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Clinical Trial Results:
A Multicenter, Randomized, Double-Blinded, Parallel Group Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Second Generation VIR-7831 Materian in Non-Hospitalized Participants with Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Summary
EudraCT number	2021-000724-35
Trial protocol	DE IT ES
Global end of trial date

Results information
Results version number	v1
This version publication date	01 Nov 2022
First version publication date	01 Nov 2022
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

VIR-7831-5006

ISRCTN number

US NCT number

NCT04779879

WHO universal trial number (UTN)

Other trial identifiers

VIR-7831-5006: GSK216912

Sponsor organisation name

Vir Biotechnology, Inc.

Sponsor organisation address

499 Illinois St , San Francisco , United States, 94158

Public contact

n/a, GlaxoSmithKline (Ireland) Limited, 1415 6545281, na.na@na.com

Scientific contact

n/a, GlaxoSmithKline (Ireland) Limited, 1415 6545281, na.na@na.com

Sponsor organisation name

Vir Biotechnology, Inc.

Sponsor organisation address

499 Illinois St , San Francisco , United States, 94158

Public contact

Study Inquiry, Vir Biotechnology, Inc., 415 6545281, clinicaltrials@vir.bio

Scientific contact

Study Inquiry, Vir Biotechnology, Inc., clinicaltrials@vir.bio

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

18 Nov 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Aug 2021

Global end of trial reached?

Main objective of the trial

Safety (Part A): To evaluate the safety and tolerability profile of intravenous (IV) VIR-7831 Generation (Gen2) and IV Gen1 Pharmacodynamics (Part B): To evaluate the virological response of VIR-7831 Gen2 administered IV and via intramuscular (IM) injection in the upper respiratory tract

Protection of trial subjects

Study participants were closely monitored for the occurrence of infusion reactions. The study intervention was administered in a clinic/study unit where participants were monitored closely for adverse events in the post-infusion period. Subsequent visits for study activities and clinical monitoring were conducted via clinic or home nursing visits (except for Week 16 which was a follow-up by telephone).

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Feb 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 276

Country: Number of subjects enrolled

Canada: 28

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 3

Country: Number of subjects enrolled

Spain: 46

Worldwide total number of subjects

353

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

337

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Randomized, parallel group study conducted in non-hospitalized participants with mild to moderate Coronavirus Disease 2019 (COVID-19) who received Sotrovimab (VIR-7831) Generation1 (Gen 1) and Gen2. Results presented are based on the primary analysis (data up to Day 29). Additional results will be provided within 1 year after study completion.

Screening details

Total of 354 participants (30 participants in Part A, 167 participants in Part B, 157 participants in Part C) were enrolled in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A- Sotrovimab Gen1: 500 mg IV

Arm description

Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Sotrovimab was administered as IV infusion

Part A- Sotrovimab Gen2: 500 mg IV

Arm description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Sotrovimab was administered as IV infusion

Part B- Sotrovimab Gen2: 500 mg IV

Arm description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Sotrovimab was administered as IV infusion and IM injection

Part B- Sotrovimab Gen2: 500 mg IM

Arm description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Sotrovimab was administered as IM injection

Part C- Sotrovimab Gen2: 500 mg IV

Arm description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Sotrovimab was administered as IV infusion

Part C- Sotrovimab Gen2: 250 mg IM

Arm description

Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C.

Arm type

Experimental

Investigational medicinal product name

Sotrovimab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Sotrovimab was administered as IM injection

Number of subjects in period 1	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Started	8	22	84	82	79	78
Completed	0	0	0	0	0	0
Not completed	8	22	84	82	79	78
Consent withdrawn by subject	-	-	-	-	1	-
Death	-	-	-	-	-	1
Ongoing in the study	8	22	84	82	78	77

Baseline characteristics

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Reporting group title

Part A- Sotrovimab Gen1: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A.

Reporting group title

Part A- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A.

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B.

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IM

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B.

Reporting group title

Part C- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C.

Reporting group title

Part C- Sotrovimab Gen2: 250 mg IM

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C.

Reporting group values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM	Total
Number of subjects	8	22	84	82	79	78	353
Age categorical
Safety Population consisted of all randomized participants who were exposed to study intervention.
Units: Subjects
<=18 years	0	1	0	1	0	0	2
19-64 years	8	20	80	76	77	74	335
>=65 years	0	1	4	5	2	4	16
Gender categorical
Safety Population consisted of all randomized participants who were exposed to study intervention.
Units: Subjects
Female	5	10	45	42	39	42	183
Male	3	12	39	40	40	36	170
Race/ Ethnicity, Customized
Safety Population consisted of all randomized participants who were exposed to study intervention.
Units: Subjects
Black or African American	2	1	4	1	7	9	24
White - White/Caucasian/European Heritage	6	21	62	64	66	63	282
White - Arabic/North African Heritage	0	0	5	0	6	5	16
Asian - East Asian Heritage	0	0	2	2	0	0	4
Asian - South East Asian Heritage	0	0	11	13	0	0	24
Asian - Central/South Asian Heritage	0	0	0	1	0	0	1
American Indian Or Alaska Native	0	0	0	0	0	1	1
Mixed Asian Race	0	0	0	1	0	0	1

End points

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Reporting group title

Part A- Sotrovimab Gen1: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen1 500 milligrams (mg) intravenous (IV) infusion on Day 1 in Part A.

