sotrovimab at 3000 mg dose 
Strategy for Intercurrent 
Events or Events 
Leading to Missing Data  
The intercurrent event of interest is participants receiving incomplete IV 
dose. The strategy for handling this intercurrent event will be a Treatment 
Policy Strategy, where all safety data after the intercurrent event will be 
included. 
Missing data will not be imputed. 
Population-Level 
Summary 
Frequency and percentages of participants 
For Part C optional Cohort 2, similar Estimand strategy will be followed for treatment: 
Single IV infusion of sotrovimab at up to 3000 mg dose. 
Occurrence of AEs, SAEs, and AESIs will be displayed in the form of summaries and 
listings using the Safety population. Further details will be provided in the SAP. 

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9.3.3. 
Secondary Endpoint(s) 
9.3.3.1. 
Pharmacokinetics 
Table 9 
Primary Estimand for Secondary Pharmacokinetics Endpoint 
(Part A) 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years who 
would be able to complete the IM dose  
Variable/Endpoints 
• 
AUCD1-29 and Cmax through Day 29 
• 
AUCinf through Week 24 
• 
Serum PK of sotrovimab through Day 29 and Week 24 
Treatment Conditions 
• 
AUCD1-29 and Cmax through Day 29: 100 mg/mL 
sotrovimab (anterolateral thigh, deltoid) vs 62.5 mg/mL 
sotrovimab (dorsogluteal) 
• 
AUCinf through Week 24: 100 mg/mL IM sotrovimab at 
three injection sites (dorsogluteal, anterolateral thigh, 
and deltoid) compared to the 62.5 mg/mL formulation 
administered dorsogluteally 
• 
Serum PK of sotrovimab through Day 29 and Week 24: 
100 mg/mL and 62.5 mg/mL IM sotrovimab 
Strategy for Intercurrent Events or 
Events Leading to Missing Data  
The intercurrent event of interest is participants receiving an 
incomplete IM dose. The strategy for handling this intercurrent 
event will be a Principal Stratum Strategy, where we are only 
interested in the strata of participants who would be able to 
receive a complete IM dose. Exclusion of participants who did 
not receive a complete IM dose will not introduce bias as the 
reasons for dose interruption are not related to their PK.  
Population-Level Summary 
• 
AUCD1-29 and Cmax through Day 29: The point estimate 
for the ratio of the geometric mean of 100 mg/mL 
treatment group compared to the 62.5 mg/mL 
treatment group and the related 90% CI will be 
calculated 
• 
AUCinf through Week 24: The point estimate for the 
ratio of treatment group geometric means and the 
related 90% CI will be calculated 
• 
Serum PK of sotrovimab through Day 29 and Week 24: 
geometric mean 
 
The estimand strategy for secondary PK endpoints, including those for Part B, will be 
similar to the strategy described above; further details will be provided in the SAP. 

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Table 10 
Primary Estimand for Secondary Pharmacokinetics Endpoint (Part C 
Cohort 1) 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years who 
would be able to complete the IV dose  
Variable/Endpoints 
• 
AUCD1-29 and Cmax through Day 29  
• 
Serum PK of sotrovimab through Day 29 and Week 24 
Treatment Conditions 
• 
AUCD1-29 and Cmax through Day 29: Single IV infusion 
of sotrovimab at 3000 mg dose  
• 
Serum PK of sotrovimab through Day 29 and Week 24: 
Single IV infusion of sotrovimab at 3000 mg dose 
Strategy for Intercurrent Events or 
Events Leading to Missing Data  
The intercurrent event of interest is participants receiving an 
incomplete IV dose. The strategy for handling this intercurrent 
event will be a Principal Stratum Strategy, where we are only 
interested in the strata of participants who would be able to 
receive a complete IV dose. Exclusion of participants who did 
not receive a complete IV dose will not introduce bias as the 
reasons for dose interruption are not related to their PK.  
Population-Level Summary 
• 
AUCD1-29 and Cmax through Day 29: geometric mean 
• 
Serum PK of sotrovimab through Day 29 and Week 24: 
geometric mean 
For Part C optional Cohort 2, similar Estimand strategy will be followed for treatment: 
Single IV infusion of sotrovimab at up to 3000 mg dose. 
9.3.3.2. 
Safety  
Table 11 
Primary Estimand for Secondary Safety Endpoint (Part A and Part B) 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years 
Variable/Endpoints 
Incidence of all AEs, SAEs, and AESI through Day 29a/Week 35 
Treatment 
100 mg/mL IM sotrovimab administered at dorsogluteal, 
anterolateral thigh, and deltoid injection sites and 62.5 mg/mL IM 
sotrovimab administered dorsogluteally 
Strategy for Intercurrent Events 
or Events Leading to Missing 
Data  
The intercurrent event of interest is participants receiving 
incomplete IM dose. The strategy of handling this intercurrent event 
will be a Treatment Policy Strategy, where all safety data after the 
intercurrent event will be included. 
Missing data will not be imputed. 
Population-Level Summary 
Frequency and Percentages of participants 
aDay 29 for anterolateral thigh and deltoid injection sites only as dorsogluteal injection sites are included in the primary 
safety endpoint. 
 

