Trial Outcomes & Findings for Intramuscular and Intravenous VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19. (NCT NCT04913675)

Results Overview

Progression of COVID-19 through Day 29 as defined by hospitalization \>24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1065 participants

Primary outcome timeframe

Up to Day 29

Results posted on

2024-03-07

Participant Flow

This study consists of Main study and Safety sub-study. Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.

A total of 1065 participants were enrolled in this study (983 in main study and 82 in safety sub-study), of which 10 participants from main study and 1 from safety sub-study did not receive study intervention. Hence, a total of 973 from main study and 81 from safety sub-study were exposed to study intervention constituting the Safety Populations.

Participant milestones

Participant milestones
Measure	Main Study: Sotrovimab 500 mg IV Participants received a single dose of sotrovimab 500 milligram (mg), intravenous (IV) infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, intramuscular (IM) dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.	Safety Sub-study: Sotrovimab (2000 mg IV) Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes.
Main Study (Up to Week 36) STARTED	393	385	195	0
Main Study (Up to Week 36) COMPLETED	356	341	176	0
Main Study (Up to Week 36) NOT COMPLETED	37	44	19	0
Safety Sub-study (Up to Week 36) STARTED	0	0	0	81
Safety Sub-study (Up to Week 36) COMPLETED	0	0	0	80
Safety Sub-study (Up to Week 36) NOT COMPLETED	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study: Sotrovimab 500 mg IV Participants received a single dose of sotrovimab 500 milligram (mg), intravenous (IV) infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, intramuscular (IM) dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.	Safety Sub-study: Sotrovimab (2000 mg IV) Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes.
Main Study (Up to Week 36) Death	0	2	2	0
Main Study (Up to Week 36) Lost to Follow-up	12	8	4	0
Main Study (Up to Week 36) Physician Decision	0	1	1	0
Main Study (Up to Week 36) Withdrawal by Subject	25	33	12	0
Safety Sub-study (Up to Week 36) Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Intramuscular and Intravenous VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.	Safety Sub-study: Sotrovimab (2000 mg IV) n=81 Participants Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes.	Total n=1054 Participants Total of all reporting groups
Age, Customized 12-17 years	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Age, Customized 18-64 years	291 Participants n=5 Participants	289 Participants n=7 Participants	163 Participants n=5 Participants	66 Participants n=4 Participants	809 Participants n=21 Participants
Age, Customized >=65 years	100 Participants n=5 Participants	96 Participants n=7 Participants	31 Participants n=5 Participants	15 Participants n=4 Participants	242 Participants n=21 Participants
Sex: Female, Male Female	224 Participants n=5 Participants	197 Participants n=7 Participants	113 Participants n=5 Participants	47 Participants n=4 Participants	581 Participants n=21 Participants
Sex: Female, Male Male	169 Participants n=5 Participants	188 Participants n=7 Participants	82 Participants n=5 Participants	34 Participants n=4 Participants	473 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	17 Participants n=5 Participants	19 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	48 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	10 Participants n=5 Participants	21 Participants n=7 Participants	8 Participants n=5 Participants	0 Participants n=4 Participants	39 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	362 Participants n=5 Participants	336 Participants n=7 Participants	176 Participants n=5 Participants	77 Participants n=4 Participants	951 Participants n=21 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Day 29

Population: Primary Analysis Population consisted of all randomized participants excluding participants who were randomized under Protocol Amendment Version 1 and were immunocompetent and fully vaccinated at randomization and participants who did not meet key eligibility criteria. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.

Progression of COVID-19 through Day 29 as defined by hospitalization \>24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=378 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=376 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=183 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)	1.3 Percentage of participants	2.7 Percentage of participants	5.5 Percentage of participants

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population consisted of all enrolled participants who were exposed to study intervention.

An adverse event (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. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8 Non-SAE	0 Participants	—	—
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8 SAE	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population

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. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population

AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8	2 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 12

Population: Safety Population consisted of all randomized participants who were exposed to study intervention.

