Safety, Tolerability and Pharmacokinetics of Second Generation VIR-7831 Material in Non-hospitalized Participants With Mild to Moderate COVID-19

Study Overview
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Brief Summary
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This is a phase 2 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 (Sotrovimab) Generation 1 (Gen1) or VIR-7831 (Sotrovimab) Generation 2 (Gen2) and will be assessed for safety, tolerability, and pharmacokinetics.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel Group Phase II Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Second Generation VIR-7831 Material in Non-Hospitalized Participants With Mild to Moderate Coronavirus Disease 2019 (COVID-19)

Conditions
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Covid19

Intervention / Treatment
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* Biological: Sotrovimab (Gen1)
* Biological: Sotrovimab (Gen2)
* Biological: Sotrovimab (Gen2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Part A, participants must be aged 18 years or older at the time of obtaining informed consent For Parts B and C, participants must be aged between 18 years and 69 years old at the time of obtaining informed consent Participants who have a positive SARS-CoV-2 test result ≤7 days prior to enrollment and oxygen saturation ≥94% on room air and have COVID-19 symptoms and ≤7 days from onset of symptoms Exclusion Criteria: Currently hospitalized or judged by the investigator as likely to require hospitalization in the next 24 hours Symptoms consistent with severe COVID-19 Participants who, in the judgement of the investigator are likely to die in the next 7 days. Severely immunocompromised participants For Parts A and B, prior receipt of a SARS-CoV-2 vaccine at any time prior to enrollment (vaccination with an authorized or approved SARS-CoV-2 vaccine will not be allowed for 90 days after dosing) For Parts B and C, conditions that would prohibit receipt of IM injections in the investigator's opinion For Parts A, B and C, receipt of any vaccine within 48 hours prior to enrollment (vaccination with an authorized or approved SARS-CoV-2 vaccine will not be allowed for 90 days after dosing)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sotrovimab (Gen1)<br>Part A (double-blinded) participants will be randomized to receive 500 mg of an IV infusion of Sotrovimab Gen 1 material or 500 mg of an IV infusion of VIR-7831 Gen 2 material | Biological: Sotrovimab (Gen1)<br>* Participants will be randomized to receive an IV infusion of Sotrovimab Gen 1 material<br>Biological: Sotrovimab (Gen2)<br>* Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion<br>|
| Active Comparator: Sotrovimab (Gen2)<br>Part B (open-label) participants will be randomized to receive 500 mg of Sotrovimab Gen2 material by IV infusion or by IM injection Part C (open-label) participants will be randomized to receive 500 mg of Sotrovimab Gen2 material by IV infusion or 250 mg by IM injection | Biological: Sotrovimab (Gen2)<br>* Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion or by IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants With All Adverse Events (AEs) and Serious Adverse Events (SAEs) Through Day 29 | 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. | Up to Day 29 | 
| Part A: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | 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-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. | Up to Day 29 | 
| Part A: Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings Through Day 29 | 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 were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. | Up to Day 29 | 
| Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Day 29 | 
| 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) | 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. | Day 1 to Day 8 | 
| Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 (AUCD1-8) | 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). | Day 1 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants With Non-Serious AEs Through Week 12 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events which were not Serious were considered as Non-Serious adverse events. | Up to Week 12 | 
| Part A: Number of Participants With SAEs Through Week 24 | 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. | Up to Week 24 | 
| Part A: Number of Participants With AESI Through Week 24 | 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 are infusion-related reactions (IRR) including hypersensitivity, events related to antibody-dependent enhancement, and events related to immunogenicity. | Up to Week 24 | 
| Part A: Number of Participants With Abnormal ECG Findings at Indicated Time Points | 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 were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. | Days 1, 5, 11 and 85 (Week 12) | 
| Part A: Number of Participants With Disease Progression Events (Disease-Related Events) Through Week 24 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Week 24 | 
| Part B: Number of Participants With All AEs and SAEs Through Day 29 | 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. | Up to Day 29 | 
| Part B: Number of Participants With AESI Through Day 29 | 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/injection-related reactions (IRR) including hypersensitivity; injection site reactions (ISRs); events related to antibody-dependent enhancement; events related to immunogenicity. | Up to Day 29 | 
| Part B: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 | 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 were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. | Up to Day 29 | 
| Part B: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Day 29 | 
| Part C: Number of Participants With All AEs and SAEs Through Day 29 | 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. | Up to Day 29 | 
| Part C: Number of Participants With AESI Through Day 29 | 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/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. | Up to Day 29 | 
| Part C: Number of Participants With Worst-case Post Baseline Abnormal ECG Findings Through Day 29 | 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 were determined as per clinical judgement by the investigator. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. | Up to Day 29 | 
| Part C: Number of Participants With Disease Progression Events (Disease-Related Events) Through Day 29 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Day 29 | 
| Part B: Number of Participants With Non-Serious AEs Through Week 12 | 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. | Up to Week 12 | 
| Part B: Number of Participants With SAEs Through Week 36 | 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. | Up to Week 36 | 
| Part B: Number of Participants With AESI Through Week 36 | 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 are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. | up to Week 36 | 
| Part B: Number of Participants With Abnormal ECG Findings at Indicated Time Points | 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 were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. | Days 1, 5, 11 and 85 (Week 12) | 
| Part B: Number of Participants With Disease Progression Events Through Week 36 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Week 36 | 
| Part C: Number of Participants With Non-Serious AEs Through Week 12 | 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. | Up to Week 12 | 
| Part C: Number of Participants With SAEs Through Week 36 | 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. | Up to Week 36 | 
| Part C: Number of Participants With AESI Through Week 36 | 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 are infusion/injection-related reactions (IRR) including hypersensitivity reactions; injection site reactions (ISRs); events related to antibody-dependent enhancement, and events related to immunogenicity. | Up to Week 36 | 