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Table 12 
Primary Estimand for Secondary Safety Endpoint (Part C Cohort 1) 
Primary Estimand 
Population 
Male or female healthy participants aged 18 to 65 years 
Variable/Endpoints 
Incidence of all AEs, SAEs, and AESI through Week 35 (i.e., all events on 
the database at the time of DCO)  
Treatment 
Single IV infusion of sotrovimab at 3000 mg dose  
Strategy for Intercurrent 
Events or Events 
Leading to Missing Data  
The intercurrent event of interest is participants receiving incomplete IV 
dose. The strategy for handling this intercurrent event will be a Treatment 
Policy Strategy, where all safety data after the intercurrent event will be 
included. 
Missing data will not be imputed. 
Population-Level 
Summary 
Frequency and percentages of participants 
For Part C optional Cohort 2, similar Estimand strategy will be followed for treatment: 
Single IV infusion of sotrovimab at up to 3000 mg dose. 
9.3.4. 
Other Safety Endpoints 
The estimand strategy for other safety endpoints, for all study parts, will be provided in 
the SAP. 
9.3.5. 
Exploratory Endpoints 
Further details of the analysis methods for the exploratory endpoints for all study parts 
will be provided in the SAP.  
9.4. 
Interim Analysis 
Part A and B: 
In Part A and B, safety and tolerability data aggregated by treatment arm will be 
reviewed in-stream by the JSRT (see Section 10.1.5). A planned sentinel review will be 
conducted after approximately 5 participants per treatment arm complete at least Day 8 
visit as described in Section 4.1.  
Data from JSRT reviews may be used to inform study conduct or wider program 
decisions. These data will not be fully cleaned or undergo formal statistical analysis.  
An IA will be conducted to review Part A data after approximately half of the 
participants in Part A complete at least Day 8 visit. The purpose of this interim is to 
inform the decision on whether to open Part B, and if needed the selection of treatment 
arms; further details of this IA will be specified in the SAP. Recruitment into Part A will 
continue with no pause at the time of the interim. 
Thereafter, participants will continue to complete the remaining schedule of assessments 
as per the protocol.  
Part C: 

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In Part C, aggregated safety and tolerability data will be reviewed in-stream by the JSRT 
(see Section 10.1.5). A planned in-stream review of safety lead-in data from Cohort 1 
will be conducted after approximately 30 participants complete at least Day 8 visit as 
described in Section 4.1. The purpose of this review is to inform the decision to continue 
with Cohort 1 and whether to proceed with Cohort 2 including the selection of dose and 
infusion rate made by the JSRT and the clinical team. No dosing of further participants 
will take place until after the review is completed.  
Data from JSRT reviews may be used to inform study conduct or wider program 
decisions. These data will not be fully cleaned or undergo formal statistical analysis.  
An IA, including all data collected, will be conducted after approximately half of the 
participants in Cohort 1 complete at least Day 15, to support periodic data reviews across 
the program. Further details of this IA will be specified in the SAP.  
Thereafter, participants will continue to complete the remaining schedule of assessments 
as per the protocol.  
9.5. 
Sample Size Determination 
Part A and B 
The planned sample sizes for the number of evaluable participants in each treatment arm 
in Part A and Part B are based on precision estimation (using width of 90% CI) to assess 
the relative bioavailability. A sample size of approximately 50 evaluable participants is 
selected for the 2 dorsogluteal arms in Part A (i.e., 500 mg IM of 62.5 mg/mL and 
100 mg/mL sotrovimab arms, respectively) and approximately 25 evaluable participants 
is selected for each of the 100 mg/mL sotrovimab thigh and deltoid arms in Part A and 
the 2 optional treatment arms in Part B. Therefore, the total number of evaluable 
participants planned in this study is 150 in Part A and 25 per treatment arm in Part B 
(which may contain 1 or 2 treatment arms). To account for an expected 20% rate of non-
evaluable participants approximately 190 participants will be randomized into Part A and 
32 participants per/arm will be enrolled into Part B. 
Sample size determinations are based on an assumed between participant coefficient of 
variation (CVb) for AUCD1-29, AUCinf, and Cmax of 50%.  
For the primary PK objective, assuming a point estimate of 1 for the ratio of each 
primary PK endpoints (i.e., AUCD1-29 and Cmax) between the treatment arms under the 
variability assumptions and the planned sample size of evaluable participants described 
above, the 90% CIs are predicted to be: 