Reporting group title

Part A- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part A.

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part B.

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IM

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg intramuscular (IM) injection on Day 1 in Part B.

Reporting group title

Part C- Sotrovimab Gen2: 500 mg IV

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 500 mg IV infusion on Day 1 in Part C.

Reporting group title

Part C- Sotrovimab Gen2: 250 mg IM

Reporting group description

Participants received Sotrovimab (VIR-7831) Gen2 250 mg IM injection on Day 1 in Part C.

Primary: Part A: Number of Participants With all Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29

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End point title

Part A: Number of Participants With all Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29 ^[1] ^[2]

End point description

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

End point type

Primary

End point timeframe

Up to Day 29

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	8 ^[3]	22 ^[4]
Units: Participants
All AEs	0	3
SAEs	0	0

Notes
[3] - Safety Population
[4] - Safety Population

No statistical analyses for this end point

Primary: Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29

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End point title

Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 ^[5] ^[6]

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were infusion site reactions; cardiac events of special interest and renal events of special interest.

End point type

Primary

End point timeframe

Up to Day 29

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	8	22
Units: Participants
Infusion site reactions	0	0
Cardiac events of special interest	0	0
Renal events of special interest	0	0

No statistical analyses for this end point

Primary: Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29

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End point title

Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29 ^[7] ^[8]

End point description

Twelve-lead ECGs were recorded with the participant in a semi-supine position after being at rest for at least 10 minutes using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented.

End point type

Primary

End point timeframe

Up to Day 29

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	8	22
Units: Participants
Abnormal-Clinically significant	0	0
Abnormal-Not Clinically significant	6	17

No statistical analyses for this end point

Primary: Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

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End point title

Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 ^[9] ^[10]

End point description

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 (DRE).

End point type

Primary

End point timeframe

Up to Day 29

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical data to report.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	8	22
Units: Participants	0	0

No statistical analyses for this end point

Primary: Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8)

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End point title

Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8) ^[11]

End point description

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 (NP) swab samples. Analysis was performed using an Analysis of covariance (ANCOVA) model with covariates of treatment and Baseline logarithm (base 10) viral load. Viral Pharmacodynamic Population consisted of all participants in the Safety Population who had a Baseline (Day 1) quantifiable viral load as assessed using qRT-PCR from NP swabs. Only those participants with data available at the specified time points without missing covariate information were analyzed.

End point type

Primary

End point timeframe

Day 1 to Day 8

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	64	65
Units: Day*log10 copies per (/) milliliter (mL)
least squares mean (confidence interval 90%)	24.40 (23.53 to 25.31)	25.28 (24.38 to 26.21)

Statistical analysis 1

Statistical analysis description

Analysis was performed using an Analysis of covariance (ANCOVA) model with covariates of treatment and Baseline logarithm (base 10) viral load.

Comparison groups

Part B- Sotrovimab Gen2: 500 mg IV v Part B- Sotrovimab Gen2: 500 mg IM

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.04

Confidence interval

level

90%

sides

2-sided

lower limit

0.98

upper limit

1.09

Primary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8)

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End point title

Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8) ^[12]

End point description

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in NP swab samples. Analysis was performed using an ANCOVA model with covariates of treatment, and Baseline logarithm (base10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine).

End point type

Primary

End point timeframe

Day 1 to Day 8

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	55	62
Units: Day*log10 copies/mL
least squares mean (confidence interval 90%)	26.20 (24.68 to 27.81)	26.72 (25.26 to 28.27)

Statistical analysis 1

Statistical analysis description

Analysis was performed using an ANCOVA model with covariates of treatment, and Baseline logarithm (base10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine).

Comparison groups

Part C- Sotrovimab Gen2: 500 mg IV v Part C- Sotrovimab Gen2: 250 mg IM

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.02

Confidence interval

level

90%

sides

2-sided

lower limit

0.94

upper limit

1.11

Secondary: Part B: Number of Participants with AEs and SAEs Through Day 29

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End point title

Part B: Number of Participants with AEs and SAEs Through Day 29 ^[13]

End point description

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. A 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. Adverse events include both Serious and Other Adverse Events.