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. Data for Common (\>=1%) non-SAEs are presented.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)	8 Participants	5 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to Week 36

Population: Safety Population

An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Serious Adverse Events (SAEs)	3 Participants	7 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to Week 36

Population: Safety Population.

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. AESI included infusion- or injection-related reaction including hypersensitivity. Data for number of participants with any infusion- or injection-related reaction including hypersensitivity has been presented.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 36

Population: Safety Population.

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. AESIs included any solicited local site reactions. AESI were graded according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007, Food and Drug Administration, where Grade 1=Mild toxicity; Grade 2=Moderate toxicity; Grade 3=Severe toxicity; and Grade 4= Potentially life-threatening toxicity. Higher Grade indicates higher severity. Data for any worst case post-Baseline has been presented.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=385 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=195 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration Grade 1	39 Participants	22 Participants	—
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration Grade 2	7 Participants	2 Participants	—
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration Grade 3	1 Participants	0 Participants	—
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration Grade 4	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to Week 36

Population: Safety Population.

AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Any Disease Related Events	18 Participants	16 Participants	20 Participants

SECONDARY outcome

Timeframe: Up to Week 12

Population: Safety Population.

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. Adverse events which were no serious, were considered as non-SAEs.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Non-SAEs Through Week 12	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 36

Population: Safety Population

An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With SAEs Through Week 36	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 12

Population: Safety Population.

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. AESI is infusion-related reaction including hypersensitivity.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 12

Population: Safety Population.

AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12	4 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population.

Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody	25 Participants	51 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population. Only those participants with data available at the specified data points were analyzed.

Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=45 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=60 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=31 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Titers of Anti-drug Antibodies Against Sotrovimab Treatment-induced	80.0 Titers Interval 40.0 to 40960.0	80.0 Titers Interval 40.0 to 5120.0	80.0 Titers Interval 40.0 to 20480.0
Main Study: Titers of Anti-drug Antibodies Against Sotrovimab Treatment-unaffected	40.0 Titers Interval 40.0 to 1280.0	60.0 Titers Interval 40.0 to 640.0	40.0 Titers Interval 40.0 to 160.0

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population.

Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24	3 Participants	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24 Treatment-induced	160.0 Titers Interval 40.0 to 320.0	—	—
Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24 Treatment-unaffected ADA	160.0 Titers Interval 40.0 to 320.0	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: Safety Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=9 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to Day 29

Population: Primary Analysis Population. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.

Progression of COVID-19 through Day 29 as defined by visit to a hospital emergency room for management of illness or hospitalization for acute management of illness for any duration and for any cause or death. Percentage values are rounded off.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=378 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=376 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=183 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)	2.4 Percentage of participants	3.2 Percentage of participants	6.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 8, Day 15, Day 22, and Day 29

Population: Intent-to-Treat (ITT) Population consisted of all randomized participants excluding participants who were randomized under Protocol Amendment Version 1 and were immunocompetent and fully vaccinated at randomization.

Participants were defined as progressing to develop severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progressing to develop critical respiratory COVID-19 if they required invasive mechanical ventilation or extracorporeal membrane oxygenation. Percentage values are rounded off.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=385 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=383 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=185 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit Day 8	0.3 Percentage of participants	1.0 Percentage of participants	3.8 Percentage of participants
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit Day 15	0.3 Percentage of participants	1.3 Percentage of participants	4.3 Percentage of participants
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit Day 22	0.3 Percentage of participants	1.6 Percentage of participants	4.3 Percentage of participants
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit Day 29	0.3 Percentage of participants	1.6 Percentage of participants	4.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: Virology Population consisted of all participants in the ITT Population with a central laboratory confirmed quantifiable Baseline nasopharyngeal swab at Day 1. Only those participants with data available at the specified time points were analyzed.