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Parameters 
Treatment Comparison 
Sample Size 
CVb 
90% CI 
AUCD1-29 and 
Cmax 
100 mg/mL sotrovimab dorsogluteal 
arm 
vs 
62.5 mg/mL sotrovimab dorsogluteal 
arm 
50 per arm 
50% 
(0.85, 1.17) 
Similarly, for the secondary PK objective, assuming a point estimate of 1 for the ratio of 
each secondary PK endpoints (i.e., AUCD1-29, AUCinf, and Cmax) between the treatment 
arms under the variability assumptions and the planned sample size of evaluable 
participants described above, the 90% CIs are predicted to be: 
Parameters 
Treatment Comparisons 
Sample Size 
CVb 
90% CI 
AUCD1-29 and 
Cmax  
100 mg/mL sotrovimab anterolateral 
thigh or deltoid arm  
vs 
62.5 mg/mL sotrovimab dorsogluteal arm
25 vs 50 
50% 
(0.80, 1.25) 
AUCinf 
100 mg/mL sotrovimab dorsogluteal arm 
vs 
62.5 mg/mL sotrovimab dorsogluteal arm
50 per arm 
50% 
(0.85, 1.17) 
AUCinf 
100 mg/mL sotrovimab anterolateral 
thigh or deltoid arm  
vs 
62.5 mg/mL sotrovimab dorsogluteal arm 
25 vs 50 
50% 
(0.80, 1.25) 
Part C 
The planned sample size for the number of evaluable participants in Part C Cohort 1 is 
200. With 200 participants (intend to target up to approximately 20 Japanese 
participants), there is a 90% chance of observing at least 1 AE of interest, if the true 
incidence rate of that AE is not below 1.14%. Of note, in COMET-ICE, the IRR rate was 
1.14%. The sample size has been selected to provide sufficient safety and tolerability data 
to evaluate the higher IV dose of sotrovimab proposed for this part.   
Part C Cohort 2 will be considered optional and will be opened following safety lead-in 
review based on Part C Cohort 1 data. The planned sample size for the number of 
evaluable participants in Part C Cohort 2 is 50. With 50 participants, there is a 90% 

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chance of observing at least 1 AE of interest, if the true incidence rate of that AE is not 
below 4.5%. Cohort 2 will supplement the data from Cohort 1 and may be combined at 
the end of study if the same dose is administered in both cohorts.  
The precision of event rate estimation is shown in the table below, as indicated by the 
width of 95% CIs. More specifically, the total number of 250 participants reflects the 
precisions when summarizing over both the cohorts at the end of study if the same dose is 
administered. 
Precision of Estimated Event Rate:  
Total Number of 
Participants 
Observed 
Event Rate 
Number of 
Participants 
with a 
Particular 
Event 
Observed 
95% CI 
200 (individual study size for 
Part C Cohort 1) 
0.5% 
1 
(0.01%, 2.75%) 
 
1.0% 
2 
(0.12%, 3.57%) 
 
2.0% 
4 
(0.55%, 5.04%) 
 
5.0% 
10 
(2.42%, 9.00%) 
 
10.0% 
20 
(6.22%, 15.02%) 
 
50.0% 
100 
(42.87%, 57.13%) 
 
 
 
 
50 (individual study size for 
Part C Optional Cohort 2) 
0.5% 
1 
(0.05%, 10.65 %) 
 
1.0% 
1 
(0.05%, 10.65%) 
 
2.0% 
1 
(0.05%, 10.65%) 
 
5.0% 
3 
(1.25%, 16.55%) 
 
10.0% 
5 
(3.33%, 21.81%) 
 
50.0% 
25 
(35.53%, 64.47%) 

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Total Number of 
Participants 
Observed 
Event Rate 
Number of 
Participants 
with a 
Particular 
Event 
Observed 
95% CI 
 
 
 
 
250 (combined study size for 
Part C Cohort 1 and Optional 
Cohort 2 if dose is the same) 
0.5% 
2 
(0.10%, 2.86%) 
 
1.0% 
3 
(0.25%, 3.47%) 
 
2.0% 
5 
(0.65%, 4.61%) 
 