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	84	82
Units: Participants
AEs	8	17
SAEs	1	2

No statistical analyses for this end point

Secondary: Part B: Number of Participants With AESI Through Day 29

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End point title

Part B: Number of Participants With AESI Through Day 29 ^[14]

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); cardiac events of special interest and renal events of special interest.

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	84	82
Units: Participants
IRR including hypersensitivity	0	1
Injection site reactions	0	9
Cardiac events of special interest	0	0
Renal events of special interest	0	0

No statistical analyses for this end point

Secondary: Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

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End point title

Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 ^[15]

End point description

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	84	82
Units: Participants
Abnormal-Clinically significant	1	1
Abnormal-Not Clinically significant	43	39

No statistical analyses for this end point

Secondary: Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

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End point title

Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 ^[16]

End point description

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	84	82
Units: Participants	0	3

No statistical analyses for this end point

Secondary: Part C: Number of Participants With AEs and SAEs Through Day 29

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End point title

Part C: Number of Participants With AEs and SAEs Through Day 29 ^[17]

End point description

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	79	78
Units: Participants
AEs	10	13
SAEs	1	3

No statistical analyses for this end point

Secondary: Part C: Number of Participants With AESI Through Day 29

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End point title

Part C: Number of Participants With AESI Through Day 29 ^[18]

End point description

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs were injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); cardiac events of special interest and renal events of special interest.

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	79	78
Units: Participants
IRR including hypersensitivity	0	0
Injection site reactions	0	3
Cardiac events of special interest	0	0
Renal events of special interest	0	0

No statistical analyses for this end point

Secondary: Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

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End point title

Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 ^[19]

End point description

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	79	78
Units: Participants
Abnormal-Clinically significant	0	0
Abnormal-Not Clinically significant	38	37

No statistical analyses for this end point

Secondary: Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

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End point title

Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 ^[20]

End point description

End point type

Secondary

End point timeframe

Up to Day 29

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	79	78
Units: Participants	0	0

No statistical analyses for this end point

Secondary: Part A: Change from Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load

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End point title

Part A: Change from Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load ^[21]

End point description

SARS-CoV-2 viral load was based on saliva and nasal mid-turbinate swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the NEG and <2.08 results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

End point type

Secondary

End point timeframe

Baseline, Days 2, 5, 8, 11, 15, 22 and 29

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	6	16
Units: Log10 copies/mL
arithmetic mean (standard deviation)
Day 2: Saliva, n=4,11	-0.270 ( 0.4290 )	-1.114 ( 0.9201 )
Day 5: Saliva, n=3,11	-0.780 ( 0.3404 )	-2.620 ( 1.0199 )
Day 8: Saliva, n=3,11	-0.507 ( 0.5689 )	-2.605 ( 1.4982 )
Day 11: Saliva, n=4,10	-1.043 ( 0.5940 )	-2.881 ( 1.3963 )
Day 15: Saliva, n=4,11	-0.610 ( 1.3444 )	-3.179 ( 1.2132 )
Day 22: Saliva, n=4,11	-1.043 ( 0.5940 )	-3.284 ( 1.3210 )
Day 29: Saliva, n=4,11	-1.043 ( 0.5940 )	-3.223 ( 1.3123 )
Day 2: Nasal mid-turbinate, n=5,16	-1.252 ( 0.9726 )	-1.006 ( 1.2277 )
Day 5: Nasal mid-turbinate, n=4,16	-1.755 ( 1.1230 )	-2.111 ( 1.2100 )
Day 8: Nasal mid-turbinate, n=4,16	-1.705 ( 0.7839 )	-2.703 ( 1.7842 )
Day 11: Nasal mid-turbinate, n=5,16	-2.810 ( 1.3363 )	-2.923 ( 1.5656 )
Day 15: Nasal mid-turbinate, n=5,16	-2.490 ( 1.3243 )	-3.445 ( 1.7103 )
Day 22: Nasal mid-turbinate, n=5,16	-2.668 ( 1.2826 )	-3.873 ( 1.9434 )
Day 29: Nasal mid-turbinate, n=5,16	-2.810 ( 1.3363 )	-3.752 ( 1.8030 )

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

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End point title

Part B: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples ^[22]

End point description

Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Viral Pharmacodynamic Population consisted of all participants in the Safety Population who had a Baseline (Day 1) quantifiable viral load as assessed using qRT-PCR from NP swabs. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	66	68
Units: Log10 copies/mL
arithmetic mean (standard deviation)
Day 2: n=63,68	-1.146 ( 1.1558 )	-0.611 ( 1.1518 )
Day 3: n=63,66	-1.438 ( 1.2033 )	-1.306 ( 1.3132 )
Day 5: n=62,64	-2.578 ( 1.2480 )	-2.352 ( 1.1655 )
Day 8: n=64,64	-3.069 ( 1.4553 )	-3.254 ( 1.4193 )
Day 11: n=62,63	-3.522 ( 1.7148 )	-3.574 ( 1.4907 )
Day 15: n=62,66	-3.705 ( 1.7443 )	-3.733 ( 1.5525 )
Day 22: n=64,66	-3.831 ( 1.7994 )	-3.778 ( 1.7476 )
Day 29: n=62,64	-3.933 ( 1.8253 )	-3.857 ( 1.7455 )