AUC of SARS-CoV-2 viral load was measured by Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from Day 1 to Day 8 in nasopharyngeal swab samples.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=287 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=278 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=136 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8	25.42 Day*log10 copies/mL Geometric Coefficient of Variation 34.144	25.56 Day*log10 copies/mL Geometric Coefficient of Variation 36.936	25.46 Day*log10 copies/mL Geometric Coefficient of Variation 37.899

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: Virology Population. Only those participants with data available at the specified time points were analyzed. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in nasopharyngeal swab samples. Least squares geometric mean and 90 percent (%) confidence interval has been presented.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=287 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=278 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM	25.03 Day*log10 copies/mL Interval 24.45 to 25.63	25.96 Day*log10 copies/mL Interval 25.35 to 26.59	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and at Day 8

Population: Virology Population. Only those participants with data available at the specified time points were analyzed.

Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline was defined as the latest non-missing value prior to dosing (or latest value on or prior to nominal Day 1 for participants that were not dosed). Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=279 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=271 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=132 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8	-2.979 Log10 copies/mL Standard Deviation 1.6965	-2.752 Log10 copies/mL Standard Deviation 1.7594	-2.488 Log10 copies/mL Standard Deviation 1.6628

SECONDARY outcome

Timeframe: At Day 8

Population: Virology Population. Only those participants with data available at the specified time points were analyzed.

Percentage of participants with a persistently high viral load were categorized as \>=4.1 log10 copies/mL and \<4.1 log10 copies/mL. Percentage of participants with a persistently high SARS-CoV-2 viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage values are rounded off.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=279 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=271 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=132 Participants Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 >=4.1 log 10 copies/mL	13 Percentage of participants	12 Percentage of participants	17 Percentage of participants
Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 <4.1 log 10 copies/mL	87 Percentage of participants	88 Percentage of participants	83 Percentage of participants

SECONDARY outcome

Timeframe: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=393 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Day 1: Pre-dose	NA Microgram per mL Geometric Coefficient of Variation NA NA indicates that, data was not available as all concentration values were below the lower limit of quantification.	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Day 8	53.67 Microgram per mL Geometric Coefficient of Variation 54.21	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Day 15	44.62 Microgram per mL Geometric Coefficient of Variation 51.54	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Day 29	33.89 Microgram per mL Geometric Coefficient of Variation 72.61	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Week 12	19.10 Microgram per mL Geometric Coefficient of Variation 55.20	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Week 20	9.96 Microgram per mL Geometric Coefficient of Variation 53.24	—	—
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration Week 24	7.66 Microgram per mL Geometric Coefficient of Variation 56.73	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24

Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for PK analysis of Sotrovimab.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=385 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=195 Participants Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Day 1: Pre-dose	NA Microgram per mL Geometric Coefficient of Variation NA NA indicates that, data was not available as all concentration values were below the lower limit of quantification.	NA Microgram per mL Geometric Coefficient of Variation NA NA indicates that, data was not available as all concentration values were below the lower limit of quantification.	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Day 8	20.50 Microgram per mL Geometric Coefficient of Variation 88.70	10.93 Microgram per mL Geometric Coefficient of Variation 92.47	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Day 15	20.60 Microgram per mL Geometric Coefficient of Variation 84.01	10.90 Microgram per mL Geometric Coefficient of Variation 77.68	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Day 29	18.92 Microgram per mL Geometric Coefficient of Variation 77.00	10.20 Microgram per mL Geometric Coefficient of Variation 61.80	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Week 12	11.15 Microgram per mL Geometric Coefficient of Variation 64.01	6.15 Microgram per mL Geometric Coefficient of Variation 54.22	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Week 20	5.83 Microgram per mL Geometric Coefficient of Variation 65.44	3.19 Microgram per mL Geometric Coefficient of Variation 57.05	—
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration Week 24	4.48 Microgram per mL Geometric Coefficient of Variation 71.57	2.34 Microgram per mL Geometric Coefficient of Variation 62.49	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=81 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 1, End of Infusion	709.18 Microgram per mL Geometric Coefficient of Variation 40.19	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 1, Pre-dose	NA Microgram per mL Geometric Coefficient of Variation NA NA indicates that, data was not available as all concentration values were below the lower limit of quantification.	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 3	428.75 Microgram per mL Geometric Coefficient of Variation 37.94	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 5	343.51 Microgram per mL Geometric Coefficient of Variation 35.31	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 8	289.16 Microgram per mL Geometric Coefficient of Variation 36.24	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 15	239.79 Microgram per mL Geometric Coefficient of Variation 35.37	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Day 29	203.44 Microgram per mL Geometric Coefficient of Variation 35.51	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Week 12	94.80 Microgram per mL Geometric Coefficient of Variation 33.55	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Week 20	52.96 Microgram per mL Geometric Coefficient of Variation 39.66	—	—
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration Week 24	40.82 Microgram per mL Geometric Coefficient of Variation 37.08	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=80 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab	7493.9 day*µg/mL Geometric Coefficient of Variation 34.68	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=53 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)	732.5 µg/mL Geometric Coefficient of Variation 42.23	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=67 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)	6.81 Liter Geometric Coefficient of Variation 37.72	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=67 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])	23992.5 day*µg/mL Geometric Coefficient of Variation 34.90	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=67 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)	59.432 Day Interval 45.36 to 72.87	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=67 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)	7.05 Liter Geometric Coefficient of Variation 37.66	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=67 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)	83.4 mL/day Geometric Coefficient of Variation 34.90	—	—