5.0% 
13 
(2.80%, 8.73%) 
 
10.0% 
25 
(6.58%, 14.41%) 
 
50.0% 
125 
(43.63%, 56.37%) 

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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 CIOMS international ethical 
guidelines 
▪ Applicable ICH GCP guidelines 
▪ Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• The investigator will be responsible for the following: 
▪ Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
▪ Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
▪ Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), European Medical 
Device Regulation 2017/745 for clinical device research (if applicable), 
and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor/designee with sufficient, 
accurate financial information as requested to allow the sponsor/designee to submit 
complete and accurate financial certification or disclosure statements to the appropriate 
regulatory authorities. Investigators are responsible for providing information on 

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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, 
including the risk and benefits, 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, privacy and data 
protect 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.  
• If follow-up information from a treating physician or other licensed medical 
practitioner is required for a medical device incident with an AE/SAE involving 
an associated person(s), the Associated Person Safety Reporting Information and 
Authorization Letter must be signed by the associated person to obtain consent.    
• Participants who are rescreened are required to sign a new ICF. 
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about sotrovimab or about the study disease; publish the results of these research 
efforts; work with government agencies or insurers to have 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/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 
10.1.5.1. 
Joint Safety Review Team 
A JSRT comprised of team members from clinical research, global safety, and statistics 
from GSK and Vir, will review safety data throughout the study from all participants. The 
responsibilities of the JSRT and frequency of assessments will be outlined in the JSRT 
charter. The JSRT will review safety data from a sentinel cohort for each study Part and 
will review Part A data to inform Part B decisions, as described in Section 4.1. 
Additionally, the JSRT will review safety lead-in data from Part C Cohort 1 to decide to 
continue with Cohort 1 and whether to proceed with Cohort 2 (with a selection of 
different dose and infusion rate than Cohort 1). JSRT may request additional data before 
making a decision. 
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 CSR. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have 
the opportunity to review the complete study results at a GSK site or other 
mutually agreeable location. 
• 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 study available to external researchers for 
scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and 
understanding. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
• The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with the sponsor/GSK Policy. 
• The sponsor/GSK intends to make anonymized patient-level data from this study 
available to external researchers for scientific analyses or to conduct further 
research that can help advance medical science or improve patient care. This 
helps ensure the data provided by study participants are used to maximum effect 
in the creation of knowledge and understanding. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate 
and correct by physically or electronically signing the CRF.  

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• Guidance on completion of CRFs will be provided in eCRF completion 
guidelines. 
• Quality tolerance limits (QTLs) will be pre-defined in the Data Surveillance 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 CSR. 
• 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 organization (CRO) 
document. 
• The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
• Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
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. 

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• 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.  
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
Study/Site Termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by GSK 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/designee'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/designee 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 

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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 will be performed by central or local laboratory and the details are 
described in Table 13.  
• 
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 13 
Protocol-required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Coagulation 
International 
normalized ratio 
(INR) 
Prothrombin time 
(PT) 
Activated partial thromboplastin time 
(aPTT) 
Clinical 
Chemistry1 
Blood urea 
nitrogen 
Potassium 
Aspartate 
aminotransferase 
(AST)/Serum 
glutamic-oxaloacetic 
transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Sodium 
Alanine 
aminotransferase 
(ALT)/Serum 
glutamic-pyruvic 
transaminase 
(SGPT) 
Total protein 
 
Glucose (fasting 
at Screening and 
non-fasting at all 
other timepoints) 
Calcium 
Total blood/serum 
alkaline 
phosphatase2 
 
Urine Testing 
• 
Routine Urinalysis 
o Specific gravity 
o pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase by dipstick 
o Microscopic examination (if blood or protein is abnormal) 
• 
Urine creatinine and urine albumin 
Pregnancy 
testing 
• 
Highly sensitive serum or urine human chorionic gonadotropin (hCG) pregnancy 
test (as needed for WOCBP)3 

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Laboratory 
Assessments 
Parameters 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in WOCBP only) 
• 
Serum or urine alcohol and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, marijuana and benzodiazepines) 
• 
 Serology (HIV antibody, hepatitis B surface antigen [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 × upper limit of normal 
(ULN) and total bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and international normalized ratio 
(INR) >1.5, if INR measured, which may indicate severe liver injury (possible Hy’s law), must be reported 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. 
 
Investigators must document their review of each laboratory safety report. 
 

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10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
• Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a participant diary or form 
with pre-specified criteria. Unsolicited AEs 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 hospitalization, emergency room visit, or visit to/by a healthcare 
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 the 
participant will be collected during an 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 
increase in frequency and/or intensity of the condition. 