| Part C: Number of Participants With Abnormal ECG Findings at Indicated Time Points | 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 were determined as per clinical judgement by the investigator. Number of participants with clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. | Days 1, 5, 11 and 85 (Week 12) | 
| Part C: Number of Participants With Disease Progression Events Through Week 36 | 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, and considered to be not causally-related to the study agent or study procedures by the Investigator, were reported as a Disease-Related Events (DRE). | Up to Week 36 | 
| Part A: Change From Baseline in SARS-CoV-2 Saliva and Nasal Mid-Turbinate Viral Load | 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. | Baseline, Days 2, 5, 8, 11, 15, 22 and 29 | 
| Part B: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples | 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. | Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 | 
| Part C: Change From Baseline in Viral Load as Measured by qRT-PCR From Nasopharyngeal Swab Samples | 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. | Baseline, Days 2, 3, 5, 8, 11, 15, 22 and 29 | 
| Part B: Percentage of Participants With Undetectable Viral Load | 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. | Days 2, 3, 5, 8, 11, 15, 22 and 29 | 
| Part C: Percentage of Participants With Undetectable Viral Load | 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. | Days 2, 3, 5, 8, 11, 15, 22 and 29 | 
| Part B: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) | 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. | Day 1 to Day 5 | 
| Part B: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) | 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. | Day 1 to Day 11 | 
| Part C: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 5 (AUCD1-5) | 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). | Day 1 to Day 5 | 
| Part C: Mean Area Under the Curve (AUC) of SARS-CoV-2 Viral Load From Day 1 to Day 11 (AUCD1-11) | 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). | Day 1 to Day 11 | 
| Part B: Percentage of Participants With a Persistently High Viral Load at Day 8 | 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. | Day 8 | 
| Part C: Percentage of Participants With a Persistently High Viral Load at Day 8 | 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. | Day 8 | 
| Part A: Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Cmax of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Cmax of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Cmax of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: Cmax of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Concentration at Last Quantifiable Time-point (Clast) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Clast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Clast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Clast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: Clast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Time to Reach Cmax (Tmax) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Tmax of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Tmax of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Tmax of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: Tmax of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Tlast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Tlast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Tlast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: Tlast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: AUC From Day 1 to 29 (AUCD1-29) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29 | 
| Part B: AUCD1-29 of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) | 
| Part B: AUCD1-29 of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) | 
| Part C: AUCD1-29 of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29 (+/-2 days) | 
| Part C: AUCD1-29 of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) | 
| Part A: Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUC[0-inf]) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: AUC(0-inf) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: AUC(0-inf) of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: AUC(0-inf) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: AUC(0-inf) of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: AUClast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: AUClast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: AUClast of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: AUClast of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Percentage of AUC(Infinity) Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: %AUCexp of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: %AUCexp of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: %AUCexp of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: %AUCexp of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: t1/2 of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: t1/2 of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: t1/2 of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: t1/2 of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Apparent Volume of Distribution During the Elimination Phase Following Intravascular Administrtion (Vz) of VIR-7831 | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Vz of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Apparent Volume of Distribution During the Elimination Phase Following Extravascular Administration (Vz/F) of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Vz of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: Vz/F of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: Vss of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: Vss of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part A: Clearance (CL) of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion and at 1, 2, 6, and 8 hours following end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, and 169 (+/-12 days) | 
| Part B: CL of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part B: Apparent Clearance (CL/F) of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-7 days) | 
| Part C: CL of VIR-7831 After IV Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose, end of infusion; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Part C: CL/F of VIR-7831 After IM Administration | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Three Dose Levels (250 mg IM in Part C, 500 mg IM in Part B and 500 mg IV in Parts B and C) | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). Dose-normalized least square geometric mean ratio of AUCinf was derived based on collected assessments up to 169 (+/-7 days) for Part B- Sotrovimab Gen2: 500 mg IV arm, and up to 169 (+/-18 days) for Part C- Sotrovimab Gen2: 500 mg IV arm. | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Dose-normalized Least Square Geometric Mean Ratio of AUCinf for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Dose-normalized Least Square Geometric Mean Ratio of AUClast for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 
| Dose-normalized Least Square Geometric Mean Ratio of AUCD1-D29 for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29 (+/-2 days) | 
| Dose-normalized Least Square Geometric Mean Ratio of Cmax for VIR-7831 Gen2 Between the Two IM Dose Levels (250 mg IM in Part C and 500 mg IM in Part B) | Blood samples were collected at indicated time points for pharmacokinetic analysis of VIR-7831 (Sotrovimab). | Day 1: Pre-dose; Days 2, 3, 5, 8, 15, 29, 57, 85, 141, and 169 (+/-18 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, coronavirus, coronavirus disease 2019, COVID-19