No statistical analyses for this end point

Secondary: Part C: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

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End point title

Part C: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples ^[23]

End point description

Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline log10 viral load was defined as the non-missing assessment taken at Day 1 excluding the "NEG" and "<2.08" results. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	61	66
Units: Log10 copies per milliliter
log mean (standard deviation)
Day 2: n=59,64	-0.429 ( 1.3835 )	-0.519 ( 1.3273 )
Day 3: n=50,57	-0.905 ( 1.5202 )	-1.123 ( 1.6172 )
Day 5: n=57,62	-2.076 ( 1.9648 )	-1.967 ( 2.0218 )
Day 8: n=55,62	-3.122 ( 1.8234 )	-3.180 ( 1.8324 )
Day 11: n=52,61	-3.617 ( 1.6870 )	-3.738 ( 1.8168 )
Day 15: n=50,61	-3.719 ( 1.8248 )	-3.836 ( 1.8148 )
Day 22: n=55,65	-3.693 ( 1.7647 )	-3.956 ( 1.7492 )
Day 29: n=56,63	-3.761 ( 1.8167 )	-3.963 ( 1.7189 )

No statistical analyses for this end point

Secondary: Part B: Percentage of Participants With Undetectable Viral Load

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End point title

Part B: Percentage of Participants With Undetectable Viral Load ^[24]

End point description

Viral load was measured by qRT-PCR from nasopharyngeal swab samples. Viral load (log10 copies/mL) values recorded as negative were considered as undetectable viral load. Percentage of participants with undetectable viral load have been presented. Percentage values are rounded off. Viral Pharmacodynamic Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Days 2, 3, 5, 8, 11, 15, 22 and 29

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	66	68
Units: Percentage of participants
number (not applicable)
Day 2: n=63,68	10	4
Day 3: n=63,66	11	9
Day 5: n=62,64	23	27
Day 8: n=64,64	34	38
Day 11: n=62,63	58	51
Day 15: n=62,66	61	73
Day 22: n=64,66	73	74
Day 29: n=62,64	81	84

No statistical analyses for this end point

Secondary: Part C: Percentage of Participants With Undetectable Viral Load

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End point title

Part C: Percentage of Participants With Undetectable Viral Load ^[25]

End point description

End point type

Secondary

End point timeframe

Days 2, 3, 5, 8, 11, 15, 22 and 29

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	61	66
Units: Percentage of participants
number (not applicable)
Day 2: n=59,64	10	5
Day 3: n=50,57	10	14
Day 5: n=57,62	28	16
Day 8: n=55,62	42	39
Day 11: n=52,61	63	72
Day 15: n=50,61	82	80
Day 22: n=55,65	80	88
Day 29: n=56,63	88	86

No statistical analyses for this end point

Secondary: Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

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End point title

Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) ^[26]

End point description

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load. Viral Pharmacodynamic Population. Only those participants with data available at the specified time points without missing covariate information were analyzed.

End point type

Secondary

End point timeframe

Day 1 to Day 5

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	63 ^[27]	65 ^[28]
Units: Day*log10 copies/mL
least squares mean (confidence interval 90%)	16.4 (15.53 to 16.77)	16.97 (16.34 to 17.62)

Notes
[27] - Viral Pharmacodynamic Population.
[28] - Viral Pharmacodynamic Population.

Statistical analysis 1

Statistical analysis description

Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load.

Comparison groups

Part B- Sotrovimab Gen2: 500 mg IV v Part B- Sotrovimab Gen2: 500 mg IM

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.05

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

1.11

Secondary: Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

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End point title

Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) ^[29]

End point description

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load.

End point type

Secondary

End point timeframe

Day 1 to Day 11

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	64	65
Units: Day*log10 copies/mL
least squares mean (confidence interval 90%)	31.69 (30.60 to 32.82)	32.39 (31.28 to 33.53)

Statistical analysis 1

Statistical analysis description

Analysis was performed using an ANCOVA model with covariates of treatment and Baseline logarithm (base 10) viral load.

Comparison groups

Part B- Sotrovimab Gen2: 500 mg IV v Part B- Sotrovimab Gen2: 500 mg IM

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.02

Confidence interval

level

90%

sides

2-sided

lower limit

0.97

upper limit

1.07

Secondary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

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End point title

Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) ^[30]

End point description

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 5. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine).