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• New condition 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 that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. Is life threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted 
(usually involving at least an overnight stay) at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether 

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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) that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, 
intensive treatment for allergic bronchospasm, blood dyscrasias, 
convulsions, or development of intervention dependency or intervention 
abuse. 
 
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 

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participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
Standard toxicity grading according to the DAIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events, version 2.1 (July 2017) will be used to grade all 
AEs.  
Table 14 should be used to grade the severity of an AE that is not specifically 
identified in the grading tables within DAIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events, version 2.1 (July 2017). In addition, all deaths related to 
an AE are to be classified as Grade 5. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE as per Section 10.3.2, NOT when it is rated as 
severe. 
Table 14 
DAIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events Not Otherwise Specified in DAIDS version 2.1 
PARAMETER Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Potentially life-
threatening 
Clinical AE 
NOT identified 
elsewhere in 
the grading 
table 
Mild 
symptoms 
causing no or 
minimal 
interference 
with usual 
social and 
functional 
activities 
with 
intervention 
not indicated 
Moderate 
symptoms 
causing 
greater than 
minimal 
interference 
with usual 
social and 
functional 
activities with 
intervention 
indicated 
Severe 
symptoms 
causing 
inability to 
perform usual 
social and 
functional 
activities with 
intervention or 
hospitalization 
indicated 
Potentially life-
threatening 
symptoms 
causing inability 
to perform basic 
self-care 
functions with 
intervention 
indicated to 
prevent 
permanent 
impairment, 
persistent 
disability, or 
death 

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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. The investigator will use clinical judgment 
to determine the relationship. 
• A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The investigator will also consult the 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 postmortem 
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. 
• 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 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 FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or 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: 
1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 

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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 FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or 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. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly. 

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• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
o oral 
o intravaginal 
o transdermal 
o injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o oral 
o injectable 
Sexual abstinence 
• 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 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 
international normalized ratio (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, stabilize, 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, stabilize 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, within 168 days after the 
most recent dose4  
• Obtain serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), 
gammaglutamyl 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 IgG or gamma globulins. 
• Serum acetaminophen adduct assay 
should be done (where available) to 
assess potential acetaminophen 
contribution to liver injury unless 
acetaminophen use is very unlikely in the 
preceding week (e.g., where the 
participant has been resident in the 
clinical unit throughout) 
• Liver imaging (ultrasound, magnetic 
resonance, or computed 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 participants when serology 
raises the possibility of 
autoimmune hepatitis 
o In participants when suspected 
DILI progresses or fails to resolve 
on withdrawal of study 
intervention 
o In participants 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. 

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3. Includes: hepatitis A immunoglobulin (IgM) antibody; HBsAg and 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 dose of study intervention prior to PK 
blood sample draw. 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 intervention 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: 
o Administer epinephrine (1.0 mg/mL) aqueous solution (1:1000 dilution) – 
0.5 mg (0.5 mL) IM in the anterolateral thigh 
o If using an epinephrine auto-injector – use 0.3 mg IM into the anterolateral 
thigh 
o May be repeated every 5 to 15 minutes up to 3 times 
4. Optional treatment (antihistamine): 
o Diphenhydramine 50 mg oral/IV/IM 
OR 
o 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 to 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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CCI

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10.8. 
Appendix 8: Abbreviations and Definitions and Trademarks 
Term 
Definition 
z 
Terminal elimination rate constant 
%AUCexp 
Area under the plasma concentration-time curve extrapolated 
from time to infinity as a percentage of total AUC 
Ab 
Antibody 
ADA 
Anti-drug antibodies 
ADE 
Antibody-dependent enhancement 
AE(s) 
Adverse event(s) 
AESI 
Adverse events of special interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
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 from time zero to 
infinity 
AUClast 
Area under the serum concentration-time curve from time zero to 
time of last measurable concentration 
BMI 
Body mass index 
BP 
Blood pressure 
Clast 
Last measurable serum concentration 
Cmax 
Maximum observed concentration 
CA 
Competent Authority 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CL 
Clearance 
CL/F 
Apparent clearance following extravascular route of administration 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
CSR 
Clinical study report 
CVb 
Coefficient of variation 
DAIDS 
Division of Acquired Immune-Deficiency Syndrome 
DCO 
Data cut-off 