SECONDARY outcome

Timeframe: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose

Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.

Outcome measures

Outcome measures
Measure	Main Study: Sotrovimab 500 mg IV n=53 Participants Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.
Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)	0.044 Day Interval 0.04 to 4.07	—	—

Adverse Events

Main Study: Sotrovimab 500 mg IV

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Main Study: Sotrovimab 500 mg IM

Serious events: 7 serious events

Other events: 5 other events

Deaths: 2 deaths

Main Study: Sotrovimab 250 mg IM

Serious events: 3 serious events

Other events: 12 other events

Deaths: 2 deaths

Safety Sub-study: Sotrovimab (2000 mg IV)

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Main Study: Sotrovimab 500 mg IV n=393 participants at risk Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 participants at risk Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 participants at risk Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.	Safety Sub-study: Sotrovimab (2000 mg IV) n=81 participants at risk Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes.
Investigations Activated partial thromboplastin time prolonged	1.3% 5/393 • Number of events 5 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.52% 2/385 • Number of events 2 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	1.5% 3/195 • Number of events 3 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Investigations Alanine aminotransferase increased	0.51% 2/393 • Number of events 2 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.78% 3/385 • Number of events 3 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	1.0% 2/195 • Number of events 2 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Infections and infestations Upper respiratory tract infection	0.25% 1/393 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	2.1% 4/195 • Number of events 4 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Infections and infestations Gastroenteritis	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	1.0% 2/195 • Number of events 2 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	1.0% 2/195 • Number of events 2 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population

Additional Information

Study Inquiry

Vir Biotechnology, Inc.

Phone: 415-654-5281

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Main Study: Sotrovimab 500 mg IV n=393 participants at risk Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1.	Main Study: Sotrovimab 500 mg IM n=385 participants at risk Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1.	Main Study: Sotrovimab 250 mg IM n=195 participants at risk Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1.	Safety Sub-study: Sotrovimab (2000 mg IV) n=81 participants at risk Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes.
Infections and infestations Appendicitis	0.25% 1/393 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Infections and infestations Herpes zoster	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Infections and infestations Pneumonia bacterial	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Nervous system disorders Cerebrovascular accident	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Nervous system disorders Hemiparesis	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Nervous system disorders Intracranial mass	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.51% 1/195 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Nervous system disorders Seizure	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.51% 1/195 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.51% 1/195 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.51% 1/195 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Cardiac disorders Cardiac failure	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Immune system disorders Kidney transplant rejection	0.25% 1/393 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Investigations Blood glucose increased	0.25% 1/393 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.26% 1/385 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Renal and urinary disorders Acute kidney injury	0.25% 1/393 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/81 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population
Cardiac disorders Acute myocardial infarction	0.00% 0/393 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/385 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	0.00% 0/195 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population	1.2% 1/81 • Number of events 1 • All-cause mortality, SAEs were collected up to Week 36 and non-serious AEs were collected up to Week 12 for main study and safety sub-study All-cause mortality, non-SAE and SAEs were collected for main study and safety sub-study using Safety Population