End point type

Secondary

End point timeframe

Day 1 to Day 5

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	57	63
Units: Day*log10 copies/mL
least squares mean (confidence interval 90%)	17.42 (16.49 to 18.41)	17.56 (16.66 to 18.51)

Statistical analysis 1

Statistical analysis description

Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine).

Comparison groups

Part C- Sotrovimab Gen2: 500 mg IV v Part C- Sotrovimab Gen2: 250 mg IM

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.01

Confidence interval

level

90%

sides

2-sided

lower limit

0.93

upper limit

1.09

Secondary: Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

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End point title

Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) ^[31]

End point description

AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 11. Analysis was performed using an ANCOVA model with covariates of treatment, Baseline logarithm (base 10) viral load and randomization stratification factor (prior exposure to an authorized or approved SARS-CoV-2 vaccine).

End point type

Secondary

End point timeframe

Day 1 to Day 11

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	53	62
Units: Day*log10 copies/mL
least squares mean (confidence interval 90%)	33.02 (31.17 to 34.97)	33.63 (31.89 to 35.47)

Statistical analysis 1

Statistical analysis description

Comparison groups

Part C- Sotrovimab Gen2: 500 mg IV v Part C- Sotrovimab Gen2: 250 mg IM

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Ratio of geometric least squares mean

Point estimate

1.02

Confidence interval

level

90%

sides

2-sided

lower limit

0.94

upper limit

1.1

Secondary: Part B: Percentage of Participants With a Persistently High Viral Load at Day 8

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End point title

Part B: Percentage of Participants With a Persistently High Viral Load at Day 8 ^[32]

End point description

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 viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage of participants with a persistently high viral load at Day 8 has been presented. Percentage values are rounded off.

End point type

Secondary

End point timeframe

Day 8

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	64	64
Units: Percentage of participants
number (not applicable)
>=4.1 log 10 copies/mL	17	11
<4.1 log 10 copies/mL	83	89

No statistical analyses for this end point

Secondary: Part C: Percentage of Participants With a Persistently High Viral Load at Day 8

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End point title

Part C: Percentage of Participants With a Persistently High Viral Load at Day 8 ^[33]

End point description

End point type

Secondary

End point timeframe

Day 8

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	55	62
Units: Percentage of participants
number (not applicable)
>=4.1 log 10 copies/mL	15	13
<4.1 log 10 copies/mL	85	87

No statistical analyses for this end point

Secondary: Part B: Cmax of VIR-7831 after IV administration

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End point title

Part B: Cmax of VIR-7831 after IV administration ^[34]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	5
Units: Microgram per mL
arithmetic mean (standard deviation)	140.2 ( 9.36 )

No statistical analyses for this end point

Secondary: Part B: Cmax of VIR-7831 after IM administration

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End point title

Part B: Cmax of VIR-7831 after IM administration ^[35]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	11
Units: Microgram per mL
arithmetic mean (standard deviation)	28.2 ( 15.98 )

No statistical analyses for this end point

Secondary: Part C: Cmax of VIR-7831 after IV administration

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End point title

Part C: Cmax of VIR-7831 after IV administration ^[36]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	5
Units: Microgram per mL
arithmetic mean (standard deviation)	137.4 ( 32.97 )

No statistical analyses for this end point

Secondary: Part C: Cmax of VIR-7831 after IM administration

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End point title

Part C: Cmax of VIR-7831 after IM administration ^[37]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	7
Units: Microgram per mL
arithmetic mean (standard deviation)	11.4 ( 6.02 )

No statistical analyses for this end point

Secondary: Part B: Clast of VIR-7831 after IV administration

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End point title

Part B: Clast of VIR-7831 after IV administration ^[38]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	11
Units: Microgram per mL
arithmetic mean (standard deviation)	37.5 ( 11.01 )

No statistical analyses for this end point

Secondary: Part B: Clast of VIR-7831 after IM administration

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End point title

Part B: Clast of VIR-7831 after IM administration ^[39]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	11
Units: Microgram per mL
arithmetic mean (standard deviation)	24.6 ( 12.05 )

No statistical analyses for this end point

Secondary: Part C: Clast of VIR-7831 after IV administration

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End point title

Part C: Clast of VIR-7831 after IV administration ^[40]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	10
Units: Microgram per mL
arithmetic mean (standard deviation)	34.4 ( 13.03 )

No statistical analyses for this end point

Secondary: Part C: Clast of VIR-7831 after IM administration

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End point title

Part C: Clast of VIR-7831 after IM administration ^[41]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	10
Units: Microgram per mL
arithmetic mean (standard deviation)	11.1 ( 7.08 )

No statistical analyses for this end point

Secondary: Part B: Tmax of VIR-7831 after IV administration

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End point title

Part B: Tmax of VIR-7831 after IV administration ^[42]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	5
Units: Day
median (full range (min-max))	0.028 (0.01 to 0.03)