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Term 
Definition 
DILI 
Drug-induced liver injury 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
EC50 
Half maximal effective concentration 
EC90 
90% effective concentration 
ECG 
Electrocardiogram 
EoS 
End of study 
eCRF 
Electronic case report form 
ePRO 
Electronic device for participants to complete patient-reported 
outcome measure 
EUA 
Emergency use authorization 
F 
Bioavailability 
Fc 
Fragment crystallizable 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
FSH 
Follicle-stimulating hormone 
Gen2 
Generation 2 
GCP 
Good clinical practice 
GSK 
GlaxoSmithKline 
HIV 
Human immunodeficiency virus 
HRT 
Hormonal replacement therapy 
HSR(s) 
Hypersensitivity reaction(s) 
IA 
Interim analysis 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization of technical 
requirements for registration of pharmaceuticals for human use 
ICU 
Intensive care unit 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgG1 
Immunoglobulin G1 
IgG1 
Immunoglobulin G1 kappa 
IM 
Intramuscular 

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Term 
Definition 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IRR(s) 
Infusion-related reaction(s) 
ISR(s) 
Injection site reaction(s) 
IV 
Intravenous 
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web Response System 
JSRT 
Joint Safety Review Team 
LS 
Fc modification 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular volume 
MCV 
Mean corpuscular hemoglobin 
MSDS 
Material Safety Data Sheet 
NCA 
Non-compartmental analysis 
NI 
Non-inferiority 
NIH 
National Institutes of Health 
NIMP 
Non-investigational medicinal product 
NOAEL 
No-observed-adverse-effect-level 
Pain-NRS 
Injection site pain numeric rating scale 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PI 
Principal investigator 
PIN_TS3.0 
Perception of Injection version 3 
PK 
Pharmacokinetic(s) 
PR 
Pulse rate 
PRO 
Patient-reported outcome 
QTcF 
QT interval corrected using Fridericia’s formula 
QTLs 
Quality tolerance limits 
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
RT-PCR 
Reverse transcriptase polymerase chain reaction 
SAE(s) 
Serious adverse event(s) 

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Term 
Definition 
SAP 
Statistical Analysis Plan 
SARS-CoV-1 
Severe acute respiratory syndrome coronavirus-1 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus-2  
SoA 
Schedule of activities 
SRM 
Study Reference Manual 
SUSAR 
Suspected unexpected serious adverse reaction 
t1/2 
Terminal elimination half-life 
Tlast 
Time of the last quantifiable concentration 
Tmax 
Time to reach Cmax 
ULN 
Upper limit of normal 
UK 
United Kingdom 
US 
United States 
V 
Variance 
V/F 
Apparent volume of distribution following extravascular route of 
administration 
Vz 
Apparent volume of distribution during the elimination phase 
Vss 
Apparent volume of distribution at steady state 
VAPI 
Vaccines Perception of Injection Questionnaire 
Vir 
Vir Biotechnology, Inc. 
VOC(s) 
Variant(s) of concern 
VOI(s) 
Variant(s) of interest 
WBC 
White blood cell 
WOCBP 
Woman of childbearing potential 
WONCBP 
Woman of non-childbearing potential 
 
Trademark Information 
Trademarks of the GSK group of 
companies 
 
Trademarks not owned by the GSK 
group of companies 
Xevudy 
 
None 
 
 
 

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10.9. 
Appendix 9: Protocol Amendment History 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 2 
06-SEP-2022 
TMF-14575517 
Amendment 1 
01-FEB-2022 
TMF-14439761 
Original Protocol 
13-DEC-2021 
TMF-14082482 
Amendment 2: 06-SEP-2022 
This amendment is considered to be substantial based on the description of change and 
rationale mentioned in the below table. 
Overall Rationale for the Amendment: The protocol has been amended to include 
Part C to the study design to characterize the safety and tolerability of single IV infusion 
of sotrovimab in Cohort 1 and an optional Cohort 2. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1: Protocol Summary 
Section 1.1 Synopsis 
Section 1.2 Schema 
Section 1.3 Schedule of Activities 
(SoA)  
Section 2: Introduction 
Section 2.1 Study rationale 
Section 3: Objectives and Endpoints 
Section 4: Study Design 
Section 4.1 Overall Design 
Section 4.2 Scientific Rationale for 
Study Design 
Section 4.3 Justification for Dose 
Section 4.4 End of Study Definition 
Section 9: Statistical Considerations 
 
