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

Covid19 Clinical Trial

— COMET-PEAK  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04779879
• Other study ID #: VIR-7831-5006
• Secondary ID: GSK Study 216912
• Status: Completed
• Phase: Phase 2
• Start date: February 18, 2021
• Est. completion date: April 6, 2022

Study information

• Verified date: April 2023
• Source: Vir Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 354
• Est. completion date: April 6, 2022
• Est. primary completion date: August 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• Sotrovimab (Gen1)
Participants will be randomized to receive an IV infusion of Sotrovimab Gen 1 material
• Sotrovimab (Gen2)
Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion or by IM injection
• Sotrovimab (Gen2)
Participants will be randomized to receive Sotrovimab Gen2 material by IV infusion

Locations

Country	Name	City	State
Canada	Investigative Site	Sarnia	Ontario
Canada	Investigative Site	Toronto	Ontario
Italy	Investigative Site	Milano
Korea, Republic of	Investigative Site	Daejeon
Spain	Investigative Site	Alicante
Spain	Investigative Site	Barcelona
Spain	Investigative Site	Centelles
Spain	Investigative Site	Granada
Spain	Investigative Site	La Roca Del Vallès
Spain	Investigative Site	Madrid
Spain	Investigative Site	Madrid
Spain	Investigative Site	Pozuelo De Alarcón
Spain	Investigative Site	Vigo
United States	Investigative Site	Anniston	Alabama
United States	Investigative Site	Bakersfield	California
United States	Investigative Site	Bronx	New York
United States	Investigative Site	Columbus	Georgia
United States	Investigative Site	Fort Pierce	Florida
United States	Investigative Site	Gainesville	Florida
United States	Investigative Site	Hialeah	Florida
United States	Investigative Site	Houston	Texas
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Miami	Florida
United States	Investigative Site	Northridge	California
United States	Investigative Site	Orlando	Florida
United States	Investigative Site	Pembroke Pines	Florida
United States	Investigative Site	Rockville	Maryland
United States	Investigative Site	Tampa	Florida
United States	Investigative Site	Winfield	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Vir Biotechnology, Inc.	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Part A: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part B: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part C: Number of Participants With Presence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with presence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part A: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part B: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part C: Number of Participants With Emergence of SARS-CoV-2 Viral Resistance Mutants Against VIR-7831	Number of participants with emergence of SARS-CoV-2 viral resistance mutants against VIR-7831 was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Day 28
Other	Part A: Number of Participants With the Presence of Anti-VIR-7831 Antibody	Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part B: Number of Participants With the Presence of Anti-VIR-7831 Antibody	Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part C: Number of Participants With the Presence of Anti-VIR-7831 Antibody	Number of participants with the presence of anti-VIR-7831 antibody was planned to be evaluated. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part A: Titers of Anti-drug Antibody to VIR-7831	Serum samples were planned to be collected for the determination of anti-drug antibody using a validated electrochemiluminescent (ECL) immunoassay. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part B: Titers of Anti-drug Antibody to VIR-7831	Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part C: Titers of Anti-drug Antibody to VIR-7831	Serum samples were planned to be collected for the determination of anti-drug antibody using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Up to Week 24
Other	Part A: Number of Participants With the Presence of Anti-nucleocapsid (Anti-N), Anti-spike (Anti-S) and Anti-Receptor Binding Domain (Anti-RBD) SARS-CoV-2 Antibodies at Baseline	Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part B: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline	Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part C: Number of Participants With the Presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline	Number of participants with the presence of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part A: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part B: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part C: Titers of Anti-N, Anti-S and Anti-RBD SARS-CoV-2 Antibodies at Baseline	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Baseline (Day 1)
Other	Part A: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29	Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Day 29
Other	Part B: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29	Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Day 29
Other	Part C: Number of Participants With the Presence of Anti-N SARS-CoV-2 Antibodies at Day 29	Number of participants with the presence of Anti-N SARS-CoV-2 antibodies were planned to be evaluated. The results for this outcome measure will never be posted.	Day 29
Other	Part A: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Day 29
Other	Part B: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Day 29
Other	Part C: Titers of Anti-N SARS-CoV-2 Antibodies at Day 29	Serum samples were planned to be collected for the determination of anti-drug antibodies using a validated ECL immunoassay. The results for this outcome measure will never be posted.	Day 29
Primary	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
Primary	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
Primary	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
Primary	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
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)	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)