No statistical analyses for this end point

Secondary: Part B: Tmax of VIR-7831 after IM administration

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End point title

Part B: Tmax of VIR-7831 after IM administration ^[43]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	11
Units: Day
median (full range (min-max))	6.878 (3.68 to 28.94)

No statistical analyses for this end point

Secondary: Part C: Tmax of VIR-7831 after IV administration

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End point title

Part C: Tmax of VIR-7831 after IV administration ^[44]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	5
Units: Day
median (full range (min-max))	0.014 (0.01 to 0.02)

No statistical analyses for this end point

Secondary: Part C: Tmax of VIR-7831 after IM administration

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End point title

Part C: Tmax of VIR-7831 after IM administration ^[45]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed. The time frame is beyond Day 29 as there were available pharmacokinetic (PK) data for some participants up to Day 57 (+/-4 days per protocol defined time point) that were included in the analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	7
Units: Day
median (full range (min-max))	13.993 (6.93 to 33.89)

No statistical analyses for this end point

Secondary: Part B: tlast of VIR-7831 after IV administration

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End point title

Part B: tlast of VIR-7831 after IV administration ^[46]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	11
Units: Day
median (full range (min-max))	27.580 (6.70 to 28.68)

No statistical analyses for this end point

Secondary: Part B: tlast of VIR-7831 after IM administration

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End point title

Part B: tlast of VIR-7831 after IM administration ^[47]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). The upper value of the full range is outside of the time frame due to the protocol defined time point of Day 29+/-2 days.

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	11 ^[48]
Units: Day
median (full range (min-max))	27.820 (14.10 to 29.78)

Notes
[48] - Pharmacokinetic Population.

No statistical analyses for this end point

Secondary: Part C: tlast of VIR-7831 after IV administration

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End point title

Part C: tlast of VIR-7831 after IV administration ^[49]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). The time frame is beyond Day 29 as there were available PK data for some participants up to Day 57 (+/-4 days per protocol defined time point) that were included in the analysis.

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	10
Units: Day
median (full range (min-max))	27.809 (25.91 to 53.05)

No statistical analyses for this end point

Secondary: Part C: tlast of VIR-7831 after IM administration

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End point title

Part C: tlast of VIR-7831 after IM administration ^[50]

End point description

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	10
Units: Day
median (full range (min-max))	28.552 (25.93 to 52.03)

No statistical analyses for this end point

Secondary: Part B: AUCD1-29 of VIR-7831 after IV administration

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End point title

Part B: AUCD1-29 of VIR-7831 after IV administration ^[51]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29

Notes
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	11
Units: Day*microgram/mL
arithmetic mean (standard deviation)	1407.6 ( 285.53 )

No statistical analyses for this end point

Secondary: Part B: AUCD1-29 of VIR-7831 after IM administration

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End point title

Part B: AUCD1-29 of VIR-7831 after IM administration ^[52]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	9
Units: Day*microgram/mL
arithmetic mean (standard deviation)	671.3 ( 415.34 )

No statistical analyses for this end point

Secondary: Part C: AUCD1-29 of VIR-7831 after IV administration

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End point title

Part C: AUCD1-29 of VIR-7831 after IV administration ^[53]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	9
Units: Day*microgram/mL
arithmetic mean (standard deviation)	1510.3 ( 444.32 )

No statistical analyses for this end point

Secondary: Part C: AUCD1-29 of VIR-7831 after IM administration

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End point title

Part C: AUCD1-29 of VIR-7831 after IM administration ^[54]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	8
Units: Day*microgram/mL
arithmetic mean (standard deviation)	380.8 ( 251.26 )

No statistical analyses for this end point

Secondary: Part B: AUClast of VIR-7831 after IV administration

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End point title

Part B: AUClast of VIR-7831 after IV administration ^[55]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	11
Units: Day*microgram/mL
arithmetic mean (standard deviation)	1307.7 ( 398.12 )

No statistical analyses for this end point

Secondary: Part B: AUClast of VIR-7831 after IM administration

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End point title

Part B: AUClast of VIR-7831 after IM administration ^[56]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days)

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part B- Sotrovimab Gen2: 500 mg IM
Number of subjects analysed	11
Units: Day*microgram/mL
arithmetic mean (standard deviation)	642.7 ( 373.53 )

No statistical analyses for this end point

Secondary: Part C: AUClast of VIR-7831 after IV administration

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End point title

Part C: AUClast of VIR-7831 after IV administration ^[57]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 500 mg IV
Number of subjects analysed	10
Units: Day*microgram/mL
arithmetic mean (standard deviation)	1563.8 ( 492.08 )

No statistical analyses for this end point

Secondary: Part C: AUClast of VIR-7831 after IM administration

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End point title

Part C: AUClast of VIR-7831 after IM administration ^[58]

End point description

Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab).