Updated the rationale in the 
synopsis and study rationale 
sections as per the recent 
information available on 
sotrovimab development and 
authorization.  
Added the rationale and design of 
Part C in various sections of the 
protocol where applicable. Part C 
will be open-label, wherein 
participants will receive a single 
3000 mg dose of IV sotrovimab in 
Cohort 1 and up to 3000 mg dose 
of IV sotrovimab in an optional 
Cohort 2. The rationale for 
conducting this part and the 
number of participants considered 
for Part C is explained across the 
synopsis and overall design 
sections. 
Added the language for in-stream 
safety lead-in data review at Day 
8, and also modified the JSRT 
review language for Part C in 
Synopsis and JSRT charter. 
Added a new Schema and SoA 
table for Part C, which describes 
the design, treatment duration, 
visit frequency and study 
assessments.  
Added new Part C objectives and 
endpoints. 
To characterize the safety 
and tolerability of IV 
sotrovimab and to potentially 
explore further IV doses of 
sotrovimab and/or 
alternative infusion rates. 
The proposed range of IV 
doses/infusion rates was 
chosen to support clinical 
doses for potential future 
clinical studies. 
Section 2.2 Background 
Updated the number of COVID-19 
cases and associated deaths 
reported globally and in the US. 
Added Omicron BA.2 virus 
information with fold change in 
EC50 and EC90 values. 
Added Omicron BA.4 and Omicron 
BA.5 virus information with fold 
change in EC50 values. 
New information available. 
Section 2.2.1 Clinical Experience 
with Sotrovimab 
Included information from the 
RECOVERY Trial, COMET-TAIL 
safety sub-study and PROTECT-V 
study. 
To evaluate the safety and 
tolerability of IV sotrovimab 
at 1000 mg and 2000 mg at 
different study population. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 2.3.1 Risk Assessment 
table 
Section 2.3.2 Benefit Assessment 
Section 2.3.3 Overall benefit: Risk 
Conclusion 
Included IRR and ADE information 
and made updates related to Parts 
A, B and C in all the applicable 
risks described in risk assessment 
table.  
Updated these sections with the 
recently available information on 
sotrovimab and also included Part 
C, which may support options for 
therapeutics and effective 
preventive measures. 
New and relevant 
information available for 
IRRs, ADE, ISR and HSRs, 
and for Parts A, B, and C. 
Section 3 Objectives and Endpoints 
Added new Part C objectives and 
endpoints. Updated primary 
estimand for Part C. 
New and relevant safety 
primary estimand 
information available for Part 
C. 
Section 4.2 Scientific Rationale for 
Study Design 
Added data from preclinical 
toxicology studies to support Part 
C design. 
Information added to 
support Part C design. 
Section 4.3 Justification for Dose 
Added data from preclinical 
toxicology studies to support Part 
C design. 
 
 
 
 
 
 
Section 5.1 Inclusion Criteria 
Added an inclusion criterion to 
define the type of participant and 
disease characteristics in 
Japanese population. 
Updated relevant 
information to align with Part 
C enrollment. 
Section 5.2 Exclusion Criteria 
Updated the medical condition for 
HSR. 
New and relevant 
information available. 
Section 6.1 Study Intervention(s) 
Administered table 
Added sotrovimab dose 
information for Part C. 
Included study arms table for Part 
C. 
New and relevant 
information available for Part 
C. 
Section 6.3 Measures to Minimize 
Bias: Randomization and Blinding 
Added information regarding the 
design and conduct of Part C.  
New and relevant 
information available for Part 
C. 
Section 7.1 Discontinuation of Study 
Intervention 
Section 7.1.2 Temporary 
Discontinuation 
Updated the criteria for permanent 
and temporary discontinuation of 
study intervention. 
Relevant information 
available for Part C. 
Section 8.2 Efficacy Assessments 
Updated the language of the 
efficacy assessment to align with 
Part C design. 
New and relevant 
information available for Part 
C. 
CCI
CCI
CCI

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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.4.7 Adverse Events of 
Special Interest 
Section 8.4.7.1 Injection-Related 
Reactions and Serious 
Hypersensitivity 
Section 8.4.7.2 Injection Site 
Reactions 
Section 8.4.7.4 Antibody-dependent 
Enhancement 
Updated the language of these 
sections to align with Part C 
design. 
Added ADE as a new AESI in 
Section 8.4.7. 
New and relevant 
information available for Part 
C. 
Section 8.5 Pharmacokinetics 
Updated the PK parameters. 
New and relevant 
information available. 
Section 9.1 Statistical Hypotheses 
Section 9.3 Statistical Analyses 
Section 9.4 Interim Analysis 
Section 9.5 Sample Size 
Determination 
Updated the text in the sub-
sections of the protocol listed to 
the left column to add clarity and 
rationale for the data analysis that 
will be performed for Part C. 
New and relevant 
information available for Part 
C.  
Section 10.1.5 Committees 
Structure 
Added additional text to the JSRT 
charter to include Part C review. 
New and relevant 
information available for Part 
C. 
Throughout document 
Minor editorial updates, formatting 
and stylistic changes are made to 
align the content with the newly 
added information of Part C. 
Updates are made to 
maintain consistency, for 
better clarity, and to improve 
readability. 
Amendment 1: 01-FEB-2022 
This amendment is considered to be substantial based on the description of change and 
rationale mentioned in the below table. 
Overall Rationale for the Amendment:  
Based on Food and Drug Administration (FDA) feedback, protocol changes were made 
to add an additional pharmacokinetics (PK) blood sample collection on Day 5 for better 
characterization of the absorption phase of intramuscular (IM) sotrovimab and to extend 
the safety follow-up through Week 35 (~5 half lives of sotrovimab). 
CCI
CCI

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1: Protocol Summary 
1.1 Synopsis 
1.3 Schedule of Activities (SoA)  
Section 2: Introduction 
2.3.1 Risk Assessment table 
Section 4: Study Design 
4.1 Overall Design 
Added a Day 5 on-site visit that 
includes brief physical 
examination, vital signs, local 
injection site tolerability 
assessment, safety laboratory 
assessments, and PK blood 
sample.  
The patient-reported outcome 
(PRO) assessments which 
were going to be performed at 
home will now occur at the site 
visit.  
Changes made to include 
a PK blood sampling visit 
on Day 5. Since the Day 5 
PK blood sampling 
requires a site visit, other 
Day 5 assessments were 
updated.  
 
Section 1: Protocol Summary 
1.1 Synopsis 
1.2 Schema 
1.3 SoA 
Section 3: Objectives and 
Endpoints 
Section 4: Study Design 
4.1 Overall Design 
4.4 End of Study Definition 
Section 5: Study Population 
5.1 Inclusion Criteria 
Section 8: Study Assessments 
and Procedures 
8.4.1 Time Period and 
Frequency for Collecting AE and 
SAE Information 
8.4.5 Pregnancy 
8.4.7 Adverse Events of Special 
Interest 
Section 9: Statistical 
Considerations 
9.3.3.2 Safety 
9.4 Interim Analysis 
Added a phone call visit at 
Week 35 to capture AEs, SAEs, 
AESI and pregnancy status.  
Extended the safety follow-up 
period through Week 35.  
Added instructions for all 
WOCBP to continue 
contraception through 
Week 35. 
 
Given that the half-life of 
sotrovimab is 
approximately 48.8 days, 
a decision was made to 
extend the safety follow-
up through Week 35 
(~5 half-lives of 
sotrovimab). 
Section 1: Protocol Summary 
1.1 Synopsis 
Section 4: Study Design 
4.1 Overall Design 
Added the maximum duration a 
participant will be in the study 
as 39 weeks 
Change made due to 
extension of safety follow-
up period through 
Week 35 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1: Protocol Summary 
1.1 Synopsis 
1.2 Schema 
Section 2: Introduction 
2.1 Study Rationale 
Section 3: Objectives and 
Endpoints 
Section 4: Study Design 
4.1 Overall Design 
4.2 Scientific Rationale for Study 
Design 
Section 6: Study Intervention(s) 
and Concomitant Therapy 
6.1 Study Intervention(s) 
Administered: Table 3, Study 
Arms – Part B 
6.3 Measures to Minimize Bias: 
Randomization and Blinding 
Added the 62.5 mg/mL 
concentration as an option in 
Part B of this study  
The 62.5 mg/mL 
concentration was added 
as an option in Part B to 
align with Part A 
Section 2: Introduction 
2.2 Background 
11 References 
Updated the background on 
Emergency Use Authorization 
(EUA) for SARS-CoV-2 mAbs 
and included a new reference 
and deleted 3 old references 
Updated to align with FDA 
EUA updates, January 
2022 
Section 1: Protocol Summary 
1.1 Synopsis 
Section 4: Study Design 
4.1 Overall Design 
Section 9: Statistical 
Considerations 
9.4 Interim Analysis 
Updated the text in Section 9.4 
(Interim Analysis) to add clarity 
and rationale for the data 
analysis that will be performed 
once half of the participants in 
Part A complete at least Day 8 
To improve clarity and 
readability 
Section 1: Protocol Summary 
1.3 SoA 
Added additional hematology 
laboratory assessments on Day 
2, 5, 8, and 29 
Expanded laboratory 
assessments to include 
further hematology 
assessments in addition 
to baseline 
Throughout document 
Other minor edits, formatting 
and typographical corrections 
are made 
To improve readability 
 

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11. 
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