End point type

Secondary

End point timeframe

Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57 (+/-4 days)

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	Part C- Sotrovimab Gen2: 250 mg IM
Number of subjects analysed	10
Units: Day*microgram/mL
arithmetic mean (standard deviation)	380.6 ( 259.90 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality, non-serious AEs and SAEs were collected up to Day 29 in Parts A, B and C

Adverse event reporting additional description

Safety Population consisted of all randomized participants who were exposed to study intervention. The results presented are based on the primary analysis (data up to Day 29). Additional results will be provided within one year after study completion.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Part A- Sotrovimab Gen1: 500 mg IV

Reporting group description

Reporting group title

Part A- Sotrovimab Gen2: 500 mg IV

Reporting group description

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IV

Reporting group description

Reporting group title

Part B- Sotrovimab Gen2: 500 mg IM

Reporting group description

Reporting group title

Part C- Sotrovimab Gen2: 500 mg IV

Reporting group description

Reporting group title

Part C- Sotrovimab Gen2: 250 mg IM

Reporting group description

Serious adverse events	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	2 / 82 (2.44%)	1 / 79 (1.27%)	3 / 78 (3.85%)
number of deaths (all causes)	0	0	0	0	0	1
number of deaths resulting from adverse events
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	1 / 82 (1.22%)	1 / 79 (1.27%)	2 / 78 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Pneumonia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Part A- Sotrovimab Gen1: 500 mg IV	Part A- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IV	Part B- Sotrovimab Gen2: 500 mg IM	Part C- Sotrovimab Gen2: 500 mg IV	Part C- Sotrovimab Gen2: 250 mg IM
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 8 (0.00%)	3 / 22 (13.64%)	7 / 84 (8.33%)	17 / 82 (20.73%)	9 / 79 (11.39%)	11 / 78 (14.10%)
Vascular disorders
Haematoma
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Hypertension
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	9 / 82 (10.98%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	11	0	1
Injection site nodule
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	1	0	1
Injection site discomfort
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Peripheral swelling
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Rhinorrhoea
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Anxiety
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Depression
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Investigations
Brain natriuretic peptide increased
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Transaminases increased
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Hepatic enzyme increased
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Lipase increased
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	2	0	0	0
Restless legs syndrome
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	2 / 84 (2.38%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	2	0	0	0
Headache
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Migraine
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Blood and lymphatic system disorders
Anemia
subjects affected / exposed	0 / 8 (0.00%)	1 / 22 (4.55%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	1	1	0	0	0
Iron deficiency anemia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	1	0	1
Motion sickness
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Aphthous ulcer
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Diarrhea
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Dyspepsia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Paraesthesia oral
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Nausea
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Vomiting
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	1	0	1
Rash
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	2 / 82 (2.44%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	2	0	0
Myalgia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	2	0	1
Neck pain
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Pain in extremity
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Pain in jaw
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Infections and infestations
Blister infected
subjects affected / exposed	0 / 8 (0.00%)	1 / 22 (4.55%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	1	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	1	0
Sinusitis
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	1 / 79 (1.27%)	1 / 78 (1.28%)
occurrences all number	0	0	0	1	1	1
Urinary tract infection
subjects affected / exposed	0 / 8 (0.00%)	1 / 22 (4.55%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	1	0	0	1	0
Cellulitis
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Herpes zoster
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	1 / 79 (1.27%)	0 / 78 (0.00%)
occurrences all number	0	0	0	0	1	0
Otitis media acute
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	1 / 84 (1.19%)	0 / 82 (0.00%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	1	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	1 / 82 (1.22%)	0 / 79 (0.00%)	0 / 78 (0.00%)
occurrences all number	0	0	0	1	0	0
Gout
subjects affected / exposed	0 / 8 (0.00%)	0 / 22 (0.00%)	0 / 84 (0.00%)	0 / 82 (0.00%)	0 / 79 (0.00%)	1 / 78 (1.28%)
occurrences all number	0	0	0	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

19 Jan 2021

Amendment 1: Protocol changes have been made to include nasal mid-turbinate swabs and resistance testing at the request of regulatory agencies.

03 Mar 2021

Amendment 2: Protocol changes have been made to add a second part (Part B) to this study to assess IM injection of VIR-7831 Gen2 material. The original treatment arms evaluating Gen2 and Gen1 material administered IV is designated Part A. Changes were made throughout the protocol to add information necessary for conducting Part B and to differentiate Part A and Part B procedures. Other changes include: removal of home nursing option for Part A study visits, an additional endpoint for the secondary safety objective for Part A, updates to endpoint wording for Part A, the addition of resistance analyses, updated background information based on new data, and clarifications throughout the protocol

08 Apr 2021

Amendment 3: Adding measurement of anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibody at Baseline and Day 29 to the study procedures to allow for exploratory analysis of immune response. Removing the requirement that at least 15 participants are enrolled in Part A before enrollment in Part B can begin so that Part B can begin without delay

18 May 2021

Amendment 4: Protocol changes have been made to add a third part (Part C) to this study to assess the safety, tolerability, immunogenicity, pharmacokinetics, and viral pharmacodynamics of a 250 milligram (mg) dose of VIR-7831 administered by IM injection. Changes were made throughout the protocol to add information necessary for conducting Part C procedures. Additionally, the post-dose monitoring time for Part B has been reduced to 1 hour after Joint Safety Review Team (JSRT) review on 13 May 2021. Other changes include: moving resistance analysis to an exploratory objective, providing updated data, clarification of inclusion and exclusion criteria, incorporated information from the Germany-specific protocol amendment, and other clarifications throughout the protocol.

29 Oct 2021

Amendment 5: Expanded the safety follow-up of all active participants through Week 36 (~5 half lives of sotrovimab).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blinded, Parallel Group Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Second Generation VIR-7831 Materian in Non-Hospitalized Participants with Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Number of Participants With all Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29

Primary: Part A: Number of Participants With all Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29

Primary: Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29

Primary: Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29

Primary: Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29

Primary: Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29

Primary: Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Primary: Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Primary: Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8)

Primary: Part B: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 (AUCD1-8)

Primary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8)

Primary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8)

Secondary: Part B: Number of Participants with AEs and SAEs Through Day 29

Secondary: Part B: Number of Participants with AEs and SAEs Through Day 29

Secondary: Part B: Number of Participants With AESI Through Day 29

Secondary: Part B: Number of Participants With AESI Through Day 29

Secondary: Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

Secondary: Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

Secondary: Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Secondary: Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Secondary: Part C: Number of Participants With AEs and SAEs Through Day 29

Secondary: Part C: Number of Participants With AEs and SAEs Through Day 29

Secondary: Part C: Number of Participants With AESI Through Day 29

Secondary: Part C: Number of Participants With AESI Through Day 29

Secondary: Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

Secondary: Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29

Secondary: Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Secondary: Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29

Secondary: Part A: Change from Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load

Secondary: Part A: Change from Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load

Secondary: Part B: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

Secondary: Part B: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

Secondary: Part C: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

Secondary: Part C: Change from Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples

Secondary: Part B: Percentage of Participants With Undetectable Viral Load

Secondary: Part B: Percentage of Participants With Undetectable Viral Load

Secondary: Part C: Percentage of Participants With Undetectable Viral Load

Secondary: Part C: Percentage of Participants With Undetectable Viral Load

Secondary: Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

Secondary: Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

Secondary: Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

Secondary: Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

Secondary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

Secondary: Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5)

Secondary: Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

Secondary: Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11)

Secondary: Part B: Percentage of Participants With a Persistently High Viral Load at Day 8

Secondary: Part B: Percentage of Participants With a Persistently High Viral Load at Day 8

Secondary: Part C: Percentage of Participants With a Persistently High Viral Load at Day 8

Secondary: Part C: Percentage of Participants With a Persistently High Viral Load at Day 8

Secondary: Part B: Cmax of VIR-7831 after IV administration

Secondary: Part B: Cmax of VIR-7831 after IV administration

Secondary: Part B: Cmax of VIR-7831 after IM administration

Secondary: Part B: Cmax of VIR-7831 after IM administration

Secondary: Part C: Cmax of VIR-7831 after IV administration

Secondary: Part C: Cmax of VIR-7831 after IV administration

Secondary: Part C: Cmax of VIR-7831 after IM administration

Secondary: Part C: Cmax of VIR-7831 after IM administration

Secondary: Part B: Clast of VIR-7831 after IV administration

Secondary: Part B: Clast of VIR-7831 after IV administration

Secondary: Part B: Clast of VIR-7831 after IM administration

Secondary: Part B: Clast of VIR-7831 after IM administration

Secondary: Part C: Clast of VIR-7831 after IV administration

Secondary: Part C: Clast of VIR-7831 after IV administration

Secondary: Part C: Clast of VIR-7831 after IM administration

Secondary: Part C: Clast of VIR-7831 after IM administration

Secondary: Part B: Tmax of VIR-7831 after IV administration

Secondary: Part B: Tmax of VIR-7831 after IV administration

Secondary: Part B: Tmax of VIR-7831 after IM administration

Secondary: Part B: Tmax of VIR-7831 after IM administration

Clinical Trial Results:
A Multicenter, Randomized, Double-Blinded, Parallel Group Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Second Generation VIR-7831 Materian in Non-Hospitalized Participants with Mild to Moderate Coronavirus Disease 2019 (COVID-19)